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Abstract Background Genomic epidemiology has helped reconstruct the global and regional movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is still a lack of understanding of SARS-CoV-2 spread in some of the world’s least developed countries (LDCs). Methods To begin to address this disparity, we studied the transmission dynamics of the virus in Bangladesh during the country’s first COVID-19 wave by analysing case reports and whole-genome sequences from all eight divisions of the country. Results We detected > 50 virus introductions to the country during the period, including during a period of national lockdown. Additionally, through discrete phylogeographic analyses, we identified that geographical distance and population -density and/or -size influenced virus spatial dispersal in Bangladesh. Conclusions Overall, this study expands our knowledge of SARS-CoV-2 genomic epidemiology in Bangladesh, shedding light on crucial transmission characteristics within the country, while also acknowledging resemblances and differences to patterns observed in other nations.

Abstract Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition with rising global incidence. Identifying factors contributing to seasonal variations in RRD would allow a better understanding of RRD pathophysiology. We therefore performed a retrospective case series study investigating the relationship between RRD occurrence and meteorological factors throughout metropolitan France (the METEO-POC study), particularly the mean temperature over the preceding 10-day period (T-1). Adult patients having undergone RRD surgery and residing in one of the three most populated urban areas of each French region were included (January 2011–December 2018). The study involved 21,166 patients with idiopathic RRD (61.1% males, mean age 59.8–65.1 years). RRD incidence per 100,000 inhabitants increased from 7.79 to 11.81. RRD occurrence was not significantly associated with mean temperature over T-1 in the majority of urban areas (31/36). In a minority of areas (5/36) we observed correlations between RRD incidence and mean temperature over T-1, however these were extremely weak (r = 0.1–0.2; p

Abstract Cancer metabolic reprogramming has been recognized as one of the cancer hallmarks that promote cell proliferation, survival, as well as therapeutic resistance. Up-to-date regulation of metabolism in T-cell lymphoma is poorly understood. In particular, for human angioimmunoblastic T-cell lymphoma (AITL) the metabolic profile is not known. Metabolic intervention could help identify new treatment options for this cancer with very poor outcomes and no effective medication. Transcriptomic analysis of AITL tumor cells, identified that these cells use preferentially mitochondrial metabolism. By using our preclinical AITL mouse model, mimicking closely human AITL features, we confirmed that T follicular helper (Tfh) tumor cells exhibit a strong enrichment of mitochondrial metabolic signatures. Consistent with these results, disruption of mitochondrial metabolism using metformin or a mitochondrial complex I inhibitor such as IACS improved the survival of AITL lymphoma-bearing mice. Additionally, we confirmed a selective elimination of the malignant human AITL T cells in patient biopsies upon mitochondrial respiration inhibition. Moreover, we confirmed that diabetic patients suffering from T-cell lymphoma, treated with metformin survived longer as compared to patients receiving alternative treatments. Taking together, our findings suggest that targeting the mitochondrial metabolic pathway could be a clinically efficient approach to inhibit aggressive cancers such as peripheral T-cell lymphoma.

Abstract H9N2 avian influenza viruses (AIVs) are a major concern for the poultry sector and human health in countries where this subtype is endemic. By fitting a model simulating H9N2 AIV transmission to data from a field experiment, we characterise the epidemiology of the virus in a live bird market in Bangladesh. Many supplied birds arrive already exposed to H9N2 AIVs, resulting in many broiler chickens entering the market as infected, and many indigenous backyard chickens entering with pre-existing immunity. Most susceptible chickens become infected within one day spent at the market, owing to high levels of viral transmission within market and short latent periods, as brief as 5.3 hours. Although H9N2 AIV transmission can be substantially reduced under moderate levels of cleaning and disinfection, effective risk mitigation also requires a range of additional interventions targeting markets and other nodes along the poultry production and distribution network.

Introduction and aim: Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. Methods: HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. Results: When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (>90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. Conclusion: HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming. Resumen: Introducción: En Perú, el carcinoma hepatocelular (CHC) ocupa el tercer lugar en incidencia entre los tumores del sistema digestivo, y tiene una alta tasa de mortalidad, 17.7 por 100 000 habitantes. La mayoría de los casos reportados no presentan la epidemiología clínica clásica del CHC observado en otras partes del mundo. Además, se ha identificado que estos pacientes presentan un perfil transcriptómico distinto y un proceso tumoral singular, sugiriendo un proceso particular de hepatocarcinogénesis en una fracción de la población peruana. Objetivo: El presente estudio busca comprender la implicancia clínica y biológica del perfil epigenético (metilación) y de expresión de los genes (transcriptómico) del CHC en los pacientes peruanos. Métodos: Se evaluó el perfil de transcriptómico y de metilación de ADN de hígado y CHC en 74 pacientes peruanos. Resultados: El agrupamiento por edades mostró una mayor metilación del ADN en los pacientes jóvenes con CHC, en contraste no se observaron diferencias en el perfil transcriptómico. Adicionalmente, también se evidenció una alta prevalencia del virus de la hepatitis B (VHB) (>90%) en los pacientes jóvenes con CHC. El análisis de enriquecimiento en ambos perfiles moleculares demostró que PRC2 es posiblemente uno de los principales actores moleculares en este proceso tumoral hepático en pacientes peruanos. Conclusión: El CHC peruano presenta un perfil molecular único, asociado a la presencia del VHB, y con una hipermetilación global del ADN asociado a células hepáticas indiferenciadas o a una reprogramación celular.

Abstract Introduction The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies). Methods This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24 months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups). Results Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2 ± 7.8 years). After 24 months, mean BCVA significantly improved (65.22 ± 14 vs. 71.96 ± 13 Early Treatment Diabetic Retinopathy Study letters; p

Antimicrobial resistance has emerged as a significant health problem worldwide, including in Bangladesh, where chickens are an important protein source for human nutrition. One of the factors accelerating the development of antimicrobial resistance is the inappropriate use of antimicrobials on commercial chicken farms. A cross-sectional study was conducted in 2019 on 140 commercial chicken farms in the Chattogram district of Bangladesh to investigate the association between antimicrobial use and resistance in Escherichia coli and Salmonella spp. cultured from cloacal swabs of chickens and from the poultry shed environment. All E. coli and Salmonella spp. isolates were resistant to multiple antimicrobial classes, including those categorized as “Highest Priority Critically Important Antimicrobials” for human medicine. Notably, resistance was observed in E. coli isolates from farms that did not use these antimicrobial classes in the current production cycle. For example, although quinolones were not used on 43.9% of E. coli positive farms, 95.7% of these farms had quinolone-resistant E. coli isolates. The results of the path analysis revealed that there was a “direct effect” of the frequency of antimicrobial usage on “high” resistance, with resistance increasing when antimicrobials were administered more frequently (β = 0.28, p = 0.002). There was a “direct effect” of the purpose of antimicrobial use on “low” resistance, with resistance marginally decreasing when antimicrobials were administered solely for therapeutic use (β = −0.17, p = 0.062), but increasing when they were used prophylactically. Overall, the study results could be used to educate farmers on better practices for antimicrobial administration, and to guide government agencies to update policies on antimicrobial use and resistance surveillance in the poultry sector of Bangladesh.

Abstract Background Angioimmunoblastic T-cell lymphoma (AITL) is a malignancy with very poor survival outcome, in urgent need of more specific therapeutic strategies. The drivers of malignancy in this disease are CD4+ follicular helper T cells (Tfh). The metabolism of these malignant Tfh cells was not yet elucidated. Therefore, we decided to identify their metabolic requirements with the objective to propose a novel therapeutic option. Methods To reveal the prominent metabolic pathways used by the AITL lymphoma cells, we relied on metabolomic and proteomic analysis of murine AITL (mAITL) T cells isolated from our established mAITL model. We confirmed these results using AITL patient and healthy T cell expression data. Results Strikingly, the mAITL Tfh cells were highly dependent on the second branch of the Kennedy pathway, the choline lipid pathway, responsible for the production of the major membrane constituent phosphatidylcholine. Moreover, gene expression data from Tfh cells isolated from AITL patient tumors, confirmed the upregulation of the choline lipid pathway. Several enzymes involved in this pathway such as choline kinase, catalyzing the first step in the phosphatidylcholine pathway, are upregulated in multiple tumors other than AITL. Here we showed that treatment of our mAITL preclinical mouse model with a fatty acid oxydation inhibitor, significantly increased their survival and even reverted the exhausted CD8 T cells in the tumor into potent cytotoxic anti-tumor cells. Specific inhibition of Chokα confirmed the importance of the phosphatidylcholine production pathway in neoplastic CD4 + T cells, nearly eradicating mAITL Tfh cells from the tumors. Finally, the same inhibitor induced in human AITL lymphoma biopsies cell death of the majority of the hAITL PD-1high neoplastic cells. Conclusion Our results suggest that interfering with choline metabolism in AITL reveals a specific metabolic vulnerability and might represent a new therapeutic strategy for these patients.

Abstract After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called “spaceflight associated neuro-ocular syndrome” (SANS). The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spaceflight on SANS in women due to the fact that fewer female astronauts have spent time in long-term missions. The objective is to determine whether similar ophthalmological changes occur in healthy women after short-term exposure to microgravity. The auto-refractometer was used to determine objective refraction. The best corrected distance visual acuity was assessed with a Monoyer chart. The ocular axial length was assessed using optical biometry. The applanation tonometry was used to determine intraocular pressure. Peripapillary retinal nerve fibre layer thickness (pRNFLT), macular total retinal thickness, and ganglion cell complex (GCC) were measured using optical coherence tomography. Ocular axial length is reduced after DI. pRNFL is thickest after DI specifically in the temporal, temporal-inferior, and nasal-inferior quadrants. Macular total retinal at the inferior quadrant of the 6-mm ring is thickest after DI. Global GCC is thinnest after DI. In this study, 5 days of DI induces slight but significant ophthalmological changes in women. However, these subtle changes do not correspond to criteria defined in SANS.

Optic Atrophy (OA) can be associated with the development of microcystic macular edema (MME) in the perifoveal retinal inner nuclear layer (INL). We aimed here to retrospectively determine the prevalence of MME in patients with non-glaucomatous OA in our tertiary ophthalmology department between 2015 and 2020. We then examined how MME affected the thicknesses of the different retinal layers and the differences in demographic and clinical characteristics between those patients who developed MME and those who did not. A total of 643 eyes (429 patients) were included (mean age 45.9 ± 17.8 years, 52% female). MME developed in 95 (15%) eyes and across all etiologies of OA except for toxic/nutritional causes, but the prevalence of MME varied between the different etiologies. The development of MME was associated with thinning of the ganglion cell layer (11.0 vs. 9.6 μm; p = 0.001) and the retinal nerve fiber layer (10.1 vs. 9.15 μm; p = 0.024), with INL thickening in the 3- and 6-mm diameter areas of the central fovea. Patients developing MME had significantly worse distance best-corrected visual acuity than those not developing MME (0.62 vs. 0.38 logMAR; p = 0.002). Overall, the presence of MME in OA cannot be used to guide the diagnostic work-up of OA.

The rapid intensification of poultry production raises important concerns about the associated risks of zoonotic infections. Here, we introduce EPINEST (EPIdemic NEtwork Simulation in poultry Transportation systems): an agent-based modelling framework designed to simulate pathogen transmission within realistic poultry production and distribution networks. We provide example applications to broiler production in Bangladesh, but the modular structure of the model allows for easy parameterization to suit specific countries and system configurations. Moreover, the framework enables the replication of a wide range of eco-epidemiological scenarios by incorporating diverse pathogen life-history traits, modes of transmission and interactions between multiple strains and/or pathogens. EPINEST was developed in the context of an interdisciplinary multi-centre study conducted in Bangladesh, India, Vietnam and Sri Lanka, and will facilitate the investigation of the spreading patterns of various health hazards such as avian influenza, Campylobacter, Salmonella and antimicrobial resistance in these countries. Furthermore, this modelling framework holds potential for broader application in veterinary epidemiology and One Health research, extending its relevance beyond poultry to encompass other livestock species and disease systems.

N-retinylidene-N-retinylethanolamine (A2E) has been associated with age-related macular degeneration (AMD) physiopathology by inducing cell death, angiogenesis and inflammation in retinal pigmented epithelial (RPE) cells. It was previously thought that the A2E effects were solely mediated via the retinoic acid receptor (RAR)-α activation. However, this conclusion was based on experiments using the RAR “specific” antagonist RO-41-5253, which was found to also be a ligand and partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ. Moreover, we previously reported that inhibiting PPAR and retinoid X receptor (RXR) transactivation with norbixin also modulated inflammation and angiogenesis in RPE cells challenged in the presence of A2E. Here, using several RAR inhibitors, we deciphered the respective roles of RAR, PPAR and RXR transactivations in an in vitro model of AMD. We showed that BMS 195614 (a selective RAR-α antagonist) displayed photoprotective properties against toxic blue light exposure in the presence of A2E. BMS 195614 also significantly reduced the AP-1 transactivation and mRNA expression of the inflammatory interleukin (IL)-6 and vascular endothelial growth factor (VEGF) induced by A2E in RPE cells in vitro, suggesting a major role of RAR in these processes. Surprisingly, however, we showed that (1) Norbixin increased the RAR transactivation and (2) AGN 193109 (a high affinity pan-RAR antagonist) and BMS 493 (a pan-RAR inverse agonist), which are photoprotective against toxic blue light exposure in the presence of A2E, also inhibited PPARs transactivation and RXR transactivation, respectively. Therefore, in our in vitro model of AMD, several commercialized RAR inhibitors appear to be non-specific, and we propose that the phototoxicity and expression of IL-6 and VEGF induced by A2E in RPE cells operates through the activation of PPAR or RXR rather than by RAR transactivation.

Purpose: The purpose of this study was to describe the surgical management of bilateral giant full-thickness macular hole with sudden onset two months after cataract surgery in a patient with Alport syndrome. Methods: This was an observational, single-case report. Results: A 54-year-old woman with a history of Alport syndrome presented with severe bilateral visual loss two months after cataract surgery. The diagnosis of bilateral giant fullthickness macular hole was made. We found the absence of the internal limiting membrane and the inability to lift and peel a continuous posterior hyaloid sheet during surgical management with 25-gauge pars plana vitrectomy (left eye). Amniotic membrane grafting followed by gas tamponade were performed for hole closure. The hole remained closed but vision was poorly restored two months after. Conclusion: Cataract surgery in patients with Alport syndrome could promote early development of giant full-thickness macular hole. Collagen defects could underlie internal limiting membrane absence and the inability to properly peel the posterior hyaloid. [ABSTRACT FROM AUTHOR]

Optic Atrophy (OA) can be associated with the development of microcystic macular edema (MME) in the perifoveal retinal inner nuclear layer (INL). We aimed here to retrospectively determine the prevalence of MME in patients with non-glaucomatous OA in our tertiary ophthalmology department between 2015 and 2020. We then examined how MME affected the thicknesses of the different retinal layers and the differences in demographic and clinical characteristics between those patients who developed MME and those who did not. A total of 643 eyes (429 patients) were included (mean age 45.9 ± 17.8 years, 52% female). MME developed in 95 (15%) eyes and across all etiologies of OA except for toxic/nutritional causes, but the prevalence of MME varied between the different etiologies. The development of MME was associated with thinning of the ganglion cell layer (11.0 vs. 9.6 μm; p = 0.001) and the retinal nerve fiber layer (10.1 vs. 9.15 μm; p = 0.024), with INL thickening in the 3- and 6-mm diameter areas of the central fovea. Patients developing MME had significantly worse distance best-corrected visual acuity than those not developing MME (0.62 vs. 0.38 logMAR; p = 0.002). Overall, the presence of MME in OA cannot be used to guide the diagnostic work-up of OA.

The association of early-onset non-progressive ataxia and miosis is an extremely rare phenotypic entity occasionally reported in the literature. To date, only one family (two siblings and their mother) has benefited from a genetic diagnosis by the identification of a missense heterozygous variant (p.Arg36Cys) in the ITPR1 gene. This gene encodes the inositol 1,4,5-trisphosphate receptor type 1, an intracellular channel that mediates calcium release from the endoplasmic reticulum. Deleterious variants in this gene are known to be associated with two types of spinocerebellar ataxia, SCA15 and SCA29, and with Gillespie syndrome that is associated with ataxia, partial iris hypoplasia, and intellectual disability. In this work, we describe a novel individual carrying a heterozygous missense variant (p.Arg36Pro) at the same position in the N-terminal suppressor domain of ITPR1 as the family previously reported, with the same phenotype associating early-onset non-progressive ataxia and miosis. This second report confirms the implication of ITPR1 in the miosis-ataxia syndrome and therefore broadens the clinical spectrum of the gene. Moreover, the high specificity of the phenotype makes it a recognizable syndrome of genetic origin., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition with rising global incidence. Identifying factors contributing to seasonal variations in RRD would allow a better understanding of RRD pathophysiology. We therefore performed a retrospective case series study investigating the relationship between RRD occurrence and meteorological factors throughout metropolitan France (the METEO-POC study), particularly the mean temperature over the preceding 10-day period (T-1). Adult patients having undergone RRD surgery and residing in one of the three most populated urban areas of each French region were included (January 2011-December 2018). The study involved 21,166 patients with idiopathic RRD (61.1% males, mean age 59.8-65.1 years). RRD incidence per 100,000 inhabitants increased from 7.79 to 11.81. RRD occurrence was not significantly associated with mean temperature over T-1 in the majority of urban areas (31/36). In a minority of areas (5/36) we observed correlations between RRD incidence and mean temperature over T-1, however these were extremely weak (r = 0.1-0.2; p < 0.05). No associations were found between RRD incidence and secondary outcomes: mean daily temperature over the 10 days prior T-1, minimum/maximum temperatures, rainfall, duration of sunshine, atmospheric pressure, overall radiation, relative humidity, wind speed. Overall, we found no relationships between meteorological parameters and RRD occurrence., (© 2024. The Author(s).)

Purpose: Corneal crosslinking (CXL) is the standard treatment of progressive keratoconus (KC). We evaluated the safety and 10-year outcomes of conventional "epithelial-off" CXL for progressive KC for the first time in a cohort in France., Methods: We conducted a retrospective review of patients undergoing conventional CXL (Dresden protocol) in our tertiary ophthalmology department from 2006 to 2011 with 10-year follow-up. The primary outcome was change in preoperative versus postoperative keratometry measured by maximum keratometry (Kmax), steep keratometry (K2), flat keratometry (K1), mean keratometry (Km), and topographic cylinder. Secondary outcomes were changes in visual and refractive outcomes. We report postoperative complications and adverse events., Results: Eighty-nine eyes from 76 patients (67% male patients, mean age 22.7 ± 7.6 years) were included. Mean Kmax (-2.31 ± 2.98 diopters (D); P < 0.00001), K2 (-2.07 ± 3.15 D; P < 0.00001), K1 (-1.00 ± 2.29 D; P = 0.00008), Km (-1.53 ± 2.47 D; P < 0.00001), and topographic cylinder (-1.15 ± 2.53 D; P = 0.00004) significantly decreased 10 years after CXL compared with preoperative baseline. Significant decreases were still observed between 5 and 10 years after for mean Kmax, mean K2, mean K1, and mean Km. Mean distance best spectacle-corrected visual acuity and mean manifest refraction spherical equivalent were significantly improved after 10 years versus before CXL. The 10-year rate of repeat CXL was n = 3/76 patients (4%) (all younger than 18 years at first CXL) and of loss of >3 lines in best spectacle-corrected visual acuity was n = 1/76 patients (1%)., Conclusions: Progressive KC was effectively stabilized with a prolonged flattening and maintenance of functional vision improvements after 10 years. Repeat CXL was rare and only required among younger patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called "spaceflight associated neuro-ocular syndrome" (SANS). The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spaceflight on SANS in women due to the fact that fewer female astronauts have spent time in long-term missions. The objective is to determine whether similar ophthalmological changes occur in healthy women after short-term exposure to microgravity. The auto-refractometer was used to determine objective refraction. The best corrected distance visual acuity was assessed with a Monoyer chart. The ocular axial length was assessed using optical biometry. The applanation tonometry was used to determine intraocular pressure. Peripapillary retinal nerve fibre layer thickness (pRNFLT), macular total retinal thickness, and ganglion cell complex (GCC) were measured using optical coherence tomography. Ocular axial length is reduced after DI. pRNFL is thickest after DI specifically in the temporal, temporal-inferior, and nasal-inferior quadrants. Macular total retinal at the inferior quadrant of the 6-mm ring is thickest after DI. Global GCC is thinnest after DI. In this study, 5 days of DI induces slight but significant ophthalmological changes in women. However, these subtle changes do not correspond to criteria defined in SANS., (© 2024. The Author(s).)