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Background: In gastrointestinal surgery after resection of bowel loops, anastomosis of the bowel loops forms the main part of the surgery. The evolution of mechanical sutures by stapler devices is a technological advancement which helps anastomosis of bowel loops with less tissue injury and decreased time duration of procedure. Objective of current study was to compare the hand sewn anastomosis with stapler anastomosis in various types of elective gastrointestinal surgeries. Methods: A retrospective comparative study was conducted in department of general surgery at New Civil Hospital, Surat. The study included 50 patients of either gender and different age groups. Results: Out of 50 patients, 7 patients had Benign Gastric Outlet Obstruction (GOO), 18 patients had Post corrosive esophageal stricture, 5 patients had obstruction, 6 patients had post ileostomy status, 5 patients had carcinoma of ascending colon, 1 patient had carcinoma of caecum, 4 patients had ileo-caecal growth, 3 patients had carcinoma of descending colon, and 1 patient had sigmoid colon growth. In stapler anastomosis group Mean Total operative time was (156.20±45.21) mins whereas in handsewn anastomosis group Mean Total operative time was (188.40±48.32) mins with p value of 0.019. Conclusions: In this study, one distinct advantage of staplers was the consistent reduction in operating time. However, no significant difference was found between the stapler and hand-sewn groups with respect to other parameters such as restoration of intestinal function, postoperative hospital stay, and postoperative complications like leakage, fistula or stricture formation.

Background The Omicron B.1.1.529 variant increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in doubly vaccinated individuals, particularly in the Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1) recipients. To tackle infections, the UK’s booster vaccination programmes used messenger ribonucleic acid (mRNA) vaccines irrespective of an individual’s primary course vaccine type, and prioritized the clinically vulnerable. These mRNA vaccines included the Pfizer–BioNTech COVID-19 vaccine (BNT162b2) the Moderna COVID-19 vaccine (mRNA-1273). There is limited understanding of the effectiveness of different primary vaccination courses on mRNA booster vaccines against SARs-COV-2 infections and how time-varying confounders affect these evaluations. Methods Trial emulation was applied to a prospective community observational cohort in England and Wales to reduce time-varying confounding-by-indication driven by prioritizing vaccination based upon age, vulnerability and exposure. Trial emulation was conducted by meta-analysing eight adult cohort results whose booster vaccinations were staggered between 16 September 2021 and 05 January 2022 and followed until 23 January 2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end of study was modelled using Cox proportional hazard models and adjusted for age, sex, minority ethnic status, clinically vulnerability and deprivation. Results A total of 19 159 participants were analysed, with 11 709 ChAdOx1 primary courses and 7450 BNT162b2 primary courses. Median age, clinical vulnerability status and infection rates fluctuate through time. In mRNA-boosted adults, 7.4% (n = 863) of boosted adults with a ChAdOx1 primary course experienced a SARS-CoV-2 infection compared with 7.7% (n = 571) of those who had BNT162b2 as a primary course. The pooled adjusted hazard ratio (aHR) was 1.01 with a 95% confidence interval (CI) of: 0.90 to 1.13. Conclusion After an mRNA booster dose, we found no difference in protection comparing those with a primary course of BNT162b2 with those with a ChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection.

Gold nanoparticles (GNPs) are noble metal nanocarriers that have been recently researched upon for pharmaceutical applications, imaging, and diagnosis. These metallic nanocarriers are easy to synthesize using chemical reduction techniques as their surface can be easily modified. Also, the properties of GNP are significantly affected by its size and shape which mandates its stabilization using suitable techniques of surface modification. Over the past decade, research has focused on surface modification of GNP and its stabilization using polymers, polysaccharides, proteins, dendrimers, and phase-stabilizers like gel phase or ionic liquid phase. The use of GNP for pharmaceutical applications requires its surface modification using biocompatible and inert surface modifiers. The stabilizers used, interact with the surface of GNP to provide either electrostatic stabilization or steric stabilization. This review extensively discusses the surface modification techniques for GNP and the related molecular level interactions involved in the same. The influence of various factors like the concentration of stabilizers used, their characteristics like chain length and thickness, pH of the surrounding media, etc., on the surface of GNP resulting in stability have been discussed in detail. Further, this review highlights the recent applications of surface-modified GNP in the management of tumor microenvironment and cancer therapy.

Atherosclerosis is a multifactorial inflammatory disease characterized by the development of plaque formation leading to occlusion of the vessel and hypoxia of the tissue supplied by the vessel. Chronic inflammation and altered collagen expression render stable plaque to unstable and increase plaque vulnerability. Thinned and weakened fibrous cap results in plaque rupture and formation of thrombosis and emboli formation leading to acute ischemic events such as stroke and myocardial infarction. Inflammatory mediators including TREM-1, TLRs, MMPs, and immune cells play a critical role in plaque vulnerability. Among the other inflammatory mediators, oncostatin-M (OSM), a pro-inflammatory cytokine, play an important role in the development and progression of atherosclerosis, however, the role of OSM in plaque vulnerability and extracellular matrix remodeling (ECM) is not well understood and studied. Since ECM remodeling plays an important role in atherosclerosis and plaque vulnerability, a detailed investigation on the role of OSM in ECM remodeling and plaque vulnerability is critical. This is important because the role of OSM has been discussed in the context of proliferation of vascular smooth muscle cells and regulation of cytokine expression but the role of OSM is scarcely discussed in relation to ECM remodeling and plaque vulnerability. This review focuses on critically discussing the role of OSM in ECM remodeling and plaque vulnerability.

Figure created with BioRender.com. OBJECTIVES Outcomes beyond 10 years for David V valve-sparing aortic root replacement (VSARR) in bicuspid aortic valve (BAV) patients have yet to be explored. We investigated long-term outcomes after BAV VSARR compared to VSARR for tricuspid aortic valve (TAV) patients. METHODS A total of 677 patients with BAV (n = 171) and TAV (n = 506) underwent VSARR between 2005 and 2020 from 2 aortic centres, excluding those with dissection, endocarditis, stenosis or prior aortic valve (AV) surgery. Multivariable Cox regression compared adjusted survival over a 12-year period. Fine and Gray competing risk regression compared risk and cumulative incidence of reoperation/reintervention. Propensity score matching created balanced groups, and landmark analysis isolated outcomes beginning 4 years postoperatively. Finally, longitudinal mixed modelling assessed AV deterioration on echocardiogram. RESULTS No difference was observed in 12-year survival of BAV versus TAV (propensity score matching 92.0% vs 89.9%, P = 0.97; multivariable hazard ratio 0.76, 95% confidence interval 0.34–1.69, P = 0.51). Adjusted 12-year cumulative incidence and risk of AV and/or proximal aorta reoperation/reintervention were not observed to be different (15.7% BAV vs 5.7% TAV, P = 0.37; subdistribution hazard ratio 1.54, 95% confidence interval 0.60–3.94, P = 0.36); however, landmark analysis showed increased incidence of late reoperation/reintervention in BAV versus TAV (11.7% vs 0.0%, P = 0.04). BAV was not associated with AV deterioration over time (BAV coefficient ± standard error: 0 ± 0.30, P = 1). CONCLUSIONS VSARR for BAV patients has excellent 12-year survival and low reoperation/reintervention rates, which were not observed to be different from TAV patients. However, higher incidence of reoperation/reintervention was observed in the late years after BAV VSARR. Our study provides key information for surgical consultation of patients with bicuspid aortopathy.

Objective This study aimed to assess diagnostic radiology training and exposure during medical school, from the perspective of medical students in Brazil. Methods In this multicenter study approved by the Institutional Review Board, medical students from multiple universities in Brazil filled out an online questionnaire regarding their perception about diagnostic radiology training during medical school, including knowledge and use of the American College of Radiology Appropriateness Criteria and their confidence level in interpreting common radiological findings. Medical students from different regions of Brazil were sent invitations to participate in the anonymous survey through radiology group emails initiated by radiology professors and a group of ambassadors representing different institutions. Informed consent was obtained electronically at the beginning of the survey. Results The survey demonstrated diagnostic radiology is frequently included in preclinical exams; however, radiology training during medical school was considered inadequate from the medical students´ perspective. Overall, radiological imaging teaching was provided by radiologists for more than half of the survey respondents; however, radiological imaging is frequently shown to students by non-radiologist physicians during case discussion rounds. Moreover, few respondents had a mandatory radiology training rotation during medical school. Conclusion This Brazilian medical student survey demonstrated that from the medical students’ perspective, diagnostic radiology is an important subject in clinical practice; however, their radiology training and exposure are overall heterogeneous.

Purpose: To construct, apply, and evaluate a multidisciplinary approach in teaching radiology to Canadian medical students. Methods: A multidisciplinary team of radiology and other disciplines experts designed an online 5-session course that was delivered to medical students. The topics of each session were clinical cases involving different systems. The target audience was medical students of Canadian schools. Pretests and post-tests were administered before and after each session respectively. An evaluation survey was distributed at the end of the course to gauge students’ perceptions of this experience. Results: An average of 425 medical students attended the live sessions. For each session, 405 students completed both the pre-tests and post-tests. In general, students scored an average of 56% higher on the post-test than on the pre-test. The final course survey was completed by 469 students. The survey results show that more than 98% of students found the course to meet or exceed their expectations. Over 80% of students agreed that the course increased their interest in radiology and about 81% agree that the topics presented were excellent and clinically important. The ratings in the final survey results also indicate that students increased their confidence in basic radiology skills after completing the course. Conclusions: The implementation of an integrative clinical approach to teaching radiology in a virtual setting is achievable. It provides efficient use of educational resources while being accessible by a large number of students across different medical schools.

According to the World Health Organization (WHO), particulate matter (PM) contamination causes around 800,000 premature deaths per year, ranking 13th in the world in terms of mortality. However, several findings revealed that the correlation is much stronger and more complicated than previously believed. PM is an element of emissions comprised of very small, acidic, organic compounds, metals, and particulate soil or dust particles or fluid droplets. The most consistent air quality component linked to human illness is PM, which is categorized by size. PM is likely to develop cardiovascular and cerebrovascular disorders due to the mechanisms of inflammation, overt and indirect coagulation activation, and direct translocation to the systemic circulation. The evidence on the cardiovascular system that shows a PM effect is strong. Coronary incidence and mortality rates in populations prone to long-term PM toxicity were significantly higher. Short-term acute emissions increase coronary incidence rates subtly within days of the pollution peak. While some evidence and associated mechanisms show a smaller outcome, the findings for PM’s cortical disease symptoms are not as promising. Respiratory infections are aggravated by exposure to PM. More analysis is needed to clarify the effects of structure, chemistry, and PM for vulnerable groups. The existing research indicates that PM toxicity causes a minor but significant increase in human morbidity and mortality. Air conditioners and particulate matter filters reduced internal heating, and cooking combustion and smoking cessation will reduce indoor PM exposure. These fundamental improvements can be beneficial to patients with acute and chronic cardiovascular and respiratory symptoms. This article provides an overview of the effects of atmospheric airborne suspended particulate matter on population morbidity and mortality. This critical review concludes with public health recommendations based on a summary of the published literature’s findings.

Trichilemmal cysts (TCs) are the most common cystic lesions arising on the scalp and up to 2% give rise to a proliferating trichilemmal tumor (PTT). A rare subset of PTTs are termed malignant due to their histologic characteristics, aggressive behavior and potential for metastasis. The histological hallmark of TCs and PTTs is the absence of a granular layer resulting in abrupt trichilemmal keritanization.

Herbal teas are nutrient, antioxidant, and hydration rich brews made from herbs and spices and taken for various purposes. The objective of this study was to formulate tea from clove (Syzygium aromaticum), leaves of lemongrass (Cymbopogon citratus), guava (Psidium guajava), and moringa (Moringa oleifera), as well as compared with Chinese and yellow Lipton Tea. The samples were analyzed for comparative sensory analysis using the 7 points hedonic scale. The sensory evaluation result demonstrated that the color of the clove tea sample (5.87) was most acceptable by participants, while the lemongrass tea (4.46) sample was least acceptable amongst all the tea samples. The clove remained the most accepted tea for aroma (6.07), taste (5.92), texture (5.76), general appearance (5.74), and general acceptability (5.93), in 7 points hedonic scale. However, all tea samples were had significant acceptable scores above average (p

Traditional in-person discussion alone is often used for preoperative education in Mohs micrographic surgery (MMS). The appropriate use of more modern education techniques is not well defined in the MMS literature. The authors aim to evaluate patient education techniques for MMS, address education in special populations, and highlight opportunities for improvement. We performed a PubMed literature search with keywords “Mohs” and “education”, “teaching”, “understanding”, “explanation”, “preoperative”, or “consent” with no restriction on publication time frame due to literature scarcity. Teledermatology consultation, MMS videos, 3D models, pamphlets/online materials, and shared medical appointments appear to be effective techniques (GRADE B). Analogies are also anecdotally helpful when integrated into traditional verbal education (GRADE C). The role of preoperative educational phone calls is more controversial (GRADE C). Regardless of the education technique utilized, no singular technique entirely replaces the traditional in-person discussion. Having access to multiple modalities can be beneficial for patients, allowing them options to choose their preferred method(s) of education. MMS is a difficult topic to conceptualize, and further research into educational techniques is needed to provide clear guidelines for Mohs surgeons.

Seroprevalence studies can provide a measure of SARS-CoV-2 cumulative incidence, but a better understanding of spike and nucleocapsid (anti-N) antibody dynamics following infection is needed to assess the longevity of detectability.Adults aged ≥18 years, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary blood samples, which were tested for spike antibody and anti-N. Participants self-reported vaccination dates and past medical history. Previous polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System linkage data. The primary outcome variables were seropositivity and total anti-N and spike antibody levels after PCR-confirmed infection.A total of 13,802 eligible individuals provided 58,770 capillary blood samples. A total of 537 of these had a previous positive PCR-confirmed SARS-CoV-2 infection within 0-269 days of antibody sample date, among them 432 (80.45%) having a positive anti-N result. Median anti-N levels peaked between days 90 and 119 after PCR results and then began to decline. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories.Our findings suggest that anti-N has around 80% sensitivity for identifying previous COVID-19 infection, and the duration of detectability is affected by sex and age.

Key Points Question To what extent does stage shift act as a confounding variable in the evaluation of population mortality of non–small cell lung cancer? Findings In this cohort study of 312 382 patients, stage shift from later to earlier stage disease over the last decade was associated with improved mortality among people with lung cancer. Meaning These findings suggest that studies investigating treatments for lung cancer must take into account stage shift and the confounding association with survival and mortality outcome., This cohort study investigates the association of stage shift with population mortality among patients diagnosed with non–small cell lung cancer between 2006 and 2016., Importance Early detection by computed tomography and a more attention-oriented approach to incidentally identified pulmonary nodules in the last decade has led to population stage shift for non–small cell lung cancer (NSCLC). This stage shift could substantially confound the evaluation of newer therapeutics and mortality outcomes. Objective To investigate the association of stage shift with population mortality among patients with NSCLC. Design, Setting, and Participants This retrospective cohort study was performed from October 2020 to June 2021 and used data from the Surveillance, Epidemiology, and End Results (SEER) registries to assess all patients from 2006 to 2016 with NSCLC. Main Outcomes and Measures Incidence-based mortality was evaluated by year-of-death. To assess shifts in diagnostic characteristics, clinical stage and histology distributions were examined by year using χ2 tests. Trends were assessed using the average annual percentage change (AAPC), calculated with JoinPoint software. Kaplan-Meier survival analysis assessed overall survival according to stage and compared those missing any stage with those with a reported stage. Results The final sample contained 312 382 patients; 166 657 (53.4%) were male, 38 201 (12.2%) were Black, and 249 062 (79.7%) were White; the median (IQR) age was 68 (60-76) years; 163 086 (52.2%) had adenocarcinoma histology. Incidence-based mortality within 5 years of diagnosis decreased from 2006 to 2016 (AAPC, −3.7; 95% CI, −4.1 to −3.4). When assessing stage shift, there was significant association between year-of-diagnosis and clinical stage, with stage I/II diagnosis increasing from 26.5% to 31.2% (AAPC, 1.5; 95% CI, 0.5 to 2.5); and stage III/IV diagnosis decreasing significantly from 70.8% to 66.1% (AAPC, −0.6; 95% CI, −1.0 to −0.2). Missing staging information was not associated with year-of-diagnosis (AAPC, −1.6; 95% CI, −7.4 to 4.5). Year-of-diagnosis was significantly associated with tumor histology (χ2 = 8990.0; P

Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters the myelin ultrastructure. However, the impact of such alterations on adolescent white matter maturation is yet to be investigated. To address this, female piebald-virol-glaxo rats underwent partial transection of the optic nerve during early adolescence (postnatal day (PND) 56) with tissue collection two weeks (PND 70) or three months later (PND 140). Axons and myelin in the transmission electron micrographs of tissue adjacent to the injury were classified and measured based on the appearance of the myelin laminae. Injury in adolescence impaired the myelin structure in adulthood, resulting in a lower percentage of axons with compact myelin and a higher percentage of axons with severe myelin decompaction. Myelin thickness did not increase as expected into adulthood after injury and the relationship between the axon diameter and myelin thickness in adulthood was altered. Notably, dysmyelination was not observed 2 weeks postinjury. In conclusion, injury in adolescence altered the developmental trajectory, resulting in impaired myelin maturation when assessed at the ultrastructural level in adulthood.

Background:Respiratory protective equipment recommended in the UK for healthcare workers (HCWs) caring for patients with COVID-19 comprises a fluid-resistant surgical mask (FRSM), except in the context of aerosol generating procedures (AGPs). We previously demonstrated frequent pauci- and asymptomatic severe acute respiratory syndrome coronavirus 2 infection HCWs during the first wave of the COVID-19 pandemic in the UK, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020).Methods:Here, we use observational data and mathematical modelling to analyse infection rates amongst HCWs working on ‘red’ (coronavirus disease 2019, COVID-19) and ‘green’ (non-COVID-19) wards during the second wave of the pandemic, before and after the substitution of filtering face piece 3 (FFP3) respirators for FRSMs.Results:Whilst using FRSMs, HCWs working on red wards faced an approximately 31-fold (and at least fivefold) increased risk of direct, ward-based infection. Conversely, after changing to FFP3 respirators, this risk was significantly reduced (52–100% protection).Conclusions:FFP3 respirators may therefore provide more effective protection than FRSMs for HCWs caring for patients with COVID-19, whether or not AGPs are undertaken.Funding:Wellcome Trust, Medical Research Council, Addenbrooke’s Charitable Trust, NIHR Cambridge Biomedical Research Centre, NHS Blood and Transfusion, UKRI.

IntroductionThe Coronavirus (COVID-19) Pandemic has caused significant global mortality and impacted lives around the world. Virus Watch aims to provide evidence on which public health approaches are most likely to be effective in reducing transmission and impact of the virus, and will investigate community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviours.Methods and analysisVirus Watch is a household community cohort study of acute respiratory infections in England & Wales and will run from June 2020 to August 2021. The study aims to recruit 50,000 people, including 12,500 from minority ethnic backgrounds, for an online survey cohort and monthly antibody testing using home finger prick kits. Nested within this larger study will be a sub-cohort of 10,000 individuals, including 3,000 people from minority ethnic backgrounds. This cohort of 10,000 people will have full blood serology taken between October 2020 and January 2021 and repeat serology between May 2021 and August 2021. Participants will also post self-administered nasal swabs for PCR assays of SARS-CoV-2 and will follow one of three different PCR testing schedules based upon symptoms.Ethics and disseminationThis study has been approved by the Hampstead NHS Health Research Authority Ethics Committee. Ethics approval number – 20/HRA/2320. We are monitoring participant queries and using these to refine methodology where necessary, and are providing summaries and policy briefings of our preliminary findings to inform public health action by working through our partnerships with our study advisory group, Public Health England, NHS and Government Scientific Advisory panels.Strengths and limitations of this studyVirus Watch is a large national household community cohort study of the occurrence and risk factors for COVID-19 infection that aims to recruit 50,000 people, including 12,500 from minority ethnic backgrounds.Virus Watch is designed to estimate incidence of PCR confirmed COVID-19 in those with respiratory and non-respiratory presentations and the incidence of hospitalisation among PCR confirmed COVID-19 cases.Virus Watch will measure effectiveness and impact of recommended COVID-19 control measures including testing, isolation, social distancing, respiratory and hand hygiene measures on risk of respiratory infection.Only households with a lead householder able to speak English were able to take part in the study up until March 2021.Only households of up to six people were eligible for inclusion and they were also required to have access to an internet connection. These restrictions will limit the generalisability to large or multigenerational households, and those without access to the internet.

Before the coronavirus disease 2019 (COVID-19) pandemic, use of telehealth services had been limited in cardiovascular care. Potential benefits of telehealth include improved access to care, more efficient care management, reduced costs, the ability to assess patients within their homes while involving key caretakers in medical decisions, maintaining social distance, and increased patient satisfaction. Challenges include changes in payment models, issues with data security and privacy, potential depersonalization of the patient-clinician relationship, limitations in the use of digital health technologies, and the potential impact on disparities, including socioeconomic, gender, and age-related issues and access to technology and broadband. Implementation and expansion of telehealth from a policy and reimbursement practice standpoint are filled with difficult decisions, yet addressing these are critical to the future of health care.

Despite the difficulties of this pandemic year, The Lancet received fascinating and varied entries for our Highlights 2020 photography competition. 15 striking photographs were selected for publication in this issue. Each picture captures a unique moment, highlighting a health story.

Introduction: COVID-19 is a global public health threat that Africa faces including the country Malawi. With an already burdened health system and an economically challenged population due to the poverty level, Malawi is suddenly faced by a pandemic that will test the country’s healthcare systems. Its government has already instituted an array of initiatives and plans and funding efforts toward the effective containment of the pandemic. Some of these efforts include reorientation and training for health workers, securing funding to procure and distribute needed personal protective equipment, medicine supply, health promotion, surveillance and case management. These efforts are being done in the context of an already heavy burden of diseases such as HIV/AIDS, malnutrition and poor health literacy. Whether efforts of the government and other stakeholders are enough, these remain to be seen in containing the virus and its aftermath. Until an effective treatment or vaccine is available, Malawi has to remain vigilant and needs to continue all its efforts to address its COVID-19 epidemic.

Backgroud Modern day cataract surgery aims at a spectacle free vision which becomes difficult in cases with pre-operative astigmatism more than 1.5 D. Implantation of toric intra-ocular lenses (IOL) after phacoemulsification in such eyes is one of the ways to counteract this problem. Methods Thirty eyes with pre-operative astigmatism between 1.5 D and 4.5 D were implanted with toric IOLs following uneventful phaco-emulsification. The estimation of the axis of implantation of this toric IOL included calculating the surgically induced astigmatism (SIA) of the surgeon. Results Post-operatively, 20 (66.67%) patients had a visual acuity 6/9 or better and 17 (57%) had a visual acuity of 6/6 at 12 weeks. The mean postoperative uncorrected visual acuity (UCVA) was 0.12 ± 0.15 at 12 weeks. The difference between means of preoperative best corrected visual acuity (BCVA) LogMAR and postoperative UCVA at 12 wk LogMAR was found to be statistically significant at p = 0.001. Mean (SD) scores of pre-op astigmatism of study group was −2.20 (0.67) and residual astigmatism was −0.32 (0.44). Conclusions The difference between means of pre-op astigmatism and residual astigmatism in the study group was significant at p = 0.001 with 95% CI −2.22 to −1.50. This significant difference was because of the toric IOL implantation.

Based on surveys by Robinson1nbsp;in 2001 and Trimble and Cherpeli2nbsp;in 2013, Immunohistochemistry (IHC) utilization in Mohs micrographic surgery (MMS) has been rising. Although these surveys provided important subjective data regarding IHC use in MMS, there is a paucity of objective data describing its current utilization patterns. The objective of this study is to characterize IHC utilization during MMS by Mohs surgeons in the treatment of Medicare beneficiaries from 2012-2017.

Introduction Si les Canadiens vivent plus longtemps qu’avant, bon nombre d’entre eux souffrent cependant d’obésité. Cette étude vise à décrire, par un examen de mesures du bien-être social, fonctionnel et mental, le vieillissement des personnes âgées souffrant d’obésité ayant participé à l’Étude longitudinale canadienne sur le vieillissement (ELCV). Méthodologie Nous avons extrait des données du premier cycle de l’ELCV portant sur les personnes de 55 à 85 ans. Nous avons utilisé des statistiques descriptives pour caractériser cette population et ajusté des modèles logistiques généralisés pour comparer les mesures du bien-être social, fonctionnel et mental chez les participants souffrant d'obésité (indice de masse corporelle de 30 kg/m2 et plus) et chez les participants n'en souffrant pas. Nos résultats sont présentés en fonction du sexe. Résultats Plus de la moitié des participants ont déclaré avoir un revenu personnel relativement faible (moins de 50 000 $), les femmes étant particulièrement affectées. Moins de la moitié des participants souffraient d'obésité et la multimorbidité était plus fréquente parmi ceux souffrant d'obésité que parmi ceux n'en souffrant pas (participants de 55 à 64 ans; rapport de cotes [RC] : 2,7; intervalle de confiance [IC] à 95 % : 2,0 à 3,5 chez les hommes; RC : 2,8; IC à 95 % : 2,2 à 2,5 chez les femmes). La faible participation sociale était associée à l’obésité chez les femmes plus âgées mais pas chez les hommes plus âgés. La présence de problèmes de fonctionnement physique et de limitations dans la vie quotidienne était fortement associée à l’obésité tant chez les femmes que chez les hommes. Bien que le bonheur et la satisfaction à l’égard de la vie ne soient pas associés à l'obésité, les femmes âgées souffrant d’obésité ont déclaré avoir une perception défavorable de leur état de santé. Conclusion La multimorbidité était plus fréquente chez les participants souffrant d'obésité que chez ceux n'en souffrant pas. Les femmes souffrant d'obésité étaient plus nombreuses que les hommes à avoir une perception défavorable de leur état de santé et à ne pas prendre part à des activités sociales. Les participants des deux sexes ont fait état de problèmes de santé fonctionnelle. Les associations observées, qui sont indépendantes de la multimorbidité chez les personnes âgées, mettent en relief les secteurs où des actions en faveur d'un vieillissement en santé pourraient être bénéfiques.

With the long-standing controversy surrounding the use of prostate-specific antigen (PSA) for the detection, evaluation, and surveillance of prostate cancer, there is a need for a minimally invasive technique to identify and risk-stratify these patients. Additionally, in an effort to reduce the number of unnecessary biopsies and identify clinically significant prostate cancer (csPCa), there has been a shift in practice towards the use of multiparametric magnetic resonance imaging (mpMRI) in conjunction with decision-making regarding prostate cancer diagnosis and management. In the current review, we summarize the data regarding the use of mpMRI in the detection, evaluation, and surveillance of csPCa. Recent prospective clinical trials have determined that a pre-biopsy mpMRI may rule out insignificant prostate cancers, thereby reducing the number of patients who require a biopsy. The anatomic information gathered from these pre-biopsy mpMRI performed during MRI fusion biopsy in csPCa increases the accuracy of pathologic staging in terms of Gleason scores. In regard to active surveillance, prospective trials suggest little to no clinical utility for mpMRI and fusion biopsy in the surveillance of prostate cancer despite conflicting findings from retrospective studies. Recent trials suggest that mpMRI can play an important role in the detection and evaluation of csPCa. The ideal role for mpMRI in active surveillance remains limited.

Modafinil is an approved drug for the treatment of narcolepsy and have a strong market presence in many countries. The drug is widely consumed for off-label uses and currently listed as a restricted drug. Modafinil has very low water solubility. To enhance the aqueous solubility of modafinil by the formation of a ternary complex with Hydroxypropyl-β-cyclodextrin and two hydrophilic polymers was the main objective of the present study. Pyrrolidone (PVP K30) and a water soluble chitosan derivative, trimethyl chitosan (TMC) were studied by solution state and solid state characterization methods for their discriminatory efficiency in solubility enhancement of modafinil. Phase solubility study depicted the highest complexation efficiency (2.22) of cyclodextrin derivative in the presence of TMC compared to the same in the presence of PVP K30 (0.08) and in the absence of any polymer (0.92). FT-IR analysis of binary and ternary complex expressed comparable contribution of both polymers in formation of inclusion complex. The thermal behaviour of binary and ternary complex, involving individual polymers disclosed the influence of TMC on polymorphism of the drug. DSC study revealed efficiency of TMC to prevent conversion of metastable polymorphic form to stable polymorphic form. Ternary complex, involving TMC enhanced water solubility of the drug 1.5 times more compared to the binary complex of the drug whereas PVP K30 reduced the Solubility.

Sudden onset myopia is seen in several local or systemic conditions.1 Local conditions include blunt ocular trauma and ocular inflammation. Systemic conditions include diabetes, pregnancy and certain drugs like hydrochlorothiazide and topiramate.1 However Systemic Lupus Erythematosus (SLE) as a cause of transient myopia is so rare that it has not been reported in these articles. Neither has sudden onset transient myopia been included in the ocular manifestations of SLE.2, 3 A case of SLE which presented with acute myopia is presented herewith.

Mevalonate diphosphate decarboxylase (MDD; EC 4.1.1.33) is an important enzyme in the mevalonic acid pathway catalyzing the Mg(2+)-ATP dependant decarboxylation of mevalonate 5-diphosphate (MVAPP) to isopentenyl diphosphate (IPP). Bacopa monniera recombinant MDD (BmMDD) protein was overexpressed in Escherichia coli BL21 (DE3) strain and purified to apparent homogeneity. Km and Vmax for MVAPP were 144 μM and 52 U mg(-1) respectively. The values of turnover (kcat) and kcat/Km for mevalonate 5-diphosphate were determined to be 40s(-1) and 2.77×10(5) M(-1) s(-1) and kcat and kcat/Km values for ATP were found to be 30 s(-1) and 2.20×10(4) M(-1) s(-1), respectively. pH activity profile indicated the involvement of carboxylate ion, lysine and arginine for the activity of enzyme. The apparent activation energy for the BmMDD catalyzed reaction was 12.7 kJ mol(-1). Optimum pH and temperature for the forward reaction was found to be 8.0 and 45 °C. The enzyme was most stable at pH 7 at 20 °C with the deactivation rate constant (Kd(*)) of 1.69×10(-4) and half life (t1/2) of 68 h. The cation studies suggested that BmMDD is a cation dependant enzyme and optimum activity was achieved in the presence of Mg(2+).

Background: 258 million people - 3% of the world's adult population - reside outside of their country of birth, yet there has been no previous global systematic review and meta-analysis of mortality data for these international migrants. We undertook a systematic review and meta-analysis to investigate current knowledge about mortality in international migrants. Methods: The review was carried out in line with PRISMA guidelines and was registered on Prospero (CRD42017073608). We searched the MEDLINE, EMBASE, and Global Health databases for studies on international migrants published between 1 Jan 2001 and 31 March 2017. Primary outcomes were standardised mortality ratios (SMRs) and absolute mortality rates. Meta-analyses were conducted using random effects models. Findings: We identified 12480 articles, of which 106 met our inclusion criteria. Data were included from all global regions and for 92 countries. 5498 SMR or absolute mortality estimates on more than 15.2 million migrants were included. The summary estimate of all-cause SMR for international migrants was lower than one (indicating lower mortality) when compared to the general population in host countries to which they migrate 0·70 (95%CI: 0·65-0·76;I2=99·8%). We estimated that all-cause SMR was lower in both male (0·72 [0·63-0·81]; I2=99·8%) and female (0·75 [0·66-0·84]; I2=99·8%) international migrants compared to the host population. The mortality advantage was evident for refugees (0.50 [0.46-0.56];I2=89·8%), but not for asylum seekers (1.05 [0.89-1.24];I2=54·4%), though there were limited data on these groups. SMRs for all causes of mortality were lower in migrants compared to the host population in the destination country with only two exceptions - infectious diseases and external causes - out of 13 ICD-10 categories. Heterogeneity was high across analyses. Point estimates of age-standardised mortality ranged from 488 in women to 874 in men per 100,000 population. Interpretation: Our analyses found that international migrants experience a mortality advantage compared to host populations, and this advantage persisted across the majority of ICD-10 disease categories. This finding is in contrast to the portrayal of migrants as a health burden and demonstrates that international migrants provide a major health benefit for host countries. Our research also highlights the need for better data on underrepresented and potentially more marginalised groups such as asylum seekers and undocumented migrants. Funding Statement: Wellcome Trust, NIHR, MRC, Alliance for Health Policy and Systems Research, DFID, Fogarty International Center, Grand Challenges Canada, International Development Research Center Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre and the the Imperial College Healthcare Charity. Declaration of Interests: RWA and IA undertook paid consultancy work in support of the Doctors of the World 2017 Observatory report - Falling through the cracks: The Failure of Universal Healthcare Coverage in Europe. JSF, LBN, and SH have collaborated on research projects with Doctors of the World UK, which includes research commissioned by the Equality and Human Rights Commission on barriers and enablers to care for asylum seekers and refused asylum seekers in the UK. RWA is supported by a Wellcome Trust Clinical Research Career Development Fellowship (206602/Z/17/Z). SB is supported by an NIHR research methods fellowship. JJM acknowledges receiving additional support from the Alliance for Health Policy and Systems Research (HQHSR1206660), DFID/MRC/Wellcome Global Health Trials (MR/M007405/1), Fogarty International Center (R21TW009982, D71TW010877), Grand Challenges Canada (0335-04), International Development Research Center Canada (106887, 108167), Inter-American Institute for Global Change Research (IAI CRN3036), Medical Research Council (MR/P008984/1, MR/P024408/1, MR/P02386X/1), National Cancer Institute (1P20CA217231), National Heart, Lung and Blood Institute (HHSN268200900033C, 5U01HL114180, 1UM1HL134590), National Institute of Mental Health (1U19MH098780), Swiss National Science Foundation (40P740-160366), Wellcome Trust (074833/Z/04/Z, 205177/Z/16/Z) and the World Diabetes Foundation (WDF15-1224). LBN, SH, and JSF receive funding from the UK National Institute for Health Research Imperial Biomedical Research Centre and the Imperial College Healthcare Charity; SH and LN are funded by the Wellcome Trust (Grant number 209993/Z/17/Z) with co-applicants of RWA, JSF and IA for this work. The views expressed are those of the authors and not those of the Wellcome Trust, NIHR, NHS, NHS Research Scotland, Medical Research Council, Chief Scientist’s Office. Ethics Approval Statement: The review was carried out in line with PRISMA guidelines and was registered on Prospero (CRD42017073608).

Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is an autosomal dominant, tumor predisposing disorder usuallycaused by germline mutations in mismatch repair (MMR) genes. A subset of HNPCC, Muir-Torre Syndrome (MTS) also involves MMR gene defects and is generally accepted as a variant of HNPCC. MTS is typicallycharacterized by at least one visceral malignancy and one cutaneous neoplasm of sebaceous differentiation, with or without keratoacanthomas. In either version of the disorder, nonfunctional MMR systems lead tothe loss of genomic integrity, marked commonly by mismatches in repetitive DNA sequences, resulting in microsatellite instabilities. Deleterious nucleotide alterations ultimately drive the process of tumorigenesis in both HNPCC and MTS. The following article reviews the epidemiology, genetics, clinical presentation, and management of HNPCC and its MTS variant.

Angiotensin-I-converting enzyme (ACE) inhibitors have been very effective in treating cardiac hypertension since their clinical inception over four decades ago. Since then, it has been established that angiotensin II, the product of ACE, has oncogenic and pro-proliferative qualities, which begs the question as to whether ACE inhibitors may have oncolytic characteristics. In fact, scattered reports suggest that ACE inhibitors are oncolytic and oncopreventive, but the available literature has yet to be thoroughly examined. In the present review, we examine the available literature and determine that ACE inhibitors would have great utility in the prevention and treatment of cancer. At the same time, they would augment the efficacy of chemo- and radiotherapy as well as mitigating damage to healthy tissue by standard chemotherapeutic regimens. We review some of the mounting clinical evidence and show that ACE inhibitors have oncolytic activity in multiple types of cancer and discuss the ability of ACE inhibitors to prevent cardiotoxicity of multiple chemotherapies. Our analysis demonstrates that the actions of ACE inhibitors converge on vascular endolthelial growth factor to reduce its levels in tumors and prevent construction of blood vessels to masses, leaving them nutrient-depleted and subsequently hindering their growth. Given that ACE inhibitors are approved by the Federal Drug Administration and the therapeutic dose for hypertension treatment also slows the growth of multiple cancers types, ACE inhibitors are in a perfect position to be repurposed as oncolytic agents, that would widely increase their utility in the clinic.

Neurotrophins are a family of growth factors that are vital to the proper development of the central nervous system. Their effects on cells are governed by the expression and activation of the tyrosine kinase receptors TrkA, TrkB and TrkC. TrkB has been immensely implicated in mediating neuronal migration, development and differentiation. It has also been shown to protect several neuronal cell types from an array of cytotoxic stressors after activation by its conjugate ligand brain-derived neurotrophic factor (BDNF). Over the past two decades, it has been shown that TrkB and BDNF are up-regulated in many types of cancers, conferring aggressive phenotypes underpinned by their resistance to several standard chemotherapeutic agents. This resistance to chemotherapy is modulated by the downstream targets of the TrkB receptor which include the well-characterized PI3K /Akt growth pathway, a hallmark of uncontrolled cancer cell growth and proliferation. Pre-clinical efforts to develop inhibitors of this receptor are promising, and such inhibitors also seem to sensitize cancer cells to standard chemotherapies. However, new evidence suggests that BDNF overexpression in the hypothalamus has immunoaugmenting properties, eliciting an increased anti-tumor immune response and reducing the activity of several proteins that would normally confer resistance to chemotherapeutic agents. In the current work, we provide a global analysis of the physiological consequences of TrkB receptor activation in vitro and discuss the dynamic consequences of TrkB activation in vivo. Finally, we propose a clinically-feasible option for increasing BDNF expression in the hypothalamus to more readily utilize the oncolytic effects of BDNF.

Background Esophageal Squamous Cell Carcinoma(ESCC) comprises 90% of esophageal cancer worldwide which typically presents at advanced stages and has extremely poor outcomes. Established risk factors for ESCC include tobacco, alcohol and betel nut use. We hypothesized that a screening program for high risk subjects could be established in a low- to middle-income country, using a low-cost, non-endoscopic, retrievable capsule sponge device called EsophaCap(EC). Methods The Institutional Review Board-approved study was conducted in western India from March 2017 through February 2018. Patients with high risk characteristics(smoking, tobacco, betel nut, alcohol, hot beverage consumption) were included. Patients with severe dysphagia, current upper aerodigestive tract cancer, metastatic cancer, esophageal varices, cirrhosis, and portal hypertension were excluded. Following EC specimen retrieval, endoscopic biopsies were collected at 20cm, 30cm and from any visible mucosal abnormalities. Cytology and biopsy specimens underwent H&E staining. An interim analysis was performed to make necessary changes given the lack of baseline data in this field. Results Of the 100 enrolled subjects(85% males, median age 50 years), 93% successfully swallowed the EC and 90% completed endoscopy. The median patient experience score on a 6-point visual analog scale was 5(‘minimal discomfort’). Six(7%) subjects had ESCC on their biopsy. In 2 ESCC patients with mild dysphagia, sponge cytology accurately detected atypical squamous cells(ASC) and dysplasia(100% Sensitivity & Specificity). The other 4 ESCC patients had moderate dysphagia with a near-complete obstruction. In 2 asymptomatic patients with no mucosal abnormalities on endoscopy or biopsies, sponge cytology detected ASC. Longitudinal follow-up of these patients is ongoing. On biopsies from twenty-one(23%) patients, leukoplakia was identified. Conclusion ESCC screening using the EC is feasible with good patient tolerance. Analysis of the cytology samples with H&E staining is potentially accurate for patients with non-obstructive lesions but has a high false negative rate in patients with advanced lesions, when the EC can’t traverse the obstruction. An unusually high rate of leukoplakia was detected in this population and will be evaluated as a potentially pre-malignant lesion with increased risk for development of ESCC. Future studies will include high-throughput sequencing to identify molecular changes that may correspond with leukoplakia or dysplastic cells retrieved with the EC. Disclosure All authors have declared no conflicts of interest.

BACKGROUND Randomized controlled trials are the gold standard for comparing safety and effectiveness of surgical interventions. Reporting guidelines are available for conveying the results of such trials. OBJECTIVE To assess adherence to standard reporting guidelines among randomized controlled trials in dermatologic surgery. MATERIALS AND METHODS Systematic review. Data source was randomized controlled trials in the journal Dermatologic Surgery, per PubMed search, 1995 to 2014. Studies were appraised for the number of the 37 CONSORT 2010 Checklist criteria reported in each. Analysis included comparison of reporting across 4 consecutive periods. RESULTS Three hundred sixty-three studies were eligible. The mean number of items reported per study increased monotonically from 14.5 in 1995 to 1999 to 16.2 in 2002 to 2004, 17.7 in 2005 to 2009, and 18.0 in 2010 to 2014 (p < .0001). A limitation was that study procedures may have been performed without being reported. CONCLUSION Completeness of reporting in randomized controlled trials in dermatologic surgery has improved significantly during the preceding 2 decades. Some elements are still reported at lower rates.

Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers. In the current work, we discuss how the secondary mechanisms of action associated with these drugs mediate their oncolytic effect. In particular, sertraline limits tumor growth by abrogating the PI3K/akt signaling pathway, a growth pathway shown to be constitutively active in multiple cancers. Fluoxetine has been shown to activate the AMPA-type glutamate receptor, induce massive calcium influx and mitochondrial calcium overload and induce caspase-9-dependent apoptosis. This receptor being highly overexpressed in cancer stem cells may explain why SSRIs lower the risk of multiple types of cancer. Fluoxetine has also been shown to inhibit multidrug resistance pumps, increasing the efficacy of several standard chemotherapies. Given the vast potential of SSRIs in treating cancer, these drugs should be more heavily used not only in treating cancer-related depression, but in combating cancer and increasing the efficacy of standard of care chemotherapies.

A 77-year-old white male presented to the clinic with two isolated cutaneous tumors on his forehead. A cutaneous biopsy showed a focally folliculotropic CD4 cutaneous lymphoma. The tumors were irradiated with a complete response, and he was started on oral bexarotene. He experienced localized cutaneous relapse 3 months into treatment. These new tumors now revealed a surprisingly CD8 cytotoxic phenotype, but with the same clone. A systemic workup was negative. His regimen was switched to romidepsin, and he was treated with local radiation again. Another 3.5 months passed in remission until he developed widespread cutaneous tumors. Positron emission tomography/computed tomography revealed multifocal systemic disease involving his diaphragm, liver, distal duodenum, proximal jejunum, anterior chest wall including pectoral muscles, and lungs without significant adenopathy. He died a few days later. Given his full clinical and pathological course, he was given the diagnosis of an aggressive primary cutaneous T-cell lymphoma, unspecified.