Author: "Eddie" / Topic: medicine.disease - Searchworks@Jio Institute Digital Library Search Results

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2,016 results on '"Eddie"'

1. C4: 'Command, control, coordination and communication' at NHS Nightingale, London: introducing the tactical commander

Author: C. E. Webster, Richard J. Schilling, Ben O’Brien, Max Marsden, Doug Bowley, Eddie Chaloner, Lalin Navaratne, and Matthew Wordsworth
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Critical Care, business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Critical Illness, Control (management), Pneumonia, Viral, COVID-19, General Medicine, medicine.disease, State Medicine, Tertiary Care Centers, Betacoronavirus, London, medicine, Emergency Medicine, Humans, Medical emergency, business, Coronavirus Infections, Pandemics
Published: 2023

2. Prenatal Δ9-Tetrahydrocannabinol Exposure in Males Leads to Motivational Disturbances Related to Striatal Epigenetic Dysregulation

Author: Teddy O. Uzamere, Prashanth Rajarajan, Aarthi Ramakrishnan, Henrietta Szutorisz, Joseph A. Landry, James E. Callens, Li Shen, Anissa Bara, Kristen J. Brennand, Claudia A. Vargas, Qammarah Martin, Yasmin L. Hurd, Eddie Loh, Randall J. Ellis, and Amy L. Frick
Subjects: Offspring, Anhedonia, Learned helplessness, Nucleus accumbens, Biology, medicine.disease, Transcriptome, medicine, Major depressive disorder, H3K4me3, Epigenetics, medicine.symptom, Neuroscience, Biological Psychiatry
Abstract: Background Cannabis remains one of the most widely abused drugs during pregnancy. In utero exposure to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), can result in long-term neuropsychiatric risk for the progeny. The current study investigated epigenetic signatures underlying these enduring consequences. Methods Rat dams were exposed daily to THC (0.15mg/kg) during pregnancy and adult male offspring were examined for reward and depressive-like behavioral endophenotypes. Using unbiased sequencing approaches, we explored transcriptional and epigenetic profiles in the nucleus accumbens (NAc), a brain area central to reward and emotional processing. An in vitro CRISPRa model coupled with RNA-sequencing was also applied to study specific consequences of epigenetic dysregulation and altered molecular signatures were compared to human major depressive disorder (MDD) transcriptome datasets. Results Prenatal THC-exposure induced increased motivation for food, heightened learned helplessness and anhedonia, and altered stress sensitivity. We identified a robust increase specific to males in the expression of Histone-Lysine N-Methyltransferase 2A (Kmt2a) that targets lysine 4 on histone H3 (H3K4me) in cellular chromatin. Normalizing Kmt2a in the NAc restored the motivational phenotype of prenatally THC-exposed animals. Comparison of RNA and H3K4me3 sequencing datasets from the NAc of rat offspring with the in vitro model of Kmt2a upregulation revealed overlapping, significant disturbances in pathways that mediate synaptic plasticity. Similar epigenetic alterations were detected in human MDD. Conclusions These studies provide direct evidence for the persistent effects of prenatal cannabis exposure on transcriptional and epigenetic deviations in the NAc via Kmt2a dysregulation and associated psychiatric vulnerability.
Published: 2022
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3. Genetic Diversity and Transmission of Multidrug-Resistant Mycobacterium tuberculosis strains in Lusaka, Zambia

Author: Mwangala Lonah Akapelwa, Precious Bwalya, Chie Nakajima, Victor Mukonka, Thoko Flav Kapalamula, Dipti Shrestha, Yukari Fukushima, Jeewan Thapa, Patrick Lungu, Joseph Yamweka Chizimu, Eddie Samuneti Solo, and Yasuhiko Suzuki
Subjects: Microbiology (medical), Tuberculosis, Genotype, Zambia, Minisatellite Repeats, Infectious and parasitic diseases, RC109-216, mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), law.invention, Mycobacterium tuberculosis, law, multidrug resistance, Tuberculosis, Multidrug-Resistant, medicine, Humans, Multidrug-Resistant Mycobacterium tuberculosis, Genotyping, Genetic diversity, biology, mycobacterial interspersed repetitive, Genetic Variation, General Medicine, medicine.disease, biology.organism_classification, Virology, Multiple drug resistance, units-variable number of tandem repeats (MIRU-VNTR), Infectious Diseases, Transmission (mechanics)
Abstract: Objective: Zambia is among the 30 high tuberculosis burden countries in the world. Despite increasing reports of multidrug-resistant tuberculosis (MDR-TB) in routine surveillance, information on the transmission of MDR Mycobacterium tuberculosis strains is largely unknown. This study elucidated the genetic diversity and transmission of MDR M. tuberculosis strains in Lusaka, Zambia. Methods: Eighty-five MDR M. tuberculosis samples collected from 2013 to 2017 at the University Teaching Hospital were used. Drug-resistance associated gene sequencing, spoligotyping, 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), and multiplex PCR for RD Rio sub-lineage identification were applied. Results: The identified clades were LAM (48%), CAS (29%), T (14%), X (6%) and Harlem (2%). Strains belonging to SITs 21/CAS1-Kili and 20/LAM1 formed the largest clonal complexes. Combined spoligotyping and 24 loci-MIRU-VNTR revealed 47 genotypic patterns with a clustering rate of 63%. Ninety-five percent of LAM strains belonged to the RD-Rio sub-lineage. Conclusion: The high clustering rate suggested that a large proportion of MDR-TB was due to recent transmission rather than the independent acquisition of MDR. This spread was attributed to clonal expansion of SIT21/CAS1-Kili and SIT20/LAM1 strains. Therefore, TB control programs recommending genotyping coupled with conventional epidemiological methods can guide measures for stopping the spread of MDR-TB. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Published: 2022

4. Risk factors for hospital readmission among infants with prolonged neonatal intensive care stays

Author: Alexis Snyder, Jay G. Berry, Laura H. Rubinos, Elizabeth Casto, Eddie Simpser, Kerri Z. Machut, Matthew Hall, and Carolyn C. Foster
Subjects: medicine.medical_specialty, Hospital readmission, Public health insurance, business.industry, MEDLINE, Obstetrics and Gynecology, Readmission rate, medicine.disease, Hydrocephalus, Gastrostomy tube, Intensive care, Pediatrics, Perinatology and Child Health, Emergency medicine, medicine, business, High risk infants
Abstract: OBJECTIVE To assess risk factors associated with 30-day hospital readmission after a prolonged neonatal intensive care stay. STUDY DESIGN Retrospective analysis of 57,035 infants discharged >14 days from the NICU between 2013 and 2016. Primary outcome was 30-day, all-cause hospital readmission. Adjusted likelihood of readmission accounting for demographic and clinical characteristics, including chronic conditions was also estimated. RESULTS The 30-day readmission rate was 10.7%. Respiratory problems accounted for most (31.0%) readmissions. In multivariable analysis, shunted hydrocephalus [OR 2.2 (95%CI 1.8-2.7)], gastrostomy tube [OR 2.0 (95%CI 1.8-2.3)], tracheostomy [OR 1.5 (95%CI 1.2-1.8)], and use of public insurance [OR 1.3 (95%CI 1.2-1.4)] had the highest likelihood of readmission. Adjusted hospital readmission rates varied significantly (p
Published: 2021
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5. Prior shoulder surgery and rheumatoid arthritis increase early risk of infection after primary reverse total shoulder arthroplasty

Author: Teron A. Nezwek, Alyssa Woltemath, Lincoln Dutcher, Jeyvikram Thirumavalavan, Julia Lund, Luke Mascarenhas, Sumant G. Krishnan, and Eddie Y. Lo
Subjects: rheumatoid arthritis, Shoulder, medicine.medical_specialty, Shoulder surgery, complications, medicine.medical_treatment, Inflammatory arthritis, primary arthroplasty, Diseases of the musculoskeletal system, Arthropathy, medicine, risk factors, Orthopedics and Sports Medicine, Rotator cuff, Medical history, Antibiotic prophylaxis, Orthopedic surgery, business.industry, postoperative infection, medicine.disease, Arthroplasty, Shoulder Arthroplasty, Surgery, medicine.anatomical_structure, RC925-935, previous nonarthroplasty surgery, Rheumatoid arthritis, business, Reverse total shoulder arthroplasty, RD701-811
Abstract: Background Reverse total shoulder arthroplasty (RTSA) has become an increasingly popular surgery for patients with rotator cuff arthropathy, unreconstructible proximal humeral fracture, and end-stage glenohumeral arthritis. The increased annual volume of RTSAs has resulted in more postoperative complications and revision rates between 3.3% and 10.1%. Postoperative infection is one of the most common complications requiring revision surgery after primary RTSA. This study assesses patient-specific risk factors for development of early infection after primary RTSA in a single high-volume shoulder arthroplasty institution. Methods From 2014 to 2019, 902 consecutive primary RTSAs were performed for surgical treatment of rotator cuff arthropathy, glenohumeral arthritis, inflammatory arthropathy, and/or dislocation. Excluding proximal humeral or scapula fractures, 756 cases met the inclusion criteria and had a minimum of 3-month follow-up. All surgeries were performed using the same surgical technique and received similar antibiotic prophylaxis. Age, patient demographics, medical history, smoking history, and prior ipsilateral shoulder treatment and/or surgery were recorded. Multivariable logistic regression analysis was used to determine risk factors associated with development of postoperative shoulder infection. Results Thirty-five patients did not meet minimum follow-up criteria and were lost to follow-up. Overall, of 721, 22 patients (3%) developed a postoperative ipsilateral shoulder infection. Previous nonarthroplasty surgery and history of rheumatoid arthritis were significantly associated with the development of postoperative shoulder infection. Amongst 196 patients who had previous nonarthroplasty shoulder surgery, there were 12 postoperative shoulder infections (6%) compared with those without previous shoulder surgery (10 of 525, 2%) (P = .003). Among 58 patients with rheumatoid arthritis, there were 5 postoperative shoulder infections (9%) compared with patients without rheumatoid arthritis (17 of 663, 3%) (P = .010). Patient age, gender, smoking status, history of diabetes mellitus, history of cancer/immunosuppression, and prior cortisone injection did not demonstrate significant associations with the development of postoperative infection. Conclusion Prior nonarthroplasty shoulder surgery and/or rheumatoid arthritis are independently associated with the development of postoperative infection after primary RTSA. Patients who demonstrate these risk factors should be appropriately evaluated and preoperatively counseled before undergoing primary RTSA. Strong consideration should be given to avoid minimally invasive nonarthroplasty surgery as a temporizing measure to delay definitive RTSA.
Published: 2021

6. Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

Author: D. Ross Camidge, Martin Dunbar, Jyoti D. Patel, Jeffrey M. Clarke, Bruce A. Bach, Eddie Thara, Francisco Robert, Silpa Nuthalapati, Ebenezer A. Kio, and Minh H. Dinh
Subjects: Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Veliparib, medicine.medical_treatment, chemistry.chemical_compound, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lung cancer, Platinum, Chemotherapy, business.industry, Combination chemotherapy, medicine.disease, Carboplatin, Nivolumab, Pemetrexed, Tolerability, chemistry, Benzimidazoles, business, medicine.drug
Abstract: Objectives Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/metastatic NSCLC. Materials and Methods Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and paclitaxel 200 mg/m2 (C/PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and pemetrexed 500 mg/m2 (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed. Results Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80–240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range 80–240 mg BID combined with nivolumab and C/PEM, with no effects on pemetrexed pharmacokinetics. Overall, the confirmed objective response rate was 40%, and best overall response was 64%. Conclusion Veliparib combined with nivolumab and platinum doublet CT was tolerated in patients with advanced/metastatic NSCLC, and no evidence of drug–drug interaction was observed. Although preliminary, this quadruple therapy may have promising antitumor activity.
Published: 2021
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7. Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy

Author: Laura A. Robertson, Julia Schaletzky, Xiaolin Wang, Chihyuan Chuang, Yangsong Wu, James J. Hartman, Jingying Wang, Eddie Wehri, Eva R. Chin, Fady I. Malik, Scott Collibee, Mark Vander Wal, Jeanelle Zamora, Peadar Cremin, Morgan Bradley P, Luke W. Ashcraft, Darren T. Hwee, and Wenyue Wang
Subjects: Dose-Response Relationship, Drug, Molecular Structure, biology, Chemistry, Hypertrophic cardiomyopathy, Cytochrome P450, Phases of clinical research, Cardiomyopathy, Hypertrophic, Pharmacology, medicine.disease, Sarcomere, Muscle hypertrophy, Structure-Activity Relationship, Fibrosis, In vivo, Drug Discovery, medicine, biology.protein, Humans, Molecular Medicine, Steady state (chemistry), Cardiac Myosins
Abstract: Hypercontractility of the cardiac sarcomere may be essential for the underlying pathological hypertrophy and fibrosis in genetic hypertrophic cardiomyopathies. Aficamten (CK-274) is a novel cardiac myosin inhibitor that was discovered from the optimization of indoline compound 1. The important advancement of the optimization was discovery of an Indane analogue (12) with a less restrictive structure-activity relationship that allowed for the rapid improvement of drug-like properties. Aficamten was designed to provide a predicted human half-life (t1/2) appropriate for once a day (qd) dosing, to reach steady state within two weeks, to have no substantial cytochrome P450 induction or inhibition, and to have a wide therapeutic window in vivo with a clear pharmacokinetic/pharmacodynamic relationship. In a phase I clinical trial, aficamten demonstrated a human t1/2 similar to predictions and was able to reach steady state concentration within the desired two-week window.
Published: 2021
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8. Mean Versus Variability: Disentangling Stress Effects on Alcohol Lapses Among Individuals in the First Year of Alcohol Use Disorder Recovery

Author: Noah N. Emery, Maya Barr, Lili Njeim, and David Eddie
Subjects: medicine.medical_specialty, Health (social science), Alcohol Drinking, Stress effects, business.industry, Ecological Momentary Assessment, Alcohol, Treatment, Early Intervention, and Prevention, Alcohol use disorder, Toxicology, medicine.disease, Alcoholism, Psychiatry and Mental health, chemistry.chemical_compound, chemistry, Humans, Medicine, Self Report, business, Psychiatry, Retrospective Studies
Abstract: OBJECTIVE: Although stress is a well-known predictor of alcohol use lapses among individuals seeking recovery from alcohol use disorder (AUD), most research has relied on retrospective self-report using conventional questionnaires that explore stress effects at the level of the mean. Ecological momentary assessment (EMA) overcomes many of the shortcomings of questionnaire-based, retrospective self-report by using real-time, in-the-environment evaluations for the acquisition of ecologically valid data that can also capture stress variability. The present investigation used EMA to disentangle stress effects on alcohol lapses among individuals in the first year of an AUD recovery attempt by exploring associations between mean-level stress, stress variability, and subsequent alcohol use. METHOD: Participants (N = 42) completed 6 days of EMA monitoring and were then followed up 90 days later to assess alcohol use. Putative associations were explored using hierarchical regression controlling for demographic factors and pre-baseline alcohol use, with percentage days abstinent from alcohol at follow-up as the outcome variable. RESULTS: An interaction effect was observed such that the combination of high mean stress level and high stress variability was associated with the lowest percentage of days abstinent. For those with high mean stress levels, this relationship was attenuated as stress variability decreased. CONCLUSIONS: The findings support previous research linking stress to alcohol use lapses; however, these results indicate that the stress/alcohol use relationship is more nuanced than previously described. Our findings suggest that stress variability should also be considered in clinical contexts when assessing risk conferred by mean-level stress.
Published: 2021
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9. Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study

Author: Waasila Jassat, Cheryl Cohen, Stefano Tempia, Maureen Masha, Susan Goldstein, Tendesayi Kufa, Pelagia Murangandi, Dana Savulescu, Sibongile Walaza, Jamy-Lee Bam, Mary-Ann Davies, Hans W Prozesky, Jonathan Naude, Ayanda T Mnguni, Charlene A Lawrence, Hlengani T Mathema, Jarrod Zamparini, John Black, Ruchika Mehta, Arifa Parker, Perpetual Chikobvu, Halima Dawood, Ntshengedzeni Muvhango, Riaan Strydom, Tsholofelo Adelekan, Bhekizizwe Mdlovu, Nirvasha Moodley, Eunice L Namavhandu, Paul Rheeder, Jacqueline Venturas, Nombulelo Magula, Lucille Blumberg, Shaina Abdullah, Fiona Abrahams, Vincentius Adams, Fhima Adnane, Sonia Adoni, Dieketso Melitta Adoons, Veronique Africa, D Aguinaga, Susan Akach, Prisha Alakram Khelawon, George Aldrich, Olatunde Alesinloye, Mathale Biniki Aletta, Mametja Alice, Tebogo Aphane, Moherndran Archary, Felicity Arends, Shireen Arends, Munonde Aser, T Asmal, Mohammed Asvat, Theunis Avenant, Muvhali Avhazwivhoni, Magnolia Azuike, Johanna Baartman, Dlava Babalwa, Johan Badenhorst, Miranda Badenhorst, Bianca Badripersad, Lalihla Badul, M Bagananeng, Mncedisi Bahle, Liezl Balfour, T C Baloyi, S Baloyi, Tinyiko Baloyi, Tshepo Mpho Baloyi, Thokozani Banda, Shimon Barit, Nicole Bartsch, Junaid Bayat, Siyabulela Bazana, Marlene Beetge, Nosindiso Bekapezulu, Rammala Belebele, Phala Bella, Zanenkululeko Belot, Lindi Gladys Bembe, Sonja Bensch, Gishma Beukes, Karla Bezuidenhout, Themba Bhembe, N A Bikisha, Ben Bilenge, Leesa Bishop, Baphamandla Biyela, Cyntheola Blaauw, Mark Blaylock, Nicola Bodley, Power Bogale, Sibongile Bokolo, Stefan Bolon, Mary Booysen, Eldereze Booysen, Lia Boretti, Paula Borges, Millicent Boshoga, Natasha Bosman, Lucinda Bosvark, Nicky Botes, Adele Botha, Chantall Botha, Jana Botha, Chantall botha, Mandlakayise Irvin Botha, Alet Botha, Janet Bradbury, Zandisile Breakfast, Maria Breed, Molele Brenda, Moshito Brice, Jolene Britz, Amanda Brown, T Buchanan, Thozama Bucwa, Crystelle Burger, Ziyanda Busakwe, Nosiviwe Bushula, Zinhle Buthelezi, Dumsile Buthelezi, Thubelihle Buthelezi, Mpumelelo Basil Buthelezi, Fundiswa Lidwina Buthelezi, Nadia Bux, Christoff Buys, Anneline Buys, Ernestina Caka, Armando Sanchez Canal, Sithole Caroline, Monrick Casper, Shannon Cawood, Oratile Cebisa, Nothando Cele, Sboniso Cele, Sthembile Goodness Cele, Mkhacani Chauke, Pinkie Chauke, Nevil Chelin, Xiaohui Chen, Venmalla Chetty, Kerisse Chetty, Christinah Cheu, Vindana Chibabhai, Takudzwa Chirima, Mantwa ChisaleMabotja, Charity Chivenge, Ngoasheng Choene, Mbali Nosisa Choko, Martin Choshi, Sabbir Chowdhury, Anastacia Christoforou, S L S Chuene, T S Chueu, Dale Cilliers, Vanessa Cilliers, Marcel Claassen, Jeané Cloete, Chantelle Coelho, Carol Coetzee, Hans Jurgens Coetzee, Christine Coetzee, Marelize Coetzee, Dane Coetzer, Sizwe Coka, M Colane, Herkulaas Combrink, Songezo Conjwa, Colleen Contrad, Faith Cornelissen, Leezelle Cronje, Christine Crouse, Tshidi Dabi, Ziyanda Dandala, Ziyaad Dangor, Gildenhuys Daniel, Ngwana Daniel, Alfred Daumas, Madelein Dauth, Mongalo David, Wayne Davids, Nozuko Daweti, Wandisa Dayile, B De Bruin, Karin De Klerk, Tanya De la Rosa, Marice de Nysschen, Marie De vos, Darien De Wet, Mohith Debising, Darshan Deenadayalu, Babalwa Dekeda, Mofokeng Desiree, Annelise Deysel, Abram Dhlamini, Makgethwa Dhlala Diala, Mathapelo Diale, Bella Diketane, Nosisa Dingani, Siyabonga Diniso, Lesego Diphatse, Anele Diya, Zihloniphile Dladla, Nompumelelo Dladla, Mlungisi Dladla, Patience Dladla, Baphilie Dlamini, Nonhlanhla Dlamini, Linda Dlamini, Nonzwakazi Dlamini, Wendy Dlamini, Ncomeka Dlamini, Siyabonga Dlamini, Nicodemus Dlamini, Lebohang Dlamini, Motshedise Dlamini, Babalwa Christine Dlava, Phikiwe Dlova, Lindiwe Dlozi, Maenetja Doreen, Vumile Doyi, Athini Doyi, Belinda Du Plessis, Johanna Aletta du Plessis, Eddie du Plessis, Nicolette du Plessis, Karin du Plessis, Briette du Toit, Narissa du Toit, Jabulile Dube, Athayanda Dubula, Msomi Duduzile, Sechaba Duiker, Unati Bongile Duma, Kholiwe Duma, Kella Dunne, Kholeka Dyantyi, Avile Dyantyi, Simphiwe Dyasi, Chauke Dyondzo, Phelisa Dyubhele, B J Dywili, Letitia Edwards, Madie Eksteen, Tersia Ellis, Tia Ellis, Glenda Emmerson, Theusia Enslin, Odimula Epule, Lana Erasmus, Mathonsi Erick, Lerato Etsane, Shimange Eunice, Zanele Fani, Mariette Ferreira, K L Finger-Motsepe, Fabion Floris, Tseko Fobo, Keresemetse Fokotsane, Duduzile Emmelda Fokwana, Genevieve Marion Fords, Juanita Fortein, Christine Fouche, Rulandi Fourie, Andrew Frean, Ludwig Fredericks, Wandile Funda, kabelo funjwa, Martha Futhane, Amanda Futuse, Dora Gabaediwe, Nonhlanhla Gabuza, Janycke Galant, Zanele Gama, Thobile Gano, Emma Cora Gardiner, Henri Gastrow, Kelly Gate, Ben Gaunt, Rikhotso Gavaza, Thapelo Gayi, Nkosinathi Gcakasi, Nomusa Gcobo, Leon Geffen, S Geldenhuys, Jenny George, Martha Gerber, Zolisa Getyengana, Nkululo Gigi, Radha Gihwala, Mitchell Gilliland, Zandile Gloria, Elitia Glover, Ellen Gokailemang, Suseth Goosen, Maria Gopane, Thandazile Gosa-Lufuta, Bernadett Gosnell, Sharleen Gouws, Christina Govender, Raksha Govender, Pearl Govender, Sally Govender, Roxanne Govender, K Govender, Savie Govender, Rashika Govinden, Luphumlo Gqabuza, Nomthandazo Gqaji, Maneo Gqetywa, Caroline Green, Nathan Green, Neera Green, Hendrik Grobler, Pamela Groenwald, Daniel Grootboom, Beatrice Gumede, Nomonde Gumede, Simphiwe Gumede, Slindile Gumede, Ntombikayise Gumede, Zenande Gumede, Thandiswa Gxotiwe, Makhubela H L, Nonhlanhla Hadebe, Skhumbuzo Hadebe, Christos Halkas, Ansie Hamer, Ebrahim Hamida, Juan Hammond, Sumayia Haniff, Annelise Hare, lorinda Hattingh, Thenjiwe Hendricks, Philip-George Henecke, Brends Henly-Smith, Glynis Herselman, Ansie Heymans, Chantel Heyns, Golekane Hlabahlaba, Lucky Hlabangwane, Simango Hlamarisa, Ntokozo Hlanzi, Hlengiwe Hlela, Katlego Hlokwe, Thembinkosi Hlongwa, Anele Hlongwana, Themba Hlubi, Tozama Hobo, Nare Nathaniel Hopane, Mariska House, Catharina Hudson, Marinda Huysamen, Jezreen Indheren, Samantha Ingle, Gavin Isaacs, T S Thekiso Isaacs, Maringa Itumeleng, Karien J van Rensburg, Saloshni Jackson, Neziswa Jacob, Burton Jacobs, Tshireletso Jacobs, Gugulethu Jacobs, Mesadi Jaftha, Zimkhitha Jaji, Sibusiso Jali, Gcobisa James, Gillian January, Andiswa Jeke, Laurent Jeremiah, L S Jeremiah, Mubeen Jhetam, Maureen John, Chuene John, Thandiwe Jola, Yolande Jonas, Anovick Jonas, Amilcar Juggernath, Eileen Kaba, Venetia Kabo, Disebo Kadi, Karabo Kaizer, Moshaya Peter Kambule, Lorraine Kapp, Tshepo Kau, Nchabeleng Keneth, O Kgabi, Tebogo Audrey Kgafela, Vincent Kgakgadi, Isabella Kgaswe, Tsholofelo Kgathlane, Vuyelwa Julia Kgetha, Mmaselloane Kgomojoo, B Kgoro, Christinah Kgosiemang, Gloria Kgosiencho, Stephen Khambula, Ariffa Khan, Refemetswe Khanare, Ncamsile Khanyase, Nokwethemba Khanyile, Fillip Kharatsi, Simangele Khawula, Themba Khohlakala, Letitia Khomo, Isabel Khoza, Sinethemba Khoza, Nombulelo Khukule, Busisiwe Khumalo, Tracy Khumalo, Zinhle khumalo, Vuyelwa Khumalo, Delisile Khumalo, Lebohang Khumalo, Boitumelo Khumalo, Thuli Khumalo, Gugu Khumalo, Bongiwe Khuzwayo, Thembhelihle Khuzwayo, Hennie Kidson, Jesne Kistan, Gugu Klaas, Marilyn Klassen, Josehine Koeberg, Marizel Koen, Simphiwe Koena, Ina Kok, Imraan Kola, Karabo Kolokoto, Ramachandra Konar, Dr Kotsedi, Jaline Kotze, Martins Koupis, Helen Kritzinger, Marlize Kruger, Henk Kruger, Tlangelani Kubayi, Thabisile Kubeka, Nonjabulo Kubheka, Melusi Kubheka, Sibusiso Clifford Kubheka, Erol Kubheka, Monica Kumalo, Thulani Kunene, Siphilile Candy Kunene, Yvette Kunneke, R P Kupa, Rachel Kutama, Nompumelelo Kwakwazi, Lwanele Kweyama, Maureen Labuschagne, Marina Labuschagne, Prabha Lakshman, Lungelo Lamani, Thembela Lamani, Naomi Langa, Khangelani Langeni, Aphelele Langeni, Nwabisa Hazel Langeni, Gena Langeveldt, Anchen Laubscher, Laetitia Le Roux, Magagane Leah, Collen Lebea, Sello Lebea, Viyella Phumla Cynthia Lebenya, Lorraine Lebogang, P K Leboho, Chantel Lee, Kelebogile Rejoice Lefakane, Zandile Legoabe, Patrick Lekala, Motsitsi Lekhoaba, Tanki Shadrack Lekunutu, Galaletsang Lerefolo, N Letebele, Tsepo Patric Lethoba, Emission Letlalo, Ofentse Letlhage, D S V Letshufi, Dineo Fiona Letsoalo, Seleka Jones Letsoalo, Pennelope Letsoalo, Getrude Letwaba, Sobekwa Linda, Katleho Lipholo, Sabata Litabe, Harsha Lochan, Linda Lomax, Francina Lombaard, Elmarie Loots, Ariana Lourens, Celeste Louw, Rianna Louw, Zikhona Lubambo, Msebenzi Moises Lubambo, Gregory Ludada, Michael Lukas, Thembela Lungu, Nomvume Lupindo, Emmah Lusenga, Happiness Luthuli, Zoleka Sylvia Luvuno, Gwangwa M H, Mustafa Maarman, Buyisiwe Mabaso, Cynthia Mabaso, Morena Mabitle, Grace Mabogoane, Kgakgamatso Mabone, Rueben Mabuza, Velaphi Mabuza, Mogantla Madiseng, Thobile Madlala, Mashooase Madolo, Thabiso Madonsela, Lesetsa Madubanya, Amukelani Maepa, Namhla Mafumana, Caroline Mafumo, Pumeza Magadla, Viscah Magale, Nompumelelo Magaqa, Oberholzer Magda, Rakgoale Magdeline, Tswai Maggie, Bongeka Maginxa, Cathrine Maite Magoba, Caroline Magongwa, Agretia Magubane, Agretia Ntombizodwa Magubane, R Magwai, D I Mahabane, Padmini Mahabeer, Elsie Mahadulula, Lungiswa Mahanjana, Amy Maharaj, Qedusiza Mahlambi, Yvonne Mahlangu, Lerato Mahlangu, Ntombifikile Mahlangu, Makhosazana Mahlangu, Mahlatsi Mahlangu, Penelope Mahlasela, Thosago Mahlatse, Regina Mahlobo, Dikhing Mahole, Adam Mahomed, Mapeu Debora Mahubane, Peter Mahume, Lehlogonolo Maifo, Vincent Maimane, Petunia Maimele, Phakoe Maine, Patricia Senyanyathi Mainongwane, Nomalungisa Majamani, Amahle Majozini, Noluthando Makalima, Nomfundo Makam, Khanyisa Makamba, R Makan, Mashiane Makarapa, Malesela Makgahlela, Mogoiwa David Makgisa, Makgoba Makgomo, M A Makgopa, Mabone Makhalema, Lindokuhle Lizo Makhanya, Philile Valentia Makhanya, Tolerance Makharaedzha, Nathi Makhathini, Elizabeth Makhesi, Cinile Makhubela, Nkululeko Freedom Makhunga, Nomalinge Makhupula, R R Makhura, Rangwato Makola, Zingisa Makuba, Asanda Makubalo, Lonwabo Makumsha, George Makuya, Levy Mmachuene Malaka, Themba Malangeni, M L Malatji, Pelonomi Malebana-Metsing, Malek Malek, Luthando Malevu, Juanita Malgas, Dimakatso Malgas, Paul Makgasane Malope, Monyeki Malose, Katekani Maluleke, Kato Mambane, Nthabiseng Mamorobela, Kukami Manamela, Tshepo Manana, Sathiel Maneto, Aron Kabelo Manganye, Pheto Mangena, Anna Mangoale, Tinotenda Florence Mangozho, Pariva Manickchund, Zandisile Mankayi, Arthur Manning, Kelebogile Manyaapelo Manyaapelo, Tabea Manyane, Zoliswa Manzana, Milton Manzini, Busisiwe Mapasa-Dube, Siboniso Maphumulo, Ntombifuthi Maphumulo, Sindy Maponya, Khomotso Mumsy Maponya, Napjadi Maponya, Lami Maqubela, Lizeka Maqubela, Vuyo Maqungo, Marisa Marais, Chantal Marais, Nondumiso Maramba, Annelize Mare, Madumetsa Maredi, Afikile Martins, Johanna Marule, Refilwe Marumo, N N Masakona, Kedibone Vincentia Masehla, Eric Maseko, Tshilidzi Maselesele, Mojalefa Maselo, M Maseloa, M E Masemola, Thembi Masemola, Bella Mashaba, James Mashangwane, Mantebele Mashao, Shalom Mashego, Lerato Mashele, Ester Mashiane, Joyce Mashibini, J Mashilo, Tumi Mashiloane, Charity Mashishi, Ngazibini Mashiyi, Khomola Mashudu, Aluwani Masindi, Caroline Maslo, Nduduzo Masondo, Dumisile Masuku, Cry Matamela, Mirriam Matandela, Nontokozo Mathabela, T Mathabi, Keitumetse Mathe, Mathabo Mathebula, Catherine Mathebula, Mdungazi Andres Mathebula, Nqobizwe Mathenjwa, Jane Mathibe, Lebohang Mathibela, Makwela Mathilda, Khakhu Mathiva, Mokgadi Alinah Mathobela, Fikile Pearl Mathonsi, K P Mathonsi, Katlego Mathosa, Noluvo Matiwane, Emma Matjeke, Bella Matjiane, Thabang Matjila, Chidi Matlala, Petlo Matome, Nolusindiso Matoti, C Matseliso, Dineo Matsemela, Phumeza Matsha, Gaalebale Prudence Matshediso, Motsumi Matshediso, Esther Matshela, Bongeka Mavuma, Pearl Mavundla, Nomthandazo Mavuso, Lovender Mawasha, Rebecca Mawelela, Nelisiwe Mazibuko, Phumlani Mazibuko, Lindiwe Mazubane, Bavumile Mbanjwa, Ayanda Mbasa, Nosimilo Mbatha, Zanele Mbatha, Rudolph Zenzele Mbatha, Gift Mbedzi, Tatenda Trevor Mbizi, Khumbulani Mbonambi, Nondumiso Mboniswa, Nomfanelo Mbonisweni, Jody Mbuilu, Siyabonga Mbulawa, Zama Mbutho, Natasha Mbuzi, Nonkululeko Mchunu, Cyprian Mchunu, Nokuzola Mchunu, Masesi Thandeka Mchunu, Vuyokazi Mciteka, Solly Mdaka, Neho Mdakane, Siyabonga Mdediswa, Melusi Mdima, Nozipho Mdima Masondo, Siviwe Mdindana, Ntombizikhona Mdleleni, Sibusiso Mdletshe, Gcobisa Precious Mdoda, Ntombi Mdolo, Anele Mdontsane, Ruchikas Mehta, Philile Rittah Memela, Masande Methuse, Keatlaretse Metshile, Pheliswa Metuse, Anton Meyer, Gavin Meyer, Cameron Meyer, Sisonke Mfazwe, Andiswa Mfecane, Bongeka Mfecane, Nelisiwe Mfeka, Busisiwe Mgaga, Thandiwe Portia Mgauli, Thembekile Mgedezi, Vuyokazi Mgedezi, Kalipile Mgevane, Bongni Mgiba, Babalwa Mgoduka, Patrick Mhlaba, Zeldah Mhlaba, Ntombizodwa Mhlanga, Vangile Mhlinza, Nokuthula Mhlongo, sibongiseni Mhlongo, Unamandla Mhlotshana, Mabaso Mikateko, Helena Minnie, Karen Mintoor, Bongi Miyeni, Mabelane M J, Rosy Mjethu, Gloria Mkhize, Mvuselelo Mkhize, Ntokozo Siyabonga Mkhize, Victoria Mkhize, Nomkhosi Mkhize, Nokuthula Mkhize, Mathini Mkhwanazi, Nolwandle Mkile, Kholofelo Mkise, Nokwandiso Mkiya, Pearl Mkongi, Mnonopheli Mkungeka, Hlomile Mlahleki, Nolukholo Mlibali, Sakhumzi Mlungwana, Jonas Mmachele, Mashatole Mmateka, Molebatsi Mmokwa, Thembisa Mmutlane, Zanele Olive Mndebele, Nonhlanhla Mngomezulu, Noluthando Millicent Mnguni, Pumza Mngunyana, Nomxolisi Mngunyana, Ntombebongo Mngxekeza, Zenzele Mnisi, Hlengiwe Precious Mnqayi, Phumzile Mnqayi, Thabiso Mntungwa, Siya Mnyaka, Ntombikayise Mnyakeni, Vuyani Mnyamana, Nomzingisi Mnyipika, Koena Moabelo, Mmakgoshi Alseria Moatshe, Jennifer Mochaki-Senoge, Sharon Moche, Tebello Mocwagae, Koeikantse Modibane, Tebogo godfrey Modimoeng, Obakeng Modisa, Itumeleng Modisane, Olebogeng Modise, Makaepeaa Flovia Modjadji, Sharon Modupe, Maja Moeketsi, Ntswaki Moeketsi, Kereditse Kingsley Moeng, Naledi Nthabiseng Mofamere, Samuel Mofokeng, Thabo Mofokeng, Jonas Mofomme, Vicky Mogakane, Lehlohonolo Mogale, Audrey Mogapi, Thomas Mogashoa, Mphaka James Mogatla, Kgaladi Mogoale, Dikeledi Maggie Mohajane, Nkuba Mohapi, Mthoamihla Mohatsela, Irene Mohlala, Daphney Mohlala, Mpho Mohlamonyane, Bonolo Millord Mohutsiwa, Selemela Moipone, Tshepang Moisi, Nelly Mojalefa, Vuyo Moji, Buhle Mokangwana, Matloa Mokgabo, Manaka Mokgaetji, Jane Mokgaotsi, Neo Theodore Mokgoro, Thalitha Mokhatla, Lerato Lovedalia Mokhele, Sheila Mokhema, Mamoya Mokoena, Mojalefa Mokoena, Lleka Mokome, Cynthia Mokone, Ipeleng Mokono, Thabiso Mokonyama, Josiah Mokori, Dolores Mokuena, Danny Mokumo, Oddy Mokwena, Kgaogelo Mokwena, Kgantshi Sam Mokwena, Lebogang Mokwene, Thato Elliott Molate, Ditoche Molebalwa, Boingotlo Molefe, Kgopa Stanley Molehe, Kgomotso Moleme, Sarah Moliane, Fanyana Moloi, Retshepile Joseph Molorane, Glenda Tsholanang Molotsi, Lerato Molukanele, Joy Monareng, Thapelo Moncho, Modiadie Monica, Refilwe Monnane, Andile Monqo, Neo Montewa, Kgalalelo Montsioa, Reitumetse Monyaki, Masekhobe Jeanett Monyane, Lipson Monyela, Yudeshan Moodley, Kriesen Moodley, Kaira Moodley, Boitumelo Donald Mooka, Prea Moonsamy, Simmi Moopanar, David Moore, Lineo Mophethe, Tshegohatso Moremedi, Kealeboga Moremong, Nthangeni Morgan, Egma Moripa, Lulamile Morris, Me. A.M. Mosala, Thabo Mosana, Alice Mosase, Yolanda Mose, Maponya Mosehlo, Mothusi Moseki, Mojalefa David Moshabe, D A Moshai, Mbulelo Moshani, Pelisa Moshani, Ledwaba Mosima, Ezrom Mosima, M P Mosoma, Lebohang Motaung, Mokete Motaung, Thozama Charmain Motaung Xhama, Purine Khethiwe Motha, Lerato Motimele, Boitumelo Motimeng, Shirley Motladiile, Otsile Motlhabane, Joshua Motlhamme, Mandla Motloba, Kagiso Motse, Sophia Motshegoa, Edward Moutlana, Irma Mouton, Zanele Moya, Nomonde Moyake, Maja M P, Jenny Mpete, Luamba Meltha Mpfuni, Seputule Mphahlele Mphahlele, Mashadi Mphake, Ephraim Letlhogonolo Mphanya, Mashudu Mphaphuli, Tebogo Chwene Mphela, MS Mpontshane, Thabile Mqotyana, Babalwa Mqungquthu, Noluthando Busane Msane, Malusi Mseleku, Sibusiso Msibi, Mancele Msibi, Thulisile Msibi, Siyabonga Linda Msibi, Clement Nhlanhla Msiza, Lungelo Msomi, Mandlenkosi Mtatambi, Thembisa Mthathambi, December Mthembu, Nhlahla Mthembu, Fezile Mbali Mthembu, Lungiswa Mthembu, Nompumelelo Petunia Mthethwa, Khulekani Mthimkhulu, Lungani Percival Mthuli, Ashley Mthunzi, Xolani Sydney Mtolo, Nomonde Precious Mtolo, Linda Mtshali, Neliswa Mtwa, Fezeka Mtyobile, Kanyisa Mtyobile, Mpfariseni Mudau, Magwabeni Muemeleli, Isaac Mulaudzi, Rebecca Mulaudzi, Mhlelekedzeni Mulaudzi, Dakalo Rejoyce Muligwe, Blessing Muponda, Mmbangiseni Stella Mushadi, M Mushid, Konanani Muthaphuli, J Muthavhine, Mpho Muthika, Samkelisiwe Mvelase, Vusi Mvelase, Laurent Kayumba Mwehu, Thabile Myaka, Magriet myburgh, Zimkhitha Mzamo, Fezeka Mzawuziwa, Mfundo Lunga Mzini, Oscar Mzizana, Ntokozo Mzobe, Thokozile Mzobe, Zamaswazi Mzobe, Mtimkulu Mzwandile, Fathima Naby, Keshnee Naicker, Pregashnie Naicker, Saroja Naicker, Pershen Naicker, Saiyen Virgil Naicker, Ria Naidoo, Sam Naidoo, Mergan Naidoo, Kamalambal Naidoo, Aroomugam Naidoo, Sivuyile Naku, Firdose Nakwa, Masoga Nancy, Rita Nathan, Maritsa Naude, Gcobisa Ncaza, Aviwe Ncaza, Relebohile Ncha, Yanelisa Ncoyini, Snothile Ncube, Mrs Ndaba, Vusumuzi Ndaba, Mmapula Ndaba, Siziwe Ndawonde, Ziphozihle Ndevu, Nonhlanhla Faith Ndhlovu, Simphiwe Ndima, Sindisiwe Ndlela, Thobsile P Ndlela, Nobuhle Ndlovu, Nwabisa Ndlovu, Virginia Dipuo Ndlovu, Sombekhaya Ndlumbini, Khululiwe Nduli, Priscilla Nontokozo Nduli, Michael Ndwambi, Jeremy Nel, Rina Nel, Lizelle Nel, Ntsundeni florah Nemanashi, Usinkhangwe Nyaphophi Nemudivhiso, Joyce Nemutavhanani Nemutavhanani, Jabu Nene, Xolani Nene, David Netshilonga, Rendani Netsianda, Charmaine Newton, Vuyo Leroy Ngalo, Ncumisa Ngani, Thabisa Monica Ngcakaza, Thamela Ngcobo, Trulove Nonhlanhla Ngcobo, Richards Ngcobo, Gcinile Ngcobo, Guguletu Ngcobo, Thozama Ngetu, Pinkie Ngewu, Tshepo Ngobeni, Providence Ngobeni, Khanyisile Ngobeni, Prudence Ngobeni, Thembisile Ngobese, Tracy Ngomane, Nolusindiso Ngondo, Nokukhanya Ngubane, Sithembiso Ngubane, Ntombizodwa Praxedise Nguse, Tholakele Ngwane, Elizabeth Ngwasheng, Siphamandla Ngwenya, Gugu Ngwenya, Nomthandazo Ngwenya, Themba Ngwenya, Eva Ngwenya, Zintlanu Ngxola, Tshegofatso Nhabe, Jabulile Nhlabathi, Ishmael Nhlangwana, Sithembile Nhlapo, Matlala Nick, Vicky Niemand, Carina Nienaber, Louise Nix, Chumisa Njikelana, Masiza Njomi, Lucia Nkabinde, M NKABINDE, Boitumelo Nkabiti, Gugu Nkabule, Mankopodi Nkadimeng, Nonkanyiso Nkanjeni, Palesa Portia Nkatlo, Bongani Nkewana, Audrey Nkhwashu, Ngokoana Nkoana, Mmathapelo Nkoane, M Nkogatse, Fezile Nkomo, Ntando Nkomo, Nontobeko Nkonyane, Sydney Nkosi, Ntombikayise Nkosi, Phumzile Nkosi, Ntombifuthi Nkosi, TINTSWALO NKOSI, ML Nkosi, Godfrey Nkosi, Amukelani Nkosi, Fikile Vinoliah Nkosi, Mbali Nkosi, Nomcebo Lucia Nkosi, Siphokazi Nkosi, Amanda Nkuhlu, Phumzile Nkumane, Malebo Nkuna, Wendy Nkwakwha, Sesi Noge, Elizabeth Nolte, Peko Nomawabo, Malibongwe Nombita, Nandipha Nophale, Jeanetta Nothnagel, Bongiwe Novokoza, Zanele Nqaphi, Thobekile Nqondo, Siphokazi Nqwelo, Nkoana N S, Sindiswa Ntabeni, Mr Ntabeni, mawethu Ntampula, Mthutuzeli Ntebe, Mokwabo Ntela, Hezekiah Ntimbane, Xolisa Ntintsilana, Patrick Ntleki, Zanele Ntobela, Bandile Ntombela, Zamaswazi Ntombela, Khonelihle Zandile Ntombela, Praisegod Samkelo Thobani Ntombela, Lindiwe Ntonintshi, Dipuo Ntseane, Thobeka Ntseane, Xolelwa Ntsham, Mbalenhle Ntshele, Amanda Ntshewula, Zinzi Ntsoko, Athini Ntsoto, Nomsa Ntuli, Nokwazi Ntuli, Nomvula Ntuli, Andrew Diffar Ntuli, Faith Ntuli, Margrit Nurnberger, Ntsikelelo Nxala, Sithandiwe Nxasane, Thanda Nxumalo, Xolani Nyathi, Nontobeko Nyawula, Nhlakanipho Nzama, Maila Nkuneng Obed, Florence Ogwal, Maureen Olifant, B Oliphant, Monota Olive, Kagisho Olyn, Raymond Omoighe, Phumeza One, Ratombo Oscar, Nkuna Owen, Mailula P, Nalini Padayachee, Vasaily Padayachy, Ntombizakhe Pakade, Mosiuoa Palime, Jane Palisa, Lesenyeho Parkies, Andy Parrish, Nilesh Patel, Anastasia Pather, Mkhombo Tsakani Patience, Marisa Patzke, Akhumzi Pawuli, Ntandokazi Pelako, Phaswana Sibasa Penrose, Litha Peppeta, Santosh Pershad, Makheda Pertunia, Nkuna Pertunia, Dane Perumal, Mongameli Peter, Justin Peters, Vatiswa Petlane, Harideen Petrus, Kgomotso Phahladira, Matebesi John Phakisa, R Phale, Livhuwani Phathela, Sekate Daniel Phillip, Beverly Phiri, Mapule Precious Phiri, Thapelo Phokane, Frank Phokoane, Moele Pholosho, Sekoro Phooko, Sekodi Geoffrey Phooko, Maponya Phutiane, Faiza Pillay, Melanie Pillay, Sayuri Pillay, C R Pillay, Zikhona Plaatjie, James Pootona, Samantha Potgieter, Marius Potgieter, Mulaudzi Mulatedzi Precious, Paul Janus Pretorius, Hans Prozesky, Mokhethi Pule, Jayshina Punwasi, Dot Putzier, Lutho Qankqiso, Siphokazi Qebedu, Phozisa Qhola, Ntombesithathu Qotoyi, Sipho Victor Qotso, Zanele Qwabe, Helena Rabie, Phoebe Rabothata, Christina Rachoene, Mteteleli Radana, Maria Radebe, Dr. Valentino Radebe, Nonkululeko Radebe, Ella Radinne, Sherly Raduvha, Shamintha Raghunath, Claudine Rajagopaul, Mary Rakgwale, Malumbete Michael Ralethe, Kenneth Ralimo, Motlalepule Ramafoko, Maduvhahafani Ramagoma, Charlotte Raman, Dr Ramavhuya, Molly Rambally, Nivasha Ramdeen, Tanusha Ramdin, Sharita Rameshwarnath, Yeishna Ramkillawan, null Ramotlou, Faith Rampedi, Vijayluxmi Rampersad, Avhashoni Ramuima, Noluthando Ranone, Mabohlale Portia Rapasa, Mpharoane rapelang, Nika Raphaely, Lesiba Rashokeng, Caroline Rashopola, Tebogo Ratau, M Ratau, Mpfariseni David Ratshili, Elmari Rautenbach, Rofhiwa Ravele, Johannes Reachable, Peta Mmalahla Rebecca, Kessendri Reddy, Andrew Redfern, Robertha Reed, Mumsy Rees, Dr Reji, Gary Reubenson, Veena Rewthinarain, Nkonayani Rhulani, Mufamadi Richard, J S Rikhotso, Shatimone Beverley Rikhotso, Lavhelani Ndivhaleni Robert, Noncedo Roto, Gideon Ruder, Kapil Rugnath, Lizette Ruiters, Mina Ruiters, Sue Russell, Lynn Ruwiza, Molokoane R Y, Mandy Saaiman, Emmanuel Sabela, Lerato Sadiq, Litha Saki, Hyppolite Salambwa, Menitha Samjowan, Nazlee Samodien, Rakgolele Samuel, Fakudze Sandile, Cekuse Sanelisiwe, Mandlankosi Sani, Simangele Sawuka, Lelani Schoeman, Magriet Scholts, Ronel Schroder, Mamotetekoane Sebalabala, Selwalenkwe Collet Sebati, Jacoline Seboko, Wilheminah Sebuthoma, Annah Segami, Ruth Segokotlo, MR Sehloho, Khutjo Seisa, Antony Sekgobela, Monica Sekhosana, John Sekonyela, Mpho Sekoto, Naledi Sekulisa, Mokgadi Vanessa Sekwadi, Lebogo Selaelo, Johannes Selatlha, Kgomotso Selekolo, William Selfridge, Lucy Semenya, Ivy Sengakane, Masabata Sengata, Petronella Sentle, Malebo Seoketsa, Pratheesha Seonandan, Thomas Mambushi Serumula, Nkululeko Setheni, Refiloe Setlale, Tumediso Setlhodi, Barbara Setlhodi, Robert Setloghele, Aarthi Sewpersad, Ryan Sewpersadh, Phumlile Shabalala, Owen Shabangu, Kungesihe Shabangu, Harriet Sbonangaye Shabangu, Thokozani Shabangu, Clifford Shadi, Hasifa Shaik, Tseliso Shale, Qedani Shandu, Nomvelo Shandu, Ntswaki Marcia Shange, Abongile Shenxane, A Sherriff, Sebenzile Shezi, Thenjiwe Shezi, Scally Shihangule, Cheyeza Shikwambana, Lungisani Shoba, Kamogelo shokane, Nora Sibande, Lydia Sibeko, Xolani Sibeko, Zanele Sibiya, Mncedisi Sibiya, Sphamandla Sibuta, Thembakazi Sifumba, Sipho Sigcau, Lutho Sigila, Kayakazi Sihentshe, Bongani Sihlangu, Daisy Sikhakhane, Shaun Nhlanhla Sikhakhane, Mbali Siko, Sipho Sikonje, Khumbulekile Simanga, Nomsa Simango, Thulisile Simela, Ntombikayise Simelane, Sashah Singh, Marjorie Singh, Ragani Singh, Shash Singh, Anita Singh, Hitekani Sithole, Senzekile Sithole, Ntokozo Danielle Sithole, Koketso Maxwell Sithole, Jonnie Situma, Annie Sivraman, Katekani Siwela, Nonqubela Siyewuyewu, Maweya Sizeka, Nonceba Siziba, Andrew Skhosana, Khanyisile Skhosana, Rorisang Skhosana, Tandiwe Skoko, Sunet Slabbert, Ntombela Smangaliso, Christine Smedley, Lydia Smit, Natassia Smit, Lizelle Smit, Michelle Smit, Fasie Smith, Lizzie Smith, Sunell Smith, Cassius Smith, Stefan Smuts, Ayanda Sofe, Khobane Solomon, L J Solomon, chauke Sombani, Richard Songca, Anga Sontamo, Supriya Soorju, Zubenathi Sopazi, Brian Soqasha, Bongiwe Sosibo, Ntsika Sotsaka, Mandy Soula, Simon Spoor, Sarah Stacey, Asanda Stali, Mutele Mmboniseni Stephina, Myra Steup, Sinoxolo Steven, AW Stevens, Vincent Stevens, Dewald Steyn, Bianca Steyn, Pat Stocks, Henk Stolk, Alida Stoltz, Renate Strehlau, Anneke Stroebel, Loraine Strydom, Jean-Marie Strydom, Anton Strydom, Ursula Strydom, Midhu Sunnyraj, Nwabisa Swana, Winnie Swanepoel, Suzan Swanepoel, Elsie Swartbooi, Estley Swartz Swartz, Casandra Syce, Shihambi T E, Joyce Tabane, N E Tabane, Mrs Tawana, Ntene Tebello, Siphosetu Wiseman Tembe, Samantha Terblanche, Ntombifuthi Thabede, Nkhumeleni Thabelo, Sibusiso Thabethe, Lekhanya Thabo George, Keorapetse Thare, Makofane Thebogo, Lerato Thekiso, Lloyd Theko, Celimphilo Zandi Themba, Danie Theron, Henda Theron, Ilze Theron, Thandiwe Thingathinga, M M Thlabadira, Dikeledi Thoka, Zanele Thokwana, Gustav Thom, Mamphot Joel Thubakgale, Theodora Thwala, P Thys, Monethi Tieho, Matodzi Timothy, Ndlovu Tintswalo, Babalwa Tivana, Molefi Tladi, Bongiwe Tokota, Simthandile Toni, Ariel Torres, Mande Toubkin, Marinda Tsatsi, Khanyisile Tshabalala, Nozibele Tshamase, Gontse Tshefu, Makgoga Tshegofatjo, Given Tshikomba, Thapelo Tshilo, Lerato Tshira, S T Tshirado, Maipfi Tshisikule, G Tsoke, N TSOKE, Alatha Tsoko, Mosele Tsotetsi, Sandeva Tsubella, Noxolo Tuswa, Maipato Tutse, Nomayenzeke Tutu, Sphephelo Twala, Nhlanhla Twala, Simphiwe Twala, John Ubisi, Tefo Unathi, A Van Aswegen, Marietjie van der Merwe, Trudie van der Merwe, Patience van der Plank, Elmarie van der Spuy, Linda Van Der Westhuizen, Adele Van Der Westhuizen, Talana van der Westhuizen, Mene van der Westhuyzen, Thea Van Dyk, Ingrid van Heerden, Ryno van Jaarsveld, M Van Lill, Heidi van Niekerk, Ben van Niekerk, Amanda van Rensburg, Judy van Schallwyk, Zeitschke Yarnrich Van Sensie, Magda van Vuuren, Cloete van Vuuren, Olga Funiswa Vandu, Mandisa Vane, Lucia VanZyl, Ebrahim Variava, Mariam Veerus, Nokhwezi Velapi, Sebina Veleko, Z Velezantsi, Retha Venter, Corlia Vergottini, Inga Vermeulen, Liabara Lufuluvhi Vidah, Bongani Vilakazi, Treasure N Vilakazi, Mbalenhle Precious Vilakazi, Karen Viljoen, Werner Viljoen, Zuretha Volschenk, Angelo Vos, Matlala V V, Jacques Walters, Kate Webb, John Welsh, D Wessels, Judy Wheller, Fundile White, Priscilla White, Carmen Whyte, Ansie Willemse, Sape William, Daniel Williams, Kamielah Williams, Mercia Williams, Anne Williamson, Cherade Wilson, Boipelo Wolff, Michelle Wray, Ntombizonke B Xaba, Thabang Jabulani Xaba, Thanks Xiniwe, Mtshali Xoliswa, Funokwakhe Xulu, Gibson Xulu, Sandlakazi Yam, NM Zakhura, Mashela Zareloa, Sive Zinto, Dyibeni Zinziswa, Lulamile Ziselo, Zakhele Zitha, Emmanuel Zitha, Anele Zokufa, Innocent Zondi, Sikhumbuzo Bernard Zondi, Sbuyi Zondi, Thulani Zondi, Wandiswa Zongola, Liesl Zühlke, Zandile Zulu, Lungelo Zulu, Thandeka Zulu, Slindili Zulu, Nkosinathi Zulu, Angel Zuma, Precious Zungu, Pamela Zungu, Melusi Zungu, Priscilla Zungu, Bongo Lihle Zwakala, Antonia Zwane, Promise Zwane, Muziwendoda Zwane, Hlengiwe Priscila Zwane, and Nomgcobo Zwane
Subjects: Male, Pediatrics, medicine.medical_specialty, Tuberculosis, Epidemiology, Immunology, HIV Infections, Comorbidity, Disease, Cohort Studies, South Africa, Risk Factors, Virology, Diabetes mellitus, Prevalence, Humans, Medicine, Hospital Mortality, Asthma, SARS-CoV-2, business.industry, Public health, COVID-19, Articles, Odds ratio, medicine.disease, Infectious Diseases, Anti-Retroviral Agents, Female, business, Cohort study
Abstract: Summary Background The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15–49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. Methods In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. Findings Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27–1·43), past tuberculosis (1·26, 1·15–1·38), current tuberculosis (1·42, 1·22–1·64), and both past and current tuberculosis (1·48, 1·32–1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22–1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. Interpretation Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. Funding South African National Government.
Published: 2021
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10. Identification of Genetic Causes of Focal Segmental Glomerulosclerosis Increases With Proper Patient Selection

Author: Stephen B. Erickson, Andrew Bentall, Mireille El Ters, Pavel N. Pichurin, Fernando C. Fervenza, Marie C. Hogan, Loren P. Herrera Hernandez, Ladan Zand, Jing Miao, Aleksandra Kukla, Eddie L. Greene, Konstantinos N. Lazaridis, Carri A. Prochnow, Sanjeev Sethi, Filippo Vairo, and Emily C. Lisi
Subjects: medicine.medical_specialty, Univariate analysis, medicine.diagnostic_test, urogenital system, business.industry, General Medicine, Odds ratio, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, Focal segmental glomerulosclerosis, Internal medicine, Biopsy, medicine, Family history, business, Nephrotic syndrome, Kidney disease, Genetic testing
Abstract: Objective To increase the likelihood of finding a causative genetic variant in patients with a focal segmental glomerulosclerosis (FSGS) lesion, clinical and histologic characteristics were analyzed. Patients and Methods Individuals 18 years and older with an FSGS lesion on kidney biopsy evaluated at Mayo Clinic from November 1, 1999, through October 31, 2019, were divided into 4 groups based on clinical and histologic characteristics: primary FSGS, secondary FSGS with known cause, secondary FSGS without known cause, and undetermined FSGS. A targeted gene panel and a customized gene panel retrieved from exome sequencing were performed. Results The overall rate of detection of a monogenic cause was 42.9% (21/49). Individuals with undetermined FSGS had the highest rate of positivity (87.5%; 7/8) followed by secondary FSGS without an identifiable cause (61.5%; 8/13) and secondary FSGS with known cause (33.3%; 5/15). Four of 5 (80%) individuals in the latter group who had positive genetic testing results also had a family history of kidney disease. Univariate analysis showed that family history of kidney disease (odds ratio [OR], 13.8; 95% CI, 3.7 to 62.4; P Conclusion In adults with FSGS lesions, proper selection of patients increases the rate of positive genetic testing significantly. The majority of individuals with undetermined FSGS in whom the clinical presentation and histologic parameters are discordant had a genetic diagnosis.
Published: 2021
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11. Defendants with intellectual disability and autism spectrum conditions: the perspective of clinicians working across three jurisdictions

Author: Verity Chester, Jane McCarthy, Catrin Morrissey, Andrew Forrester, Susan Hayes, Erik Søndenaa, Clare S. Allely, and Eddie Chaplin
Subjects: Psychiatry and Mental health, Perspective (graphical), Intellectual disability, medicine, Autism, Psychology (miscellaneous), Criminology, medicine.disease, Psychology, Law, Pathology and Forensic Medicine, Criminal justice
Abstract: The treatment of vulnerable defendants by criminal justice systems or correctional systems varies within and between countries. The purpose of this paper is to examine three legal jurisdictions - New South Wales in Australia, Norway, England and Wales - to understand the extent of variation in practice within the Court systems for defendants with intellectual disabilities (ID) and/or autism spectrum conditions (ASC). \ud Two of the jurisdictions had a process for screening in place, either in police custody or at court, but this was not universally implemented across each jurisdiction. All three jurisdictions had a process for supporting vulnerable defendants through the legal system. Across the three jurisdictions, there was variation in disposal options from a mandatory care setting to hospital treatment to a custodial sentence for serious offences. This variation requires further international exploration to ensure the rights of defendants with ID or ASC are understood and safeguarded.\ud Evidence is provided by clinical experts who describe the current context within and between countries. Finally, we discuss the most challenging issues identified by authors including screening, support in Court, legal frameworks, options for disposal, implications for practice and future research directions.
Published: 2022

12. Prescribing Patterns of Antidiabetic in Patients with Type 2 Diabetes Mellitus at Levy and Chilenje Hospitals in Zambia

Author: Lawrence Mvula and Eddie M. Mulenga
Subjects: medicine.medical_specialty, Combination therapy, business.industry, Type 2 Diabetes Mellitus, Ocean Engineering, Type 2 diabetes, medicine.disease, Metformin, Glibenclamide, Diabetes mellitus, Internal medicine, medicine, Outpatient clinic, Medical prescription, Safety, Risk, Reliability and Quality, business, medicine.drug
Abstract: Objective: To determine the prescription pattern of anti-diabetics drugs in patients with type 2 diabetes at Levy Mwanawasa General and Chilenje Level 1 Hospitals. Methods: A cross-sectional study was conducted by reviewing the diabetic patients’ prescriptions with diabetic drugs from outpatient department from January to December, 2016. Data generated from this study was analyzed using SPSS version 23. The P value < 0.05 was considered as significant. Descriptive statistics and one way analysis of variance (One way -ANOVA) statistical techniques were used to analyze data. Results: Of the total of 384 patients’ prescriptions, 63% were female and the majority of patients belonged to the age group 51-60 years indicating 28%. 51% of the prescriptions had 2 to 3 antidiabetic drugs written by generic name. Metformin/Daonil combination was highly prescribed with 57%, followed by Metformin as Monotherapy at 19%. Conclusion: This study reported that female patients were significantly more affected with diabetes associated with cardiovascular complications than male patients reviewing 37% for male and 67% female. Most of the patients were on combination therapy of Metformin /Glibenclamide in the frequency TDS/OD. The choice of drug based on demographic data, economic status, associated conditions and complications would give additional insights into prescribing patterns in type 2 diabetes mellitus.
Published: 2021
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13. Prisoners with Attention Deficit Hyperactivity Disorder: co-morbidities and service pathways

Author: Susan Young, Philip Asherson, Andrew Forrester, Amina Rawat, Lisa Underwood, Declan G. Murphy, Ken Courtenay, Jane McCarthy, Richard Mills, Jess Sabet, Eddie Chaplin, Bhathika Perera, and Hannah Hayward
Subjects: medicine.medical_specialty, Prison population, Routine screening, High prevalence, business.industry, media_common.quotation_subject, virus diseases, Prison, social sciences, medicine.disease, behavioral disciplines and activities, Health Professions (miscellaneous), Prevalence of mental disorders, mental disorders, medicine, population characteristics, Attention deficit hyperactivity disorder, Co morbidity, National level, Psychiatry, business, media_common
Abstract: Purpose This paper aims to examine effective diagnostic and treatment pathways for attention deficit hyperactivity disorder (ADHD) in prison settings given the high prevalence of ADHD and comorbidities in the prison population. Design/methodology/approach Two studies were carried out in two separate prisons in London. Firstly, data were collected to understand the prevalence of ADHD and the comorbidities. The second study used quality improvement (QI) methodology to assess the impact of a diagnostic and treatment pathway for prisoners with ADHD. Findings Of the prisoners, 22.5% met the diagnostic criteria for ADHD. Nearly half of them were screened positive for autistic traits, with a higher prevalence of mental disorders among prisoners with ADHD compared to those without. The QI project led to a significant increase in the number of prisoners identified as requiring ADHD assessment but a modest increase in the number of prisoners diagnosed or treated for ADHD. Originality/value Despite various challenges, an ADHD diagnostic and treatment pathway was set up in a prison using adapted QI methodology. Further research is needed to explore the feasibility of routine screening for ADHD in prison and examine at a national level the effectiveness of current ADHD prison pathways.
Published: 2021
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14. Response to mRNA vaccination for COVID-19 among patients with multiple myeloma

Author: Samuel D. Stampfer, Aaron J. Feinstein, Haiming Chen, Tracy Green, Scott Jew, Tanya M. Spektor, Sean Bujarski, Marissa-Skye Goldwater, Shahrooz Eshaghian, Elias Aquino, Ning Xu, Bernard Regidor, James R. Berenson, David Daniely, Mingjie Li, Eddie Fung, Kurt Preugschat, and Regina A. Swift
Subjects: Adult, Male, Cancer Research, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Myeloma, Disease, Antibodies, Viral, Article, medicine, Humans, BNT162 Vaccine, Multiple myeloma, Aged, Aged, 80 and over, Public health, Messenger RNA, biology, SARS-CoV-2, business.industry, Vaccination, COVID-19, Hematology, Middle Aged, medicine.disease, Oncology, Immunization, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Immunology, biology.protein, Female, Antibody, Multiple Myeloma, business, 2019-nCoV Vaccine mRNA-1273
Abstract: Multiple myeloma (MM) patients are at higher risk for severe COVID-19. Their mRNA vaccination response against SARS-CoV-2 is unknown. Thus, we analyzed responses to mRNA vaccination against COVID-19 among these patients. Using an ELISA-based assay that detects IgG antibodies to SARS-CoV-2 spike protein, we determined serum antibody levels prior to immunization and 12–21 and 14–21 days following the first and second vaccinations, respectively, with mRNA-1273 (Moderna) or BNT162b2 (Pfizer/BioNTech) among 103 MM patients (96 and 7 with active and smoldering disease, respectively). We stratified patients into clinically relevant responders (>250 IU/mL), partial responders (50–250 IU/mL, which was above pre-COVID-19 background), and nonresponders ( second line of treatment, and among those not in complete remission. Patients who received mRNA-1273 vaccine had higher anti-spike antibody levels than those who were vaccinated with BNT162b2. Thus, most MM patients have impaired responses to mRNA vaccination against COVID-19, and specific clinical and myeloma-related characteristics predict vaccine responsiveness.
Published: 2021
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15. Association of body composition with risk of overall and site‐specific cancers: A population‐based prospective cohort study

Author: Min Li, Zhijun Zhou, Bin Xia, Bo Wang, Jinqiu Yuan, Yanhong Jessika Hu, Rui Sun, Changhua Zhang, Eddie C. Cheung, Anran Liu, Fangping Li, Zi Chong Kuo, Wenbo Meng, Yulong He, Qiangsheng He, Zilong Zheng, and Yan Tang
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Lower risk, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Prostate, Neoplasms, Internal medicine, medicine, Humans, Obesity, Prospective Studies, Prospective cohort study, Lung cancer, Adiposity, business.industry, Stomach, Hazard ratio, Cancer, Middle Aged, Prognosis, medicine.disease, United Kingdom, Confidence interval, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Body Composition, Female, business, Follow-Up Studies
Abstract: Although excess adiposity has been linked with various cancers, association between body composition and some cancers remains unclear, like lung and prostate cancers. We investigated associations of body composition with risk of overall cancer and major site-specific cancers in a prospective cohort of 454,079 cancer-free participants from UK-Biobank. Body composition was measured with bioimpedance analysis. We evaluated hazard ratio (HR) and 95% confidence interval (CI) with multivariate Cox linear and nonlinear models in men and women separately. We identified 27,794 cancers over 7.6 years of follow-up. Multivariable adjusted models including fat-free mass (FFM) and fat mass (FM) showed that FFM was positively associated with overall cancer risk in men and women (HR 1.03, 95% CI 1.01-1.04 and 1.07, 1.04-1.10, respectively); while the association between FM and overall cancer disappeared after adjusting for FFM. FFM was associated with higher risks of obesity-related cancers combined, stomach (women only), malignant melanoma, postmenopausal breast, corpus uteri, prostate, kidney (men only), and blood cancers, and lower risk of lung cancer. FM was associated with higher risks of obesity-related cancers combined, esophageal, colon, lung (men only), postmenopausal breast (at the lower end of FM range), and corpus uteri cancers, and lower risks of rectal, malignant melanoma (women only), prostate and blood cancers. FFM and FM seemed to have different effects on cancer risk, and the effects varied substantially by cancer type, in both direction and size. Higher FM/FFM ratio was also associated with some cancers risk, and might be a useful predictor of cancer risk. This article is protected by copyright. All rights reserved.
Published: 2021
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16. The Relationship of Pleural and Pericardial Effusion With Pulmonary Hemodynamics in Patients With Pulmonary Hypertension

Author: John T. Huggins, Amit Chopra, Kristin B. Highland, and Eddie Kilb
Subjects: Adult, Male, Cardiac Catheterization, medicine.medical_specialty, Pleural effusion, Hypertension, Pulmonary, Population, 030204 cardiovascular system & hematology, Pericardial effusion, Pericardial Effusion, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine.artery, medicine, Humans, 030212 general & internal medicine, education, Pulmonary wedge pressure, Ultrasonography, Interventional, Aged, education.field_of_study, business.industry, Hemodynamics, Central venous pressure, General Medicine, Middle Aged, medicine.disease, Pulmonary hypertension, Pleural Effusion, Cross-Sectional Studies, Point-of-Care Testing, Pulmonary artery, Cardiology, Female, Pulmonary venous hypertension, business
Abstract: Background The relationship between the presence of pleural and pericardial effusion in reference to hemodynamic parameters remains unclear in ambulatory patients with pulmonary hypertension (PH). Methods Consecutive patients who underwent right catheterization (RHC) for the evaluation of pulmonary hypertension were enrolled. Point-of- care ultrasound was performed prior to the RHC to determine the presence of pleural effusion and pericardial effusion. We conducted a cross-sectional study to determine the association between presence of pericardial and pleural effusion with pulmonary hemodynamic variables. Results Twenty-five (78.1%) of 32 patients had evidence of PH by RHC. Mean pulmonary artery pressure of the population was 40.6 mmHg, and 68% (17/25) had WHO group I PH. Six (24.0%) of 25 PH patients had pleural effusions identified, of which 4 out of 6 (66.7%) had a pulmonary artery wedge pressure >15 mmHg. Eleven (44.0%) of the 25 PH patients were also found to have pericardial effusions, and most of those patients 10/11(90.9%) had an elevated right atrial pressure >10 mmHg. The presence of a pleural effusion was associated with a pulmonary artery wedge pressure >15 mmHg (p = 0.032) and the presence of a pericardial effusion was associated with a right atrial pressure >10 mmHg (p = 0.004). Detection of pleural effusion had a poor positive predictive value (67%) for the presence of pulmonary venous hypertension, whereas presence of a pericardial effusion was highly predictive (89%) of the presence of systemic venous hypertension. Conclusions Systemic venous hypertension was associated with the presence of pericardial effusions, while pulmonary venous hypertension is associated with pleural effusion development in ambulatory patients with pulmonary hypertension.
Published: 2021
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17. Association of laboratorial parameters and prognostic factors in uterine corpus cancer

Author: Kaio Raffael Valotta Bezerra, Agrimaldo Martins-Filho, Marta Carolina Marques Sousa, Eddie Fernando Candido Murta, and Rosekeila Simões Nomelini
Subjects: Medicine (General), medicine.medical_specialty, Survival, Gastroenterology, R5-920, Blood platelets, Internal medicine, Humans, Uterine neoplasms, Medicine, Cutoff, Lymphocytes, Uterine Neoplasm, Retrospective Studies, Receiver operating characteristic, business.industry, Cancer, Retrospective cohort study, Red blood cell distribution width, General Medicine, Prognosis, medicine.disease, Uterine Neoplasms, Mann–Whitney U test, Female, Hemoglobin, Laboratories, business
Abstract: SUMMARY OBJECTIVE: The aims were to compare the red blood cells, platelet count, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, red cell distribution width, and fasting glucose in peripheral blood of patients with benign and malignant uterine neoplasms and to relate these laboratory parameters with prognostic factors and overall survival in cancer. METHODS: The results of the laboratory parameters were analyzed using the Mann-Whitney U test. Receiver operating characteristic curves were used to find the cutoff values. Overall survival was estimated using the Kaplan-Meyer method. RESULTS: Higher values of neutrophil-lymphocyte ratio and fasting glucose were found in cancer patients. Higher platelet-lymphocyte ratio values were associated with other subtypes when compared with endometrioid subtype; higher values of red cell distribution width were found in stage II/IV when compared with stage I; lower hemoglobin values were related to stage II/IV and nonendometrioid histological type. Platelet-lymphocyte ratio
Published: 2021
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18. Rapid and Simple Detection of Isoniazid-Resistant Mycobacterium tuberculosis Utilizing a DNA Chromatography-Based Technique

Author: Yasuhiko Suzuki, Kumi Kobayashi, Joseph Yamweka Chizimu, Patrick Lungu, Yukari Fukushima, Takuya Kodera, Tomoyuki Yamaguchi, Yutaka Takarada, Chie Nakajima, Eddie Samuneti Solo, and Mitsuo Kawase
Subjects: 0301 basic medicine, Microbiology (medical), Sanger sequencing, Tuberculosis, biology, 030106 microbiology, Isoniazid, Early detection, General Medicine, Drug resistance, Rifampicin resistance, Isoniazid resistance, biology.organism_classification, medicine.disease, Virology, Mycobacterium tuberculosis, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Infectious Diseases, medicine, symbols, 030212 general & internal medicine, medicine.drug
Abstract: Despite the availability of anti-tuberculosis drugs, the treatment of tuberculosis has been complicated by drug-resistant tuberculosis. The early detection of drug resistance makes early treatment possible. However, the available tools are mainly for rifampicin resistance detection, and the existing isoniazid resistance detection method is expensive, highly technical, and complicated, making it unsustainable for use in developing nations. This study aimed to develop a simple, rapid, and low-cost diagnostic kit for isoniazid-resistant tuberculosis using the single-stranded tag hybridization method to target an isoniazid resistance-conferring mutation. Specificity and sensitivity were assessed using DNA extracted from 49 isoniazid-resistant and 41 isoniazid-susceptible Mycobacterium tuberculosis clinical isolates cultured in mycobacterial growth indicator tubes. Positive signals were observed on mutant and wild-type lines with 100% sensitivity and specificity compared with Sanger sequencing results. In contrast, no positive signal was observed for non-tuberculosis mycobacteria. The detection limit of this method was 103 CFU or less. The STH-PAS system for isoniazid-resistant M. tuberculosis detection developed in this study offers a better alternative to conventional phenotypic isoniazid resistance determination, which will be of both clinical and epidemiological significance in resource-limited nations.
Published: 2021
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19. Effect of a 6 am–9 am Dedicated Orthopaedic Trauma Room on Hip Fracture Outcomes in a Community Level II Trauma Center

Author: Lawrence B Ward, Eddie El-Yussif, Robert Jarski, Michael McDonald, Breanna Sorenson, and Heather Wortham
Subjects: Operating Rooms, medicine.medical_specialty, MEDLINE, law.invention, 03 medical and health sciences, 0302 clinical medicine, Trauma Centers, law, medicine, Humans, Orthopedics and Sports Medicine, Aged, Retrospective Studies, 030222 orthopedics, Hip fracture, Hip Fractures, business.industry, General surgery, Trauma center, 030208 emergency & critical care medicine, Retrospective cohort study, General Medicine, Evidence-based medicine, medicine.disease, Intensive care unit, Pulmonary embolism, Pneumonia, Orthopedics, Surgery, business
Abstract: OBJECTIVE To assess the outcomes of elderly hip fracture surgeries performed 12 months before and 12 months after the implementation of a daily 6 am-9 am dedicated orthopaedic trauma room (DOTR) at a Level II community trauma center. DESIGN Retrospective cohort study. SETTING Level II academic trauma center. PATIENTS A total of 431 consecutive trauma patients undergoing surgical management of isolated low-energy hip fractures from January 1, 2018, to December 31, 2019. INTERVENTION Implementation of a 6 am-9 am DOTR Monday through Friday. MAIN OUTCOME MEASURES Time to surgery, number of cases performed after hours, surgical time, 90-day morbidity and mortality, and time to therapy. RESULTS Retrospective analysis showed that despite a 24% increase in surgical hip fracture volume, implementation of a part-time DOTR led to a decrease in after-hours surgery (32.4% vs. 19.6%; P = 0.008) and patients requiring the intensive care unit postoperatively (7% vs. 3.8%; P = 0.036). Surgeries performed after hours were longer than that of surgeries performed during the daytime (82.0 vs. 68 minutes; P = 0.003) and had more complications (pneumonia, pulmonary embolism, and surgical site infection; P = 0.002, 0.047, 0.024, respectively). CONCLUSIONS Our results show that a part-time DOTR in a community Level II hospital is associated with improvement in patient care. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Published: 2021
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20. Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study

Author: Eddie Chong, Chuen Seng Tan, Christopher Chen, Henri A. Vrooman, Saima Hilal, Bibek Gyanwali, Benedict Lui, Radiology & Nuclear Medicine, and Epidemiology
Subjects: Male, Canada, medicine.medical_specialty, Neuropsychological Tests, Executive Function, Cognition, Asian People, Internal medicine, Humans, Medicine, Dementia, Cognitive Dysfunction, Longitudinal Studies, Cognitive decline, Stroke, Aged, business.industry, Memory clinic, Brain, medicine.disease, Magnetic Resonance Imaging, White Matter, Confidence interval, Hyperintensity, Neurology, Cerebral Small Vessel Diseases, Cardiology, Female, Neurology (clinical), Cerebral amyloid angiopathy, business
Abstract: Background: Cerebral Small Vessel Disease (SVD); lacunes, Cerebral Microbleeds (CMBs), and White Matter Hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hypertensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive decline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. Methods: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuropsychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. Results: Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed similar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cognition, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. Conclusion: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.
Published: 2021
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21. Autism Spectrum Disorder Behavioral Implications of the Covid-19 Process, and Individuals’ Awareness and Reactions to Pandemic Conditions based on California, USA

Author: Irene Chon, Myung Suh Choi, Juno Kim, Eddie Bae, Kevin Kang, and Katherine Lee
Subjects: education.field_of_study, Aggression, Social distance, 05 social sciences, Population, Psychological intervention, Special education, medicine.disease, 03 medical and health sciences, Lethargy, 0302 clinical medicine, Autism spectrum disorder, medicine, Anxiety, 0501 psychology and cognitive sciences, medicine.symptom, education, Psychology, 030217 neurology & neurosurgery, 050104 developmental & child psychology, Clinical psychology
Abstract: Vulnerable populations, such as patients with mental illnesses, are known to be overly influenced during disasters and pandemics. However, little is known about how people with autism spectrum disorder (ASD), one of the most common neurodevelopmental conditions in the world with a prevalence of 1%, are affected by health-related disasters, particularly the current Covid-19 pandemic. We investigated how individuals with ASD responded to Covid-19 in terms of comprehension and adherence to implemented measures; changes in their behavioral problems; and how the anxiety levels of their caregivers relate to these behavioral changes. Our sample consisted of 50 individuals with ASD (30 male and 20 female; ages ranged from 3 to 14). The majority of our participants had trouble grasping what Covid-19 is and the measurements it necessitates. They also encountered difficulties in implementing pandemic-related social distance and hygiene regulations. During this time, the majority of students stopped receiving special education. In terms of increased stereo-types, aggression, hypersensitivity, behavioral problems, and sleep and appetite changes, we observed a Covid-19-related clinical presentation that resembled PTSD in individuals with ASD. Aberrant Behavior Checklist (ABC) subscales differed significantly before and after the pandemic conditions. There were differences among the caregivers’ anxiety levels between the current behavioral problem levels to the behavioral problem levels prior to the pandemic. The difference in ABC total score, and specifically the lethargy/social withdrawal subscale score, predicted the anxiety score of the parents. Our findings suggest that the Covid-19 period poses unique challenges for people with ASD and their caregivers, emphasizing the importance of targeted, distance special education interventions and other support services for this population.
Published: 2021
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22. Consensus statements on the management of metastatic renal cell carcinoma from the Hong Kong Urological Association and the Hong Kong Society of Uro‐Oncology 2019

Author: Philip W.K. Kwong, Wayne Lam, Pak-Ling Liu, Eric Ka-Chai Lee, Ka-Suet Law, Darren Ming-Chun Poon, J. Wong, Kuen Chan, Chun-Ki Chan, Eddie Shu-Yin Chan, Wing-Hong Chu, and Henry Chun-Kin Sze
Subjects: medicine.medical_specialty, business.industry, education, Modified delphi, Expert consensus, General Medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Oncology, Renal cell carcinoma, 030220 oncology & carcinogenesis, Family medicine, medicine, Professional association, 030212 general & internal medicine, Clinical care, business
Abstract: Background To establish a set of consensus statements for the management of metastatic renal cell carcinoma, a total of 12 urologists and clinical oncologists from two professional associations in Hong Kong formed an expert consensus panel. Methods Through a series of meetings and using the modified Delphi method, the panelists presented recent evidence, discussed clinical experiences, and drafted consensus statements on several areas of focus regarding the management of metastatic renal cell carcinoma. Each statement was eventually voted upon by every panelist based on the practicability of recommendation. Results A total of 46 consensus statements were ultimately accepted and established by panel voting. Conclusions Derived from recent evidence and expert insights, these consensus statements were aimed at providing practical guidance to optimize metastatic renal cell carcinoma management and promote a higher standard of clinical care.
Published: 2021
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23. Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure

Author: Scott K. Ferguson, Daniel M. Hirai, Michael D. Belbis, Michael J. Holmes, Jason D. Allen, Eddie Weitzberg, Mary N. Woessner, and Mattias Carlström
Subjects: 0301 basic medicine, Cardiac output, medicine.medical_specialty, beetroot juice, Physiology, 030204 cardiovascular system & hematology, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Oxygen Consumption, 0302 clinical medicine, Nitrate, nitric oxide, Physiology (medical), Internal medicine, medicine, Humans, skeletal muscle, nitrite, Heart Failure, Exercise Tolerance, Nitrates, Ejection fraction, business.industry, Skeletal muscle, VO2 max, Stroke Volume, Mini-Review, medicine.disease, Bioavailability, 030104 developmental biology, medicine.anatomical_structure, chemistry, Heart failure, Dietary Supplements, Cardiology, fatigue, business
Abstract: Heart failure (HF) results in a myriad of central and peripheral abnormalities that impair the ability to sustain skeletal muscle contractions and, therefore, limit tolerance to exercise. Chief among these abnormalities is the lowered maximal oxygen uptake, which is brought about by reduced cardiac output and exacerbated by O2delivery-utilization mismatch within the active skeletal muscle. Impaired nitric oxide (NO) bioavailability is considered to play a vital role in the vascular dysfunction of both reduced and preserved ejection fraction HF (HFrEF and HFpEF, respectively), leading to the pursuit of therapies aimed at restoring NO levels in these patient populations. Considering the complementary role of the nitrate-nitrite-NO pathway in the regulation of enzymatic NO signaling, this review explores the potential utility of inorganic nitrate interventions to increase NO bioavailability in the HFrEF and HFpEF patient population. Although many preclinical investigations have suggested that enhanced reduction of nitrite to NO in low Po2and pH environments may make a nitrate-based therapy especially efficacious in patients with HF, inconsistent results have been found thus far in clinical settings. This brief review provides a summary of the effectiveness (or lack thereof) of inorganic nitrate interventions on exercise tolerance in patients with HFrEF and HFpEF. Focus is also given to practical considerations and current gaps in the literature to facilitate the development of effective nitrate-based interventions to improve exercise tolerance in patients with HF.
Published: 2021
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24. Providing live black soldier fly larvae (Hermetia illucens) improves welfare while maintaining performance of piglets post-weaning

Author: Allyson F. Ipema, J. Elizabeth Bolhuis, Eddie A.M. Bokkers, Walter J. J. Gerrits, and Bas Kemp
Subjects: Hermetia illucens, Animal Nutrition, Swine, Soldier fly, Behavioural methods, Eating, Feces, Animal physiology, Animal Husbandry, media_common, Dierlijke Productiesystemen, Larva, Multidisciplinary, Behavior, Animal, 05 social sciences, Neophobia, 04 agricultural and veterinary sciences, Animal behaviour, Diervoeding, Adaptation Physiology, Post weaning, Medicine, Female, media_common.quotation_subject, Science, Weaning, Biology, Feed conversion ratio, Article, Animal Production Systems, Animal science, medicine, Animals, Life Science, 0501 psychology and cognitive sciences, 050102 behavioral science & comparative psychology, Adaptatiefysiologie, Animal Nutrition Sciences, Diptera, Body Weight, 0402 animal and dairy science, medicine.disease, biology.organism_classification, Animal Feed, 040201 dairy & animal science, Animals, Newborn, WIAS, Welfare
Abstract: During weaning, piglets experience concurrent social, physical, and nutritional stressors. Consequently, piglets often have poor feed intake and display increased oral manipulative behaviours post-weaning, indicative of compromised welfare. Black soldier fly larvae (BSFL) possess many attractive properties for pigs and could therefore function as effective edible enrichment, potentially alleviating weaning stress by facilitating exploration and promoting feed intake. In this study, pairs of piglets received a small amount of either live BSFL or wood shavings (8 pens/treatment) scattered throughout the pen twice a day for 11 days after weaning. Home-pen behaviour was scored by instantaneous scan sampling on day 2, 5 and 8, and behavioural responses to a novel environment and novel object were scored on day 10/11. Performance-related parameters were observed regularly. Larvae provisioning increased floor-directed exploration and decreased object-directed exploration, pig-directed oral manipulation, fighting and eating of pellets, and reduced neophobia towards a novel object. Pellet intake was significantly decreased by BSFL provisioning during day 4–11 post-weaning, although feed and net energy intake including BSFL never differed between treatments. BSFL provisioning did not influence piglet growth, feed efficiency, energy efficiency, and faecal consistency. To conclude, live BSFL provisioning positively affected post-weaning piglet behaviour while maintaining performance.
Published: 2021

25. Imaging Somatostatin Positive Tumors with Tyr3-Octreotate/Octreotide Conjugated to Desferrioxamine B Squaramide Radiolabeled with either Zirconium-89 or Gallium-68

Author: Michael P Wheatcroft, Asif Noor, Rodney J. Hicks, Stacey E Rudd, Peter Roselt, Carleen Cullinane, Jessica Van Zuylekom, Eddie Yan, Mohammad B. Haskali, and Paul S. Donnelly
Subjects: Biomedical Engineering, Pharmaceutical Science, Octreotide, Bioengineering, 02 engineering and technology, Neuroendocrine tumors, 01 natural sciences, chemistry.chemical_compound, medicine, Somatostatin receptor 2, Pharmacology, Octreotate, medicine.diagnostic_test, 010405 organic chemistry, Chemistry, Somatostatin receptor, Organic Chemistry, Radiochemistry, Squaramide, 021001 nanoscience & nanotechnology, medicine.disease, 0104 chemical sciences, Somatostatin, Positron emission tomography, 0210 nano-technology, Biotechnology, medicine.drug
Abstract: Radiolabeled derivatives of Tyr3-octreotide and Tyr3-octreotate, synthetic analogues of the peptide hormone somatostatin, can be used for positron emission tomography (PET) imaging of somatostatin receptor expression in neuroendocrine tumors. In this work, a squaramide ester derivative of desferrioxamine B (H3DFOSq) was used attach either Tyr3-octreotide or Tyr3-octreotate to the metal binding ligand to give H3DFOSq-TIDE and H3DFOSq-TATE. These new peptide-H3DFOSq conjugates form stable complexes with either of the positron-emitting radionuclides gallium-68 (t1/2 = 68 min) or zirconium-89 (t1/2 = 3.3 days). The new complexes were evaluated in an AR42J xenograft model that has endogenous expression of SSTR2. All four agents displayed good tumor uptake and produced high-quality PET images. For both radionuclides, the complexes formed with H3DFOSq-TATE performed better, with higher tumor uptake and retention than the complexes formed with H3DFOSq-TIDE. The versatile ligands presented here can be radiolabeled with either gallium-68 or zirconium-89 at room temperature. The long radioactive half-life of zirconium-89 makes distribution of pre-synthesized tracers produced to certified standards feasible and could increase the number of clinical centers that can perform diagnostic PET imaging of neuroendocrine tumors.
Published: 2021
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26. Age of hypertension onset in multiple sclerosis patients

Author: Devon S. Conway, Farren B.S. Briggs, Diane Krill, and Eddie Hill
Subjects: medicine.medical_specialty, Multiple Sclerosis, business.industry, Multiple sclerosis, medicine.disease, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Neurology, Internal medicine, Hypertension, Epidemiology, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background/Objective: Hypertension (HTN) is common in multiple sclerosis (MS), and it is associated with poorer outcomes. We sought to characterize HTN age at onset (AAO) by MS status. Methods/Results: There were 130,050 incident HTN patients, among whom there were 892 MS patients. We conducted multivariable linear regression adjusting for patient attributes. Sex- and race-stratified models were conducted. HTN AAO did not differ in patients with and without MS ( p = 0.17). Similar null associations were observed in the sex- and race-specific analyses. Conclusion: While there are complex relationships between HTN and MS, there are no differences in HTN AAO by MS status.
Published: 2021
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27. Pharmacological Inhibition of Brain EGFR Activation By a BBB-penetrating Inhibitor, AZD3759, Attenuates α-synuclein Pathology in a Mouse Model of α-Synuclein Propagation

Author: Thomas M. Durcan, Eddie Cai, Wen Luo, Frédérique Larroquette, Rhalena A. Thomas, Omid Tavassoly, Edward A. Fon, Esther Del Cid Pellitero, and Vincent Soubannier
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Neurology, Parkinson's disease, Synucleinopathies, animal diseases, Endogeny, Substantia nigra, Striatum, Piperazines, Mice, 03 medical and health sciences, 0302 clinical medicine, Dopamine, medicine, Animals, Humans, Pharmacology (medical), RNA, Small Interfering, Cells, Cultured, EGFR inhibitors, Pharmacology, Dose-Response Relationship, Drug, Chemistry, Brain, medicine.disease, nervous system diseases, ErbB Receptors, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, nervous system, Blood-Brain Barrier, Quinazolines, alpha-Synuclein, Phosphorylation, Original Article, Neurology (clinical), 030217 neurology & neurosurgery, medicine.drug
Abstract: Aggregation and deposition of α-synuclein (α-syn) in Lewy bodies within dopamine neurons of substantia nigra (SN) is the pathological hallmark of Parkinson’s disease (PD). These toxic α-syn aggregates are believed to propagate from neuron-to-neuron and spread the α-syn pathology throughout the brain beyond dopamine neurons in a prion-like manner. Targeting propagation of such α-syn aggregates is of high interest but requires identifying pathways involving in this process. Evidence from previous Alzheimer’s disease reports suggests that EGFR may be involved in the prion-like propagation and seeding of amyloid-β. We show here that EGFR regulates the uptake of exogenous α-syn-PFFs and the levels of endogenous α-syn in cell cultures and a mouse model of α-syn propagation, respectively. Thus, we tested the therapeutic potentials of AZD3759, a highly selective BBB-penetrating EGFR inhibitor, in a preclinical mouse model of α-syn propagation. AZD3759 decreases activated EGFR levels in the brain and reduces phosphorylated α-synuclein (pSyn) pathology in brain sections, including striatum and SN. As AZD3759 is already in the clinic, this paper’s results suggest a possible repositioning of AZD3759 as a disease-modifying approach for PD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01017-6.
Published: 2021
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28. Red blood cells from patients with pre-eclampsia induce endothelial dysfunction

Author: Matilda Fornell Von Rosen, Rafael T. Krmar, Eddie Weitzberg, Sarah McCann Haworth, Josefine Nasiell, Jon O. Lundberg, Mattias Carlström, Zhengbing Zhuge, and Carina Nihlen
Subjects: medicine.medical_specialty, Erythrocytes, Endothelium, Physiology, Nitric Oxide, medicine.disease_cause, Nitric oxide, Mice, chemistry.chemical_compound, Pre-Eclampsia, Pregnancy, Internal medicine, Internal Medicine, Animals, Humans, Medicine, Endothelial dysfunction, chemistry.chemical_classification, Reactive oxygen species, Arginase, biology, business.industry, Haemolysis, medicine.disease, Nitric oxide synthase, Endocrinology, medicine.anatomical_structure, chemistry, biology.protein, Female, Endothelium, Vascular, Nitric Oxide Synthase, Cardiology and Cardiovascular Medicine, business, Oxidative stress
Abstract: Rationale Pre-eclampsia is a multisystem disorder associated with systemic vascular dysfunction and decreased nitric oxide (NO) bioactivity. Arginase competes with NO synthase (NOS) for l-arginine, and its upregulation may reduce NOS-derived NO formation or induce production of reactive oxygen species (ROS) via uncoupling of NOS, resulting in endothelial dysfunction. Red blood cells (RBCs) have emerged as key players in NO homeostasis via their interactions with the endothelium. Studies have demonstrated that abnormal RBC arginase function in patients with diabetes contributes to oxidative stress and endothelial dysfunction. Aim The aim of the study was to investigate if reduced NO bioavailability and increased ROS in pre-eclampsia is mediated via RBC-dependent mechanisms. Methods In this translational study, plasma and RBCs were isolated from gestationally matched pre-eclamptic and healthy pregnant women and co-incubated overnight with mouse aortas for vascular reactivity studies. NO bioactivity, that is, nitrate, nitrite and cGMP, was assessed in plasma. Arginase activity and expression were analysed in RBCs. Results Plasma markers of NO homeostasis and signalling were decreased in pre-eclamptic women vs. healthy pregnant women. Co-incubation of aorta with pre-eclamptic RBCs, but not healthy pregnant RBCs, induced endothelial dysfunction, which was ameliorated by pharmacological inhibition of arginase, scavenging of ROS, and by nitrite treatment. This pathological vascular phenotype was not observed following incubation with pre-eclamptic plasma. Arginase expression and activity in RBCs were increased in pre-eclamptic vs. healthy pregnant women and was associated with pre-eclampsia severity. Pre-eclamptic RBC-induced endothelial dysfunction was not because of increased haemolysis/cell-free haemoglobin. Conclusion This study demonstrates a novel role of the RBC in mediating the endothelial dysfunction associated with pre-eclampsia through arginase-dependent and oxidative stress-dependent mechanisms. Targeting of RBC arginase may provide a novel treatment modality for pre-eclampsia.
Published: 2021
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29. Body composition and risk of gastric cancer: A population‐based prospective cohort study

Author: Eddie C. Cheung, Bin Xia, Anran Liu, Jian-Liang Du, Gang Sun, Wenhui Wu, Peng Yun, Changhua Zhang, Yan Tang, You-Zhen Tang, Jinqiu Yuan, Yulong He, Zi-Chong Kuo, and Qiangsheng He
Subjects: 0301 basic medicine, Male, Cancer Research, medicine.medical_specialty, UK Biobank, fat‐free mass, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Risk Factors, Stomach Neoplasms, Internal medicine, Weight management, Confidence Intervals, Electric Impedance, cohort study, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Registries, Risk factor, Prospective cohort study, Adiposity, Proportional Hazards Models, Original Research, business.industry, Proportional hazards model, gastric cancer, Hazard ratio, Age Factors, Cancer, fat mass, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Body Composition, Female, business, Body mass index, Cancer Prevention, Cohort study
Abstract: The recognition of adiposity as a risk factor for gastric cancer is mainly based on traditional anthropometric indices, such as body mass index, which are unable to discriminate between lean and fat mass. We undertook this study to examine body composition and subsequent risk of gastric cancer. This is a prospective analysis of participants free of cancer from the UK Biobank. We measured baseline body composition with electrical bioimpedance analysis and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. We documented 326 cases of cancer from 474,929 participants over a median follow‐up of 6.6 years. Both male (HR 1.70, 95% CI 1.01 to 2.89) and female participants (HR 2.47, 95% CI 1.15 to 5.32) in the highest quartile of whole body fat‐free mass were associated with increased risk of gastric cancer as compared with those in the lowest quartile.Whole body fat mass was associated with a decreased risk of gastric cancer (HR per 5‐unit increase 0.86, 95% CI 0.74 to 0.99) in females, but not in males. We concluded that fat‐free mass and fat mass may have different effects on gastric cancer risk. This study provided evidence for individualized weight management for the prevention of gastric cancer., Based on UK biobank cohort (474,929 participants and 326 cases of gastric cancer), this study found fat‐free mass is assocated with increased risk of gastric cancer in both genders while fat mass is associated with reduced risk of gastric cancer in females. Our results provide new insights into relationships between obesity and gastric cancer, and deliver important clinical and public health messages about healthy body composition beyond BMI.
Published: 2021

30. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. 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Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut 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Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta Mišigoj-Durakovic , Antonio Mistretta , Veronica Mocanu , Pietro A Modesti , Sahar Saeedi Moghaddam , Bahram Mohajer , Mostafa K Mohamed , Shukri F Mohamed , Kazem Mohammad , Zahra Mohammadi , Noushin Mohammadifard , Reza Mohammadpourhodki , Viswanathan Mohan , Salim Mohanna , Muhammad Fadhli Mohd Yusoff , Iraj Mohebbi , Farnam Mohebi , Marie Moitry , Drude Molbo , Line T Møllehave , Niels C Møller , Dénes Molnár , Amirabbas Momenan , Charles K Mondo , Michele Monroy-Valle , Eric Monterrubio-Flores , Kotsedi Daniel K Monyeki , Jin Soo Moon , Mahmood Moosazadeh , Leila B Moreira , Alain Morejon , Luis A Moreno , Karen Morgan , Suzanne N Morin , Erik Lykke Mortensen , George Moschonis , Malgorzata Mossakowska , Aya Mostafa , Anabela Mota-Pinto , Jorge Mota , Mohammad Esmaeel Motlagh , Jorge Motta , Marcos André Moura-Dos-Santos , Malay K Mridha , Kelias P Msyamboza , Thet Thet Mu , Magdalena Muc , Boban Mugoša , Maria L Muiesan , Parvina Mukhtorova , Martina Müller-Nurasyid , Neil Murphy , Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria 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Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021
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31. Using Partnerships to Create a Medical Specialty Camp for Youth with Diabetes

Author: Takeyra Collins Coats, Chet Kramer, Kent Reifschneider, Eddie Hill, and Ron Ramsing
Subjects: Gerontology, Type 1 diabetes, media_common.quotation_subject, Specialty, medicine.disease, Urban Studies, Carbohydrate counting, Quality of life (healthcare), Tourism, Leisure and Hospitality Management, medicine, Psychological resilience, Club, Disease management (health), Psychology, Positive Youth Development, Social Sciences (miscellaneous), Nature and Landscape Conservation, media_common
Abstract: Complications associated with a complex chronic illness, specifically, type 1 diabetes, negatively impact youth as they struggle to maintain healthy lifestyles. Type 1 diabetes is the second most common chronic illness affecting youth as well as one of the most psychologically and behaviorally demanding illnesses. Fortunately, organized camps have been shown to positively influence long-term outcomes for youth. Family Diabetes Camp, the only family medical program in the state where this study occurred, was created in collaboration with a local university, a diabetes center at a hospital, and a chapter of the Lions Club. This collaborative camp program aimed to test the effect of active participation in a Family Diabetes Camp upon youth outcomes for campers with type 1 diabetes. Specifically, the purpose was to evaluate the impact of a collaborative medical camp on campers’ resilience and youth developmental outcomes (e.g., independence). Family Diabetes Camp was designed using Outcome-Focused Programming (OFP) to promote positive youth development. The Family Diabetes Camp included 50 campers for the pre-test and post-test (n= 19 males and n= 31 females). While there were no statistically significant differences from pretest (M=4.97, SD= .53) to post-test scores (M=5.01, SD= .46), with t(50) = -.56, p= .57) researchers found a slight increase in resilience from pre to post-test. Using a retrospective measure, campers showed gains in the seven critical youth development outcomes identified by the American Camp Association. Finally, campers learned new knowledge about site injection, carbohydrate counting, and the use of exercise to help manage their diabetes. The impact associated with adapting activities and an environment to encourage, analyze, and challenge resilient behaviors is essential in encouraging independence, shared experiences, and effective disease management for youth living with type 1 diabetes. The camp, solely staffed by volunteers, included physicians, diabetes educators, certified therapeutic recreation specialists, dietitians, nurses, pump specialists, recreation professionals and students, and Lions Club Members. The camp program is unique not only in how it fills a void for youth with type 1 diabetes but how three large organizations work in concert to meet the needs of entire families. These types of data can be instrumental in establishing more camps and other out of school time programming that positively impacts quality of life, health care cost, and mortality among youth with type 1 diabetes. Subscribe to JPRA
Published: 2022
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32. Strontium citrate associated drug reaction with eosinophilia and systemic symptoms syndrome with granulomatous dermatitis

Author: Jennifer G. Gill, Melissa M. Mauskar, Jacqueline McKesey, Elysha Kolitz, and Eddie Kwan
Subjects: Strontium, medicine.medical_specialty, business.industry, DRESS, drug reaction with eosinophilia and systemic symptoms, granulomatous dermatitis, chemistry.chemical_element, Case Report, Dermatology, lcsh:RL1-803, medicine.disease, Drug reaction with eosinophilia and systemic symptoms, chemistry, Strontium ranelate, strontium citrate, strontium ranelate, lcsh:Dermatology, drug reaction with eosinophilia and systemic symptoms, Medicine, cutaneous adverse reaction, strontium, business, Granulomatous Dermatitis, DRESS, medicine.drug
Published: 2021

33. Vision, vision-specific functioning and mobility, and their relationship with clinically assessed cognitive impairment

Author: Christopher Chen, Ryan E. K. Man, Tien Yin Wong, Eddie J.Y. Chong, Eva K Fenwick, Kah Hie Wong, Yih Chung Tham, Preeti Gupta, Alfred Tau Liang Gan, Ecosse L. Lamoureux, Narayanaswamy Venketasubramanian, Ching-Yu Cheng, Saima Hilal, Charumathi Sabanayagam, Carol Y. Cheung, and Xin Xu
Subjects: Male, Gerontology, Aging, medicine.medical_specialty, Visual acuity, Psychological intervention, Odds, 03 medical and health sciences, 0302 clinical medicine, Quality of life, mental disorders, Epidemiology, Humans, Medicine, Dementia, Cognitive Dysfunction, Cognitive decline, Aged, Singapore, business.industry, Cognition, General Medicine, medicine.disease, Cross-Sectional Studies, Quality of Life, 030221 ophthalmology & optometry, Female, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background The relationship between self-reported visual disability and cognitive impairment in older individuals is unclear. Objective To determine the relationship of vision-specific functioning (VSF), vision-specific mobility (VSM) and visual acuity (VA) with clinically assessed cognitive impairment in the Epidemiology of Dementia in Singapore study. Design Cross-sectional. Setting Population-based. Subjects Eight hundred and seventy-four adults aged ≥60 years at higher risk of possible cognitive impairment by the Abbreviated Mental Test and progressive forgetfulness question. Methods VSF and VSM were measured using Rasch-transformed continuous scores of two Impact of Vision Impairment questionnaire domains. Cognitive impairment was objectively determined using detailed neuropsychological testing and defined as no cognitive impairment (NCI), mild cognitive impairment-no dementia (CIND), moderate CIND only and moderate CIND or dementia. Associations were assessed using multinomial logistic regression models. Results Of the 874 participants (49.0% males, mean age (SD) 65.5 (7.0) years), 277, 281 and 316 had NCI, mild CIND and moderate CIND or dementia, respectively. Compared to NCI, the odds of moderate CIND, and moderate CIND or dementia increased for every SD worsening in VSF (OR: 1.44, 95% CI 1.14–1.82, and OR: 1.52, 95%CI 1.19–1.94, respectively) and VSM (OR: 1.42, 95%CI 1.11–1.81, and OR: 1.50, 95%CI 1.15–1.95). Similarly, the odds of mild CIND (OR: 1.62, 95%CI 1.19–2.22), moderate CIND (OR: 1.93, 95%CI 1.45–2.58), and moderate CIND or dementia (OR: 2.25, 95%CI 1.62–3.11) increased significantly with every SD worsening of VA. Conclusions Our results emphasise the importance of interventions to prevent vision loss and improve quality of life to reduce likelihood of age-related cognitive decline.
Published: 2021
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34. Laboratory parameters as predictors of prognosis in uterine cervical neoplasia

Author: Rosekeila Simões Nomelini, Eddie Fernando Candido Murta, Priscila Thais Silva Mantoani, and Patrícia Santos Vaz de Lima
Subjects: Blood Platelets, medicine.medical_specialty, Multivariate analysis, Neutrophils, Uterine Cervical Neoplasms, Cervical intraepithelial neoplasia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Statistical significance, medicine, Humans, Lymphocytes, 030212 general & internal medicine, Retrospective Studies, Cervical cancer, 030219 obstetrics & reproductive medicine, Thrombocytosis, Receiver operating characteristic, Platelet Count, Proportional hazards model, business.industry, Obstetrics and Gynecology, Cancer, Prognosis, medicine.disease, Reproductive Medicine, Female, Laboratories, business
Abstract: The aims of study were to assess platelet counts, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), RWD (red cells distribution width) and fasting glucose in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer; and to relate these parameters to prognostic factors and survival in cervical cancer.We evaluated the patients with confirmed diagnosis of invasive cervical cancer (n = 102), and CIN (n = 102). Histological type, NLR, PLR, RDW, platelets count, fasting glucose, staging, overall survival (OS), and disease-free survival (DFS) were evaluated. The results of laboratory parameters were assessed by Mann-Whitney test. A receiver operating characteristic (ROC) curve was used to determine the best cut-off values. Survival was verified by the Kaplan-Meyer method followed by the Gehan-Breslow test. Multivariate analysis was performed using Cox regression. The level of significance was less than 0.05.Comparing CIN and invasive malignancies, higher values of NLR, PLR, RDW and fasting glucose were found in cancer patients (p0.0001, p = 0.011, p = 0.0153 and p = 0.0096, respectively). In cervical cancer, higher NLR and PLR values were found at stage II to IV when compared to stage I (p = 0.0066 and p = 0.005, respectively). ROC curves were performed. In invasive neoplasms, the cut-off values for NLR and PLR in the comparison between stage I and greater than I were 4 and 165.45, respectively. For survival curves, there was lower OS and DFS in patients with NLR greater than 4 (p = 0.0004 and p = 0.0153, respectively) and PLR greater than 165.45 (p = 0.0319 and p = 0.0362, respectively). After multivariate analysis, only NLR remained as an independent factor in DFS (HR = 6.095, 95 % CI = 1.120-33.177, p = 0.037) and OS (HR = 4.522, 95 % CI = 1.241-16.479, p = 0.022) CONCLUSION: Higher NLR is associated to lower OS and DFS in invasive uterine cervical neoplasia, and can be considered an independent factor of worse prognosis.
Published: 2021
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35. Influence of an Exergaming Training Program on Reducing the Expression of IL-10 and TGF-β in Cancer Patients

Author: Márcia Antoniazi Michelin, Leonardo César Carvalho, Ricardo da Silva Alves, Eddie Fernando Cândido Murta, Juliana Bassalobre Carvalho Borges, Douglas Reis Abdalla, Denise Hollanda Iunes, and Karina Oliveira Prado Mariano
Subjects: Adult, Male, Health (social science), Gene Expression, Adipokine, Neoplasms, medicine, Humans, Interferon gamma, Exercise, Aged, business.industry, Rehabilitation, Public Health, Environmental and Occupational Health, Interleukin, Cancer, Original Articles, Middle Aged, medicine.disease, Interleukin-10, TGF-beta Superfamily Proteins, Computer Science Applications, Interleukin 10, Video Games, Cancer research, Female, Tumor necrosis factor alpha, Training program, business, Transforming growth factor, medicine.drug
Abstract: Objective: To evaluate the effect of exergaming in the plasma levels of adipokines (interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor-alpha [TNF-α]), Th1 (IL-2, IL-12, and interferon gamma [IFN-γ]), Th2 (IL-4 and IL-33), Th17 (IL-17 and IL-23), and regulatory T (Treg) (IL-10 and transforming growth factor-beta [TGF-β]) in cancer patients undergoing treatment. Materials and Methods: We conducted a quasi-experimental control clinical trial using exergaming in all groups through the Xbox 360 Kinect™. The game used in this study was called Your Shape Fitness Evolved 2012. The volunteer participants played the game two to three times per week, for a total of 20 sessions. Forty-five volunteer participants were divided into 3 groups: cancer patients undergoing chemotherapy and/or radiotherapy treatment (chemotherapy and/or radiotherapy group CRG; n = 15); cancer patients who finished chemotherapy and/or radiotherapy treatment (cancer accompaniment group CAG; n = 15); and the control group (volunteers without a cancer diagnosis CG; n = 15). In the pre- and post-training period, all volunteers submitted to blood collection procedures using the enzyme-linked immunosorbent assay (ELISA). This test was used to obtain the levels of adipokines expression (IL-1β, IL-6, IL-8, and TNF-α) and the cytokine profiles Th1 (IL-2, IL-12, and IFN-γ), Th2 (IL-4 and IL-33), Th17 (IL-17 and IL-23), and Treg (IL-10 and TGF-β). Results: After exergaming, the CRG showed significant reductions in proinflammatory cytokines (IL-6: P
Published: 2020
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36. Predicting the Transition to Chronic Pain 6 Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study

Author: Andrew Chertoff, E. John Gallagher, Polly E. Bijur, Eddie Irizarry, Benjamin W. Friedman, Lorena Abril, Farnia Naeem, and Michael McGregor
Subjects: Adult, medicine.medical_specialty, Logistic regression, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, business.industry, Chronic pain, 030208 emergency & critical care medicine, Odds ratio, Emergency department, medicine.disease, Acute Pain, Confidence interval, Opioid, Emergency Medicine, Chronic Pain, Emergency Service, Hospital, business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract: Background Acute pain can transition to chronic pain, a potentially debilitating illness. Objective We determined how often acute pain transitions to chronic pain among patients in the emergency department (ED) and whether persistent pain 1 week after the ED visit was associated with chronic pain. Methods An observational cohort study conducted in two EDs. We included adults with acute pain (≤10 days) if an oral opioid was prescribed. Exclusion criteria were recent opioid use and use of any analgesics regularly prior to onset of the pain. Research associates interviewed patients during the ED visit and 1 week and 6 months later. The primary outcome, chronic pain, was defined as pain on > 50% of days since ED discharge. We constructed logistic regression models to evaluate the association between persistent pain 1 week after an ED visit and chronic pain, while adjusting for demographic and treatment variables. Results During a 9-month period, we approached 733 patients for participation and enrolled 484; 450 of 484 (93%) provided 1-week outcomes data and 410 of 484 (85%) provided 6-month outcomes data. One week after the ED visit, 348 of 453 (77%; 95% confidence interval [CI] 73–80%) patients reported pain in the affected area. New-onset chronic pain at 6 months was reported by 110 of 408 (27%; 95% CI 23–31%) patients. Presence of pain 1 week after ED visit was associated with chronic pain (odds ratio 3.6; 95% CI 1.6–8.5). Conclusions About one-quarter of ED patients with acute pain transition to chronic pain within 6 months. Persistence of pain 1 week after the ED visit can identify patients at risk of transition.
Published: 2020
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37. Work Productivity Outcomes Associated with Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis

Author: Natalie J. Engmann, Edward E. Neuberger, Ibrahim Abbass, and Eddie Jones
Subjects: Employment, Work productivity, medicine.medical_specialty, Neurology, Disease, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Disease-modifying therapies, Ocrelizumab, 030212 general & internal medicine, Young adult, Original Research, Expanded Disability Status Scale, business.industry, Odds ratio, medicine.disease, Confidence interval, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Objective This study evaluated work and activity impairment in patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs). Methods Data were obtained from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis. Patients with relapsing–remitting or secondary progressive MS who completed surveys in 2018 and 2019 and received ≥ 6 months of an eligible therapy, including OCR, injectable therapy, and oral therapy, were included. Outcomes were assessed using the patient-reported Work Productivity and Activity Impairment questionnaire. Doubly robust estimation, which combined propensity score weighting and regression modeling, was used to compare treatments, controlling for baseline clinical and demographic characteristics. Results This study included 630 patients (OCR, n = 90; injectable DMT, n = 224; oral DMT, n = 316) with a mean (standard deviation) age of 42 (11) years. A greater proportion of OCR-treated patients had an Expanded Disability Status Scale score of ≥ 3 at treatment initiation compared with those receiving oral and injectable DMTs (51 vs. 15% and 15%, respectively), and a smaller proportion of OCR-treated patients received treatment for ≥ 1 year (43 vs. 90% and 92%, respectively). OCR-treated patients had higher odds of employment [odds ratio (95% confidence interval) 3.4 (1.5–7.7) vs. oral DMT, 5.6 (2.6–12.0) vs. injectable DMT], lower overall work productivity loss [difference (95% confidence interval) − 10.0% (− 6.1 to − 15.0%) vs. oral DMT, − 13.0% (− 8.5 to − 17.0%) vs. injectable DMT] and lower activity impairment [difference (95% confidence interval) − 11% (− 7.1 to − 16.0%) vs. oral DMT, − 9.7% (− 5.0 to − 14.0%) vs. injectable DMT]. Conclusion This real-world evidence suggests that patients with MS treated with OCR experience lower work and activity impairment than patients treated with other DMTs. Electronic supplementary material The online version of this article (10.1007/s40120-020-00224-1) contains supplementary material, which is available to authorized users., Plain Language Summary Multiple sclerosis (MS) is the most common progressive neurological disease in young adults. It typically starts between the ages of 20 and 40 years—arguably some of the most productive years of an individual’s life—and it has a large impact on many aspects of everyday life for the rest of a person’s life. The reduction in the ability to do routine activities, including working, results in a large economic burden. Disease-modifying treatments (DMTs) available for MS, particularly high-efficacy DMTs, have been shown to improve work productivity. This study looked at work and activity impairment using the Work Productivity and Activity Impairment Questionnaire in patients with MS who were treated with ocrelizumab (OCR) or other DMTs for ≥ 6 months. A total of 630 patients with relapsing–remitting MS (RRMS) or secondary progressive MS (SPMS) from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis were included in the study, including 90, 316 and 224 patients who completed ≥ 6 months of treatment with OCR, oral or injectable therapy. Compared with patients receiving oral or injectable DMTs, those receiving OCR had higher odds of employment [odds ratio (OR) vs. oral DMT 3.4; OR vs. injectable DMT 5.6], lower overall work productivity impairment (difference vs. oral DMT − 10%; difference vs. injectable DMT − 13%) and lower activity impairment (difference vs. oral DMT − 11%; difference vs. injectable DMT − 9.7%). These findings in patients with RRMS or SPMS being treated in the real world suggest that OCR may reduce the impact of MS disease on work productivity more than other DMTs. Electronic supplementary material The online version of this article (10.1007/s40120-020-00224-1) contains supplementary material, which is available to authorized users.
Published: 2020
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38. A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping

Author: Aurélia Gruber, Céleste Lebbé, Julie Delyon, Fanélie Jouenne, Baptiste Louveau, Kevin Serror, Aminata Ndiaye, Aurélie Sadoux, Nicolas Dumaz, Pauline Tétu, Maxime Battistella, Laetitia Da Meda, O. Marco, Barouyr Baroudjian, Samia Mourah, Alban Lermine, Eddie Lopes, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Dumaz, Nicolas, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Université de Paris (UP)
Subjects: Male, 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Oncology, Cancer Research, medicine.medical_specialty, Genotype, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.CAN]Life Sciences [q-bio]/Cancer, DNA sequencing, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, CDKN2A, Internal medicine, medicine, Humans, Pharmacology (medical), In patient, Copy-number variation, Melanoma, Gene, Genotyping, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, High-Throughput Nucleotide Sequencing, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, 3. Good health, 030104 developmental biology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], 030220 oncology & carcinogenesis, Female, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Background: Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies.Objective: The objective of this study was to present such a customized next-generation sequencing panel in melanoma.Methods: Melanoma patients with somatic molecular profiling performed as part of routine care were included. High-throughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations.Results: Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splice-site mutations. At least one alteration was detected in 368 (87.4%) lesions, with BRAF, NRAS, CDKN2A, CCND1, and MET as the most frequently altered genes. Among patients with BRAFV600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with RAS hotspot mutated lesions and in patients with neither BRAFV600 nor RAS hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively.Conclusions: Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients' clinical management.
Published: 2020
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39. Rule Out Acute Kidney Injury in the Emergency Department With a Urinary Dipstick

Author: Lena A. Kheir, Katherine Xu, Rebecca K. Breheney, John R. Burton, Britney A. Hatcher, Ariel E. Felman, Juliana N. Gamino, Hayley A. Giordano, Eddie F. Guerrero Herrera, Andrew Beenken, Aileen Gozali, Siddarth Arumugam, Jae I. Nha, Yaagnik D. Kosuri, Saul V. Lincoln, Anjali Gehani, Jacob S. Stevens, Osman R. Sayan, Jonathan Barasch, Tejashree S. Gopal, Erika K. Mitsui, Erin P. Geraghty, Miriam P. Callahan, Samuel J. Spaiser, Yuanji Li, Kristen L. King, Alexander T. Sayan, Alexa Corker, Andrew Yaeh, Samuel K. Sia, and Sumit Mohan
Subjects: medicine.medical_specialty, emergency department, Urinary system, 030232 urology & nephrology, Urology, 030204 cardiovascular system & hematology, dipstick, 03 medical and health sciences, chemistry.chemical_compound, AKI, 0302 clinical medicine, Clinical Research, medicine, NGAL, Prospective cohort study, Creatinine, business.industry, Acute kidney injury, Dipstick, Emergency department, medicine.disease, chemistry, Nephrology, Cohort, biomarker, Biomarker (medicine), business
Abstract: Introduction The identification of acute injury of the kidney relies on serum creatinine (SCr), a functional marker with poor temporal resolution as well as limited sensitivity and specificity for cellular injury. In contrast, urinary biomarkers of kidney injury have the potential to detect cellular stress and damage in real time. Methods To detect the response of the kidney to injury, we have tested a lateral flow dipstick that measures a urinary protein called neutrophil gelatinase-associated lipocalin (NGAL). Analysis of urine was performed in a prospective cohort of 479 patients (final cohort N = 426) entering an emergency department in New York City and subsequently admitted for inpatient care. Results Colorimetric development had high interrater reliability (88% concordance rate) and correlated with traditional enzyme-linked immunosorbent assay (ELISA) measurements (ρ = 0.732, P < .0001). Of the 14% of the cohort who met Acute Kidney Injury Network (AKIN) SCr criteria for acute kidney injury (AKI), 67% demonstrated transient (2 days) elevation of SCr. Comparing the outcomes of patients with sustained versus transient or undetectable changes in SCr revealed that the urinary NGAL (uNGAL) dipstick had high specificity and negative predictive value (NPV) (high- vs. low-intermediate readings, sensitivity = 0.55, specificity = 0.91, positive predictive value = 0.24, NPV = 0.97, χ2 = 20.39, P < 0.001). Conclusion We show that the introduction of a bedside uNGAL dipstick permits accurate triage by identifying individuals who do not have tubular injury. In an era of shortening length of stay and rapid decisions based on isolated SCr measurements, real-time exclusion of kidney injury by a dipstick will be particularly useful to overcome the retrospective, insensitive, and nonspecific attributes of SCr., Graphical abstract
Published: 2020
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40. Toxicity and outcomes in older versus younger patients treated with trimodality therapy for locally advanced rectal cancer

Author: Eddie Zhang, D.Y. Lee, Joshua E. Meyer, Efrat Dotan, Rishi Jain, J. Karen Wong, Jeffrey M. Farma, Harry S. Cooper, and Elizabeth Handorf
Subjects: medicine.medical_specialty, Rectal Neoplasms, Colorectal cancer, business.industry, Rectum, Locally advanced, MEDLINE, Chemoradiotherapy, medicine.disease, Neoadjuvant Therapy, Article, Oncology, Older patients, Internal medicine, Toxicity, medicine, Humans, Geriatrics and Gerontology, business, Aged, Neoplasm Staging
Published: 2020
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41. The prevalence of hypertension in multiple sclerosis based on 37 million electronic health records from the United States

Author: Eddie Hill, Farren B.S. Briggs, and Hesham Abboud
Subjects: Male, medicine.medical_specialty, Multiple Sclerosis, Adverse outcomes, Population, Health records, Age and sex, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, Prevalence, Electronic Health Records, Humans, Medicine, cardiovascular diseases, 030212 general & internal medicine, education, education.field_of_study, business.industry, Multiple sclerosis, medicine.disease, Comorbidity, United States, Cross-Sectional Studies, Neurology, Sample size determination, Hypertension, Neurology (clinical), business, 030217 neurology & neurosurgery, Demography
Abstract: BACKGROUND AND PURPOSE Hypertension (HTN) is a common comorbidity in multiple sclerosis (MS), and it significantly contributes to adverse outcomes. Unfortunately, the distribution of HTN in persons with MS has not been well characterized, and prior estimates have primarily relied on modest sample sizes. The objective of this study was to robustly describe the distribution of HTN in the MS population in comparison to the non-MS population with considerations for age, sex, and race. To date, this is the largest investigation of its kind. METHODS We conducted a cross-sectional study of 37 million unique electronic health records available in the IBM Explorys Enterprise Performance Management: Explore database (Explorys) spanning the United States. This resource has previously been validated for use in MS. We evaluated the prevalence of HTN in MS (N = 122 660) and non-MS (N = 37 075 350) cohorts, stratifying by age, sex, and race. RESULTS The prevalence of HTN was significantly greater among those with MS than among those without MS across age, sex, and race subpopulations, even after adjusting for age and sex. HTN was 25% more common in MS. In both MS and non-MS cohorts, the prevalence of HTN progressively increased with age and was higher in Black Americans and in males. DISCUSSION This study demonstrated that HTN is significantly more common in the MS population compared to the non-MS population, irrespective of sex and race. Because HTN is the leading global risk factor for disability and death, these results emphasize the need for aggressive screening for, and management of, HTN in the MS population.
Published: 2020
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42. Lighting conditions and perceived visual function in ophthalmic conditions

Author: Eddie Appenbrick, Charles C. Barr, Guy N. Brock, and Efrat Fleissig
Subjects: Visual acuity, genetic structures, business.industry, Macular degeneration, medicine.disease, eye diseases, Sensory Systems, Odds, 03 medical and health sciences, Cellular and Molecular Neuroscience, Ophthalmology, 0302 clinical medicine, Visual function, 030221 ophthalmology & optometry, Medicine, Optometry, In patient, medicine.symptom, Prospective cohort study, business, 030217 neurology & neurosurgery, Bright light, Multinomial logistic regression
Abstract: To determine the influence of different lighting conditions on perceived visual function in patients of different age, gender, race, and in various ophthalmic diseases. A prospective study. A survey given to patients seen in general ophthalmic and retina clinics. Patients were asked four questions: Is your vision better, worse, or the same in (1) bright light vs dim light, (2) indoors or outdoors, (3) beginning or end of the day, and (4) sunny or cloudy day? Parameters tested were age, race, gender, visual acuity, and a variety of ophthalmic conditions. Multivariable models for each question were fit using multinomial regression. Association was considered significant if p < 0.05. A total of 722 patients were enrolled in the study. Patients with lower vision (LogMAR ≥ 0.3) were more likely to indicate they either had better vision indoors or outdoors compared with better vision patients (LogMAR < 0.1). Patients with pseudophakia were also more likely to indicate they had better vision on a cloudy day (OR = 1.9). White patients had double the odds of selecting bright light compared with others. Males were less likely than females to indicate better vision indoors (OR = 0.62). There were no significant associations with age-related macular degeneration (AMD) in the multivariable model. Most patients did not note any difference in lighting conditions, and although there is explanatory rational for some of the findings in this study, those questions concerning lighting conditions or time of day are not useful for screening of disease. Gender and ethnicity were found to have associations with lighting preferences which needs to be further studied.
Published: 2020
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43. Identification of Human-Derived Attractants to Simulium damnosum Sensu Stricto in the Madi-Mid North Onchocerciasis Focus of Uganda

Author: Thomas R. Unnasch, Eddie W. Cupp, Canhui Liu, Thomson Lakwo, Denis Loum, Benjamin G. Jacob, and Devon Cozart
Subjects: biology, Blindness, Zoology, biology.organism_classification, medicine.disease, Onchocerca volvulus, Principal vector, Infectious Diseases, Simulium damnosum, Virology, Vector (epidemiology), medicine, Window trap, Parasitology, Onchocerciasis, Sensu stricto
Abstract: Human landing collections (HLCs) have been the standard method for the collection of black flies that serve as vectors for Onchocerca volvulus, the causative agent of onchocerciasis or river blindness. However, HLCs are inefficient and may expose collectors to vector-borne pathogens. The Esperanza window trap (EWT) has been shown to be a potential alternative to HLCs for the collection of Simulium damnosum, the principal vector of O. volvulus in Africa. To improve the performance of the EWT, sweat from individuals highly attractive or less attractive to S. damnosum sensu stricto was examined by gas chromatography and mass spectroscopy. Twelve compounds were identified which were solely present or present in increased amounts in the sweat of the highly attractive individuals. Two of these compounds (naphthalene and tert-hexadecyl mercaptan) were found to be attractive to S. damnosum s.s. in behavioral assays. Traps baited with these compounds outperformed those baited with the current standard bait of worn socks. Using these newly identified compounds as baits will make the EWT more efficient in collecting vector black flies and may enhance the potential utility of the EWT as a local vector control measure.
Published: 2020
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44. A Randomized, Double‐Dummy, Emergency Department‐Based Study of Greater Occipital Nerve Block With Bupivacaine vs Intravenous Metoclopramide for Treatment of Migraine

Author: Matthew S. Robbins, Andrew Williams, Eddie Irizarry, Eleftheria Zias, Benjamin W. Friedman, Clemencia Solorzano, Michael Del Valle, E. John Gallagher, Melissa A. Harrilal, and Polly E. Bijur
Subjects: Adult, Male, Metoclopramide, Greater occipital nerve, Migraine Disorders, Analgesic, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Outcome Assessment, Health Care, medicine, Humans, 030212 general & internal medicine, Anesthetics, Local, Adverse effect, Cervical Plexus, Bupivacaine, business.industry, Nerve Block, Emergency department, Middle Aged, medicine.disease, Dopamine D2 Receptor Antagonists, Neurology, Migraine, Anesthesia, Acute Disease, Administration, Intravenous, Female, Neurology (clinical), Emergency Service, Hospital, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Greater occipital nerve blocks (GONB) are used increasingly to treat acute migraine. Objective We conducted a randomized controlled trial to determine whether GONB was as effective as intravenous metoclopramide for migraine. Methods This was a double-dummy, double-blind, parallel-arm, non-inferiority study conducted in 2 emergency departments (EDs). Patients with migraine of moderate or severe intensity were randomized to receive bilateral GONB with each side administered 3 mL of bupivacaine 0.5% or metoclopramide 10 mg IV, the putative standard of care. The primary outcome was improvement in pain on a 0-10 scale between time 0 and 1 hour later. To reject the null hypothesis that metoclopramide would be more efficacious in relieving pain, we required that the lower limit of the 95% CI for the difference in pain improvement between those randomized to GONB vs those randomized to metoclopramide be >-1.3, a validated minimum clinically important difference. Secondary outcomes included sustained headache relief, defined as achieving and maintaining for 48 hours a headache level of mild or none without the use of additional analgesic medication, and the use of rescue medication in the ED. Results Over a 2.5-year study period, 1358 patients were screened for participation and 99 were randomized, 51 to GONB and 48 to metoclopramide. All of these patients were included in the primary analysis. Patients who received the GONB reported mean improvement of 5.0 (95% CI: 4.1, 5.8) while those who received metoclopramide reported a larger mean improvement of 6.1 (95% CI: 5.2, 6.9). The 95% CI for the between group difference of -1.1 was -2.3, 0.1. Sustained headache relief was reported by 11/51 (22%) GONB and 18/47 (38%) metoclopramide patients (95% CI for rounded difference of 17%: -1, 35%). Of the 51 GONB patients, 17 (33%) required rescue medication in the ED vs 8/48 (17%) metoclopramide patients (95% CI for rounded difference of 17%: 0, 33%). An adverse event was reported by 16/51 (31%) GONB patients and 18/48 (38%) metoclopramide patients (95% CI for (rounded) difference of 6%: -13, 25%). Conclusion GONB with bupivacaine was not as efficacious as IV metoclopramide for the first-line treatment of migraine in the ED.
Published: 2020
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45. Mutations in rpoB and katG genes and the inhA operon in multidrug-resistant Mycobacterium tuberculosis isolates from Zambia

Author: Yukari Fukushima, Precious Bwalya, Chie Nakajima, Nanthan Kapata, Grace Mbulo, Eddie Samuneti Solo, Trevor Kaile, Yogendra Shah, Yasuhiko Suzuki, and Sylvia Chila
Subjects: 0301 basic medicine, Microbiology (medical), Tuberculosis, inhA, 030106 microbiology, Immunology, Antitubercular Agents, Zambia, MDR-TB, Biology, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Drug Resistance, Multiple, Bacterial, Operon, medicine, polycyclic compounds, Immunology and Allergy, Multidrug-Resistant Mycobacterium tuberculosis, Multidrug-resistant, 030212 general & internal medicine, Genetics, INHA, Point mutation, Isoniazid, DNA-Directed RNA Polymerases, biochemical phenomena, metabolism, and nutrition, Catalase, rpoB, medicine.disease, biology.organism_classification, bacterial infections and mycoses, QR1-502, Mutation, katG, bacteria, Rifampicin, medicine.drug
Abstract: Objectives It is established that resistance to rifampicin (RIF) in 90% of RIF-resistant Mycobacterium tuberculosis isolates is attributable to point mutations in the rpoB gene, whilst 50–95% of M. tuberculosis resistance to isoniazid (INH) is caused by mutations in the katG gene. However, the patterns and frequencies of mutations vary by geographical region. In Zambia, the genetic mechanisms of resistance of M. tuberculosis to RIF and INH were unreported before this study. Methods Using gene sequencing, the rpoB, katG and inhA genes of 99 multidrug-resistant M. tuberculosis (MDR-TB) and 49 pan-susceptible M. tuberculosis isolates stored at a tuberculosis reference laboratory from 2013 to 2016 were analysed and were compared with published profiles from other African countries. Results Of the 99 MDR-TB isolates, 95 (96.0%) carried mutations in both rpoB and katG. No mutations were detected among the pan-susceptible isolates. The most common mutations among RIF- and INH-resistant isolates were in codon 531 of the rpoB gene (55.6%; 55/99) and codon 315 of the katG gene (94.9%; 94/99), respectively. Distinctly, katG mutations were predominantly high among Zambian isolates (96.0%) compared with other countries in the region. Conclusion Resistance-associated mutations to RIF and INH circulating in Zambia are similar to those reported globally, therefore these data validate the applicability of molecular diagnostic tools in Zambia. However, katG mutations were predominantly high among M. tuberculosis isolates in this study compared with other regional countries and might distinguish cross-boundary transmission of MDR-TB from other African nations.
Published: 2020

46. Prevalence and control implications of bovine trypanosomes in endemic areas of northern Uganda

Author: Rodney Okwasiimire, J. B. Bahungirehe, Susan C. Welburn, Callistus W. Baliddawa, Wampande M. Eddie, James Bugeza, Wangoola Robert Mandela, and Charles Waiswa
Subjects: Trypanosoma, Veterinary medicine, Biology, Trypanosoma brucei, law.invention, Food Animals, law, DNA, Ribosomal Spacer, parasitic diseases, Prevalence, medicine, Animals, Uganda, Internal transcribed spacer, Ribosomal DNA, Polymerase chain reaction, High prevalence, business.industry, Trypanosomiasis, Bovine, DNA, Protozoan, biology.organism_classification, medicine.disease, Animal trypanosomiasis, Cross-Sectional Studies, Vector (epidemiology), Cattle, Animal Science and Zoology, Livestock, business
Abstract: African animal trypanosomiasis (AAT), a disease complex caused by tsetse fly-transmitted Trypanosoma brucei brucei, T. congolense savannah ITS, and T. vivax, continues to inflict heavy losses to the animal industry in terms of decreased livestock production and productivity. Live bait technology and chemotherapy have been used as a control strategy in northern Uganda since 2006 with minimal success. Here, we report the results of a cross-sectional study carried out in Lango subregion, Uganda, to assess the species prevalence of bovine trypanosome in cattle using the internal transcribed spacer (ITS) of trypanosome ribosomal DNA (rDNA). Blood samples were collected from 1090 cattle by ear vein puncture and screened using a single pair of primers designed to amplify ITS ribosomal DNA (rDNA). Our results indicate an overall prevalence of 40.18% (438/1090, 95% CI 30.82-54.51). T. vivax constituted 32.66% (356/1090), T. congolense 2.39% (26/1090), T. brucei 1.28% (14/1090), T. godfreyi 0.09%(1/1090), T. brucei and T. congolense 0.36% (4/1090), T. brucei and T. vivax 1.47% (16/1090), T. vivax and T. congolense 1.65% (18/1090), T. vivax and T. simiae 0.18% (2/1090), and T. vivax and T. godfreyi 0.09% (1/1090) of infections. Over 91.7% of infections involved single species, while 9.5% were mixed infections. Over 90.2% (37/41) of the mixed infections involved T. vivax as one of the species, while 53.7% (22/41) involved T. congolense. The high prevalence of AAT and the continued presence of T. brucei raise public health concerns because of the zoonotic implications. An integrated approach that involves mass treatment of cattle, vector, and animal movement control should be adopted to reduce the risk of both AAT and HAT.
Published: 2020
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47. Unusual location of recurrent mantle cell lymphoma on fluorodeoxyglucose-positron emission tomography despite complete metabolic resolution of previous sites of disease

Author: Raef R. Boktor, Eddie Lau, Benjamin M W Froitzheim, and Sze Ting Lee
Subjects: Treatment response, Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, mantle cell lymphoma, treatment response, Case Report, Disease, medicine.disease, 030218 nuclear medicine & medical imaging, Lymphoma, Fluorodeoxyglucose positron emission tomography, recurrent lymphoma, 03 medical and health sciences, 0302 clinical medicine, Positron emission tomography, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Recurrent Mantle Cell Lymphoma, Recurrent disease, Medicine, Mantle cell lymphoma, business, Fluorodeoxyglucose-positron emission tomography/computed tomography
Abstract: This case report presents a patient with recurrent pleomorphic mantle cell lymphoma (MCL), which is a relatively rare but aggressive type of lymphoma. A positron emission tomography/computed tomography scan performed to assess treatment response demonstrated a complete metabolic response in the sites of primary disease while also revealing new subcutaneous lesions, which were biopsy-proven recurrent disease. This case illustrates the importance of the different biological behavior of MCL, whereby new sites of metabolically active lesions can represent recurrent disease, even though there is a complete metabolic response at sites of primary disease.
Published: 2020
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48. Plasmodium falciparum histidine-rich protein 2 diversity in Ghana

Author: Mark Noagbe, Charles Gyasi, Kofi Boamah Mensah, Bismarck Dinko, Max Efui Annani-Akollor, Alexander Yaw Debrah, Constance Adu-Gyamfi, Otchere Addai-Mensah, Eddie-Williams Owiredu, Richmond Tackie, Comfort Agyare-Kwabi, Eliezer Togbe, and Selassie Louis Ameke
Subjects: Male, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, In silico, Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, Rapid diagnostic test, Ghana, Epitope, lcsh:Infectious and parasitic diseases, Epitopes, Histidine-rich protein 2, parasitic diseases, medicine, Humans, lcsh:RC109-216, Genetic variability, Malaria, Falciparum, Child, Gene, biology, Research, Infant, Newborn, Genetic Variation, medicine.disease, biology.organism_classification, Virology, Malaria, Infectious Diseases, Cross-Sectional Studies, Parasitology, Child, Preschool, Female
Abstract: Background In the absence of microscopy, Plasmodium falciparum histidine-rich proteins 2 (PfHRP2)-based rapid diagnostic tests (RDTs) are recommended for the diagnosis of falciparum malaria, particularly in endemic regions. However, genetic variability of the pfhrp2 gene threatens the usefulness of the test due to its impact on RDT sensitivity. This study aimed to investigate the diversity of pfhrp2 in malaria cases among children in Ghana. Methods A cross-sectional study was conducted at the Adidome Government Hospital in the Volta Region of Ghana. A total of 50 children with mean age of 6.6 ± 3.5 years and diagnosed falciparum malaria were included. Blood samples were collected for complete blood count, malaria parasite identification and counting using auto analyzer and microscopy, respectively. DNA was isolated from blood-spotted Whatman filters, amplified and sequenced. Nucleotide sequences were translated in silico to corresponding amino acids and the deduced amino acids sequences were analyzed for diversity using Mega X. Results The number of repeats and number of each repeat within PfHRP2 varied between isolates. Twelve rare PfHRP2 repeat types, two of which are previously unreported, were identified in this study. The HRP2 sequence obtained in this study shared high similarities with isolates from Kenya. Using Baker’s regression model, Group B was the highest occurring type (58.0%). Screening of all sequences for epitopes recognized by PfHRP2-specific monoclonal antibodies (mAbs), the predominant motif was AHHAADAHH, which is recognized by the C1-13 mAbs. Conclusion This study reports diversity of P. falciparum HRP2 in samples from Ghanaian children with symptomatic malaria. The findings of this study highlight the existence of extra amino acid repeat types which adds to the PfHRP2 antigenic variability.
Published: 2020
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49. Shared Transcriptional Signatures in Major Depressive Disorder and Mouse Chronic Stress Models

Author: Theo Stefan, Mena Fatma, Benoit Labonté, Said Romaric Traore, Joseph R. Scarpa, Yong-Hwee Eddie Loh, Ting Huei Chen, and Eric J. Nestler
Subjects: 0301 basic medicine, Gene regulatory network, Prefrontal Cortex, Biology, Nucleus accumbens, Nucleus Accumbens, Transcriptome, Social defeat, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Chronic stress, Prefrontal cortex, Biological Psychiatry, Depressive Disorder, Major, Molecular pathology, Brain, medicine.disease, 030227 psychiatry, Disease Models, Animal, 030104 developmental biology, Major depressive disorder, Neuroscience, 030217 neurology & neurosurgery
Abstract: Background Most of our knowledge of the biological basis of major depressive disorder (MDD) is derived from studies of chronic stress models in rodents. While these models capture certain aspects of the behavioral and neuroendocrine features of MDD, the extent to which they reproduce the molecular pathology of the human syndrome remains unknown. Methods We systematically compared transcriptional signatures in two brain regions implicated in depression—medial prefrontal cortex and nucleus accumbens—of humans with MDD and of 3 chronic stress models in mice: chronic variable stress, adult social isolation, and chronic social defeat stress. We used differential expression analysis combined with weighted gene coexpression network analysis to create interspecies gene networks and assess the capacity of each stress paradigm to recapitulate the transcriptional organization of gene networks in human MDD. Results Our results show significant overlap between transcriptional alterations in medial prefrontal cortex and nucleus accumbens in human MDD and the 3 mouse chronic stress models, with each of the chronic stress paradigms capturing distinct aspects of MDD abnormalities. Chronic variable stress and adult social isolation better reproduce differentially expressed genes, while chronic social defeat stress and adult social isolation better reproduce gene networks characteristic of human MDD. We also identified several gene networks and their constituent genes that are most significantly associated with human MDD and mouse stress models. Conclusions This study demonstrates the ability of 3 chronic stress models in mice to recapitulate distinct aspects of the broad molecular pathology of human MDD, with no one mouse model apparently better than another.
Published: 2020
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50. Improving mental health and reducing antipsychotic use in people with dementia in care homes: the WHELD research programme including two RCTs

Author: Yongzhong Sun, Jane Stafford, Renee Romeo, Robert T. Woods, Gareth Williams, Barbara Woodward-Carlton, Lucy Garrod, Joanna Murray, Esme Moniz-Cook, Darshan Zala, Rhiannon Whitaker, Anne Corbett, Martin Orrell, Zoe Hoare, Dag Aarsland, Eddie McLaughlin, Vanessa Lawrence, Jane Fossey, Martin Knapp, Ingelin Testad, and Clive Ballard
Subjects: psychosocial, Gerontology, programme, Psychological intervention, care staff, non-drug, law.invention, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Randomized controlled trial, law, medicine, Dementia, care, 030212 general & internal medicine, business.industry, person-centred, lcsh:Public aspects of medicine, lcsh:RA1-1270, medicine.disease, Mental health, Confidence interval, Systematic review, quality of life, agitation, care home, business, Psychosocial, 030217 neurology & neurosurgery, dementia
Abstract: Background The effective management of agitation and other neuropsychiatric and behavioural symptoms in people with dementia is a major challenge, particularly in care home settings, where dementia severity is higher and there is limited training and support for care staff. There is evidence for the value of staff training and the use of psychosocial approaches; however, no intervention currently exists that combines these elements into an intervention that is fit for purpose and effective in these settings based on evidence from a randomised controlled trial. Objective The objective was to develop and evaluate a complex intervention to improve well-being, reduce antipsychotic use and improve quality of life in people with dementia in care homes through person-centred care, management of agitation and non-drug approaches. Design This was a 5-year programme that consisted of six work packages. Work package 1 consisted of two systematic reviews of personalised psychosocial interventions for behavioural and psychological symptoms for people with dementia in care homes. Work package 2 consisted of a metasynthesis of studies examining implementation of psychosocial interventions, in addition to developing a draft Well-being and Health for people with Dementia (WHELD) programme. Work package 3 consisted of a factorial study of elements of the draft WHELD programme in 16 care homes. Work package 4 involved optimisation of the WHELD programme based on work package 3 data. Work package 5 involved a multicentre randomised controlled trial in 69 care homes, which evaluated the impact of the optimised WHELD programme on quality of life, agitation and overall neuropsychiatric symptoms in people with dementia. Work package 6 focused on dissemination of the programme. Setting This programme was carried out in care homes in the UK. Participants Participants of this programme were people with dementia living in care homes, and the health and care professionals providing treatment and care in these settings. Results Work package 1: reviews identified randomised controlled trials and qualitative evidence supporting the use of psychosocial approaches to manage behavioural symptoms, but highlighted a concerning lack of evidence-based training manuals in current use. Work package 2: the meta-analysis identified key issues in promoting the use of interventions in care homes. The WHELD programme was developed through adaptation of published approaches. Work package 3: the factorial trial showed that antipsychotic review alone significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval 0.05 to 0.60). Antipsychotic review plus social interaction significantly reduced mortality (odds ratio 0.36, 95% confidence interval 0.23 to 0.57), but this group showed significantly worse outcomes in behavioural and psychological symptoms of dementia than the group receiving neither antipsychotic review nor social interaction (mean difference 7.37 symptoms, 95% confidence interval 1.53 to 13.22 symptoms). This detrimental impact was reduced when combined with social interaction (mean difference –0.44 points, 95% confidence interval –4.39 to 3.52 points), but with no significant benefits for agitation. The exercise intervention significantly improved neuropsychiatric symptoms (mean difference –3.58 symptoms, 95% confidence interval –7.08 to –0.09 symptoms) but not depression (mean difference –1.21 points, 95% confidence interval –4.35 to 1.93 points). Qualitative work with care staff provided additional insights into the acceptability and feasibility of the intervention. Work package 4: optimisation of the WHELD programme led to a final version that combined person-centred care training with social interaction and pleasant activities. The intervention was adapted for delivery through a ‘champion’ model. Work package 5: a large-scale, multicentre randomised controlled trial in 69 care homes showed significant benefit to quality of life, agitation and overall neuropsychiatric symptoms, at reduced overall cost compared with treatment as usual. The intervention conferred a statistically significant improvement in quality of life (Dementia Quality of Life Scale – Proxy z-score of 2.82, mean difference 2.54, standard error of measurement 0.88, 95% confidence interval 0.81 to 4.28, Cohen’s d effect size of 0.24; p = 0.0042). There were also statistically significant benefits in agitation (Cohen-Mansfield Agitation Inventory z-score of 2.68, mean difference –4.27, standard error of measurement 1.59, 95% confidence interval –7.39 to –1.15, Cohen’s d effect size of 0.23; p = 0.0076) and overall neuropsychiatric symptoms (Neuropsychiatric Inventory – Nursing Home version z-score of 3.52, mean difference –4.55, standard error of measurement 1.28, 95% confidence interval –7.07 to –2.02, Cohen’s d of 0.30; p British Medical Journal e-learning module, an updated national best practice guideline and a portfolio of lay and care home outreach activities. Limitations Residents with dementia were not involved in the qualitative work. Conclusions The WHELD programme is effective in improving quality of life and reducing both agitation and overall neuropsychiatric symptoms in people with dementia in care homes. It provides a structured training and support intervention for care staff, with lower overall costs for resident care than treatment as usual. Future work It will be important to consider the long-term sustainability of the WHELD programme and cost-effective means of long-term implementation. Trial registration Current Controlled Trials ISRCTN40313497 and ISRCTN62237498. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 6. See the NIHR Journals Library website for further project information.
Published: 2020
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