HIV enteropathy and 'Slim disease': Historical and current perspectives.

OBJECTIVES: Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. METHODS: Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings 'HIVE', 'SD', and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. RESULTS: Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. CONCLUSION: Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies.

Re-examining single-moment-in-time high-stakes examinations in specialist training: A critical narrative review.

In this critical narrative review, we challenge the belief that single-moment-in-time high-stakes examinations (SMITHSEx) are an essential component of contemporary specialist training. We explore the arguments both for and against SMITHSEx, examine potential alternatives, and discuss the barriers to change.SMITHSEx are viewed as the "gold standard" assessment of competence but focus excessively on knowledge assessment rather than capturing essential competencies required for safe and competent workplace performance. Contrary to popular belief, regulatory bodies do not mandate SMITHSEx in specialist training. Though acting as significant drivers of learning and professional identity formation, these attributes are not exclusive to SMITHSEx.Skills such as crisis management, procedural skills, professionalism, communication, collaboration, lifelong learning, reflection on practice, and judgement are often overlooked by SMITHSEx. Their inherent design raises questions about the validity and objectivity of SMITHSEx as a measure of workplace competence. They have a detrimental impact on trainee well-being, contributing to burnout and differential attainment.Alternatives to SMITHSEx include continuous low-stakes assessments throughout training, ongoing evaluation of competence in the workplace, and competency-based medical education (CBME) concepts. These aim to provide a more comprehensive and context-specific assessment of trainees' competence while also improving trainee welfare.Specialist training colleges should evolve from exam providers to holistic education sources. Assessments should emphasise essential practical knowledge over trivia, align with clinical practice, aid learning, and be part of a diverse toolkit. Eliminating SMITHSEx from specialist training will foster a competency-based approach, benefiting future medical professionals' well-being and success.

Variation in Experiences and Attainment in Surgery Between Ethnicities of UK Medical Students and Doctors (ATTAIN): Protocol for a Cross-Sectional Study.

BACKGROUND: The unequal distribution of academic and professional outcomes between different minority groups is a pervasive issue in many fields, including surgery. The implications of differential attainment remain significant, not only for the individuals affected but also for the wider health care system. An inclusive health care system is crucial in meeting the needs of an increasingly diverse patient population, thereby leading to better outcomes. One barrier to diversifying the workforce is the differential attainment in educational outcomes between Black and Minority Ethnic (BME) and White medical students and doctors in the United Kingdom. BME trainees are known to have lower performance rates in medical examinations, including undergraduate and postgraduate exams, Annual Review of Competence Progression, as well as training and consultant job applications. Studies have shown that BME candidates have a higher likelihood of failing both parts of the Membership of the Royal Colleges of Surgeons exams and are 10% less likely to be considered suitable for core surgical training. Several contributing factors have been identified; however, there has been limited evidence investigating surgical training experiences and their relationship to differential attainment. To understand the nature of differential attainment in surgery and to develop effective strategies to address it, it is essential to examine the underlying causes and contributing factors. The Variation in Experiences and Attainment in Surgery Between Ethnicities of UK Medical Students and Doctors (ATTAIN) study aims to describe and compare the factors and outcomes of attainment between different ethnicities of doctors and medical students. OBJECTIVE: The primary aim will be to compare the effect of experiences and perceptions of surgical education of students and doctors of different ethnicities. METHODS: This protocol describes a nationwide cross-sectional study of medical students and nonconsultant grade doctors in the United Kingdom. Participants will complete a web-based questionnaire collecting data on experiences and perceptions of surgical placements as well as self-reported academic attainment data. A comprehensive data collection strategy will be used to collect a representative sample of the population. A set of surrogate markers relevant to surgical training will be used to establish a primary outcome to determine variations in attainment. Regression analyses will be used to identify potential causes for the variation in attainment. RESULTS: Data collected between February 2022 and September 2022 yielded 1603 respondents. Data analysis is yet to be competed. The protocol was approved by the University College London Research Ethics Committee on September 16, 2021 (ethics approval reference 19071/004). The findings will be disseminated through peer-reviewed publications and conference presentations. CONCLUSIONS: Drawing upon the conclusions of this study, we aim to make recommendations on educational policy reforms. Additionally, the creation of a large, comprehensive data set can be used for further research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40545.

No protective benefits of low dose acute L-glutamine supplementation on small intestinal permeability, epithelial injury and bacterial translocation biomarkers in response to subclinical exertional-heat stress: A randomized cross-over trial.

Exertional heat stress disrupts gastrointestinal permeability and, through subsequent bacterial translocation, can result in potentially fatal exertional heat stroke. Glutamine supplementation is a potential countermeasure although previously validated doses are not universally well tolerated. Ten males completed two 80-minute subclinical exertional heat stress tests (EHSTs) following either glutamine (0.3 g kg FFM-1) or placebo supplementation. Small intestinal permeability was assessed using the lactulose/rhamnose dual sugar absorption test and small intestinal epithelial injury using Intestinal Fatty-Acid Binding Protein (I-FABP). Bacterial translocation was assessed using the total 16S bacterial DNA and Bacteroides/total 16S DNA ratio. The glutamine bolus was well tolerated, with no participants reporting symptoms of gastrointestinal intolerance. Small intestinal permeability was not influenced by glutamine supplementation (p = 0.06) although a medium effect size favoring the placebo trial was observed (d = 0.73). Both small intestinal epithelial injury (p < 0.01) and Bacteroides/total 16S DNA (p = 0.04) increased following exertional heat stress, but were uninfluenced by glutamine supplementation. Low-dose acute oral glutamine supplementation does not protect gastrointestinal injury, permeability, or bacterial translocation in response to subclinical exertional heat stress.

Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya.

Background: Environmental Enteric Dysfunction (EED) is a chronic intestinal inflammatory disorder of unclear aetiology prevalent amongst children in low-income settings and associated with stunting. We aimed to characterise development of EED and its putative risk factors amongst rural Kenyan infants. Methods: In a birth cohort study in Junju, rural coastal Kenya, between August 2015 and January 2017, 100 infants were each followed for nine months. Breastfeeding status was recorded weekly and anthropometry monthly. Acute illnesses and antibiotics were captured by active and passive surveillance. Intestinal function and small intestinal bacterial overgrowth (SIBO) were assessed by monthly urinary lactulose mannitol (LM) and breath hydrogen tests. Faecal alpha-1-antitrypsin, myeloperoxidase and neopterin were measured as EED biomarkers, and microbiota composition assessed by 16S sequencing. Findings: Twenty nine of the 88 participants (33%) that underwent length measurement at nine months of age were stunted (length-for-age Z score <-2). During the rainy season, linear growth was slower and LM ratio was higher. In multivariable models, LM ratio, myeloperoxidase and neopterin increased after cessation of continuous-since-birth exclusive breastfeeding. For LM ratio this only occurred during the rainy season. EED markers were not associated with antibiotics, acute illnesses, SIBO, or gut microbiota diversity. Microbiota diversified with age and was not strongly associated with complementary food introduction or linear growth impairment. Interpretation: Our data suggest that intensified promotion of uninterrupted exclusive breastfeeding amongst infants under six months during the rainy season, where rainfall is seasonal, may help prevent EED. Our findings also suggest that therapeutic strategies directed towards SIBO are unlikely to impact on EED in this setting. However, further development of non-invasive diagnostic methods for SIBO is required. Funding: This research was funded in part by the Wellcome Trust (Research Training Fellowship to RJC (103376/Z/13/Z)). EPKP was supported by the MRC/DfID Newton Fund (MR/N006259/1). JAB was supported by the MRC/DFiD/Wellcome Trust Joint Global Health Trials scheme (MR/M007367/1) and the Bill & Melinda Gates Foundation (OPP1131320). HHU was supported by the NIHR Oxford Biomedical Research Centre (IS-BRC-1215-20008).

Acute L-glutamine supplementation does not improve gastrointestinal permeability, injury or microbial translocation in response to exhaustive high intensity exertional-heat stress.

Purpose: Exertional-heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), can result in potentially fatal exertional-heat stroke. Acute glutamine (GLN) supplementation is a potential nutritional countermeasure, although the practical value of current supplementation regimens is questionable.Method: Ten males completed two high-intensity exertional-heat stress tests (EHST) involving running in the heat (40°C and 40% relative humidity) at lactate threshold to volitional exhaustion. Participants ingested GLN (0.3 g kg FFM-1) or a non-calorific placebo (PLA) one hour prior to the EHST. Venous blood was drawn pre-, post- and one-hour post-EHST. GI permeability was assessed using a serum dual-sugar absorption test (DSAT) and small intestinal epithelial injury using plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using the Bacteroides/total 16S DNA ratio.Results: Volitional exhaustion occurred after 22:19 ± 2:22 (minutes: seconds) in both conditions, during which whole-body physiological responses and GI symptoms were not different (p > 0.05). GI permeability (serum DSAT) was greater following GLN (0.043 ± 0.020) than PLA (0.034 ± 0.019) (p = 0.02; d = 0.47), but small intestine epithelial injury (I-FABP) increased comparably (p = 0.22; ηp2 = 0.16) following the EHST in both trials (GLN Δ = 1.25 ± 0.63 ng ml-1; PLA Δ = 0.92 ± 0.44 ng ml-1). GI MT (Bacteroides/total 16S DNA ratio) was unchanged in either condition following the EHST (p = 0.43).Conclusion: Acute low-dose (0.3 g kg-1 fat free mass) GLN supplementation ingested one hour before high-intesity exertional-heat stress worsened GI permeability, but did not influence either small intestinal epithilial injury or microbial translocation.Abbreviations: ANOVA: Analysis of variance; CV: Coefficient of Variation; DSAT: Dual Sugar Absorption Test; EDTA: Ethylenediaminetetraacetic acid; EHST: Exertional Heat Stress Test; ELISA: Enzyme Linked Immunosorbent Assay; FFM: Fat Free Mass; GI: Gastrointestinal; GFR: Glomerular Filtration Rate; GLN: Glutamine; HPLC: High Performance Liquid Chromatography; HR: Heart Rate; I-FABP: Intestinal Fatty-Acid Binding Protein; ISAK: International Society for the Advancement of Anthropometric Kinanthropometry; L/R: Lactulose-to-Rhamnose; LT: Lactate Threshold; MT: Microbial Translocation; mVAS: Modified Visual Analogue Scale; PBS: Phosphate-Buffered Saline; PLA: Placebo; qPCR: Quantitative Polymerase Chain Reaction; RH: Relative Humidity; RPE: Rate of Perceived Exertion; SD: Standard Deviation; SEM: Sensor Electronics Module; Tcore: Core Body Temperature; Tbody: Mean Body Temperature; Tskin: Mean Skin Temperature; TS: Thermal Sensation; V̇O2max: Maximal Oxygen Uptake.Highlights The pathophysiology of exertional-heat stroke is widely hypothesised to be at least in part attributable to a systemic inflammatory response caused by the leak of gastrointestinal microbes into the circulating blood.Acute high-dose (0.9 g kg FFM-1) L-glutamine supplementation is widely promoted as a practical strategy to protect gastrointestinal barrier integrity during exertional-heat stress. However, previously validated doses are often poorly tolerated and cannot be recommended for widespread implementation.This study examined the efficacy of low-dose (0.30 g kg FFM-1; ∼20 grams) acute L-glutamine supplementation on small intestinal injury, permeability, and microbial translocation in response a high-intensity exertional-heat stress test to exhaustion (20-30 min). This type of exercise accounts for the majority of exertional-heat stroke cases in the military.Despite being universally well-tolerated across all participants, acute low-dose L-glutamine supplementation worsened gastrointestinal permeability, without influencing either small intestinal injury or microbial translocation. These findings do not support the application of low-dose L-glutamine supplementation to help prevent exertional-heat stroke.

F1-taught orthopaedic teaching programme for students (FOTS).

INTRODUCTION: The COVID-19 pandemic has impacted students learning, with the time off resulting in students 'de-skilling', increasing concerns for upcoming observed structured clinical examinations. Foundation Year 1 (F1) doctors (F1s), despite being expected to teach, rarely receive formal preparation, with COVID-19 exacerbating opportunities to practice. As such, a national orthopaedic teaching programme was designed to provide F1s with opportunities to develop their teaching skills and to synergistically teach medical students how to perform clinical orthopaedic examinations. METHODS: Six weekly sessions, each delivered by two newly qualified F1 tutors, on each joint examination were delivered online via Zoom Video Communications (USA). Presession and postsession multiple choice questions (MCQs) were provided to students to assess improvement in knowledge. Anonymous feedback forms were provided to both students and tutors. RESULTS: Of the 341 students that attended, 87.1% provided feedback. 86.2% felt that they had de-skilled due to time off, with a mean 15 weeks off from placement. Based on a 5-point Likert scale, students displayed a mean improvement in confidence (1.9±1.1, p<0.001) and MCQ scores (1.4±1.3, p<0.001) before and after the sessions. 91.6% and 95.3% agreed that the use of online teaching increased attendance and laid the foundation for practice. Of the six tutors, all reported improvement in confidence to teach and teaching skills. CONCLUSION: We demonstrate that online delivery of clinical orthopaedic examinations is effective, increasing the knowledge and confidence of students, while providing opportunities for F1s to teach. We present our findings to encourage similar teaching programmes to be adopted at other locations and specialties, to synergistically benefit students, doctors and ultimately, patients.

Analysis of muscle tissue in vivo using fiber-optic autofluorescence and diffuse reflectance spectroscopy.

SIGNIFICANCE: Current methods for analyzing pathological muscle tissue are time consuming and rarely quantitative, and they involve invasive biopsies. Faster and less invasive diagnosis of muscle disease may be achievable using marker-free in vivo optical sensing methods. AIM: It was speculated that changes in the biochemical composition and structure of muscle associated with pathology could be measured quantitatively using visible wavelength optical spectroscopy techniques enabling automated classification. APPROACH: A fiber-optic autofluorescence (AF) and diffuse reflectance (DR) spectroscopy device was manufactured. The device and data processing techniques based on principal component analysis were validated using in situ measurements on healthy skeletal and cardiac muscle. These methods were then applied to two mouse models of genetic muscle disease: a type 1 neurofibromatosis (NF1) limb-mesenchyme knockout (Nf1Prx1 - / - ) and a muscular dystrophy mouse (mdx). RESULTS: Healthy skeletal and cardiac muscle specimens were separable using AF and DR with receiver operator curve areas (ROC-AUC) of >0.79. AF and DR analyses showed optically separable changes in Nf1Prx1 - / - quadriceps muscle (ROC-AUC >0.97) with no differences detected in the heart (ROC-AUC <0.67), which does not undergo gene deletion in this model. Changes in AF spectra in mdx muscle were seen between the 3 week and 10 week time points (ROC-AUC = 0.96) and were not seen in the wild-type controls (ROC-AUC = 0.58). CONCLUSION: These findings support the utility of in vivo fiber-optic AF and DR spectroscopy for the assessment of muscle tissue. This report highlights that there is considerable scope to develop this marker-free optical technology for preclinical muscle research and for diagnostic assessment of clinical myopathies and dystrophies.

Golden Vaterite as a Mesoscopic Metamaterial for Biophotonic Applications.

Mesoscopic photonic systems with tailored optical responses have great potential to open new frontiers in implantable biomedical devices. However, biocompatibility is typically a problem, as engineering of optical properties often calls for using toxic compounds and chemicals, unsuitable for in vivo applications. Here, a unique approach to biofriendly delivery of optical resonances is demonstrated. It is shown that the controllable infusion of gold nanoseeds into polycrystalline sub-micrometer vaterite spherulites gives rise to a variety of electric and magnetic Mie resonances, producing a tuneable mesoscopic optical metamaterial. The 3D reconstruction of the spherulites demonstrates the capability of controllable gold loading with volumetric filling factors exceeding 28%. Owing to the biocompatibility of the constitutive elements, "golden vaterite" paves the way to introduce designer-made Mie resonances to cutting-edge biophotonic applications. This concept is exemplified by showing efficient laser heating of gold-filled vaterite spherulites at red and near-infrared wavelengths, highly desirable in photothermal therapy, and photoacoustic tomography.

Workplace factors associated with mental health of healthcare workers during the COVID-19 pandemic: an international cross-sectional study.

BACKGROUND: The association of workplace factors on mental health of healthcare workers (HCWs) during the COVID-19 pandemic needs to be urgently established. This will enable governments and policy-makers to make evidence-based decisions. This international study reports the association between workplace factors and the mental health of HCWs during the pandemic. METHODS: An international, cross-sectional study was conducted in 41 countries. The primary outcome was depressive symptoms, derived from the validated Patient Health Questionnaire-2 (PHQ-2). Multivariable logistic regression identified factors associated with mental health outcomes. Inter-country differences were also evaluated. RESULTS: A total of 2527 responses were received, from 41 countries, including China (n = 1213; 48.0%), UK (n = 891; 35.3%), and USA (n = 252; 10.0%). Of all participants, 1343 (57.1%) were aged 26 to 40 years, and 2021 (80.0%) were female; 874 (34.6%) were doctors, and 1367 (54.1%) were nurses. Factors associated with an increased likelihood of depressive symptoms were: working in the UK (OR = 3.63; CI = [2.90-4.54]; p < 0.001) and USA (OR = 4.10; CI = [3.03-5.54]), p < 0.001); being female (OR = 1.74; CI = [1.42-2.13]; p < 0.001); being a nurse (OR = 1.64; CI = [1.34-2.01]; p < 0.001); and caring for a COVID-19 positive patient who subsequently died (OR = 1.20; CI = [1.01-1.43]; p = 0.040). Workplace factors associated with depressive symptoms were: redeployment to Intensive Care Unit (ICU) (OR = 1.67; CI = [1.14-2.46]; p = 0.009); redeployment with perceived unsatisfactory training (OR = 1.67; CI = [1.32-2.11]; p < 0.001); not being issued with appropriate personal protective equipment (PPE) (OR = 2.49; CI = [2.03-3.04]; p < 0.001); perceived poor workplace support within area/specialty (OR = 2.49; CI = [2.03-3.04]; p < 0.001); and perceived poor mental health support (OR = 1.63; CI = [1.38-1.92]; p < 0.001). CONCLUSION: This is the first international study, demonstrating that workplace factors, including PPE availability, staff training pre-redeployment, and provision of mental health support, are significantly associated with mental health during COVID-19. Governments, policy-makers and other stakeholders need to ensure provision of these to safeguard HCWs' mental health, for future waves and other pandemics.

#OrthoTwitter: social media as an educational tool.

Aims: The increased use of social media creates opportunity for new, effective methods of delivering medical and clinical education. Twitter is a popular social media platform where users can post frequent updates and create threads containing related content using hashtags. This study aims to investigate and analyse the type of content relating to orthopaedic surgery that is being posted on the platform of Twitter. Methods: A retrospective search was performed for tweets containing the words 'orthopaedic surgery' or 'orthopedic surgery' or the use of the hashtag '#OrthoTwitter' between November 2018 to November 2019. A total of 5243 tweets were included. Results: Tweets containing 'orthopaedic surgery' or 'orthopedic surgery' most frequently contained promotional or marketing content (30% promotional, 21% marketing), and private organisations were the category of author to which the greatest number of tweets belonged (30%). Tweets containing educational or research content were the least common among all tweets containing 'orthopaedic surgery' or 'orthopedic surgery' (11%). In contrast, of the tweets containing the hashtag '#OrthoTwitter', 44% contained educational or research content, 15% contained promotional content and no tweets containing marketing content. Furthermore, 87% of all tweets using the hashtag '#OrthoTwitter' were from orthopaedic surgeons, and the least number of tweets were from private organisations (2%). Conclusion: Twitter is a widely used social media platform regarding orthopaedic surgery. We propose that the hashtag '#OrthoTwitter' can be used to create an online community of orthopaedic surgeons where members can assist one another through sharing reliable and educational content.

Thermally drawn biodegradable fibers with tailored topography for biomedical applications.

There is a growing demand for polymer fiber scaffolds for biomedical applications and tissue engineering. Biodegradable polymers such as polycaprolactone have attracted particular attention due to their applicability to tissue engineering and optical neural interfacing. Here we report on a scalable and inexpensive fiber fabrication technique, which enables the drawing of PCL fibers in a single process without the use of auxiliary cladding. We demonstrate the possibility of drawing PCL fibers of different geometries and cross-sections, including solid-core, hollow-core, and grooved fibers. The solid-core fibers of different geometries are shown to support cell growth, through successful MCF-7 breast cancer cell attachment and proliferation. We also show that the hollow-core fibers exhibit a relatively stable optical propagation loss after submersion into a biological fluid for up to 21 days with potential to be used as waveguides in optical neural interfacing. The capacity to tailor the surface morphology of biodegradable PCL fibers and their non-cytotoxicity make the proposed approach an attractive platform for biomedical applications and tissue engineering.

Fostering excellence in medical education career pathways.

High quality medical education requires committed and skilled educators, researchers, and leaders. Capacity building for future educationalists is fundamental in the pursuit of excellence in medical education. Medical education as a discipline is undervalued, underfunded, and often badmouthed. In order to pave the way to excellence, we must lay down the correct career pathways and foster a supportive climate in our speciality. In order to attract and support tomorrow's educationalists we argue that we need to champion the field, develop integrated clinical and educational training programmes, and promote role modelling and mentorship.