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Background: Battling malaria's morbidity and mortality rates demands innovative methods related to malaria diagnosis. Thick blood smears (TBS) are the gold standard for diagnosing malaria, but their coloration quality is dependent on supplies and adherence to standard protocols. Machine learning has been proposed to automate diagnosis, but the impact of smear coloration on parasite detection has not yet been fully explored., Methods: To develop Coloration Analysis in Malaria (CAM), an image database containing 600 images was created. The database was randomly divided into training (70%), validation (15%), and test (15%) sets. Nineteen feature vectors were studied based on variances, correlation coefficients, and histograms (specific variables from histograms, full histograms, and principal components from the histograms). The Machine Learning Matlab Toolbox was used to select the best candidate feature vectors and machine learning classifiers. The candidate classifiers were then tuned for validation and tested to ultimately select the best one., Results: This work introduces CAM, a machine learning system designed for automatic TBS image quality analysis. The results demonstrated that the cubic SVM classifier outperformed others in classifying coloration quality in TBS, achieving a true negative rate of 95% and a true positive rate of 97%., Conclusions: An image-based approach was developed to automatically evaluate the coloration quality of TBS. This finding highlights the potential of image-based analysis to assess TBS coloration quality. CAM is intended to function as a supportive tool for analyzing the coloration quality of thick blood smears., (© 2024. The Author(s).)

Prisons, due to various risk factors, are environments that are conducive to infectious disease transmission, with significantly higher prevalence of infectious diseases within prisons compared to the general population. This underscores the importance of preventive measures, particularly vaccination. As part of the international project "Reaching the hard-to-reach: Increasing access and vaccine uptake among the prison population in Europe" (RISE-Vac), this study aimed to map the availability and delivery framework of vaccination services in prisons across Europe and beyond. A questionnaire designed to collect data on the availability and delivery model of vaccination services in prisons was validated and uploaded in SurveyMonkey in July 2023. Then, it was submitted to potential participants, with at least one representative from each European country. Potential participants emailed an invitation letter by the RISE-Vac partners and by the European Organization of Prison and Correctional Services (EUROPRIS). Twenty European countries responded. Vaccines are available in European countries, although their availability differs by country and type of vaccine. The first dose is offered to people living in prisons (PLP), mostly within one month, COVID-19 is the most widely offered vaccine. In all countries, vaccines are actively offered by healthcare workers; in most countries, there is no evaluation of vaccination status among people who work in prison. The survey shows variance in vaccine availability for PLP and staff across countries and vaccine types. Quality healthcare in prisons is not only a matter of the right to health but also a critical public health investment: enhancing vaccine uptake consistently among PLP and staff should be prioritized., (© 2024. The Author(s).)

Objective: To compare the 1-hour postload glucose (1h-PG) value of an oral glucose tolerance test (OGTT) with the metabolic syndrome (MetS) and the Finish Diabetes Risk Score (FINDRISC) in patients with impaired fasting glucose (IFG) to predict type 2 diabetes mellitus (T2DM)., Methods: A cohort study was conducted in patients at a general hospital in Lima, Perú. An OGTT was performed in subjects with IFG who were followed-up for 7 years for T2DM development. The exposure variables were 1h-PG ≥ 155 mg/dL, MetS, and a FINDRISC ≥ 13 points, and the outcome was the presence of T2DM. The relative risk, confidence interval, and area under the curve (AU ROC ) were also estimated., Results: Among 324 subjects with IFG, 218 completed the 7-year follow-up. The mean age was 56.2 ± 11.5 years, 64.0% were woman, and 63.8% were overweight/obese. Of these, 36.8% had 1h-PG ≥ 155 mg/dL and normal glucose tolerance, 66.8% had MetS, and 64.5% had FINDRISC ≥ 13 points. After 7 years, 21.1% of participants developed T2DM, with 68.8% of them who had 1h-PG ≥ 155 mg/dL (P < .001), 62.2% had MetS (P = .013), and 67.9% had FINDRISC ≥ 13 (P = .68). After adjusting by age, sex, and body mass index, the relative risk was 3.52 (1.64-7.54; 95% CI), 1.81 (0.96-3.38; 95% CI), and 1.17 (0.51-2.70; 95% CI) for each exposure variable, respectively. Also, the AU ROC was 0.72 (0.60-0.83), 0.63 (0.51-0.75), and 0.51 (0.38-0.63) (P = .01), respectively., Conclusion: By performing an OGTT in patients with IFG, an 1h-PG ≥ 155 mg/dL value may be helpful to predict T2DM at 7 years better than the use of MetS or the FINDRISC., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Naturally Occurring Asbestos (NOA) has drawn the attention worldwide when investigation revealed an increased incidence of malignant mesothelioma in population living near NOA sites. In Basilicata region (South Italy), population living in the villages of Castelluccio Superiore and Inferiore, Lauria, Latronico, Episcopia, San Severino Lucano, and Francavilla in Sinni may be considered at high risk of asbestos exposure because these villages are either surrounded by or built on NOA-rich ophiolitic outcrops. In this work we investigated an asbestos tremolite sample coming from the ophiolitic rocks outcropping in the quarry of Iacolinei, widely used in the past to extract aggregates for various applications.  A detailed mineralogical characterization has been attained by using a multi-analytical approach (EMPA, SEM-EDS, TEM-EDS, Mössbauer, µ-Raman, X-ray powder diffraction, and thermal analysis). Morphological investigation highlighted that the sample is composed of long fibers (> 5 µm) with a significant fraction (ca. 55%) having width below 0.25 µm, considered the most biologically active fibers. Moreover, the crystal chemical characterization showed that Fe occurs at the octahedral sites of the tremolite structure. It should be noted that Fe plays a primary role in the toxicity of asbestos. Based on these results, the investigated asbestos tremolite may be considered a potent mesothelial carcinogen, requiring therefore special attention for public health protection purposes. Investigations using sentinel animals to assess the diffusion of the tremolite fibers into the environment from the serpentinite rocks and soils of Iacolinei quarry are in progress., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study aimed to model the pharmacokinetics of lamotrigine (LTG) and efavirenz (EFV) in pregnant women using physiologically based pharmacokinetic (PBPK) and pregnancy-specific PBPK (p-PBPK) models. For lamotrigine, the adult PBPK model demonstrated accurate predictions for pharmacokinetic parameters. Predictions for the area under the curve (AUC) and peak plasma concentration (Cmax) generally agreed well with observed values. During pregnancy, the PBPK model accurately predicted AUC and Cmax with a prediction error (%PE) of less than 25%. The evaluation of the EFV PBPK model revealed mixed results. While the model accurately predicted certain parameters for non-pregnant adults, significant discrepancies were observed in predictions for higher doses (600 vs. 400 mg) and pregnant individuals. The model's performance during pregnancy was poor, indicating the need for further refinement to account for genetic polymorphism. Gender differences also influenced EFV pharmacokinetics, with lower exposure levels in females compared to males. These findings highlight the complexity of modeling EFV, in general, but specifically in pregnant populations, and the importance of validating such models for accurate clinical application. The study highlights the importance of tailoring dosing regimens for pregnant individuals to ensure both safety and efficacy, particularly when using combination therapies with UGT substrate drugs. Although drug-drug interactions between LTG and EFV appear minimal, further research is needed to improve predictive models and enhance their accuracy.

Introduction: Iodine is an essential mineral for fetal growth and brain development. The aim of this research was to evaluate goiter, iodine deficiency and intrauterine growth restriction in pregnant women of minority ethnic groups in Colombia., Methods: A cross-sectional study was performed in six non-metropolitan areas of Colombia., Results: A total of 318 Indigenous and Afro-descendant pregnant women were invited to participate: 248 (83.2%) Indigenous and 50 (16.8%) Afro-descendants were studied. The mean age was 24 years (range 13-44 years). Of the women, 130 (43.5%) were from the department of Cauca, 72 (24.1%) were from C&oacute;rdoba, 28 (9.4%) were from Guajira, 26 (8.8%) were from Sierra Nevada de Santa Marta, 22 (7.4%) were from Amazonas, 16 (5.4%) were from Meta and 4 (1.3%) were from the department of Cesar. A total of 244 (81.8%) were illiterate and 291 (97.7%) were of very low socioeconomic level. Goiter was observed in 69 (23.3%) pregnant women (38 (41.7%) from the department of Cauca, 10 (35.7%) from Guajira, 5 (31.2%) from Meta, 6 (27.2%) from Amazonas and 10 (13.8%) from C&oacute;rdoba). Iodine deficiency (<100 &micro;g/L) was observed in 42 (14.9%) pregnant women (16 (11.6%) mild (50-99 &micro;g/L), 19 (13.8%) moderate (20-49 &micro;g/L) and 7 (5.1%) severe (<20 &micro;g/L)). Being literate was a protective factor for iodine deficiency (odds ratio (OR)=0.19, 95% confidence interval (CI) 0.04-0.84, p=0.016). Being illiterate and iodine deficient was only a risk factor for goiter (OR=6.72, 95%CI 3.9-9.5, p=0.038) in the department of Cauca., Conclusion: A high prevalence of goiter, iodine deficiency and intrauterine growth restriction was observed in minority ethnic groups of Colombia. The highest prevalence and risk was observed in the department of Cauca.

Background: By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023., Methods: In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature. We included data for six age groups (25-49 years, 50-59 years, ≥60 years, 60-69 years, 70-79 years, and ≥80 years). To be included in the analysis, CAT needed to have reported both COVID-19 vaccination and mortality data for at least one of the four older age groups. Only CAT that reported weekly data for both COVID-19 vaccination and mortality by age group for 90% of study weeks or more in the full study period were included. We calculated the percentage reduction in the number of expected and reported deaths., Findings: Between December, 2020, and March, 2023, in 34 of 54 CAT included in the analysis, COVID-19 vaccines reduced deaths by 59% overall (CAT range 17-82%), representing approximately 1·6 million lives saved (range 1·5-1·7 million) in those aged 25 years or older: 96% of lives saved were aged 60 years or older and 52% were aged 80 years or older; first boosters saved 51% of lives, and 60% were saved during the Omicron period., Interpretation: Over nearly 2·5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among the most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures., Funding: US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests GD reports that the predecessor of the organisation he works for, Public Health England, received an unrestricted grant from GSK to undertake a study on the outcome of patients who received parenteral zanamavir. The funder received data and interim reports from Public Health England but did not influence analysis and reporting of the study. GD had no involvement in the GSK-funded study on parenteral zanamavir. Furthermore, the currently submitted work was part of the public health response activities to COVID-19 and had no relationship to GSK or the study on parenteral zanamivir. EP has received a personal grant from the Finnish Medical Foundation for PhD studies. JM declares that Public Health Scotland received funding from the EU Horizon 2020 programme for work in describing the epidemiology of COVID-19 and its impact on primary and secondary care as a partner in the IMOVE-COVID-19 project. MK declares having received consulting fees from Gilead Sciences for advising on development of a clinical module for collection of patient-reported outcome data from people living with HIV, and having received an honoraria from GESIDA for speaking at an annual conference on patient-reported outcome measures for people with HIV. All other authors declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Staphylococcus aureus is characterized by its high resistance to conventional antibiotics, particularly methicillin-resistant (MRSA) strains, making it a predominant pathogen in acute and chronic wound infections. The persistence of acute S. aureus wound infections poses a threat by increasing the incidence of their chronicity. This study investigated the potential of photodynamic activation using phytochemical-antibiotic combinations to eliminate S. aureus under conditions representative of acute wound infections, aiming to mitigate the risk of chronicity. The strategy applied takes advantage of the promising antibacterial and photosensitising properties of phytochemicals, and their ability to act as antibiotic adjuvants. The antibacterial activity of selected phytochemicals (berberine, curcumin, farnesol, gallic acid, and quercetin; 6.25-1000 μg/mL) and antibiotics (ciprofloxacin, tetracycline, fusidic acid, oxacillin, gentamicin, mupirocin, methicillin, and tobramycin; 0.0625-1024 μg/mL) was screened individually and in combination against two S. aureus clinical strains (methicillin-resistant and -susceptible-MRSA and MSSA). The photodynamic activity of the phytochemicals was assessed using a light-emitting diode (LED) system with blue (420 nm) or UV-A (365 nm) variants, at 30 mW/cm 2 (light doses of 9, 18, 27 J/cm 2 ) and 5.5 mW/cm 2 (light doses of 1.5, 3.3 and 5.0 J/cm 2 ), respectively. Notably, all phytochemicals restored antibiotic activity, with 9 and 13 combinations exhibiting potentiating effects on MSSA and MRSA, respectively. Photodynamic activation with blue light (420 nm) resulted in an 8- to 80-fold reduction in the bactericidal concentration of berberine against MSSA and MRSA, while curcumin caused 80-fold reduction for both strains at the light dose of 18 J/cm 2 . Berberine and curcumin-antibiotic combinations when subjected to photodynamic activation (420 nm light, 10 min, 18 J/cm 2 ) reduced S. aureus culturability by ≈9 log CFU/mL. These combinations lowered the bactericidal concentration of antibiotics, achieving a 2048-fold reduction for gentamicin and 512-fold reduction for tobramycin. Overall, the dual approach involving antimicrobial photodynamic inactivation and selected phytochemical-antibiotic combinations demonstrated a synergistic effect, drastically reducing the culturability of S. aureus and restoring the activity of gentamicin and tobramycin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: ATTR-CM is becoming more prevalent, and disease-modifying therapy has been investigated in recent years with promising results. Diflunisal has shown TTR-stabilizing properties assessed by biomarkers and echocardiography, but there are no trials addressing the evolution of morphological changes with CMR. Methods and Results: AMILCA-DIFLU is an exploratory pilot study prospective, single-center, non-randomized, open-label clinical trial. Patients diagnosed with ATTR-CM underwent clinical, functional, biochemical and imaging assessment before and one year after diflunisal therapy initiation. Of the twelve ATTR-CM patients included, only nine patients completed treatment and study protocol in 12 months. To increase the sample size, we included seven real-world patients with one year of diflunisal treatment. Among the group of patients who completed treatment, diflunisal therapy did not show improvement in cardiac disease status as assessed by many cardiac and inflammatory biomarkers, 6MWT and CMR parameters after one year of treatment. However, a non-significant trend towards stabilization of CMR parameters such as LVEF, ECV and T2 at one year was found. When comparing the group of patients who completed diflunisal therapy and those who did not, a significant decrease in the distance performed in the 6MWT was found in the group of patients who completed treatment at one year (-14 ± 81.8 vs. -173 ± 122.2; p = 0.032). Diflunisal was overall well tolerated, showing only a statistically significant worsening in renal function in the group of diflunisal-treatment patients with no clinical relevance or need for treatment discontinuation. Conclusions: In patients with ATTR-CM, treatment with diflunisal was overall well tolerated and tended to stabilize or slow down amyloid cardiac disease progression assessed by CMR parameters, cardiac and inflammatory biomarkers and functional capacity.

Background: Adiposity, dysglycemia, and hypertension are metabolic drivers that have causal interactions with each other. However, the effect of neighborhood-level disadvantage on the intensity of interactions among these metabolic drivers has not been studied. The objective of this study is to determine whether the strength of the interplay between these drivers is affected by neighborhood-level disadvantage., Methods: This cross-sectional study analyzed patients presenting to a multidisciplinary preventive cardiology center in New York City, from March 2017 to February 2021. Patients' home addresses were mapped to the Area Deprivation Index to determine neighborhood disadvantage. The outcomes of interest were correlation coefficients (range from -1 to +1) among the various stages (0 - normal, 1 - risk, 2 - predisease, 3 - disease, and 4 - complications) of abnormal adiposity, dysglycemia, and hypertension at presentation, stratified by neighborhood disadvantage., Results: The cohort consisted of 963 patients (age, median [IQR] 63.8 [49.7-72.5] years; 624 [65.1 %] female). The correlation among the various stages of adiposity, dysglycemia, and hypertension was weaker with increasing neighborhood disadvantage (P for trend <0.001). Specifically, the correlation describing adiposity, dysglycemia, and hypertension interaction was weaker in the high neighborhood disadvantage group compared to the intermediate neighborhood disadvantage group (median [IQR]: 0.34 [0.27, 0.44] vs. median [IQR]: 0.39 [0.34, 0.45]; P < 0.001) and compared to the low neighborhood disadvantage group (median [IQR]: 0.34 [0.27, 0.44] vs. median [IQR]: 0.54 [0.52, 0.57]; P < 0.001), as well as weaker in the intermediate neighborhood disadvantage group compared to the low neighborhood disadvantage group (median [IQR]: 0.39 [0.34, 0.45] vs. 0.54 median [IQR]: 0.54 [0.52, 0.57]; P < 0.001)., Conclusions: Interactions among the various stages of abnormal adiposity, dysglycemia, and hypertension with each other are weaker with increasing neighborhood disadvantage. Factors related to neighborhood-level disadvantage, other than abnormal adiposity, might play a crucial role in the development of dysglycemia and hypertension., Competing Interests: Dr. Mechanick reports receiving honoraria from Abbott Nutrition for lectures and serves on the Advisory Boards for Abbott Nutrition, Aveta.Life, and Twin Health. JHS, MAB, YC, SL, PM, JJ, BI, and OL report having no disclosures., (© 2024 The Authors.)

We conducted a multicentre test-negative case-control study covering the period from October 2023 to January 2024 among adult patients aged ≥ 18 years hospitalised with severe acute respiratory infection in Europe. We provide early estimates of the effectiveness of the newly adapted XBB.1.5 COVID-19 vaccines against PCR-confirmed SARS-CoV-2 hospitalisation. Vaccine effectiveness was 49% overall, ranging between 69% at 14-29 days and 40% at 60-105 days post vaccination. The adapted XBB.1.5 COVID-19 vaccines conferred protection against COVID-19 hospitalisation in the first 3.5 months post vaccination, with VE > 70% in older adults (≥ 65 years) up to 1 month post vaccination., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Advancements in psychotropic therapy for pregnant women are pivotal for addressing maternal mental health during the perinatal period. Screening for mood and anxiety symptoms during pregnancy is recommended to enable early intervention. Psychotropic medications, including antidepressants, benzodiazepines, antipsychotics, and mood stabilizers, are commonly used, but challenges remain regarding their safety and efficacy during pregnancy. Pregnancy induces significant changes in pharmacokinetics, necessitating personalized dosing strategies and careful monitoring. Real-time monitoring technologies, such as smartphone-integrated platforms and home-based monitoring, enhance accessibility and accuracy. Prospective studies and collaboration among healthcare providers are essential for evidence-based guidelines and optimal treatment strategies. Reducing stigma around mental health during pregnancy is crucial to ensure women seek help and discuss treatment options, promoting understanding and acceptance within the community.

Drug-induced liver injury (DILI) is a significant cause of acute liver failure (ALF) and liver transplantation in the Western world. Acetaminophen (APAP) overdose is a main contributor of DILI, leading to hepatocyte cell death through necrosis. Here, we identified that neddylation, an essential post-translational modification involved in the mitochondria function, was upregulated in liver biopsies from patients with APAP-induced liver injury (AILI) and in mice treated with an APAP overdose. MLN4924, an inhibitor of the neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8)-activating enzyme (NAE-1), ameliorated necrosis and boosted liver regeneration in AILI. To understand how neddylation interferes in AILI, whole-body biotinylated NEDD8 ( bio NEDD8) and ubiquitin ( bio UB) transgenic mice were investigated under APAP overdose with and without MLN4924. The cytidine diphosphate diacylglycerol (CDP-DAG) synthase TAM41, responsible for producing cardiolipin essential for mitochondrial activity, was found modulated under AILI and restored its levels by inhibiting neddylation. Understanding this ubiquitin-like crosstalk in AILI is essential for developing promising targeted inhibitors for DILI treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes.

Refugees and migrants remain one of the most vulnerable people and the COVID-19 pandemic has posed additional challenges both in terms of increased risk of infection and death experienced, highlighting existing inequities in access to and utilization of health services, as underlined by World Health Organization in 2020 in the Health and Migration Programme. In the context of the Programme 'Epidemiological surveillance and control of COVID-19 in metropolitan urban areas and for the containment of the circulation of SARS-CoV-2 in the migrant population in Italy', coordinated by the Italian Centre for Disease Control and Prevention (CCM) and funded by the Italian Ministry of Health, an experimental epidemiological, virological, and molecular SARS-CoV-2 surveillance system addressed to migrant populations in Sicily through Mediterranean routes was implemented. To this end, a multidisciplinary network supported by a hub&spoke system of laboratories was established in Sicily Region (Southern Italy), using molecular and Next Generation Sequencing (NGS) techniques to identify different SARS-CoV-2 strains in relation to migration flows. Herein, the lesson learnt through this integrated surveillance model, that was in place from February 2021 till the end of the COVID-19 emergency in Italy, are reported. Overall, the data emphasized the need for enhancing molecular surveillance in the areas of the globe where testing and sequencing resources are limited. The epidemiological, virological, and molecular SARS-CoV-2 monitoring, targeted to the migrant population, may also provide a valuable experimental model.

Background: The benefits and harms associated with femoral artery cannulation over other sites of arterial cannulation for surgical repair of acute Stanford type A aortic dissection (TAAD) are not conclusively established., Methods: We evaluated the outcomes after surgery for TAAD using femoral artery cannulation, supra-aortic arterial cannulation (i.e., innominate/subclavian/axillary artery cannulation), and direct aortic cannulation., Results: 3751 (96.1%) patients were eligible for this analysis. In-hospital mortality using supra-aortic arterial cannulation was comparable to femoral artery cannulation (17.8% vs. 18.4%; adjusted OR 0.846, 95% CI 0.799-1.202). This finding was confirmed in 1028 propensity score-matched pairs of patients with supra-aortic arterial cannulation or femoral artery cannulation (17.5% vs. 17.0%, p = 0.770). In-hospital mortality after direct aortic cannulation was lower compared to femoral artery cannulation (14.0% vs. 18.4%, adjusted OR 0.703, 95% CI 0.529-0.934). Among 583 propensity score-matched pairs of patients, direct aortic cannulation was associated with lower rates of in-hospital mortality (13.4% vs. 19.6%, p = 0.004) compared to femoral artery cannulation. Switching of the primary site of arterial cannulation was associated with increased rate of in-hospital mortality (36.5% vs. 17.0%; adjusted OR 2.730, 95% CI 1.564-4.765). Ten-year mortality was similar in the study cohorts., Conclusions: In this study, the outcomes of surgery for TAAD using femoral arterial cannulation were comparable to those using supra-aortic arterial cannulation. However, femoral arterial cannulation was associated with higher in-hospital mortality than direct aortic cannulation., Trial Registration: ClinicalTrials.gov registration code: NCT04831073., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Walking is important for maintaining physical and mental well-being in aged residential care (ARC). Walking behaviors are not well characterized in ARC due to inconsistencies in assessment methods and metrics as well as limited research regarding the impact of care environment, cognition, or physical function on these behaviors. It is recommended that walking behaviors in ARC are assessed using validated digital methods that can capture low volumes of walking activity., Objective: This study aims to characterize and compare accelerometry-derived walking behaviors in ARC residents across different care levels, cognitive abilities, and physical capacities., Methods: A total of 306 ARC residents were recruited from the Staying UpRight randomized controlled trial from 3 care levels: rest home (n=164), hospital (n=117), and dementia care (n=25). Participants' cognitive status was classified as mild (n=87), moderate (n=128), or severe impairment (n=61); physical function was classified as high-moderate (n=74) and low-very low (n=222) using the Montreal Cognitive Assessment and the Short Physical Performance Battery cutoff scores, respectively. To assess walking, participants wore an accelerometer (Axivity AX3; dimensions: 23×32.5×7.6 mm; weight: 11 g; sampling rate: 100 Hz; range: ±8 g; and memory: 512 MB) on their lower back for 7 days. Outcomes included volume (ie, daily time spent walking, steps, and bouts), pattern (ie, mean walking bout duration and alpha), and variability (of bout length) of walking. Analysis of covariance was used to assess differences in walking behaviors between groups categorized by level of care, cognition, or physical function while controlling for age and sex. Tukey honest significant difference tests for multiple comparisons were used to determine where significant differences occurred. The effect sizes of group differences were calculated using Hedges g (0.2-0.4: small, 0.5-0.7: medium, and 0.8: large)., Results: Dementia care residents showed greater volumes of walking (P<.001; Hedges g=1.0-2.0), with longer (P<.001; Hedges g=0.7-0.8), more variable (P=.008 vs hospital; P<.001 vs rest home; Hedges g=0.6-0.9) bouts compared to other care levels with a lower alpha score (vs hospital: P<.001; Hedges g=0.9, vs rest home: P=.004; Hedges g=0.8). Residents with severe cognitive impairment took longer (P<.001; Hedges g=0.5-0.6), more variable (P<.001; Hedges g=0.4-0.6) bouts, compared to those with mild and moderate cognitive impairment. Residents with low-very low physical function had lower walking volumes (total walk time and bouts per day: P<.001; steps per day: P=.005; Hedges g=0.4-0.5) and higher variability (P=.04; Hedges g=0.2) compared to those with high-moderate capacity., Conclusions: ARC residents across different levels of care, cognition, and physical function demonstrate different walking behaviors. However, ARC residents often present with varying levels of both cognitive and physical abilities, reflecting their complex multimorbid nature, which should be considered in further work. This work has demonstrated the importance of considering a nuanced framework of digital outcomes relating to volume, pattern, and variability of walking behaviors among ARC residents., (© Ríona Mc Ardle, Lynne Taylor, Alana Cavadino, Lynn Rochester, Silvia Del Din, Ngaire Kerse. Originally published in JMIR Aging (https://aging.jmir.org).)

Background: The Rey's 15 words test is currently the most frequently used task in Italy to detect memory deficits in AD. The current standardised version is however quite outdated and lacks some cognitive indexes which may highlight problems in recall or encoding processes. The aim of the study was to update the normative data of the test and to consider some variables which were not accounted for in the original study, that is, recognition, learning rate and forgetfulness. We also adopted the process scores approach to ascertain the effects of serial position (primacy and recency)., Methods: Three hundred ninety-six healthy participants were recruited. To detect any variables useful for intercepting the early stages of dementia, a group of 208 patients in the very early stage of AD was also recruited. Linear models were used to calculate the corrections scores for age, education, and gender, and ROCs were used to calculate cut-offs based on the maximum sum of sensitivity and specificity and the positive and negative predictive values., Results: All main indexes showed excellent Area Under the Curve (0.90-1), strong sensitivity and PPVs for distinguishing between the HCs and AD participants. However, the Intrusions index performed poorly in all parameters., Conclusion: The study provides updated, normative data which may be reliably used as a cognitive marker to detect early AD. The strength of the study is the large sample size and the number of indexes which make it possible to explore the utility of memory test process scores., (© 2024. Fondazione Società Italiana di Neurologia.)

The adoption of diets that minimize both their environmental impacts and weight excess in children would be a major co-benefit for climate change mitigation. We evaluated the relationship between child diet-related environmental impact and anthropometric characteristics in an Italian birth cohort. The study involved 2127 children of the Piccolipiù birth cohort. At 4 years, their diet in the previous two months was assessed through a questionnaire, from which we derived individual: (i) diet-related daily greenhouse gas emissions (GHGE), (ii) land use (LU), (iii) adherence to the Mediterranean Diet (MD) and (iv) red meat consumption. We related these variables with overweight and obesity, waist circumference, and height at 4 years using regression models adjusted for a priori selected confounders. Diet-related GHGE and LU had a positive weak association with overweight and obesity, with an odds ratio (OR) for the fourth vs. second quartile of 1.30 for both GHGE (95% confidence intervals -CI-: 0.96; 1.77) and LU (95% CI: 0.96-1.76). Both OR estimates increased after adjustment for energy intake. GHGE and LU were not associated with height, with the exception of shorter children in the first quartile. A high vs. low MD adherence was associated with an increase in height Z-score of 0.11 (95% CI 0.01; 0.21). No association was found for red meat consumption. These results suggest that lowering the impact of high environmental impact diets may have, if anything, beneficial effects on child obesity, overweight, and height, with pro-MD patterns playing an important role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures., Methods: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia., Results: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women ( p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm 2 and 3.66 cm 2 for CSA, 32.57 mm and 40.21 mm for the X -axis, and 7.85 mm and 10.4 mm for the Y -axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women., Conclusions: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice., Competing Interests: G.G.R. and A.M are full employees of Abbott Laboratories. None of the remaining authors have any conflicts of interest. The authors declare that the project was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrP Sc immunohistochemistry staining in the brainstem and the absence of detectable PrP Sc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain., (© 2024. The Author(s).)

This study aims to explore the perspectives of Italian psychologists who work in assisted reproductive treatment (ART) centres regarding their roles within multidisciplinary teams. Twenty-eight psychologists were interviewed, recorded and their transcribed text was analysed using emotional text mining. The analysis revealed four clusters representing the psychologists' cultural symbolizations of their works: 'Clinical Practice with the patient', 'Placing Psychology within the Treatment', 'Psychologist's Loneliness' and; 'Collusion with Medicine'. The symbolic representations emerging clearly highlighted a lack of integration of psychology within the medical field. Psychologists expressed emotional and practical difficulties in trying to integrate their role, including a desire to provide psychological assistance, feelings of loneliness and concerns about jeopardizing their professional opportunities, which are intertwined with the medical field. Present findings underscore the importance of integrating psychology within ART centres and multidisciplinary teams and of establishing operational guidelines for psychologists. These steps are crucial for reaching integration of psychologists within the medical setting., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hepatocytes work in highly structured, repetitive hepatic lobules. Blood flow across the radial axis of the lobule generates oxygen, nutrient, and hormone gradients, which result in zoned spatial variability and functional diversity. This large heterogeneity suggests that hepatocytes in different lobule zones may have distinct gene expression profiles, metabolic features, regenerative capacity, and susceptibility to damage. Here, we describe the principles of liver zonation, introduce metabolomic approaches to study the spatial heterogeneity of the liver, and highlight the possibility of exploring the spatial metabolic profile, leading to a deeper understanding of the tissue metabolic organization. Spatial metabolomics can also reveal intercellular heterogeneity and its contribution to liver disease. These approaches facilitate the global characterization of liver metabolic function with high spatial resolution along physiological and pathological time scales. This review summarizes the state of the art for spatially resolved metabolomic analysis and the challenges that hinder the achievement of metabolome coverage at the single-cell level. We also discuss several major contributions to the understanding of liver spatial metabolism and conclude with our opinion on the future developments and applications of these exciting new technologies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of American Association for the Study of Liver Diseases.)

Progressive financing of health care can help advance the equity and financial protection goals of health systems. All countries' health systems are financed in part through private mechanisms, including out-of-pocket payments and voluntary health insurance. Yet little is known about how these financing schemes are structured, and the extent to which policies in place mitigate regressivity. This study identifies the potential policies to mitigate regressivity in private financing, builds two qualitative tools to comparatively assess regressivity of these two sources of revenue, and applies this tool to a selection of 29 high-income countries. It provides new evidence on the variations in policy approaches taken, and resultant regressivity, of private mechanisms of financing health care. These results inform a comprehensive assessment of progressivity of health systems financing, considering all revenue streams, that appears in this special section of the journal., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Most world countries are experiencing a remarkable aging process. Meanwhile, 50 million people are affected by Alzheimer's disease (AD) and related dementia and there is an increasing trend in the incidence of these major health problems. In order to address these, the increasing evidence suggesting the protective effect of dietary interventions against cognitive decline during aging may suggest a response to this challenge. There are nutrients with a neuroprotective effect. However, Western diets are poor in healthy n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic acid (DHA), iodine (I), and other nutrients that may protect against cognitive aging. Given DHA richness in chub mackerel ( Scomber colias ), high vitamin B9 levels in quinoa ( Chenopodium quinoa ), and I abundance in the seaweed Saccorhiza polyschides , a functional hamburger rich in these nutrients by using these ingredients was developed and its formulation was optimized in preliminary testing. The effects of culinary treatment (steaming, roasting, and grilling vs. raw) and digestion on bioaccessibility were evaluated. The hamburgers had high levels of n-3 PUFAs in the range of 42.0-46.4% and low levels of n-6 PUFAs (6.6-6.9%), resulting in high n-3/n-6 ratios (>6). Bioaccessibility studies showed that the hamburgers could provide the daily requirements of eicosapentaenoic acid (EPA) + DHA with 19.6 g raw, 18.6 g steamed, 18.9 g roasted, or 15.1 g grilled hamburgers. Polyphenol enrichment by the seaweed and antioxidant activity were limited. The hamburgers contained high levels of Se and I at 48-61 μg/100 g ww and 221-255 μg/100 g ww, respectively. Selenium (Se) and I bioaccessibility levels were 70-85% and 57-70%, respectively, which can be considered high levels. Nonetheless, for reaching dietary requirements, considering the influence of culinary treatment and bioaccessibility, 152.2-184.2 g would be necessary to ensure daily Se requirements and 92.0-118.1 g for I needs.

Purpose: To assess the relation between number of inseminated oocytes and cumulative live birth rate (CLBR) in order to provide guidance for limiting the number of surplus blastocysts., Methods: The study was a retrospective, single-center cohort analysis of 1223 ART complete cycles. Cycles were stratified according to female age (≤ 34, 35-38, and 39-42 years) and number of inseminated oocytes (1-5, 6-10, and > 10). Inclusion criteria were indication for IVF/ICSI with own spermatozoa and blastocyst culture up to day 6 of all embryos., Results: In patients younger than 35 years, insemination of more than ten oocytes produced an increase in overall blastocyst number, CLBR (40.3%, 54.3%, and 75.8%, respectively, for each oocyte group) and surplus embryo rate (12.9%, 27.8%, and 49.7% of cases for each group). Instead, in the middle age group, the use of more than ten oocytes was solely associated with an increase in the rate of surplus embryos (1.25%, 21.33%, and 28.68% of cases after stratification for oocyte number). In older patients, neither CLBR (9.1%, 23.9%, and 24.7%, respectively) nor rate of surplus embryos (2.0%, 7.1%, and 13.4% of cases for each group) were higher in cycles with more than ten inseminated oocytes., Conclusion: In women up to 38 years, sustainable CLBR are achieved while limiting the number of inseminated oocytes and the resulting blastocysts remaining unused. Based on this notion, novel treatment strategies could pursue high outcome rates, while alleviating the problems derived from surplus stored embryos., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Up to 56 million young and adult women of African origin suffer from Female Genital Schistosomiasis (FGS). The transmission of schistosomiasis happens through contact with schistosomiasis infested fresh water in rivers and lakes. The transmission vector is the snail that releases immature worms capable of penetrating the human skin. The worm then matures and mates in the blood vessels and deposits its eggs in tissues, causing urogenital disease. There is currently no gold standard for FGS diagnosis. Reliable diagnostics are challenging due to the lack of appropriate instruments and clinical skills. The World Health Organisation (WHO) recommends "screen-and-treat" cervical cancer management, by means of visual inspection of characteristic lesions on the cervix and point-of-care treatment as per the findings. FGS may be mistaken for cervical cancer or sexually transmitted diseases. Misdiagnosis may lead to the wrong treatment, increased risk of exposure to other infectious diseases (human immunodeficiency virus and human papilloma virus), infertility and stigmatisation. The necessary clinical knowledge is only available to a few experts in the world. For an appropriate diagnosis, this knowledge needs to be transferred to health professionals who have minimal or non-existing laboratory support. Co-design workshops were held with stakeholders (WHO representative, national health authority, FGS experts and researchers, gynaecologists, nurses, medical doctors, public health experts, technical experts, and members of the public) to make prototypes for the WHO Pocket Atlas for FGS, a mobile diagnostic support tool and an e-learning tool for health professionals. The dissemination targeted health facilities, including remote areas across the 51 anglophone, francophone and lusophone African countries. Outcomes were endorsed by the WHO and comprise a practical diagnostic guide for FGS in low-resource environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Martinez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrP C ) into a pathogenic form (PrP Sc ). This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications., (© 2024. The Author(s).)

One of the hallmarks of Parkinson's disease (PD) is the alteration in the expression and function of NMDA receptor (NMDAR) and cannabinoid receptor 1 (CB 1 R). The presence of CB 1 R-NMDAR complexes has been described in neuronal primary cultures. The activation of CB 1 R in CB 1 R-NMDAR complexes was suggested to counteract the detrimental NMDAR overactivation in an AD mice model. Thus, we aimed to explore the role of this receptor complex in PD. By using Bioluminescence Resonance Energy Transfer (BRET) assay, it was demonstrated that α-synuclein induces a reorganization of the CB 1 R-NMDAR complex in transfected HEK-293T cells. Moreover, α-synuclein treatment induced a decrease in the cAMP and MAP kinase (MAPK) signaling of both CB 1 R and NMDAR not only in transfected cells but also in neuronal primary cultures. Finally, the interaction between CB 1 R and NMDAR was studied by Proximity Ligation Assay (PLA) in neuronal primary cultures, where it was observed that the expression of CB 1 R-NMDAR complexes was decreased upon α-synuclein treatment. These results point to a role of CB 1 R-NMDAR complexes as a new therapeutic target in Parkinson's disease.

Objectives: to describe the results of a pilot population-based perinatal mortality surveillance system, with regards to stillbirths; to study maternal, obstetric, and foetal characteristics, evaluating risk factors and understanding causes., Design: a cross-sectional study was conducted on incident cases of stillbirths collected by the surveillance system from July 2017 to June 2019 in three Italian Regions (Lombardy, Tuscany, and Sicily)., Setting and Participants: data on stillbirths, resulting from the in-hospital multidisciplinary audits, organised using the Significant Event Audit methodology, were analysed. According to the World Health Organization (WHO) definitions, the project identified stillbirths as foetuses born dead >=28 weeks of gestation. The WHO International Classification of Diseases-Perinatal Mortality was used to categorise the causes of foetal death., Main Outcomes Measures: maternal characteristics, obstetric and foetal findings were investigated. Unadjusted relative risks and 95% confidence intervals were computed with respect to the background population. Finally, causes of death and contributing maternal conditions have been considered., Results: the maternity and neonatal units of the three participating Regions notified 520 stillbirths, of which 435 cases underwent to the multidisciplinary audit (83.7%); 40.0% of cases occurred in the gestational age range between 36 and 39 weeks. The risk of stillbirth was significantly increased in mothers with foreign citizenship (RR: 1.39; 95%CI: 1.13-1.71), multiple pregnancies (RR: 1.59; 95%CI 1.05-2.42), and pregnancies conceived with assisted reproductive technologies (RR: 2.15; 95%CI 1.45-3.19). The rate of congenital malformations was 6.0%. A diagnosis of foetal growth restriction was reported in 10.3% of cases, although the percentage of dead foetuses weighting <10° centile was at least twice in almost all gestational age periods. Post-mortem and placental histological examinations were carried out in more than 70% and more than 90% of cases, respectively., Conclusions: the implementation of a population-based surveillance system with high participation rate of maternity units and the use of universally accepted definitions could improve the identification of stillbirth avoidable risk factors and potentially modifiable predisposing maternal conditions, highlighting issues of perinatal assistance in need of improvement.

Tricuspid regurgitation (TR) is common after a heart transplant and is associated with worse clinical outcomes. The incidence ranges from 34% immediately after transplant to 20% by 10 years. Most patients can be managed medically; however, severe TR and symptomatic right heart failure warrant tricuspid valve replacement. The use of Melody transcatheter pulmonary valve in the tricuspid position is previously described. We report a unique case of posttransplant severe TR treated with surgical bioprosthetic tricuspid valve replacement who subsequently underwent successful transcatheter Melody valve placement in tricuspid position for progressive bioprosthetic valve stenosis with 11 years of follow-up., (© 2024 The Author(s).)

Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate., Competing Interests: Declaration of Interests The authors declare no competing interests.

The progression from prediabetes to type-2 diabetes depends on multiple pathophysiological, clinical, and epidemiological factors that generally overlap. Both insulin resistance and decreased insulin secretion are considered to be the main causes. The diagnosis and approach to the prediabetic patient are heterogeneous. There is no agreement on the diagnostic criteria to identify prediabetic subjects or the approach to those with insufficient responses to treatment, with respect to regression to normal glycemic values or the prevention of complications. The stratification of prediabetic patients, considering the indicators of impaired fasting glucose, impaired glucose tolerance, or HbA1c, can help to identify the sub-phenotypes of subjects at risk for T2DM. However, considering other associated risk factors, such as impaired lipid profiles, or risk scores, such as the Finnish Diabetes Risk Score, may improve classification. Nevertheless, we still do not have enough information regarding cardiovascular risk reduction. The sub-phenotyping of subjects with prediabetes may provide an opportunity to improve the screening and management of cardiometabolic risk in subjects with prediabetes.

The potential benefits of drug repurposing have gained attention as an alternative to developing de novo drugs. The potential of using central nervous system (CNS) drugs as anticancer drugs has been explored in several types of human cancers, such as breast and colon cancer, among others. Here, we examine the effect of the CNS drugs sertraline, paroxetine, and chlorpromazine on human squamous carcinoma cells of the bladder (UM-UC-5). After exposing UM-UC-5 cells to increased concentrations of each drug for 48 h, we assessed their metabolic activity using an MTT assay. Based on those results, we calculated cell viability and the half-maximal inhibitory concentration (IC 50 ) values. The results suggest that the CNS drugs were effective against UM-UC-5 in the order of potency of sertraline > chlorpromazine > paroxetine. Interestingly, sertraline was more potent than 5-fluorouracil (5-FU), a widely used anticancer drug. This study demonstrated, for the first time, the promising anticancer activity of CNS drugs on human bladder cancer cells in vitro and supports the repurposing of CNS drugs to improve cancer treatment. Nevertheless, further studies are necessary to understand their mechanism of action and in vivo activity.

Congenital cleft lip and palate represent the prevailing craniofacial birth anomalies on a global scale. Notably, a substantial proportion of patients within remote regions of Iran defer corrective surgery until later stages of life, often in childhood or adulthood, primarily due to intricate financial and cultural constraints. In response to this pressing healthcare challenge, a dedicated collective of volunteer plastic surgeons was established in 2009 with the explicit aim of providing medical care to these underserved patients. Over the subsequent years, this compassionate team embarked on 31 meticulously planned missions to underprivileged areas scattered across the country. Through these organized endeavors, a remarkable total of 20,579 medical visits were conducted, coupled with the performance of 2,303 essential surgeries, thus offering a lifeline of healthcare to these disadvantaged individuals., Competing Interests: None declared.

To monitor relative vaccine effectiveness (rVE) against COVID-19-related hospitalisation of the first, second and third COVID-19 booster (vs complete primary vaccination), we performed monthly Cox regression models using retrospective cohorts constructed from electronic health registries in eight European countries, October 2021-July 2023. Within 12 weeks of administration, each booster showed high rVE (≥ 70% for second and third boosters). However, as of July 2023, most of the relative benefit has waned, particularly in persons ≥ 80-years-old, while some protection remained in 65-79-year-olds.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.