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Detecting pathogens in endangered animal populations is vital for understanding and mitigating threats to their survival. The critically endangered western ground parrot (Pezoporus flaviventris, WGP), with a population as low as 150 individuals in Australia, faces an imminent risk of extinction. Despite this urgency, research on viral pathogens in this species remains limited. This study aimed to identify and characterise viruses present in faecal samples from seven individual WGP using a viral metagenomic approach. Analysis of the sequenced datasets revealed the presence of a novel virus belonging to the Parvoviridae family, named psittaciform chaphamaparvovirus 7 (PsChPV‐7). The genome of PsChPV‐7 contains typical structural and functional gene sequences found in Parvoviridae but is highly divergent, indicating its classification as a distinct species. Phylogenetic analysis placed PsChPV‐7 within a unique sub‐clade of the Chaphamaparvovirus genus, suggesting its evolutionary significance as an ancient lineage within this group. These findings may contribute to the development of strategic management and biosecurity plans aimed at conserving this endangered WGP. [ABSTRACT FROM AUTHOR]

Byline: P. Ramteke, V. Seenu, R. Prashad, SD. Gupta, V. Iyer, SVS. Deo, A. Gogia, S. Mathur CONTEXT: Use of neoadjuvant chemotherapy (NACT) in locally advanced breast cancer (LABC) enables [...]

Objective: To test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post-traumatic epilepsy (PTE)., Methods: Adult male Sprague-Dawley rats (n = 245) were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, United States). Video-electroencephalography (vEEG) was performed on the seventh post-injury month to detect spontaneous seizures. Tail vein plasma collected 48 h after TBI for miRNA analysis was available from 209 vEEG monitored animals (45 sham, 164 TBI [32 with epilepsy]). Based on small RNA sequencing and previous data, the seven most promising brain enriched miRNAs (miR-183-5p, miR-323-3p, miR-434-3p, miR-9a-3p, miR-124-3p, miR-132-3p, and miR-212-3p) were validated by droplet digital polymerase chain reaction (ddPCR)., Results: All seven plasma miRNAs differentiated between TBI and sham-operated rats. None of the seven miRNAs differentiated TBI rats that did and did not develop epilepsy (p > .05), or rats with ≥3 vs <3 seizures in a month (p > .05). However, miR-212-3p differentiated rats that developed epilepsy with seizure clusters (i.e., ≥3 seizures within 24 h) from those without seizure clusters (.34 ± .14 vs .60 ± .34, adj. p < .05) with an area under the curve (AUC) of .81 (95% confidence interval [CI] .65-.97, p < .01, 64% sensitivity, 95% specificity). Lack of elevation in miR-212-3p also differentiated rats that developed epilepsy with seizure clusters from all other TBI rats (n = 146, .34 ± .14 vs .55 ± .31, p < .01) with an AUC of .74 (95% CI .61-.87, p < .01, 82% sensitivity, 62% specificity). Glmnet analysis identified a combination of miR-212-3p and miR-132-3p as an optimal set to differentiate TBI rats with vs without seizure clusters (cross-validated AUC .75, 95% CI .47-.92, p < .05)., Significance: miR-212-3p alone or in combination with miR-132-3p shows promise as a translational prognostic biomarker for the development of severe PTE with seizure clusters., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Aims: Beta-blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho-inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta-blocker compared to those treated with a beta-blocker., Methods and Results: We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta-blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM-HF. The primary outcome was time to first heart failure hospitalization or cardiovascular death. Compared to the 7811 patients taking a beta-blocker, the 588 patients not receiving a beta-blocker were older, more frequently female, but had a similar mean left ventricular ejection fraction and New York Heart Association class distribution, with little difference in N-terminal pro-B-type natriuretic peptide. Patients not taking beta-blockers had a higher rate of the primary endpoint than those taking beta-blockers. The benefit of sacubitril/valsartan on the primary endpoint was evident in both the no beta-blocker subgroup (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.45-0.82) and the beta-blocker subgroup (HR 0.82, 95% CI 0.75-0.90; p-interaction = 0.06). The respective HRs for cardiovascular death were 0.47 (95% CI 0.32-0.69) versus 0.84 (95% CI 0.75-0.95; p-interaction <0.01) and for HF hospitalization 0.76 (95% CI 0.51-1.12) versus 0.80 (95% CI 0.71-0.90; p-interaction = 0.73). For all-cause death, the HR in the no beta-blocker group was 0.50 (95% CI 0.36-0.71) compared to 0.89 (95% CI 0.80-0.99) in the beta-blocker group (p-interaction <0.01). Safety outcomes related to sacubitril/valsartan versus enalapril did not differ according to background beta-blocker use., Conclusion: Sacubitril/valsartan may be more effective than enalapril in reducing the risk of death in patients not treated with a beta-blocker compared to those treated with a beta-blocker, but is effective regardless of beta-blocker use., Clinical Trial Registration: ClinicalTrials.gov NCT01035255., (© 2024 European Society of Cardiology.)

Objective: Neisseria meningitidis is an encapsulated, diplococcus, kidney bean-shaped bacteria that causes bacterial meningitis. Our study hopes to advance our understanding of disease progression, the spread frequency of the bacteria in people, and the interactions between the bacteria and human body by identifying a functional protein, potentially serving as a target for meningococcal medicine in the future., Methods: A hypothetical protein HP (PBJ89160.1) from N.   meningitidis was employed in this study for extensive structural and functional characterization. In the predictive functional role of HP, several constitutive bioinformatics approaches are applied, such as prediction of physiological properties, domain and motif family function, secondary and tertiary structure prediction, energy minimization, quality validation, docking, and ADMET analysis. To create the protein's three-dimensional (3D) structure, a template protein (PDB&#95;ID: 3GXA) is used with 99% sequence identity by homology modeling technique with the HHpred server. To mitigate the pathogenicity associated with the HP function, it was docked with the natural ligand methionine and five other drug compounds like Verapamil, Loperamide, Thioridazine, Chlorpromazine, and Auranofine., Results: The protein is predicted to be acidic, soluble and hydrophilic by physicochemical properties analysis. Subcellular localization analysis demonstrated the protein to be periplasmic. The HP has an ATP-binding cassette transporter (also known as ABC transporter) involved in uptake of methionine (MetQ) that creates nutritional virulence in host. Energy minimization, multiple quality assessments, and validation value determination led to the conclusion that the HP model had a workable and acceptable quality. Following ADMET analysis and binding affinity assessments from the docking studies, Loperamide emerged as the most promising therapeutic compound, effectively inhibiting the ATP transporter activity of the HP., Conclusion: Comparative genomic analysis revealed that this protein is specific to N. meningitidis and has no homologs in human proteins, thereby identifying it as a potential target for therapeutic intervention., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Birds are known to harbour many pathogens, including circovirus, herpesviruses, adenoviruses and Chlamydia psittaci. Some of these pose zoonotic risks, while others, such as beak and feather disease virus (BFDV), have a significant impact on the conservation of endangered bird species., Objectives: This study was aimed to determine the faecal virome of a group of apparently healthy Monk parakeet using high-throughput sequencing., Methods: Fresh faecal samples were collected from four Monk parakeets at a pet shop in Melbourne, Australia. Virus enrichment and nucleic acid extraction were performed on the faecal samples, followed by high-throughput sequencing at the Australian Genome Research Facility (AGRF)., Results: Utilising an established pipeline for high-throughput sequencing data analysis, this study revealed the presence of three viruses of the families Circoviridae, Parvoviridae and Adenoviridae. Subsequent sequence comparison and phylogenetic analyses further confirmed that the detected viruses belong to the genera Chaphamaparvovirus (unassigned species), Circovirus (species Circovirus parrot) and Siadenovirus (species Siadenovirus viridis)., Conclusion: Despite non-pathogenicity, the existence of multiple viruses within a bird species underscores the risk of these viruses spreading into the pet trade. Detection and a better understanding of avian viruses are crucial for the establishment of appropriate management and biosecurity measures in the domestic and international bird trade, which ultimately supports the conservation of vulnerable bird species., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Multi-drug resistant (MDR) Klebsiella pneumoniae is a public health concern due to its presence in Bangladeshi poultry products and its ability to spread resistance genes. This study genetically characterizes a distinct MDR K. pneumoniae isolate from the gut of poultry in Noakhali, Bangladesh, offering insights into its resistance mechanisms and public health impact., Methods: Klebsiella pneumoniae isolates from broiler and layer poultry were identified using biochemical and molecular analyses. Eleven isolates were tested for antibiotic sensitivity and categorized by their Multiple Antibiotic Resistance Index (MARI) profiles. The isolate with the highest MARI was selected for whole-genome sequencing using Illumina technology. The sequencing data were analyzed for genome annotation, pan-genome analysis, genome similarities, sequence type identification, and the identification of genetic determinants of resistance and virulence genes., Result: We identified 10 MARI profiles among 11 K. pneumoniae isolates, with values ranging from 0.64 to 0.94. The highest MARI of 0.94 was found in an isolate from a layer poultry. This isolate's genome, 5401,789 base pairs long with 89.6 % coverage, showed potential inter-species dissemination, as indicated by core genome phylogenetic analysis. It possessed genes conferring resistance to fluoroquinolones, aminoglycosides, β-lactams, folate pathway antagonists, fosfomycin, macrolides, quinolones, rifamycin, tetracyclines, and polymyxins, including colistin., Conclusion: Poultry serve as reservoirs for MDR K. pneumoniae, which can spread to other species and pose significant health risks. Rigorous monitoring of antibiotic use and genetic characterization of MDR bacterial isolates are essential to mitigate this threat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rotavirus A is a leading cause of non-bacterial gastroenteritis in humans and domesticated animals. Despite the vast diversity of bovine Rotavirus A strains documented in South Asian countries, there are very few whole genomes available for phylogenetic study. A cross-sectional study identified a high prevalence of the G6P[11] genotype of bovine Rotavirus A circulating in the commercial cattle population in Bangladesh. Next-generation sequencing and downstream phylogenetic analysis unveiled all 11 complete gene segments of this strain (BD&#95;ROTA&#95;CVASU), classifying it under the genomic constellation G6P[11]-I2-R2-C2-M2-A13-N2-T6-E2-H3, which belongs to a classical DS-1-like genomic backbone. We found strong evidence of intragenic recombination between human and bovine strains in the Non-structural protein 4 (NSP4) gene, which encodes a multifunctional enterotoxin. Our analyses highlight frequent zoonotic transmissions of rotaviruses in diverse human-animal interfaces, which might have contributed to the evolution and pathogenesis of this dominant genotype circulating in the commercial cattle population in Bangladesh., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Foysal, Imam, Das, Gibson, Mahmud, Gupta, Fournié, Hoque and Henning.)

Rapidly increasing antibiotic-resistant bacterial strains in Bangladesh's food and farm animals stem from the excessive and inappropriate use of antibiotics. To assess the prevalence of multi-drug resistant (MDR) Gram-negative bacteria in poultry chicks, we sought to isolate and identify strains carrying antimicrobial resistance genes. Isolation and identification involved biochemical tests, 16S rRNA sequencing, and PCR screening of species-specific genes. MDR patterns were evaluated using CLSI guidelines with seventeen antibiotics across twelve classes. Targeted gene sequences were amplified for the detection of Extended-spectrum β-Lactamase (ESBL), carbapenem, tetracycline, sulfonamide, and colistin resistance genes. Common isolates, such as Escherichia coli, Klebsiella pneumoniae, Proteus penneri, and Enterobacter hormaechei, exhibited average Multiple Antimicrobial Resistance (MAR) indices of 0.66, 0.76, 0.8, 0.84, and 0.81, 0.76, 0.84, 0.41 for broiler and layer chicken, respectively. Providencia stuartii and Salmonella enterica, exclusive to broiler samples, had MAR indices of 0.82 and 0.84, respectively. Additional isolates Morganella morganii, Aeromonas spp., and Wohlfahrtiimonas chitiniclastica were found in layers (Average MAR indices: 0.73, 0.71, and 0.91). Notably, M. morganii, E. hormaechei and W. chitiniclastica were identified for the first time in Bangladeshi poultry chicken, although their evolution is yet to be understood. In this study, Pan-drug resistance was observed in one P. stuartii (broiler) and one Aeromonas spp. (layer) with a MAR index 1, while all isolates exhibited MAR indices >0.2, indicating MDR. Antimicrobial resistance (AMR) gene screening identified blaTEM, blaSHV, tetA, and sul1 in a majority of the MDR strains. Interestingly, E. coli (lactose positive and negative) and E. hormaechei were exclusively found to possess the tetB gene. In addition, E. coli (lactose negative), Klebsiella pneumoniae, Enterobacter hormaechei, M. morganii, and P. stuartii were observed to carry the colistin-resistant mcr-1 gene, whereas sul2 was detected in E. coli (lactose positive and negative), E. hormaechei, P. stuartii, and P. penneri. These findings emphasize the health risk of our consumers of both broiler and layer chickens as they have turned into a potent reservoir of various AMR gene carrying MDR and Pan-drug resistant bacteria., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Munim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Annually, Sierra Leone records an estimated 301 human fatalities due to rabies. Canine vaccination is crucial for rabies prevention and control efforts. However, considerable variability exists in vaccination rates. Reasons for this variation remain unclear. We conducted a cross-sectional study across 2,558 dog-owning households (HHs) to provide insights into factors influencing canine vaccination for targeted prevention and control towards elimination by 2030. First, we described dog ownership practices, then built a probabilistic model to understand factors associated with dog vaccination, and finally used a spatial scan statistic to identify spatial clusters where vaccination rates were low. Our results indicated that only 14% (358/2,558) of participating HHs had fully vaccinated their dogs against rabies. The probability of dog vaccination increased when comparing civil servants to private workers/artisans, with an Odds Ratio(OR) of 1.14 (95% credible interval (Crl) of 0.82-1.56), residing in locations with a veterinary establishment vs. none (OR = 6.43, 95% Crl (4.97-8.35), providing care to dogs vs. allowing dogs to roam freely (OR = 2.38, 95% Crl(1.80-3.17) and owning a single dog vs multiple dogs (OR = 1.20, 95 Crl (0.92-1.56). Conversely, there was a decrease in the estimated probability of vaccination when comparing dog owners located in rural vs. urban areas (OR = 0.58, CrI 95% (0.43-0.78). Latent understanding, a measure of overall understanding of rabies virus, which we estimated using participant education levels and responses to questions about rabies epidemiology, was also an important predictor of vaccination probability (OR = 1.44, 95% Crl (1.04-2.07). The spatial analysis identified high-risk clusters for low vaccination in the cities of Moyamba, with a radius of 40 km, a relative risk (RR) of 1.10, and Bo, with a radius of 19.9 km with RR of 1.11. These data do not support Sierra Leone reaching the 2030 goal of human rabies elimination caused by dogs. Our study highlights a critical need for public outreach and education, improved vaccination rates, increased accessibility to veterinary services, and targeted interventions in Bo and Moyamba to support rabies prevention and control efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mshelbwala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To make sonographic evaluation for biliary atresia (BA) more objective and reproducible using scoring systems, and evaluate hepatic shear wave elastography (SWE) as an adjunct in sonographic diagnosis of BA., Methods: Sixty-four infants with cholestatic jaundice were enrolled between June 2016 and March 2018 in this prospective observational cohort study. Sonography and SWE was performed with SuperSonic Aixplorer system. Novel scoring systems were developed incorporating established sonographic parameters and hepatic stiffness values and analysed using SPSS software., Results: Of the 18 patients confirmed as BA, 3 were misdiagnosed on conventional sonography (16.7%) as non-BA. Gall bladder (GB) wall irregularity and fasting GB length were the most accurate (93.8%) and most specific (97.8%) individual parameters, respectively. A significant difference was noted in the triangular cord (TC) thickness of BA and non-BA infants (p <0.001), with a high specificity of 95.6% for a 4 mm cut-off value for a positive TC sign. Comparison of hepatic SWE stiffness among age-matched groups of BA and non-BA showed significant differences (≤60 d: p = 0.003; >60 d: p <0.001) but with a reduced accuracy (93.8%). Diagnostic accuracy of greyscale scoring system (96.9%), greyscale + elastography scoring system in ≤60 d (94.4%) and >60 d (97.8%) were better than that of conventional sonographic diagnosis (93.8%)., Conclusions: Grey scale scoring system improves the accuracy of sonographic diagnosis of BA without any additional cost or time penalty along with making it universally reproducible. SWE has only an adjunctive role, if any, in the sonographic diagnosis of BA., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

This study investigated the early impact of a community-based food intervention, the Good Food Junction (GFJ), a full-service grocery store (September 2012 - January 2016) in a former food desert in Saskatoon, Canada. The hypothesis tested was that frequent shopping at the GFJ improved food security and selected health-related outcomes among shoppers, and the impact was moderated by socioeconomic factors. Longitudinal data were collected from 156 GFJ shoppers, on three occasions: 12-, 18-, and 24-months post-opening. Participants were grouped into three categories based on the frequency of shopping at the GFJ: low, moderate, and high. A generalized estimating equations approach was used for model building; moderating effects were tested. Participants were predominantly female, Indigenous, low-income, and had high school or some post-secondary education. The GFJ use was associated with household food security (OR for high and moderate frequency shoppers reporting less than a high school education were 1.81 and 1.06, respectively), and mental health (OR for high and moderate frequency shoppers reporting high income were 2.82 and 0.87, respectively) exhibiting a dose-response relationship, and indicated that these outcomes were significantly moderated by participants' socioeconomic factors. Shopping at the GFJ had a positive effect on food security and mental health, but to varying levels for those with low incomes, with less than high school or high school or better levels of education., (© 2024. The Author(s).)

Objectives: We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon., Materials and Methods: We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls. All underwent screening for serum anti-tissue transglutaminase and endoscopic upper small bowel biopsy. Immunohistochemical markers were used to investigate ISC niche alterations, including LGR5 for crypt basal cells (CBC), Bmi1 for position 4+ cells, β-Defensin for Paneth cells, R-spondin1 as WNT activator, transcription factor-4 as WNT transcription factor, BMP receptor1A as WNT inhibitor, fibronectin-1 as periepithelial stromal cell marker, H2AX as apoptosis marker, and Ki67 as proliferation marker. We also analyzed IgA anti-tTG2 antibody deposits by using dual-color immunofluorescence staining., Results: We found that in biopsies from patients with treatment-naive CeD with modified Marsh grade 3a-3c changes, the epithelial H2AX apoptotic index was upregulated than in controls. LGR5+ crypt basal cells were upregulated in all modified Marsh grades compared to controls. However, the Ki67 proliferation index, expressions of WNT-activator RSPO1, and position-4 cell marker Bmi1 did not significantly alter in patients' biopsies as compared to controls ( P = 0.001). We also observed depletion of pericrypt stromal fibronectin-1 in patients with CeD compared to controls. In addition, we identified IgA anti-TG2 antibody deposits in pericrypt stroma., Conclusions: Our data suggests that ISC niche failure is a plausible hypothesis for villous flattening in patients with CeD, resulting from pericrypt IgA anti-TG2 antibody complex-mediated stromal depletion., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Introduction: Hidden hunger or micronutrient deficiencies are quite common in many parts of the world, particularly in the countries of sub-Saharan Africa and South Asia. Micronutrient deficiencies may impact insulin signalling pathways and glucose metabolism, potentially accelerating the onset and development of type 2 diabetes (T2D). This review aims to estimate the prevalence of multiple micronutrient deficiencies among patients with T2D and assess the effect of their deficiency on glycaemic control., Methodology: The review follows the Cochrane Handbook and PRISMA 2020 guidelines. It includes all eligible studies reporting the prevalence of micronutrient deficiencies and their effect on glycaemic control in T2D patients. We would undertake a comprehensive literature search across databases: PubMed, Scopus, EMBASE, LILACS, ProQuest, Google Scholar and grey literature, and identify the studies meeting the inclusion criteria. We would perform data extraction using a prepiloted data extraction sheet and record relevant study characteristics and outcomes., Analysis: Data will be analysed using JBI Sumari software and R software. Pooled prevalence/incidence of micronutrient deficiency will be estimated, and variance will be stabilised using logit transformation and a double-arcsine transformation of the data. The OR and risk ratio of glycaemic control among T2D cases with and without micronutrient deficiency will be estimated using the 'rma' function under the 'meta' and 'metafor' packages.The study findings will have implications for diabetes management strategies and may inform interventions targeting improved glycaemic control through addressing micronutrient deficiencies., Ethics and Dissemination: This systematic review will be based on the scientific information available in the public domain; therefore, ethics approval is not required. We will share the study findings at national and international conferences and submit them for publication in relevant scientific journals., Prospero Registration Number: CRD42023439780., Competing Interests: Competing interests: FA declares potential conflicts of interest as employees of Abbott, the study sponsor., (© 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.)

Self-wetting is the leakage of urine, either due to the medical condition of urinary incontinence (UI), or because a person does not want to, or cannot, access a toileting facility in time. This study explored the attitudes towards self-wetting and experiences of children (aged five to 11), their caregivers, community leaders and humanitarian practitioners in the Rohingya refugee camps in Cox's Bazar, Bangladesh. We particularly focused on how water, sanitation and hygiene (WASH) and protection interventions might assist in improving these experiences. We purposively selected participants from two camps where our partner organisation works. We conducted Key Informant Interviews (KIIs) with community leaders and camp officials, Story Book (SB) sessions with Rohingya children and in-depth Interviews (IDIs) with caregivers of children who participated in the SB sessions, as well as surveying communal toilets. Self-wetting by children was common and resulted in them feeling embarrassed, upset and uncomfortable, and frightened to use the toilet at night; many children also indicated that they would be punished by their caregivers for self-wetting. Key informants indicated that caregivers have difficulty handling children's self-wetting due to a limited amount of clothing, pillows, and blankets, and difficulty cleaning these items. It was evident that the available toilets are often not appropriate and/or accessible for children. Children in the Rohingya camps appear to self-wet due to both the medical condition of UI and because the sanitation facilities are inappropriate. They are teased by their peers and punished by their caregivers. Although WASH and protection practitioners are unable to drastically alter camp conditions or treat UI, the lives of children who self-wet in these camps could likely be improved by increasing awareness on self-wetting to decrease stigma and ease the concerns of caregivers, increasing the number of child-friendly toilets and increasing the provision of continence management materials., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Mahbub-Ul Alam is currently serving on the editorial board of PLOS Global Public Health. This does not alter our adherence to PLOS policies on sharing data and materials., (Copyright: © 2024 Alam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The homeostatic regulation of serine palmitoyltransferase (SPT) activity in yeast involves N-terminal phosphorylation of Orm proteins, while higher eukaryotes lack these phosphorylation sites. Although recent studies have indicated a conserved ceramide-mediated feedback inhibition of the SPT-ORM/ORMDL complex in higher eukaryotes, its conservation and relationship with phosphorylation regulation in yeast remain unclear. Here, we determine the structure of the yeast SPT-Orm2 complex in a dephosphomimetic state and identify an evolutionarily conserved ceramide-sensing site. Ceramide stabilizes the dephosphomimetic Orm2 in an inhibitory conformation, facilitated by an intramolecular β-sheet between the N- and C-terminal segments of Orm2. Moreover, we find that a phosphomimetic mutant of Orm2, positioned adjacent to its intramolecular β-sheet, destabilizes the inhibitory conformation of Orm2. Taken together, our findings suggest that both Orm dephosphorylation and ceramide binding are crucial for suppressing SPT activity in yeast. This highlights a distinctive regulatory mechanism in yeast involving the collaborative actions of phosphorylation and ceramide., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS., Methods: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed., Results: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2 -associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS., Conclusions: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls., Methods: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed., Results: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear β-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation., Conclusions: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Introduction: Diabetes is a chronic disorder with long-term sequelae and multisystem manifestation. Burden of diabetes in on the rise. Presence of other morbidities can not only have a detrimental effect on the disease treatment and recovery course, but also on the financial burden and quality of life. Present study aims to investigate how musculoskeletal conditions affect individuals with diabetes compared to those without the condition., Material and Methods: A comparative study was conducted among patients attending the outpatient department of a tertiary care hospital in North India to assess the burden of musculoskeletal disorders in people with and without diabetes. A total of 195 diabetes patients and an equal number of individuals without diabetes were sequentially enrolled from the outpatient department (OPD)., Results: Burden of musculoskeletal comorbidities was significantly higher (46.2%) among people with diabetes than the comparison group (25.1%). The overall odds ratio (OR) for comorbidities of musculoskeletal system was 2.5 times higher in diabetes cases as compared to individuals without diabetes. The OR for rheumatoid arthritis, chronic backache, and osteoarthritis was found to be 3.6, 2.9, and 1.7 respectively. Poor quality of life and higher direct cost of treatment were found among diabetes cases with musculoskeletal comorbidities as against those without these comorbidities., Conclusion: Presence of musculoskeletal comorbidity is high among diabetes patients, and it has an impact on the quality of life and treatment cost. Screening for musculoskeletal comorbidities should be included as part of the diabetes complication assessment to allow for early detection and treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Community Medicine.)

The demand for engineered scaffolds capable of delivering multiple cues to cells continues to grow as the interplay between cell fate with microenvironmental and external cues is revealed. Emphasis has been given to develop stimuli-responsive scaffolds. These scaffolds are designed to sense an external stimulus triggering a specific response (e.g., change in the microenvironment, release therapeutics, etc.) and then initiate/modulate a desired biofunction. Here, magnetic-responsive carboxylated multi-walled carbon nanotubes (cMWCNTs) are integrated into 3D collagen/polylactic acid (PLA) scaffold via a reproducible filtration-based method. The integrity and biomechanical performance of the collagen/PLA scaffolds are preserved after cMWCNT integration. In vitro safety assessment of cMWCNT/collagen/PLA scaffolds shows neither cytotoxicity effects nor macrophage pro-inflammatory response, supporting further in vitro studies. The cMWCNT/collagen/PLA scaffolds enhance chondrocytes metabolic activity while maintaining high cell viability and extracellular matrix (i.e., type II collagen and aggrecan) production. Comprehensive in vitro study applying static and pulsed magnetic field on seeded scaffolds shows no specific cell response in dependence with the applied field. This result is independent of the presence or absence of cMWCNT into the collagen/PLA scaffolds. Taken together, these findings provide additional evidence of the benefits to exploit the CNTs outstanding properties in the design of stimuli-responsive scaffolds., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Background: Staphylococcus aureus is a gram-positive spherical bacteria and the most common cause of nosocomial infections in the world. Given its clinical significance, the genome sequence of S. aureus has been elucidated to enhance our comprehension of its lifestyle and pathogenicity. The research aimed to summarize a potential hypothetical protein that may play an important role in S. aureus virulence and pathogenicity, covering its anticipated structure, probable biological functions, and importance in this context., Results: A hypothetical protein, YP&#95;498675.1 with 281 amino acid residues of S. aureus, was chosen for analysis and modeling by several bioinformatics tools and databases in this work. According to primary and secondary structure analyses, YP&#95;498675.1 is a stable hydrophilic protein with a significant proportion of α-helices. Subcellular localization predictions by CELLO, PSORTb, and SOSUI server indicate that it is a cytoplasmic protein. NCBI-CDD, Pfam, and InterProScan functional genomics research revealed that the hypothetical protein may include the pyridoxal phosphate (PLP)-dependent 2, 3-diaminopropionate biosynthesis protein SbnA domain. In the homology modeling method, the HHpred server was employed to create its 3D structure using the template structure of a Staphyloferrin B precursor biosynthetic enzyme SbnA bound to PLP (PDB ID: 5D84&#95;A), an X-ray diffraction model having 100% sequence identity with the hypothetical protein. After energy minimization, several quality assessments and validation factors determined that the generated protein model was reliable and of reasonable quality., Conclusion: The present study has characterized and functionally annotated the hypothetical protein YP&#95;498675.1 of S. aureus. Further experimental validation would aid in determining the actual function of YP&#95;498675.1 as well as confirm the protein's value as a therapeutic target., (© 2023. The Author(s).)

We report an unusual spin-direction-spin coupling phenomenon of light using the leaky quasiguided modes of a waveguided plasmonic crystal. This is demonstrated as simultaneous input spin-dependent directional guiding of waves (spin-direction coupling) and wave-vector-dependent spin acquisition (direction-spin coupling) of the scattered light. These effects, manifested as the forward and the inverse spin Hall effect of light in the far field, and other accompanying spin-orbit interaction effects are observed and analyzed using a momentum (k) domain polarization Mueller matrix. Resonance-enabled enhancement of these effects is also demonstrated by utilizing the spectral Fano resonance of the hybridized modes. The fundamental origin and the unconventional manifestation of the spin-direction-spin coupling phenomenon from a relatively simple system, ability to probe and interpret the resulting spin-orbit phenomena in the far field through momentum-domain polarization analysis, and their regulated control in plasmonic-photonic crystals open up exciting avenues in spin-orbit-photonic research.

Plants have diverse molecular mechanisms to protect themselves from biotic and abiotic stressors and adapt to changing environments. To uncover the genetic potential of plants, it is crucial to understand how they adapt to adverse conditions by analyzing their genomic data. We analyzed RNA-Seq data from different tomato genotypes, tissue types, and drought durations. We used a time series scale to identify early and late drought-responsive gene modules and applied a machine learning method to identify the best responsive genes to drought. We demonstrated six candidate genes of tomato viz. Fasciclin-like arabinogalactan protein 2 (FLA2), Amino acid transporter family protein (ASCT), Arginine decarboxylase 1 (ADC1), Protein NRT1/PTR family 7.3 (NPF7.3), BAG family molecular chaperone regulator 5 (BAG5) and Dicer-like 2b (DCL2b) were responsive to drought. We constructed gene association networks to identify their potential interactors and found them drought-responsive. The identified candidate genes can help to explore the adaptation of tomato plants to drought. Furthermore, these candidate genes can have far-reaching implications for molecular breeding and genome editing in tomatoes, providing insights into the molecular mechanisms that underlie drought adaptation. This research underscores the importance of the genetic basis of plant adaptation, particularly in changing climates and growing populations., (© 2023. The Author(s).)

Ganga river surface sediment was sampled from 11 locations, which revealed average concentrations (mg/kg) of metals in the order Mn (296.93) > Zn (61.94) > Cr (54.82) > Cu (30.19) > Pb (24.42) > Cd (0.36). Sediment quality guidelines showed metals rarely to occasionally exhibit adverse biological effects. Indices like potential ecological risk, contamination security index, hazard quotients, multiple probable effect concentrations quality, mean probable effects level quotients, mean effects range median quotient suggest nil to a very low level of pollution with low ecological risk. Contamination factor, geo accumulation index, enrichment factor, quantification of contamination revealed that Pb and Cd originated from anthropogenic activities. APCS-MLR model revealed that metals contributed from natural sources (Zn, Mn, Cr; 20.18 %), industrial-agricultural (Cd; 21.35 %); and discharge of paints, Pb batteries, fossil fuel (Pb; 8.49 %). Present findings will serve as an effective guideline for managing and ameliorating pollution in the river system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Hereditary tumor syndrome Von Hippel-Lindau (VHL) disease is characterized by various benign and malignant tumors that are known to express somatostatin receptors (SSTR). We evaluated the role of 68 Ga-DOTANOC PET/CT scan in patients with positive germline mutation of the VHL gene, presented initially or on follow-up, for the detection of recurrent or synchronous/metachronous lesions., Methods: Fourteen patients (8 males; 6 females) with mean age 30 ± 9.86 years were retrospectively analyzed, were tested positive for VHL on gene dosage analysis, and underwent 68  Ga-DOTANOC PET/CT scan for disease evaluation. The number and site of lesions were determined. The tracer uptake was analyzed semi-quantitatively by calculating the maximum standardized uptake values (SUVmax) of lesion., Results: Four of the 14 patients underwent scan for initial diagnosis as baseline, 6 patients for post-therapy disease status, and 4 patients for initial diagnosis as well as follow-up evaluation of the disease. A total of 67 lesions were detected in 14 patients. The sites of lesions were cerebellar/vertebral/spinal (17; mean SUVmax = 7.85); pancreatic neuroendocrine tumor (NET) (11; mean SUVmax = 20.64); retina (3; mean SUVmax = 10.46); pheochromocytoma (10; mean SUVmax = 16.32); paragangliomas (3; mean SUVmax = 10.65); pancreatic cyst (9; mean SUVmax = 2.54); and renal cyst (8; mean SUVmax = 1.56) and miscellaneous lesions constituted 6 lesions., Conclusion: Our results show that 68  Ga-DOTANOC PET/CT may be a useful modality for screening and follow-up of associated tumors in patients with germline gene mutation for VHL. It can be used as a one-stop imaging modality for VHL patients and may substitute for separate radiological investigations, making it more convenient for patients in terms of time and cost., Competing Interests: Conflict of InterestShamim Ahmed Shamim, Geetanjali Arora, Naresh Kumar, Jhangir Hussain, Shreya Datta Gupta, Arun Raj ST, Kritin Shankar, Alpesh Goyal, Rajesh Khadgawat, Sambit Sagar, and Chandrasekhar Bal declare no conflict of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Pigeon circovirus (PiCV) is considered to be genetically diverse, with a relatively small circular single-stranded DNA genome of 2 kb that encodes for a capsid protein (Cap) and a replication initiator protein (Rep). Australasia is known to be the origin of diverse species of the Order Columbiformes, but limited data on the PiCV genome sequence has hindered phylogeographic studies in this species. To fill this gap, this study was conducted to investigate PiCV in 118 characteristic samples from different birds across Australia using PCR and sequencing. Eighteen partial PiCV Rep sequences and one complete PiCV genome sequence were recovered from reservoir and aberrant hosts. Phylogenetic analyses revealed that PiCV circulating in Australia was scattered across three different subclades. Importantly, one subclade dominated within the PiCV sequenced from Australia and Poland, whereas other PiCV sequenced in this study were more closely related to the PiCV sequenced from China, USA and Japan. In addition, PiCV Rep sequences obtained from clinically affected plumed whistling duck, blue billed duck and Australian magpie demonstrated natural spillover of PiCV unveiled host generalist characteristics of the pigeon circovirus. These findings indicate that PiCV genomes circulating in Australia lack host adapted population structure but demonstrate natural spillover infection., Competing Interests: The authors declare no conflict of interest.

The frequency and intensity of climate change and resulting impacts are more prevalent in South Asian countries, particularly in Bangladesh. Relative humidity (RH) is a crucial aspect of climate, and higher RH variability has far-reaching impacts on human health, agriculture, environment, and infrastructure. While temperature and rainfall have gained much research attention, RH studies have received scant attention in the research literature. This study investigated the trends and variability of RH levels in Bangladesh and the influence of other meteorological factors over the past 40 years. Variabilities in the meteorological factors were identified by calculating descriptive statistics. Innovative trend analysis (ITA) and Mann-Kendall test (MK-test) methods were utilized to assess monthly, seasonal, and annual trends. The magnitude of temperature, rainfall, and windspeed influences on RH variability were identified using Pearson's correlation, Spearman rank correlation, and Kendall correlation model. Variability analysis showed higher spatial variations in RH levels across the country, and RH skewed negatively in all stations. Results reveal that daily, monthly, seasonal, and annual trends of RH exhibited positive trends in all stations, with an increasing rate of 0.083-0.53% per year in summer, 0.43-0.68% per year in winter, and 0.58-0.31% per year in the rainy season. Both ITA and MK-test provided consistent results, indicating no discrepancies in trend results. All three models indicate that temperature, rainfall, and windspeed have weak to moderate positive influences on changing RH levels in Bangladesh. The study will contribute to decision-making to improve crop yields, health outcomes, and infrastructure efficiency., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Type 2 diabetes mellitus (T2DM) is a multifactorial, polygenic, and metabolically complicated disease. A large number of genes are responsible for the biogenesis of T2DM and calpain10 (CAPN10) is one of them. The association of numerous CAPN10 genetic polymorphisms in the development of T2DM has been widely studied in different populations and noticed inconclusive results. The present study is an attempt to evaluate the plausible association of CAPN10 polymorphism SNP-19 (rs3842570) with T2DM and T2DM-related anthropometric and metabolic traits in the Noakhali region of Bangladesh. This case-control study included 202 T2DM patients and 75 healthy individuals from different places in Noakhali. A significant association (p < 0.05) of SNP-19 with T2DM in co-dominant 2R/3R vs. 3R/3R (odds ratio [OR], 2.7; p=0.0014) and dominant (2R/3R) + (2R/2R) vs. 3R/3R (OR, 2.47; p=0.0011) genetic models was observed. High-risk allele 2R also showed a significant association with T2DM in the allelic model (OR, 1.67; p=0.0109). The genotypic frequency of SNP-19 variants showed consistency with Hardy-Weinberg equilibrium (p > 0.05). Additionally, SNP-19 genetic variants showed potential associations with the anthropometric and metabolic traits of T2DM patients in terms of body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglycerides. Our approach identifies the 2R/3R genotype of SNP-19 as a significant risk factor for biogenesis of T2DM in the Noakhali population. Furthermore, a large-scale study could be instrumental to correlate this finding in overall Bangladeshi population.

A 5-year retrospective study was conducted to describe the mastitis-causing organisms isolated from bovine milk samples submitted to four veterinary diagnostic laboratories in Australia. The aim of this study was to identify temporal, geographical, and seasonal patterns of occurrence for the organisms and report the in vitro susceptibility of the most common mastitis-causing pathogens. In total, 22,102 milk samples were submitted between 2015 and 2019. The results were reported as positive growth for at least one significant organism ( n = 11,407; 51.6%), no growth ( n = 5,782; 26.2%), and mixed/contaminated growth ( n = 4,913; 22.2%). Culture results for no growth, gram-negative bacteria, and eukaryotic organisms were combined for each region, and they were accounted for between 23 and 46% of submissions. These results represent a subset of mastitis cases for which the antibiotic treatment may not be warranted. A total of 11,907 isolates were cultured from 11,407 milk samples. The most common isolated organisms were Streptococcus uberis [41.3%; 95% confidence interval (CI): 40.4-42.1%] and Staphylococcus aureus (23.6%; 95% CI: 22.8-24.3%). For S. uberis and S. aureus , there was an association between a positive culture result and the dairy region. All regions except for the Sub-tropical Dairy region were more likely to culture S. uberis compared to the reference, Dairy NSW ( P < 0.001). Similarly, for S. aureus , a positive culture result was more likely in all other dairy regions compared to Dairy NSW ( P < 0.001). The LISA cluster analysis identified differences between High-High (hotspot) postcodes for S . aureus and S . uberis throughout all the analyzed dairy regions. These results highlight the need for further investigations into specific risk factors, such as environmental factors and herd-level predictors, which may have influenced the observed regional variations. Common mastitis-causing pathogens showed overall good susceptibility to a range of antimicrobials used in the treatment of mastitis. On-going surveillance of mastitis-causing pathogens and their antimicrobial susceptibilities will facilitate targeted mastitis control and treatment programs., Competing Interests: MH is employed by The Milk Road. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Langhorne, Gupta, Horsman, Wood, Wood, Barker, Deutscher, Price, McGowan, Humphris, Ranjbar, Henning and Gibson.)

Objective: To report on vaccination status by 12 months of age among tribal children from nine districts of India., Methods: Cross-sectional study of 2631 tribal women having a child aged 12 months or below from nine Indian districts with a considerable proportion of the tribal population. Socio-demographic details, reception of various vaccines by 12 months of age, mother's antenatal care utilisation and health system-related details were collected through a pre-tested, interviewer-administered questionnaire from mothers. Multiple logistic regression analysis was used to identify the factors associated with complete vaccination by 12 months of age., Results: Only 52% of children were fully vaccinated by the age of 12 months among the tribal populations; 11% did not receive any vaccine, and 37% of the tribal children received some vaccines. The age-appropriate vaccination was unsatisfactory as only 75% of the infants received all birth dose vaccines, and only 60.5% received all doses by 14 weeks. Only 73% were vaccinated against measles. Illness of the child, home births and communication gaps concerning vaccination were the main reasons for an infant not being vaccinated appropriately. Frequency of health worker's visits to the village, hospital birth, reception of advice on vaccination and educational status of the head of the households were significantly associated with full vaccination status., Conclusion: A relatively low proportion of children were fully vaccinated among the tribal populations. Health systems factors, mainly the outreach services and advice by the health workers, were positively and significantly associated with a child being fully vaccinated by 12 months of age. Improving outreach services is crucial to improve vaccination coverage in tribal areas, and there is a need to address the social determinants in the long run., (© 2023 John Wiley & Sons Ltd.)

Carbon dioxide (CO 2 ) is considered one of the eco-related key factors that negatively affect global climatic change. Also, CO 2 can play an important role in the postharvest quality of the agri-products. In this study, the impact of CO 2 on the quality of postharvest onions that were stored at 23 °C for 8 weeks was investigated. The weight loss, phenolic, flavonoid, flavanol, anthocyanin, antioxidant activity, and soluble sugar were analyzed during the study period. The results showed that 20% CO 2 treatment was significantly (P > 0.05) more effective than 15% CO 2 and control in inhibiting weight loss. Additionally, 20% CO 2 treatment significantly retained higher antioxidant enzyme activities such as CAT, APX, and SOD than 15% CO 2 and control. During storage, 20% CO 2 treatment significantly (P < 0.05) improved glucose, fructose, and sucrose levels by more than 15% CO 2 exposure and control groups. Besides the chlorogenic acid, kaempferol and quercetin were significantly (P < 0.05) higher in the 20% CO 2 than in the 15% CO 2 after 2 weeks of storage. In conclusion, this study's novelty comes from the broad prospects of using CO 2 for maximizing the stored onion phytochemical functionality that is usually affected by the room temperature long storage. This will help in the onion shelf-life extension by considering the quality-related attributes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: In the Canadian province of Saskatchewan, the global COVID-19 pandemic appeared amidst existing social health challenges in food insecurity, housing precarity and homelessness, poor mental health, and substance misuse. These chronic features intersected with the pandemic, producing a moment in time when the urgency of COVID-19 brought attention to underlying shortcomings in public health services., Objective: The objectives of the program of research are (1) to identify and measure relationships between the pandemic and wider health and social impacts, namely, food insecurity, housing precarity and homelessness, and mental health and substance use in Saskatchewan, and (2) to create an oral history of the pandemic in Saskatchewan in an accessible digital public archive., Methods: We are using a mixed methods approach to identify the impacts of the pandemic on specific equity-seeking groups and areas of social health concern by developing cross-sectional population-based surveys and producing results based on statistical analysis. We augmented the quantitative analysis by conducting qualitative interviews and oral histories to generate more granular details of people's experiences of the pandemic. We are focusing on frontline workers, other service providers, and individuals within equity-seeking groups. We are capturing digital evidence and social media posts; we are collecting and organizing key threads using a free open-source research tool, Zotero, to trace the digital evidence of the pandemic in Saskatchewan. This study is approved by the Research Ethics Board at the University of Saskatchewan (Beh-1945)., Results: Funding for this program of research was received in March and April 2022. Survey data were collected between July and November 2022. The collection of oral histories began in June 2022 and concluded in March 2023. In total, 30 oral histories have been collected at the time of this writing. Qualitative interviews began in April 2022 and will continue until March 2024. Survey analysis began in January 2023, and results are expected to be published in mid-2023. All data and stories collected in this work are archived for preservation and freely accessible on the Remember Rebuild Saskatchewan project's website. We will share results in academic journals and conferences, town halls and community gatherings, social and digital media reports, and through collaborative exhibitions with public library systems., Conclusions: The pandemic's ephemeral nature poses a risk of us "forgetting" this moment and the attendant social inequities. These challenges inspired a novel fusion among health researchers, historians, librarians, and service providers in the creation of the Remember Rebuild Saskatchewan project, which focuses on preserving the legacy of the pandemic and capturing data to support an equitable recovery in Saskatchewan., International Registered Report Identifier (irrid): DERR1-10.2196/46643., (©Nazeem Muhajarine, James Dixon, Erika Dyck, Jim Clifford, Patrick Chassé, Suvadra Datta Gupta, Colleen Christopherson-Cote, Remember Rebuild Saskatchewan Team. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.06.2023.)

Purpose: The purpose of this study was to evaluate the effect of nutritional-deficiency anemia (NDA) on peripapillary retinal nerve fiber layer thickness (PPRNFLT) using spectral-domain optical coherence tomography and to determine any correlation arising thereof. This was a single-center, cross-sectional, observational study., Materials and Methods: A total 115 eyes of 115 NDA patients (50 of each with iron-deficiency anemia [IDA] and Vitamin B12-deficiency anemia [BDA], and 15 with folic acid-deficiency anemia [FDA]) aged 18-65 years were compared with a total 100 eyes of 50 age- and sex-matched healthy controls. All subjects underwent comprehensive clinical, ophthalmic, and hematological evaluation, followed by PPRNFLT assessment for the mean total, superior, inferior, nasal, and temporal quadrants., Results: PPRNFLT for the mean total and all four quadrants in IDA patients, for the mean total, inferior, nasal, and temporal quadrants in BDA patients, and for the mean total, inferior, and nasal quadrants, in FDA patients, was significantly lower as compared to the controls ( P < 0.05). The mean total PPRNFLT of all NDA patients correlated significantly ( P < 0.05) with their relevant hematological parameters with Pearson's coefficient ( r ) value of 0.613, 0.610, 0.336, 0.295, 0.337, 0.374, and - 0.509, respectively, for serum haemoglobin (Hb), iron, ferritin, mean corpuscular volume (MCV), mean cell hemoglobin, mean corpuscular hemoglobin concentration, and total iron binding capacity in IDA; 0.310, 0.435, and - 0.386, respectively, for serum Hb%, Vitamin B12, and MCV in BDA; and 0.557, 0.358, and - 0.294 for Hb%, folate, and MCV, respectively, in FDA cases. Mean total retinal nerve fiber layer thinning of all NDA patients showed progression with the increasing severity grades of anemia, except in very severe BDA where an inverse relationship was documented., Conclusion: Our study revealed that PPRNFLT is significantly thinner in all NDA patients (total and all four quadrants in IDA; total, inferior, nasal, and temporal in BDA; and total, inferior, and nasal in FDA) correlating well with their relevant hematological parameters. Early detection of this may be crucial in preventing potential blinding sequelae and differentiating glaucomatous and other neuro-ophthalmic disorders., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2023 Taiwan J Ophthalmol.)

Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they are abundant in myelin membranes. Serine palmitoyltransferase, the enzyme that catalyses the rate-limiting reaction of sphingolipid synthesis, is composed of multiple subunits including an activating subunit, SPTSSA. Sphingolipids are both essential and cytotoxic and their synthesis must therefore be tightly regulated. Key to the homeostatic regulation are the ORMDL proteins that are bound to serine palmitoyltransferase and mediate feedback inhibition of enzymatic activity when sphingolipid levels become excessive. Exome sequencing identified potential disease-causing variants in SPTSSA in three children presenting with a complex form of hereditary spastic paraplegia. The effect of these variants on the catalytic activity and homeostatic regulation of serine palmitoyltransferase was investigated in human embryonic kidney cells, patient fibroblasts and Drosophila. Our results showed that two different pathogenic variants in SPTSSA caused a hereditary spastic paraplegia resulting in progressive motor disturbance with variable sensorineural hearing loss and language/cognitive dysfunction in three individuals. The variants in SPTSSA impaired the negative regulation of serine palmitoyltransferase by ORMDLs leading to excessive sphingolipid synthesis based on biochemical studies and in vivo studies in Drosophila. These findings support the pathogenicity of the SPTSSA variants and point to excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase as responsible for defects in early brain development and function., (Published by Oxford University Press on behalf of the Guarantors of Brain 2023.)

The serine palmitoyltransferase (SPT) complex catalyzes the first and rate-limiting step in sphingolipid biosynthesis in all eukaryotes. ORM/ORMDL proteins are negative regulators of SPT that respond to cellular sphingolipid levels. However, the molecular basis underlying ORM/ORMDL-dependent homeostatic regulation of SPT is not well understood. We determined the cryo-electron microscopy structure of Arabidopsis SPT-ORM1 complex, composed of LCB1, LCB2a, SPTssa, and ORM1, in an inhibited state. A ceramide molecule is sandwiched between ORM1 and LCB2a in the cytosolic membrane leaflet. Ceramide binding is critical for the ORM1-dependent SPT repression, and dihydroceramides and phytoceramides differentially affect this repression. A hybrid β sheet, formed by the amino termini of ORM1 and LCB2a and induced by ceramide binding, stabilizes the amino terminus of ORM1 in an inhibitory conformation. Our findings provide mechanistic insights into sphingolipid homeostatic regulation via the binding of ceramide to the SPT-ORM/ORMDL complex that may have implications for plant-specific processes such as the hypersensitive response for microbial pathogen resistance.

The gram-positive bacterium Listeria monocytogenes is an important foodborne intracellular pathogen that is widespread in the environment. The functions of hypothetical proteins (HP) from various pathogenic bacteria have been successfully annotated using a variety of bioinformatics strategies. In this study, a HP Imo0888 (NP&#95;464414.1) from the Listeria monocytogenes EGD-e strain was annotated using several bioinformatics tools. Various techniques, including CELLO, PSORTb, and SOSUIGramN, identified the candidate protein as cytoplasmic. Domain and motif analysis revealed that the target protein is a PemK/MazFlike toxin protein of the type II toxin-antitoxin system (TAS) which was consistent with BLASTp analysis. Through secondary structure analysis, we found the random coil to be the most frequent. The Alpha Fold 2 Protein Structure Prediction Database was used to determine the three-dimensional (3D) structure of the HP using the template structure of a type II TAS PemK/MazF family toxin protein (DB ID&#95;AFDB: A0A4B9HQB9) with 99.1% sequence identity. Various quality evaluation tools, such as PROCHECK, ERRAT, Verify 3D, and QMEAN were used to validate the 3D structure. Following the YASARA energy minimization method, the target protein's 3D structure became more stable. The active site of the developed 3D structure was determined by the CASTp server. Most pathogens that harbor TAS create a crucial risk to human health. Our aim to annotate the HP Imo088 found in Listeria could offer a chance to understand bacterial pathogenicity and identify a number of potential targets for drug development.

Background: Building on a distinguished history of community medicine training, public health programs have been expanding in India in recent years. The COVID-19 pandemic has brought additional attention to the importance of public health programs and the need for a strong workforce. This paper aims to assess the current capacity for public health education and training in India and provide recommendations for improved approaches to meet current and future public health needs., Methods: We conducted a desk review of public health training programs via extensive internet searches, literature reviews, and expert faculty consultations. Among those programs, we purposively selected faculty members to participate in in-depth interviews. We developed summary statistics based on the desk review. For qualitative analysis, we utilized a combination of deductive and inductive coding to identify key themes and systematically reviewed the strengths and weaknesses of each theme., Results: The desk review captured 59 institutions offering public health training across India. The majority of training programs were graduate level degrees including Master of Public Health and Master of Science degrees. Key factors impacting these programs included collaborations, mentorship, curriculum standardization, tuition and funding, and student demand for public health education and careers. Collaborations and mentorship were highly valued but varied in quality across institutions. Curricula lacked standardization but also contained substantial flexibility and innovation as a result. Public sector programs were perceived to be affordable though fees and stipends varied across institutions. Further development of career opportunities in public health is needed., Conclusion: Public health education and training in India have a strong foothold. There are numerous opportunities for continued expansion and strengthening of this field, to support a robust multi-disciplinary public health workforce that will contribute towards achieving the sustainable development goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Schleiff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Heat shock protein 90 (Hsp90) is a promising anticancer target because of its chaperoning effect on multiple oncogenic proteins. The activity of Hsp90 is dependent on its ability to hydrolyze adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and free phosphate. The ATPase activity of Hsp90 is linked to its chaperoning function; ATP binds to the N-terminal domain of the Hsp90, and disrupting its binding was found to be the most successful strategy in suppressing Hsp90 function. The ATPase activity can be measured by a colorimetric malachite green assay, which determines the amount of free phosphate formed by ATP hydrolysis. Here, a procedure for determining the ATPase activity of yeast Hsp90 by using the malachite green phosphate assay kit is described. Further, detailed instructions for the discovery of Hsp90 inhibitors by taking geldanamycin as an authentic inhibitor is provided. Finally, the application of this assay protocol through the high-throughput screening (HTS) of inhibitor molecules against yeast Hsp90 is discussed.

Adapting the Social Cognitive Theory framework, we conducted a cross-sectional study on 137 commercial chicken farms in Bangladesh to investigate factors influencing the behaviour of farmers towards the application of antimicrobials to their birds. Almost all farmers used antimicrobials to treat poultry diseases, while 38.6% also were using them to promote healthy growth of chickens and 10.2% to increase egg production or improve meat quality. Using Structural Equation Modeling (SEM), we identified that inappropriate usage of antimicrobials (behaviour) was strongly driven by farmers' short-term goals to maintain the health of their chickens in a production cycle (β = 0.813, p = 0.029), rather than long-term concerns. Farmers' perception about their ability to control antimicrobial administration based on their skills and opportunities (self-efficacy) marginally influenced the short-term goals of antimicrobial usage (β = 0.301, p = 0.073). The results of this study can be used to develop targeted education programs for farmers, to reduce the application of antimicrobials in their poultry flocks., (© 2023. The Author(s).)

Non-invasive characterization of pancreatic masses aids in the management of pancreatic lesions. Intravoxel incoherent motion-diffusion kurtosis imaging (IVIM-DKI) and machine learning-based texture analysis was used to differentiate pancreatic masses such as pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine tumor (pNET), solid pseudopapillary epithelial neoplasm (SPEN), and mass-forming chronic pancreatitis (MFCP). A total of forty-eight biopsy-proven patients with pancreatic masses were recruited and classified into pNET (n = 13), MFCP (n = 6), SPEN (n = 4), and PDAC (n = 25) groups. All patients were scanned for IVIM-DKI sequences acquired with 14 b-values (0 to 2500 s/mm2) on a 1.5T MRI. An IVIM-DKI model with a 3D total variation (TV) penalty function was implemented to estimate the precise IVIM-DKI parametric maps. Texture analysis (TA) of the apparent diffusion coefficient (ADC) and IVIM-DKI parametric map was performed and reduced using the chi-square test. These features were fed to an artificial neural network (ANN) for characterization of pancreatic mass subtypes and validated by 5-fold cross-validation. Receiver operator characteristics (ROC) analyses were used to compute the area under curve (AUC). Perfusion fraction (f) was significantly higher (p < 0.05) in pNET than PDAC. The f showed better diagnostic performance for PDAC vs. MFCP with AUC:0.77. Both pseudo-diffusion coefficient (D*) and f for PDAC vs. pNET showed an AUC of 0.73. ADC and diffusion coefficient (D) showed good diagnostic performance for pNET vs. MFCP with AUC: 0.79 and 0.76, respectively. In the TA of PDAC vs. non-PDAC, f and combined IVIM-DKI parameters showed high accuracy ≥ 84.3% and AUC ≥ 0.84. Mean f and combined IVIM-DKI parameters estimated that the IVIM-DKI model with TV texture features has the potential to be helpful in characterizing pancreatic masses.

The hunt for novel antibiotics has become a global public health imperative due to the rise in multidrug-resistant microorganisms, untreatable infection cases, overuse, and inefficacy of modern antibiotics. Polyphenols are getting much attention in research due to their multiple biological effects; their use as antimicrobial agents is attributed to their activity and that microbes have a hard time developing resistance to these natural compounds. Polyphenols are secondary metabolites produced in higher plants. They are known to possess various functional properties in the human body. Polyphenols also exhibit antibacterial activities against foodborne pathogens. Their antibacterial mechanism is based on inhibiting bacterial biofilm formation or inactivating enzymes. This review focused on polyphenol-protein interactions and the creation of this complex as a possible antibacterial agent. Also, different phenolic interactions on bacterial proteins, efflux pump, cell membrane, bacterial adhesion, toxins, and other bacterial proteins will be explored; these interactions can work in a synergic combination with antibiotics or act alone to assure bacterial inhibition. Additionally, our review will focus on polyphenol-protein interaction as a possible strategy to eradicate bacteria because polyphenols have shown a robust enzyme-inhibitory characteristic and a high tendency to complex with proteins, a response that neutralizes any bactericidal potential.