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The relative effect of parasite levels, bee population size, and food reserves on winter mortality and post winter populations of honey bee colonies was estimated. More than 400 colonies were monitored throughout three seasons in Ontario, Canada. Most of the colonies were infested with varroa mites during the fall (75.7%), but only 27.9% and 6.1% tested positive to nosema disease and tracheal mites, respectively. Winter colony mortality was 27.2%, and when examined as a fraction of all morbidity factors, fall varroa mite infestations were the leading cause of colony mortality (associated to > 85% of colony deaths), followed by fall bee populations and food reserves. Varroa-infested colonies, with weak populations and low food reserves in the fall, significantly decreased spring colony populations, whereas varroa infestations and Nosema infections in the spring, significantly decreased bee populations by early summer. Overall, results suggest that varroa mites could be the main culprit for the death and reduced populations of overwintered honey bee colonies in northern climates. [ABSTRACT FROM AUTHOR]

Abstract While traditional techniques have long allowed forensic investigators to positively identify fingermarks on documents of interest, understanding the chronological sequence of events that led to their deposition is still seen as a ‘holy grail’ for forensic examinations. By way of example, the question of whether a mark is above or below printed text is crucial. The work herein reveals that a novel application of a recently established fingermark development technique readily allows such differentiation. The process in question allies forensic gelatin lifters with RECOVER, a development system that hinges on the polymerisation of disulfur dinitride. While the latter was specifically developed in its current form for the retrieval of prints from metal surfaces exposed to extreme conditions or washing, its ability to target surface effects allows for visualisation of surface interactions on forensic gelatin lifts. Crucially, in doing so the order in which the lifted material was originally deposited is also revealed. This, therefore, permits clear elucidation of the order of deposition of printed text and fingermarks—and does so both rapidly and in a non-invasive way. This long sought-after capability has the potential to revolutionise forensic document examinations.

The identification and recovery of suspected human biofluid evidence can present a bottleneck in the crime scene investigation workflow. Crime Scene Investigators typically deploy one of a number of presumptive enhancement reagents, depending on what they perceive an analyte to be; the selection of this reagent is largely based on the context of suspected evidence and their professional experience. Positively identified samples are then recovered to a forensic laboratory where confirmatory testing is carried out by large lab-based instruments, such as through mass-spectrometry-based techniques. This work proposes a proof-of-concept study into the use of a small, robust and portable ion mobility spectrometry device that can analyse samples in situ, detecting, identifying and discriminating commonly encountered body fluids from interferences. This analysis exploits the detection and identification of characteristic volatile organic compounds generated by gentle heating, at ambient temperature and pressure, and categorises samples using machine learning, providing investigators with instant identification. The device is shown to be capable of producing characteristic mobility spectra using a dual micro disc pump configuration which separates blood and urine from three visually similar interferences using an unsupervised PCA model with no misclassified samples. The device has the potential to reduce the need for potentially contaminating and destructive presumptive tests, and address the bottleneck created by the time-consuming and laborious detection, recovery and analysis workflow currently employed.

Abstract Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in pancreatic ductal adenocarcinoma (PDAC). We undertook a systematic review and meta‐analysis of immune cell infiltration, measured by immunohistochemistry (IHC), as a prognostic biomarker in PDAC. All other IHC prognostic biomarkers in PDAC were also summarised. MEDLINE, EMBASE and Web of Science were searched between 1998 and 2018. Studies investigating IHC biomarkers and prognosis in PDAC were included. REMARK score and Newcastle–Ottawa scale were used for qualitative analysis. Random‐effects meta‐analyses were used to pool results, where possible. Twenty‐six articles studied immune cell infiltration IHC biomarkers and PDAC prognosis. Meta‐analysis found high infiltration with CD4 (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.51–0.83.) and CD8 (HR = 0.68, 95% CI = 0.55–0.84.) T‐lymphocytes associated with better disease‐free survival. Reduced overall survival was associated with high CD163 (HR = 1.62, 95% CI = 1.03–2.56). Infiltration of CD3, CD20, FoxP3 and CD68 cells, and PD‐L1 expression was not prognostic. In total, 708 prognostic biomarkers were identified in 1101 studies. In summary, high CD4 and CD8 infiltration are associated with better disease‐free survival in PDAC. Increased CD163 is adversely prognostic. Despite the publication of 708 IHC prognostic biomarkers in PDAC, none has been validated for clinical use. Further research should focus on reproducibility of prognostic biomarkers in PDAC in order to achieve this.

Background: Radium-223 and enzalutamide are approved agents for patients with metastatic castration-resistant prostate cancer (mCRPC). Combining radium-223 and enzalutamide to improve outcomes is of clinical interest due to their differing modes of action and non-overlapping toxicity profiles. Methods: This phase II study enrolled patients with mCRPC and bone metastases. Patients received six cycles of radium-223 in combination with enzalutamide, followed by enzalutamide alone. The primary endpoint was safety for the combination; secondary endpoints included radiographic/clinical progression-free survival (PFS), PSA PFS, overall survival (OS), change in alkaline phosphatase, patient-reported pain outcomes and skeletal related events. Results: Forty-five patients received the combination treatment: 42 patients (93.3%) received all six cycles. Fourteen patients (31.1%) developed grade 3 or 4 toxicities, most commonly fatigue and neutropaenia. Fractures during the combination period occurred in four patients (8.9%). A further 13 patients (28.9%) developed fractures after completing combination treatment, giving a total of 17 patients (37.8%) who developed a fracture at any time on study. The median time to fracture was greater than 17.2 months [95% confidence interval (CI), 17.2–not estimable]. The median time to PSA progression was 18.1 months (95% CI, 12.68–22.60) and the median time to radiological/clinical progression was 28.0 months (95% CI, 22.54–not reached). At the primary analysis, 19 (42.2%) out of 45 patients had died with a median OS not reached (mean 34.8 months, standard error 1.4). Conclusion: In men with progressive mCRPC and bone metastases, the combination of radium-223 and enzalutamide was tolerable with the majority of patients completing the combination treatment. Bone fractures during the combination period were uncommon; however, we did identify a higher incidence of fractures occurring in patients after completing combination treatment. Bone health agents should be administered and bone health should be closely monitored following treatment with radium-223 and enzalutamide.

Alternatives to the antibiotic fumagillin for the control of Nosema ceranae, a gut parasite of the honey bee, are needed. The prebiotics eugenol, chitosan, and naringenin and the probiotic Protexin® (Enterococcus faecium) provided in sugar syrup or protein patty either in spring or fall were evaluated for their effects on N. ceranae infection, colony population, honey yield and winter survivorship using field colonies. In the first year, spring treatments with eugenol, naringenin, and Protexin® significantly reduced N. ceranae infection and increased honey production, while Protexin® also increased adult bee populations and chitosan was ineffective. Fall treatments increased survivorship and decreased N. ceranae infection the following spring. In the second year, selected compounds were further tested with a larger number of colonies per treatment and only protein patty used in the spring and sugar syrup in the fall. Protexin® and naringenin significantly decreased N. ceranae infections and increased the population of adult bees after spring treatment, but did not affect honey yields. There were no differences between treatments for colony winter mortality, but surviving colonies that had been treated with Protexin® and naringenin were significantly more populated and had lower N. ceranae spore counts than control, non-treated colonies. Protexin® and naringenin were the most promising candidates for controlling N. ceranae and promoting honey bee populations, warranting further investigation. Future research should investigate the optimal colony dose and treatment frequency to maximize colony health.

BACKGROUND:System science approaches are increasingly used to explore complex public health problems. Quantitative methods, such as participatory dynamic simulation modelling, can mobilise knowledge to inform health policy decisions. However, the analytic and practical steps required to turn collaboratively developed, qualitative system maps into rigorous and policy-relevant quantified dynamic simulation models are not well described. This paper reports on the processes, interactions and decisions that occurred at the interface between modellers and end-user participants in an applied health sector case study focusing on diabetes in pregnancy. METHODS:An analysis was conducted using qualitative data from a participatory dynamic simulation modelling case study in an Australian health policy setting. Recordings of participatory model development workshops and subsequent meetings were analysed and triangulated with field notes and other written records of discussions and decisions. Case study vignettes were collated to illustrate the deliberations and decisions made throughout the model development process. RESULTS:The key analytic objectives and decision-making processes included: defining the model scope; analysing and refining the model structure to maximise local relevance and utility; reviewing and incorporating evidence to inform model parameters and assumptions; focusing the model on priority policy questions; communicating results and applying the models to policy processes. These stages did not occur sequentially; the model development was cyclical and iterative with decisions being re-visited and refined throughout the process. Storytelling was an effective strategy to both communicate and resolve concerns about the model logic and structure, and to communicate the outputs of the model to a broader audience. CONCLUSION:The in-depth analysis reported here examined the application of participatory modelling methods to move beyond qualitative conceptual mapping to the development of a rigorously quantified and policy relevant, complex dynamic simulation model. The analytic objectives and decision-making themes identified provide guidance for interpreting, understanding and reporting future participatory modelling projects and methods.

After two years of bidirectional selection for low and high rates of Varroa destructor population growth (LVG and HVG, respectively) in honey bee (Apis mellifera) colonies in Ontario, Canada, significant differences between the two genotypes were observed. LVG colonies had V. destructor population increases over the summer of 1.7 fold compared to 9.6 fold for HVG colonies by Generation 2. Additionally, HVG colonies had significantly higher mite infestation rates in adult bees compared to LVG colonies for both selected generations. DWV prevalence and levels were significantly higher in HVG colonies than in LVG colonies in Generation 1 but not in Generation 2. Winter mortality rates of Generation 1 colonies were significantly different at 26% and 14% for the HVG and LVG genotypes, respectively. The results of this study thus far indicate that selection for LVG may result in colonies with lower V. destructor infestation rates, lower prevalence, and levels of DWV and higher colony winter survivorship. Future work will focus on determining what mechanisms are responsible for the genotypic differences, estimating genetic parameters, and molecular analyses of the genotypes to identify candidate genes associated with resistance to V. destructor and DWV that could potentially be used for marker-assisted selection.

Nosema ceranae is an emerging pathogen of the western honey bee (Apis mellifera L.), and thus its seasonality and impact on bee colonies is not sufficiently documented for North America. This study was conducted to determine the infection intensity, prevalence, and viability of N. ceranae in >200 honey bee colonies during spring, summer, and fall, in a North American region. We also determined the relationship of N. ceranae infections with colony populations, food stores, bee survivorship, and overwinter colony mortality. The highest rates of N. ceranae infection, prevalence, and spore viability were found in the spring and summer, while the lowest were recorded in the fall. N. ceranae spore viability was significantly correlated with its prevalence and infection intensity in bees. Threshold to high levels of N. ceranae infections (>1,000,000 spores/bee) were significantly associated with reduced bee populations and food stores in colonies. Furthermore, worker bee survivorship was significantly reduced by N. ceranae infections, although no association between N. ceranae and winter colony mortality was found. It is concluded that N. ceranae infections are highest in spring and summer and may be detrimental to honey bee populations and colony productivity. Our results support the notion that treatment is justified when infections of N. ceranae exceed 1,000,000 spores/bee.

BackgroundTuberculosis (TB) is a major public health problem in developing countries. Following the disruption to health services in East Timor due to violent political conflict in 1999, the National Tuberculosis Control Program was established, with a local non-government organisation as the lead agency. Within a few months, the TB program was operational in all districts.Methods and findingsUsing the East Timor TB program as a case study, we have examined the enabling factors for the implementation of this type of communicable disease control program in a post-conflict setting. Stakeholder analysis was undertaken, and semi-structured interviews were conducted in 2003 with 24 key local and international stakeholders. Coordination, cooperation, and collaboration were identified as major contributors to the success of the TB program. The existing local structure and experience of the local non-government organisation, the commitment among local personnel and international advisors to establishing an effective program, and the willingness of international advisers and local counterparts to be flexible in their approach were also important factors. This success was achieved despite major impediments, including mass population displacement, lack of infrastructure, and the competing interests of organisations working in the health sector.ConclusionsFive years after the conflict, the TB program continues to operate in all districts with high notification rates, although the lack of a feeling of ownership by government health workers remains a challenge. Lessons learned in East Timor may be applicable to other post-conflict settings where TB is highly prevalent, and may have relevance to other disease control programs.

Assessing the digestive and absorptive capacity of the gastro-intestinal tract (GIT) using minimally- or non-invasive methods, particularly in children, has been difficult owing to the complex physiology and variability in functional measurements. However, measuring GIT function is increasingly important with the emerging relevance of childhood environmental enteropathy (EE) as a mediating factor in linear growth faltering, severe acute malnutrition, poor oral vaccine uptake and impaired cognition. In EE, sub-optimal nutrient digestion and absorption (malabsorption) forms the critical link to the conditions mentioned above. The present narrative review discusses probable mechanisms that can cause malabsorption of macronutrients, along with mechanistic and experimental evidence, in children (if not, in adults) with EE. The strengths and limitations of the human experimental studies are examined in relation to a battery of existing and potential tests that are used to measure malabsorption. From the available studies conducted in children, lactose and fat malabsorption are more likely to occur in EE. Breath tests (non-invasive) measuring carbohydrate ( 13 C-starch/sucrose/lactose), fat ( 13 C-mixed triglyceride) and dipeptide (benzoyl-L-tyrosyl-L-1- 13 C-alanine) malabsorption with modifications to the existing protocols seem suitable for use in children with EE. Future research should focus on understanding the degree of macronutrient malabsorption using these tests, in different settings, and link them to functional outcomes (such as growth, muscle strength, cognition)., (© 2024. The Author(s).)

Background: Environmental enteropathy' (EE) is common among children who are highly exposed to enteric pathogens in low-resource settings. We optimised and validated a stable isotope-based breath test of intestinal sucrase activity ( 13 C-SBT) as a non-invasive test of carbohydrate digestion and metabolism., Objectives: The primary objective of this study was to assess the relationship between the 13 C-SBT and the lactulose/rhamnose ratio (LR) and growth in children. Secondary objectives were to assess the relationship between the 13 C-SBT and additional biomarkers of EE. We also characterised the relationship between the 13 C-SBT and child sex anddietary diversity, and household socioeconomic status and food security., Methods: In this cross-sectional study, 12-to-15-month-old children were recruited in Bangladesh, India, Kenya, and Peru. Children were assessed with a 4-hour 13 C-SBT and a 90-minute LR test. Plasma was collected for the determination of citrulline and the kynurenine/tryptophan ratio. Length and weight were measured, and other variables were assessed through questionnaires. For a subset of children, anthropometry was re-measured after three months. inear regression was used to examine associations corresponding to each objective., Results: Three sites generated 13 C-SBT breath curves that enabled pooled analysis. Differences in 13 C-SBT breath curves, LR ratios, and other EE biomarkers were observed between sites. No associations were observed for 13 C-SBT summary measures and LR, or child growth (e.g., association between LR and cumulative percent dose recovered at 90 minutes (cPDR90): -0.39, 95%CI: -1.79, 0.70). Length-for-age and weight-for-age were positively associated with the time to 50% of dose recovered (T 50 ) (0.05, 95%CI: 0.01, 0.09, and 0.05, 95%CI: 0.02, 0.07, respectively), and dietary diversity was associated with T 50 and cPDR90(-0.10, 95%CI: -0.18, -0.02 and 2.67, 95%CI: 0.47, 4.88, respectively)., Conclusions: In children at risk of EE there were no associations between the 13 C-SBT, LR or other EE biomarkers encompassing different pathophysiological domains of EE., Trial Registry: https://clinicaltrials.gov/study/NCT04109352., Competing Interests: Declaration of Competing Interest. The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Author Owino is employed by the funding organization., (Copyright © 2024. Published by Elsevier Inc.)

Chinese hamster ovary (CHO) cells are used to produce almost 90% of therapeutic monoclonal antibodies (mAbs) and antibody fusion proteins (Fc-fusion). The annotation of non-canonical translation events in these cellular factories remains incomplete, limiting our ability to study CHO cell biology and detect host cell protein (HCP) impurities in the final antibody drug product. We utilised ribosome footprint profiling (Ribo-seq) to identify novel open reading frames (ORFs) including N-terminal extensions and thousands of short ORFs (sORFs) predicted to encode microproteins. Mass spectrometry-based HCP analysis of eight commercial antibody drug products (7 mAbs and 1 Fc-fusion protein) using the extended protein sequence database revealed the presence of microprotein impurities. We present evidence that microprotein abundance varies with growth phase and can be affected by the cell culture environment. In addition, our work provides a vital resource to facilitate future studies of non-canonical translation and the regulation of protein synthesis in CHO cell lines., (© 2024. The Author(s).)

Background: In 2016, large-scale 20 miles per hour speed limits were introduced in the United Kingdom cities of Edinburgh and Belfast. This paper investigates the role that scientific evidence played in the policy decisions to implement lower speed limits in the two cities., Methods: Using a qualitative case study design, we undertook content analysis of a range of documents to explore and describe the evolution of the two schemes and the ways in which evidence informed decision-making. In total, we identified 16 documents for Edinburgh, published between 2006 and 2016, and 19 documents for Belfast, published between 2002 and 2016., Findings: In both cities, evidence on speed, collisions and casualties was important for initiating discussions on large-scale 20 mph policies. However, the narrative shifted over time to the idea that 20 mph would contribute to a wider range of aspirations, none of which were firmly grounded in evidence, but may have helped to neutralize opposing discourses., Discussion and Conclusions: The relationship between evidence and decision-making in Edinburgh and Belfast was neither simple nor linear. Widening of the narrative appears to have helped to frame the idea in such a way that it had broad acceptability, without which there would have been no implementation, and probably a lot more push back from vested interests and communities than there was., (© 2024. The Author(s).)

Background: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease., Objectives: The objective of this study was to determine if fecal enteropathogenic detection predicts subsequent EED histology., Methods: Fecal samples were obtained from undernourished children aged <2 y without diarrhea enrolled in 3 cohort studies, who failed nutritional intervention and subsequently underwent endoscopy. Duodenal biopsies from 245 (Bangladesh n = 120, Pakistan n = 57, and Zambia n = 68) children were scored using a semiquantitative histologic grading protocol. Thirteen enteropathogens were sought in common across the 3 centers using TaqMan array cards (TAC) (Bangladesh and Pakistan) and the Luminex platform (Zambia). An additional 18 pathogens and 32 virulence loci were sought by TAC and included in sensitivity analyses restricted to TAC data., Results: Multivariable linear regressions adjusting for study center, age at stool collection, and stool-to-biopsy interval demonstrated the following: 1) an association of norovirus and Shigella detection with subsequent enterocyte injury [β 0.2 (95% CI: 0.1, 0.3); P = 0.002 and β 0.2 (95% CI: 0.0, 0.3); P = 0.008, respectively], 2) association of Campylobacter with intraepithelial lymphocytes [β 0.2 (95% CI: 0.0, 0.4); P = 0.046], and 3) association of Campylobacter and enterotoxigenic Escherichia coli with a summative EED histopathology index score [β 4.2 (95% CI: 0.8, 7.7); P = 0.017 and β 3.9 (95% CI: 0.5, 7.3); P = 0.027, respectively]. All but 2 of these associations (Shigella-enterocyte injury and Campylobacter-index score) were also demonstrated in TAC-only sensitivity analyses, which identified additional associations between other pathogens, pathogen burden, or virulence loci primarily with the same histologic parameters., Conclusions: The detection of some enteropathogens in asymptomatic infections is associated with subsequent EED histopathology. These novel findings offer a basis for future EED etiology and pathogenesis studies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED) is an inflammatory condition of the small intestine that is prevalent in children residing in low- and middle-income countries. EED is accompanied by profound histopathologic changes in the small bowel, loss of absorptive capacity, increased intestinal permeability, increased microbial translocation, and nutrient loss., Objectives: We sought to identify dysregulated genes and pathways that might underlie pediatric EED., Methods: RNA-sequencing libraries were generated from endoscopically obtained duodenal tissue from undernourished children with EED from 3 prospective cohorts of children with EED. The EED transcriptome was defined in comparison to North American children without EED. Weighted gene coexpression network analysis (WGCNA) was tested for gene modules associated with EED and its histologic features., Results: The 1784 upregulated genes in EED were highly enriched for immune and inflammatory processes, including IL-17 and JAK-STAT signaling, and cytokine-cytokine receptor interactions. The 1388 downregulated genes included genes corresponding to xenobiotic metabolism, detoxification, and antioxidant capacities. A gene coexpression module enriched for antimicrobial responses and chemokine activity was significantly associated with villous blunting, goblet cell depletion, and overall histologic severity of EED., Conclusions: The transcriptome signatures of EED include specific innate and adaptive immune responses that are consistently elevated across study centers, coupled with reduced detoxification and antioxidant capacities. These data may have implications for targeted interventions to improve EED outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED) is characterized by reduced absorptive capacity and barrier function of the small intestine, leading to poor ponderal and linear childhood growth., Objectives: To further define gene expression patterns that are associated with EED to uncover new pathophysiology of this disorder., Methods: Duodenal biopsies from cohorts of children with EED from Bangladesh, Pakistan and Zambia were analyzed by immunohistochemistry (IHC) to interrogate gene products that distinguished differentiation and various biochemical pathways in immune and epithelial cells, some identified by prior bulk RNA sequence analyses. Immunohistochemical staining was digitally quantified from scanned images and compared to cohorts of North American children with celiac disease (gluten-sensitive enteropathy) or with no known enteric disease and no pathologic abnormality (NPA) detected in their clinical biopsies., Results: After multivariable statistical analysis, we identified statistically significant (P < 0.05, 2-tailed t-test) elevated signals representing cluster of differentiation 45 (80%; 95% confidence interval [CI]: 24%, 127%), lipocalin 2 (659%; 95% CI: 198%, 1838%), and regenerating family 1 beta (221%; 95% CI: 47%, 600%) and lower signals corresponding to granzyme B (-74%; 95% CI: -82%, -62%), and sucrase isomaltase (-58%; 95% CI: -75%, -29%) in EED biopsies compared with NPA biopsies. Computerized algorithms also detected statistically significant elevation in intraepithelial lymphocytes (49%; 95% CI: 9%, 105%) and proliferation of leukocytes (267%; 95% CI: 92%, 601%) in EED biopsies compared with NPA biopsies., Conclusions: Our results support a model of chronic epithelial stress that decreases epithelial differentiation and absorptive function. The close association of several IHC parameters with manual histologic scoring suggests that automated digital quantification of IHC panels complements traditional histomorphologic assessment in EED., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Environmental enteric dysfunction (EED) is an asymptomatic acquired disorder characterized by upper small bowel inflammation, villus blunting, and gut permeability. It is a major contributor to poor growth in childhood as well as other highly consequential outcomes such as delayed neuorcognitive development. After decades of intermittent interest in this entity, we are now seeing a resurgence in the field of EED. However, recent studies have been hampered by a lack of investigation of the target tissue-the upper small bowel. In 2016, the EEDBI (Environmental Enteric Dysfunction Biopsy Initiative) Consortium was established as a common scientific platform across 3 independent EED biopsy cohort studies in Bangladesh, Pakistan, and Zambia. Two centers in the United States recruited comparison groups of children undergoing endoscopy for clinical indications. The EEDBI Consortium goal was to augment the contributions of the individual centers and answer high-level questions amenable to analysis and interpretation across the studies. Here, we describe the Consortium and its cohorts and recruitment procedures across studies. We also offer details applicable to all papers in this supplement, which describe EED mucosal histology, morphometry, immunohistochemistry, and transcriptomics as well as histology relationship to pathogens and biomarkers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED) is a precursor of growth faltering in children living in impoverished conditions who are frequently exposed to environmental toxins and enteropathogens, leading to small bowel inflammatory, malabsorptive, and permeability derangements and low-grade chronic systemic inflammation., Objectives: We explored the association between anthropometrics and duodenal histologic features of EED among children from 3 lower middle-income country centers., Methods: In this cross-sectional study, Pakistani children (n = 63) with wasting, Bangladesh children (n = 116) with stunting or at risk for stunting (height-for-age Z score [HAZ] <-1 but ≥-2), and Zambian children (n = 108) with wasting or stunting received nutritional intervention. Children with anthropometric status refractory to intervention underwent endoscopy. Linear regression models included anthropometric around endoscopy, scores of histology parameters, and a global index score of EED-the total score percent-5 (TSP-5). Multivariable models were adjusted for center, age, sex, and histology slide quality., Results: Intersite variation was observed while exploring the association between anthropometrics and the TSP-5; for example, Pakistani children had the worst HAZ, yet their median TSP-5 score was lower than that of the other 2 centers. Even within each site, no overall pattern of higher TSP-5 score was observed with worsening HAZ. During univariate analysis, TSP-5 (coefficient: 0.01; 95% confidence interval [CI]: 0, 0.02), goblet cell depletion (coefficient: 0.22; 95% CI: 0.06, 0.37), and Paneth cell depletion (coefficient: 0.14; 95% CI: 0.01, 0.27) were associated with HAZ scores; however, they lost statistical significance in the multivariable models, with study center most strongly confounding the relationships seen in univariate models between anthropometry and histology., Conclusions: This study contributes a crucial negative finding that duodenal morphological features did not associate with anthropometric phenotypes; hence, anthropometric measurements may not be a suitable outcome measure for use in EED trials. Trial outcomes may need to be defined by combining the functional and structural elements of the gut to monitor EED., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Validated biomarkers could catalyze environmental enteric dysfunction (EED) research., Objectives: Leveraging an EED histology scoring system, this multicountry analysis examined biomarker associations with duodenal histology features among children with EED. We also examined differences in 2-h compared with 1-h urine collections in the lactulose rhamnose (LR) dual sugar test., Methods: Three cohorts of undernourished children unresponsive to nutrition intervention underwent esophagogastroduodenoscopy and duodenal biopsies. Histopathology scores were compared to fecal calprotectin (CAL), myeloperoxidase (MPO), neopterin (NEO), and urinary LR ratio and lactulose percentage recovery. Log-transformed biomarkers were used in linear regressions adjusted for age, center, and sample collection-biopsy time interval in multivariable models., Results: Data on >1 biomarker were available for 120 Bangladeshi (CAL, MPO, NEO, and LR), 63 Pakistani (MPO, NEO, and LR), and 63 Zambian children (CAL). Median age at endoscopy was similar (19 mo) across centers. Median sample collection prior to endoscopy was consistent with each center's study design: 2 wk in Bangladesh (urine and stool) and Zambia (stool), and 6 (urine) and 11 (stool) mo in Pakistan. In multivariable models, intraepithelial lymphocytes were associated with CAL (exponentiated [exp.] coefficient: 1.19; 95% confidence interval [CI]: 1, 1.41), intramucosal Brunner's glands with MPO (exp. coefficient: 1.33; 95% CI: 1.05, 1.69) and NEO (exp. coefficient: 1.37; 95% CI: 1.1, 1.7), and chronic inflammation with NEO (exp. coefficient: 1.61; 95% CI: 1.17, 2.17). Intraepithelial lymphocytes were associated with lactulose % recovery (exp. coefficient: 1.22; 95% CI: 1.05, 1.41). LR recovery was substantially lower in 1-h collections than in 2-h collections., Conclusions: Four commonly used markers of enteric dysfunction were associated with specific histologic features. One-hour urine collection may be insufficient to reflect small bowel permeability in LR testing. While acknowledging the challenges with obtaining relevant tissue, these findings form the basis for further EED biomarker validation research., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses., Objectives: We set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia ("EED") with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as "normal") or celiac disease., Methods: Five gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner's glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value., Results: Biopsies from the duodenal bulb showed higher intramucosal Brunner's gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner's glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan., Conclusions: This scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes., Objectives: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology., Methods: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n = 69), and those with no pathologic abnormality (NPA; n = 8) or celiac disease (n = 18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared with NPA or celiac disease and identify associations between morphometry and histology or immunohistochemistry among children with EED., Results: In duodenal biopsies, median EED villus height (248 μm), crypt depth (299 μm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 μm villus height; 246 μm crypt depth; 1.6 V:C ratio) and celiac disease (208 μm villus height; 365 μm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist-determined subjective semiquantitative villus architecture., Conclusions: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides, although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. Although acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Physical activity engagement following a cancer diagnosis is positively associated with survival, reduced risk of disease recurrence, and reduced cancer-specific and all-cause mortality. However, rates of physical activity engagement are low among individuals diagnosed with and being treated for breast cancer or prostate cancer., Objective: The purpose of this study was to describe the systematic process of developing an e-cycling intervention aimed at increasing physical activity among individuals living with prostate cancer or breast cancer and outline the key components to be implemented., Methods: The Medical Research Council guidance for developing complex interventions and the Behaviour Change Wheel were used to guide intervention development. Information was gathered from the literature and through discussions with end users to understand factors influencing e-cycling. These factors were mapped onto the Theoretical Domains Framework to identify potential mechanisms of action. Behavior change techniques were selected from theory and evidence to develop intervention content. Interested parties, including cycling instructors, end users, and behavior change experts, reviewed and refined the intervention., Results: Anticipated barriers and facilitators to e-cycling engagement were mapped onto 11 of the 14 domains of the Theoretical Domains Framework. A total of 23 behavior change techniques were selected to target these domains over 4 one-to-one e-cycling sessions delivered by trained cycling instructors in the community. Cycling instructors were provided a 3-hour classroom training session on delivering the intervention and a 3-hour practical session with feedback. The outcome of this work is a theory and evidence-informed intervention aimed at promoting e-cycling behavior among individuals being treated for breast cancer or prostate cancer, which is currently being implemented and evaluated., Conclusions: Transparent intervention development and reporting of content is important for comprehensively examining intervention implementation. The implementation of this intervention package is currently being evaluated in a pilot randomized controlled trial. If the intervention is found to be effective and the content and delivery are acceptable, this intervention will form a basis for the development of e-cycling interventions in other survivors of cancer., Trial Registration: ISRCTN Registry ISRCTN39112034 https://www.isrctn.com/ISRCTN39112034; and IRSCTN Registry ISRCTN42852156; https://www.isrctn.com/ISRCTN42852156., (©Jessica E Bourne, Paul Kelly, Miranda E G Armstrong. Originally published in JMIR Cancer (https://cancer.jmir.org), 16.08.2024.)

There is a knowledge gap on the epidemiology of inflammatory bowel disease in Africa. To begin to address this issue we formed a case reporting network of practitioners with an interest in inflammatory bowel disease across sub-Saharan Africa. Here we report a series of 175 cases from 12 countries over 2 years., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

A 57-year-old male underwent an open right radical nephrectomy in 2015 for a 3-cm kidney tumor which was classified at the time as a combined tubulocystic and collecting duct carcinoma. One of six nodes was positive for metastatic carcinoma and the patient received adjuvant carboplatin/gemcitabine chemotherapy. In 2020, he developed enlarging retroperitoneal adenopathy and underwent a retroperitoneal lymph node dissection with 11 of 13 nodes in the resected specimen positive for the previously described renal carcinoma, followed by adjuvant radiotherapy. In November 2022, he again underwent surgery for further locoregional recurrence with resection of a right psoas mass lesion and right hemicolectomy. Pathology on this occasion was reclassified as anaplastic lymphoma kinase-rearranged renal cell carcinoma (ALK-RCC). Shortly afterward, a restaging CT revealed multiple liver metastases and evidence of further disease recurrence in the right renal bed. He commenced alectinib with a complete radiological response and has continued on it for 12 months at the time of writing this report. To our knowledge, there are only five prior reports of ALK-RCC treated with targeted ALK inhibitor therapy in the literature. We report this case to highlight the importance of recognizing and diagnosing this rare RCC subtype since it has significant therapeutic implications. Furthermore, to our knowledge, this patient has had the longest follow-up reported to date in the literature so far. A concerted effort by the histopathology and oncology community is needed to gather more data on the incidence and treatment outcomes of these tumors so that progress can be made in optimizing their management. It is important to consider novel and emerging entities from the most recent WHO 2022 classification, many of which are defined by molecular characteristics with associated therapeutic implications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Elhassan et al.)

Leptospirosis is a global health concern, particularly in tropical regions, with clinical symptoms varying from mild fever to severe organ dysfunction. We present a case of a 57-year-old male with septic shock and acute kidney injury due to acute leptospirosis. The patient's rapid progression to shock within a day of generalized symptoms was unusual. The patient's infection ultimately resolved with ceftriaxone and he was discharged after 14 days of therapy. The pathogenesis of severe leptospirosis is believed to be due to vasculitis, with organ damage caused by the leptospira bacteria and immune-mediated mechanisms. Diagnostic investigations include blood cultures and polymerase chain reactions, which are beneficial for early diagnosis. The management of patients depends on the severity of symptoms and other health conditions, as well as antibiotics and hydration. However, leptospirosis can lead to a wide range of complications, including neurological, ocular, hematological, and gastrointestinal involvement, necessitating vigilant monitoring and management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Javed et al.)

Objectives: To evaluate the characteristics and outcomes of patients with a chronic total occlusion (CTO) in a Non-ST Elevation Myocardial Infarction (NSTEMI) cohort., Background: There is limited data on the clinical characteristics, revascularisation strategies and outcomes of patients presenting with a NSTEMI and a CTO., Methods: Retrospective analysis of a six-centre percutaneous coronary intervention (PCI) registry in the UK between January 2015 and December 2020 was performed. Patients with a NSTEMI with and without a CTO were compared for baseline characteristics and outcomes., Results: There were 17,355 NSTEMI patients in total of whom 1813 patients had a CTO (10.4 %). Patients with a CTO were more likely to be older (CTO: 67.8 (±11.5) years vs. no CTO: 67.2 (±12) years, p = 0.04), male (CTO: 81.1 % vs.71.9 %, p < 0.0001) with a greater prevalence of cardiovascular risk factors. All-cause mortality at 30 days: HR 2.63, 95 % CI 1.42-4.84, p = 0.002 and at 1 year: HR: 1.87, 95 % CI 1.25-2.81, p = 0.003 was higher in the CTO cohort. CTO patients who underwent revascularisation were younger (Revascularisation 66.4 [±11.7] years vs. no revascularisation 68.4 [±11.4] years, p = 0.001). Patients with failed CTO revascularisation had lower survival (HR 0.21, 95 % CI 0.10-0.42, p < 0.0001). The mean time to revascularisation was 13.4 days. There was variation in attempt at CTO revascularisation between the 6 centres for (16 % to 100 %) with success rates ranging from 65 to 100 %., Conclusions: In conclusion, the presence of a CTO in NSTEMI patients undergoing PCI was associated with worse in-hospital and long-term outcomes., Competing Interests: Declaration of competing interest Dr. William HT Smith has received payment from Boston and Abbott for Proctoring CTO PCI procedures locally in the past but not in the last 12 months. None of the other authors has any conflict of interest for this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Elite student-athletes (SAs) in higher education (HE) have distinct mental health (MH) risks. The COVID-19 pandemic put pressure on systems and increased elite SA vulnerability to adverse MH outcomes. The aim of this study was to explore the provision and management of MH in elite HE sports settings during the time of COVID-19 pandemic stress. The secondary aim was to identify lessons and opportunities to enhance future mental healthcare systems and services for elite SAs. A qualitative study design was used to investigate the views of three groups (athletic directors, coaches and sport healthcare providers). Ten key leaders were purposively recruited from HE institutions in Canada, the USA and the United Kingdom. They represented various universities from the National College Athletic Association, U SPORTS Canada and British Universities and Colleges Sport. Semistructured interviews were conducted, recorded, transcribed and thematically analysed. Five key themes were identified: (1) The pandemic disruption had salient impacts on motivation and how elite SAs engaged with sport (2) when student sport systems are under pressure, support staff perceive a change in duties and experience their own MH challenges, (3) the pandemic increased awareness about MH care provision and exposed systemic challenges, (4) digital transformation in MH is complex and has additional challenges for SAs and (5) there were some positive outcomes of the pandemic, lessons learnt and a resulting motivation for systems change. Participants highlighted future opportunities for MH provision in elite university sport settings. Four recommendations were generated from the results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prevention of sports injury and illness and protection of athlete health are key mandates of the IOC. Methodological limitations in Olympic Games surveillance and retired Olympian studies mean there are gaps in the available evidence on Olympian health and the varied challenges occurring at different stages throughout an athlete's career. This (protocol) paper describes the methods for implementation of the IOC Olympian Health Cohort. The study aims to establish a longitudinal cohort of current Olympians and follow them prospectively (around 15 years) throughout their Olympic careers and retirement. The study will use participants who have completed self-report questionnaires. Olympians will be recruited after each Summer and Winter Olympic Games, and all National Olympic Committee (NOC) athletes aged 16 years or older are eligible. The first phase included the Tokyo 2020/2021 and Beijing 2022 Olympians, with the study promoted via IOC platforms, Athlete365 and NOCs. Questionnaires include baseline demographics, sports exposure and history of injuries and illnesses impacting the athlete's ability to continue to train and/or compete for at least 2 weeks. Questions also address retirement from sports, musculoskeletal, mental and general health, and quality of life measures. This protocol describes the methods for the 15-year global IOC Olympian Health Cohort Study, from participant recruitment to the development and distribution of the study questionnaire. This protocol will be updated to report future changes in the study's conduct or questionnaire content. These data will help identify risk factors and inform risk-reduction strategies. The ultimate goal is to protect the health of all athletes during their careers and retirement., Competing Interests: Competing interests: TS works as a scientific manager in the Medical and Scientific Department of the IOC. LE is head of scientific activities in the Medical and Scientific Department of the IOC, editor of the British Journal of Sports Medicine and associate editor of the Journal of Bone and Joint Surgery. DP received funding from the IOC to undertake the IOC Cohort Study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Environmental enteric dysfunction (EED) is a subclinical enteropathy challenging to diagnose due to an overlap of tissue features with other inflammatory enteropathies. EED subjects ( n  = 52) from Pakistan, controls ( n  = 25), and a validation EED cohort ( n  = 30) from Zambia were used to develop a machine-learning-based image analysis classification model. We extracted histologic feature representations from the Pakistan EED model and correlated them to transcriptomics and clinical biomarkers. In-silico metabolic network modeling was used to characterize alterations in metabolic flux between EED and controls and validated using untargeted lipidomics. Genes encoding beta-ureidopropionase, CYP4F3, and epoxide hydrolase 1 correlated to numerous tissue feature representations. Fatty acid and glycerophospholipid metabolism-related reactions showed altered flux. Increased phosphatidylcholine, lysophosphatidylcholine (LPC), and ether-linked LPCs, and decreased ester-linked LPCs were observed in the duodenal lipidome of Pakistan EED subjects, while plasma levels of glycine-conjugated bile acids were significantly increased. Together, these findings elucidate a multi-omic signature of EED., Competing Interests: KDRS has equity in Asklepion Pharmaceuticals and is a consultant to Travere Therapeutics and Mirum Pharmaceuticals. All the other authors have no conflicts of interest to disclose., (© 2024 The Authors.)

Citrobacter infections have emerged as now a common nosocomial pathogen. Most of the infections manifest in patients with underlying medical conditions. The features of infection can range from infections in the lower urinary tract, respiratory tract, gastrointestinal disease, or bacteremia, however renal abscesses remain uncommon. Here we present the case of a 48-year-old female with medical history of diabetes that presented with a right renal abscess secondary to Citrobacter koseri infection managed with drainage and antimicrobial treatment., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to declare., (© 2024 Greater Baltimore Medical Center.)

Background: Helicobacter pylori (H. pylori) is a common bacterial infection which predominately drives upper gastrointestinal pathology. We carried out a nationwide serological survey in response to the deficiency of robust African data on H. pylori prevalence, age of acquisition, socio-geographic determinants, and impact on gastric physiology., Materials and Methods: This was a cross-sectional study of archival plasma samples collected during the Zambia Population-based HIV impact Assessment (ZAMPHIA) 2016 survey. ZAMPHIA used a two-stage door-to-door stratified cluster sample approach to collect samples from adults and children from age 0 to 59 years (n = 24,266). We randomly retrieved one fifth of these samples from each of Zambia's 10 provinces and used ELISA to test for H. pylori IgG antibodies, pepsinogen 1 and 2 and gastrin-17. A pepsinogen 1:2 ratio of <3 was used to define gastric atrophy., Results: The analysis of 4050 plasma samples (30% <16 years, 53% females) revealed an overall H. pylori seroprevalence of 79%. By the age of 10 years, more than 75% of the children had H. pylori. Urban residence was associated with increased odds (OR 1.8, 95% CI 1.5-2.2, p < 0.001) and HIV infection was associated with reduced odds (OR 0.7, 95% CI 0.5-0.9, p = 0.02) of H. pylori seropositivity. Gastric atrophy was detected in 6% of H. pylori seropositive adults below 45 years of age and 9% in those between 45 and 59 years., Conclusions: We have confirmed a high prevalence of H. pylori seropositivity in Zambia, predominantly in urban settings. The prevalence of gastric atrophy is broadly consistent with other populations around the globe, but our sample did not include adults over 60 years., (© 2024 John Wiley & Sons Ltd.)

Background: Walking is a key target behavior for promoting population health. This paper charts the 30-year history of walking policy in Scotland. We assess whether population walking levels among adults in Scotland have changed in recent years and identify the characteristics of those least likely to report any walking., Methods: We pooled 9 years (2012-2019 and 2021) of data from adult (≥16 y) respondents of the Scottish Health Survey (n = 41,470). The outcomes of interest were the percentage reporting (1) any walking and (2) any walking with an average pace that is of at least moderate intensity. We also investigated the contribution of walking to total nonoccupational moderate to vigorous physical activity. We used linear and logistic regressions to test linear trends over time and to identify inequalities by age, sex, and the Scottish Index of Multiple Deprivation quintile., Results: There was an increase in all measures of walking over the period 2012-2021; for example, the percentage reporting any walking increased by 7 percentage points (81.4%-88.4%). Inequalities still exist by age, sex, and the Scottish Index of Multiple Deprivation but have not grown over time. Inequalities by sex and age are most pronounced in the least affluent Scottish Index of Multiple Deprivation quintiles; less affluent older women are least likely to report any walking., Conclusions: Scotland appears to be walking in the right direction. Surveillance data support a positive trend after decades of policy and promotion efforts. The policies do not appear to be exacerbating existing inequalities, but narrowing them will require more concentrated efforts.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α 1 -antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115., (© 2024. The Author(s).)

Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure to maternal viraemia, immune dysfunction, and co-infections during pregnancy. In a secondary analysis of the SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, and maternal factors shaping immune development in HIV-exposed uninfected infants. Maternal inflammation and cytomegalovirus viraemia were independently associated with infant deaths: mortality doubled for each log 10 rise in maternal C-reactive protein (adjusted hazard ratio (aHR) 2.09; 95% CI 1.33-3.27), and increased 1.6-fold for each log 10 rise in maternal cytomegalovirus viral load (aHR 1.62; 95% CI 1.11-2.36). In girls, mortality was more strongly associated with maternal C-reactive protein than cytomegalovirus; in boys, mortality was more strongly associated with cytomegalovirus than C-reactive protein. At age one month, HIV-exposed uninfected infants had a distinct immune milieu, characterised by raised soluble CD14 and an altered CD8 + T-cell compartment. Alterations in immunophenotype and systemic inflammation were generally greater in boys than girls. Collectively, these findings show how the pregnancy immune environment in women with HIV underlies mortality and immune development in their offspring in a sex-differentiated manner, and highlights potential new intervention strategies to transform outcomes of HIV-exposed children. ClinicalTrials.gov/NCT01824940., (© 2023. The Author(s).)

Introduction: There are uncertainties surrounding the spectrum of upper gastrointestinal (UGI) diseases in sub-Saharan Africa. This is mainly due to the limitations of data collection and recording. We previously reported an audit of UGI endoscopic diagnoses in Zambia spanning from 1977 to 2014. We now have extended this analysis to include subsequent years, in order to provide a more comprehensive picture of how the diagnoses have evolved over 4 decades., Methods: We combined data collected from the endoscopy unit at the University Teaching Hospital (UTH) in Lusaka during a previous review with that collected from the beginning of 2015 to the end of 2021. Since 2015, an electronic data base of endoscopy reports at the UTH was kept. The electronic data base was composed of drop-down menus that allowed for standardised reporting of findings. Collected data were coded by two experienced endoscopists and analysed., Results: In total, the analysis included 25,849 endoscopic records covering 43 years. The number of endoscopic procedures performed per year increased drastically in 2010. With the exception of the last 2 years, the proportion of normal endoscopies also increased during the time under review. In total, the number of gastric cancer (GC) cases was 658 (3%) while that of oesophageal cancer (OC) was 1168 (5%). The number of GC and OC diagnoses increased significantly over the period under review, (p < 0.001 for both). For OC the increase remained significant when analysed as a percentage of all procedures performed (p < 0.001). Gastric ulcers (GU) were diagnosed in 2095 (8%) cases, duodenal ulcers (DU) in 2276 (9%) cases and 239 (1%) had both ulcer types. DU diagnosis showed a significantly decreasing trend over each decade (p < 0.001) while GU followed an increasing trend (p < 0.001)., Conclusions: UGI endoscopic findings in Lusaka, Zambia, have evolved over the past four decades with a significant increase of OC and GU diagnoses. Reasons for these observations are yet to be established., (© 2024. The Author(s).)