2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities. BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

Elucidating Gender-Specific Distribution of Imipramine, Chloroquine, and Their Metabolites in Mice Kidney Tissues through AP-MALDI-MSI.

Knowledge of gender-specific drug distributions in different organs are of great importance for personalized medicine and reducing toxicity. However, such drug distributions have not been well studied. In this study, we investigated potential differences in the distribution of imipramine and chloroquine, as well as their metabolites, between male and female kidneys. Kidneys were collected from mice treated with imipramine or chloroquine and then subjected to atmospheric pressure matrix-assisted laser desorption ionization-mass spectrometry imaging (AP-MALDI-MSI). We observed differential distributions of the drugs and their metabolites between male and female kidneys. Imipramine showed prominent distributions in the cortex and medulla in male and female kidneys, respectively. Desipramine, one of the metabolites of imipramine, showed significantly higher (*** p < 0.001) distributions in the medulla of the male kidney compared to that of the female kidney. Chloroquine and its metabolites were accumulated in the pelvis of both male and female kidneys. Interestingly, they showed a characteristic distribution in the medulla of the female kidney, while almost no distributions were observed in the same areas of the male kidney. For the first time, our study revealed that the distributions of imipramine, chloroquine, and their metabolites were different in male and female kidneys.

Genome-Wide Investigation Reveals Potential Therapeutic Targets in Shigella spp.

Shigella stands as a major contributor to bacterial dysentery worldwide scale, particularly in developing countries with inadequate sanitation and hygiene. The emergence of multidrug-resistant strains exacerbates the challenge of treating Shigella infections, particularly in regions where access to healthcare and alternative antibiotics is limited. Therefore, investigations on how bacteria evade antibiotics and eventually develop resistance could open new avenues for research to develop novel therapeutics. The aim of this study was to analyze whole genome sequence (WGS) of human pathogenic Shigella spp. to elucidate the antibiotic resistance genes (ARGs) and their mechanism of resistance, gene-drug interactions, protein-protein interactions, and functional pathways to screen potential therapeutic candidate(s). We comprehensively analyzed 45 WGS of Shigella, including S. flexneri (n = 17), S. dysenteriae (n = 14), S. boydii (n = 11), and S. sonnei (n = 13), through different bioinformatics tools. Evolutionary phylogenetic analysis showed three distinct clades among the circulating strains of Shigella worldwide, with less genomic diversity. In this study, 2,146 ARGs were predicted in 45 genomes (average 47.69 ARGs/genome), of which only 91 ARGs were found to be shared across the genomes. Majority of these ARGs conferred their resistance through antibiotic efflux pump (51.0%) followed by antibiotic target alteration (23%) and antibiotic target replacement (18%). We identified 13 hub proteins, of which four proteins (e.g., tolC, acrR, mdtA, and gyrA) were detected as potential hub proteins to be associated with antibiotic efflux pump and target alteration mechanisms. These hub proteins were significantly (p < 0.05) enriched in biological process, molecular function, and cellular components. Therefore, the finding of this study suggests that human pathogenic Shigella strains harbored a wide range of ARGs that confer resistance through antibiotic efflux pumps and antibiotic target modification mechanisms, which must be taken into account to devise and formulate treatment strategy against this pathogen. Moreover, the identified hub proteins could be exploited to design and develop novel therapeutics against MDR pathogens like Shigella.

Association of biosecurity and hygiene practices with avian influenza A/H5 and A/H9 virus infections in turkey farms.

High pathogenicity avian influenza (HPAI) H5N1 outbreaks pose a significant threat to the health of livestock, wildlife, and humans. Avian influenza viruses (AIVs) are enzootic in poultry in many countries, including Bangladesh, necessitating improved farm biosecurity measures. However, the comprehension of biosecurity and hygiene practices, as well as the infection of AIV in turkey farms, are poorly understood in Bangladesh. Therefore, we conducted this study to determine the prevalence of AIV subtypes and their association with biosecurity and hygiene practices in turkey farms. We collected oropharyngeal and cloacal swabs from individual turkeys from 197 farms across 9 districts in Bangladesh from March to August 2019. We tested the swab samples for the AIV matrix gene (M gene) followed by H5, H7, and H9 subtypes using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We found 24.68% (95% CI:21.54-28.04) of turkey samples were AIV positive, followed by 5.95% (95% CI: 4.33-7.97) for H5, 6.81% (95% CI: 5.06-8.93) for H9 subtype and no A/H7 was found. Using a generalized linear mixed model, we determined 10 significant risk factors associated with AIV circulation in turkey farms. We found that the absence of sick turkeys, the presence of footbaths, the absence of nearby poultry farms, concrete flooring, and the avoidance of mixing newly purchased turkeys with existing stock can substantially reduce the risk of AIV circulation in turkey farms (odds ratio ranging from 0.02 to 0.08). Furthermore, the absence of nearby live bird markets, limiting wild bird access, no visitor access, improved floor cleaning frequency, and equipment disinfection practices also had a substantial impact on lowering the AIV risk in the farms (odds ratio ranging from 0.10 to 0.13). The results of our study underscore the importance of implementing feasible and cost-effective biosecurity measures aimed at reducing AIV transmission in turkey farms. Particularly in resource-constrained environments such as Bangladesh, such findings might assist governmental entities in enhancing biosecurity protocols within their poultry sector, hence mitigating and potentially averting the transmission of AIV and spillover to humans.

Characteristics of Hospitalized COVID-19 Patients at Admission and Factors Associated with Clinical Severity in Low- and Middle-Income Countries: An Observational Study.

Despite the numerous articles published on the clinical characteristics and outcomes of COVID-19 with regard to high-income countries, little is known about patients in low- and middle-income countries (LMIC) in this context. The objective of this observational, prospective, hospital-based multicentric study was to describe clinical features and outcomes of laboratory-confirmed COVID-19 patients hospitalized in each of the participating centers in Bangladesh, Guinea, Ivory Coast, Lebanon, Madagascar, and Mali during the first year of the pandemic (March 5, 2020 to May 4, 2021). The study outcome was the clinical severity of COVID-19, defined as hospitalization in intensive care unit or death. Multivariate logistic regression models were performed to identify independent variables associated with disease severity. Overall, 1,096 patients were included. The median age was 49.0 years, ranging from 38.0 in Mali to 63.0 years in Guinea. The overall clinical severity of COVID-19 was 12.3%, ranging from 6.4% in Mali to 18.8% in Guinea. In both groups of patients <60 and ≥60 years old, cardiovascular diseases (adjusted odds ratio [aOR]: 1.99; 95% CI: 1.13-3.50, P = 0.02; aOR: 2.47; 95% CI: 1.33-4.57, P = 0.004) were independently associated with clinical severity, whereas in patients <60 years, diabetes (aOR: 2.13; 95% CI: 1.11-4.10, P = 0.02) was also associated with clinical severity. Our findings suggest that COVID-19-related severity and death in LMICs are mainly driven by older age. However, the presence of chronic diseases can also increase the risk of severity especially in younger patients.

Numerical modeling of a MHD non-linear radiative Maxwell nano fluid with activation energy.

The present research explores linear as well as nonlinear radiation patterns based on the MHD non-Newtonian (Maxwell) nanofluid flow having Arrhenius activation energy. This study's core focus is MHD properties in non-Newtonian fluid dynamics and boundary layer phenomena analysis. It initiates with time-dependent equations, employing boundary layer approximations. Extensive numerical computations, executed with custom Compact Visual Fortran code and the EFD method, provide profound insights into non-Newtonian fluid behavior, revealing intricate force interactions and fluid patterns. To check the stability of the solution, a convergence and stability analysis is performed. With the values of ΔY = 0.25, Δτ = 0.0005, and ΔX = 0.20; it is found that the model convergence occurs to the Lewis number, Le > 0.016 as well as the Prandtl number, Pr > 0.08. In this context, investigating non-dimensional results that depend on multiple physical factors. Explanation and visual representations of the effects of different physical characteristics and their resultant temperatures, concentrations, and velocity profiles are provided. As a result of the illustrations, the skin friction coefficient and Sherwood number, which are calculated, as well as Nusselt values, have all come up in discussion. Additionally, detailed representations of isothermal lines and streamlines are implemented, and it is pointed out that the development of these features occurs at the same time as Brownian motion. Furthermore, the temperature field for Maxwell fluid is modified due to the impression of chemical reaction as well as the Dufour number (Kr and Du). Our research demonstrates the superior performance of non-Newtonian solutions, notably in cases involving activation energy and nonlinear radiation. This paradigm shift carries significant implications. In another context, the interplay between Maxwell fluid and nonlinear radiation is notably affected by activation energy, offering promising applications in fields like medicine and industry, particularly in groundbreaking cancer treatment approaches.

Comparative Analysis of Humoral Immune Response and Cognate Antigen Detection in Experimentally Infected Sprague Dawley Rats with Brucella abortus Biotype 1.

Background: This study investigated the IgG-specific humoral immune responses against specific antigen-like whole-cell antigen (WCA), outer membrane protein (OMP), periplasmic protein (PP), and cytoplasmic protein (CP) during the acute and subacute stages of Brucella abortus biotype 1 infection in Sprague Dawley (SD) rats. Materials and Methods: The intraperitoneal method was used to experimentally infect forty-four 6- to 8-week-old SD rats with 1 × 109 colony-forming units (CFUs) of B. abortus biotype 1. Following inoculation, the rat was serially sampled for serum at 0, 3, 7, 14, 21, 28, 35, 42, 60, 90, and 120 days. The IgG-specific immune responses and recognition of immunodominant antigens in WCA, OMP, PP, and CP of B. abortus were assessed by indirect enzyme-linked immunosorbent assay (IELISA) and western blot (WB) assay using infected rat sera. Results: The IgG antibody response was detectable at 3 days after infection. The peak serum IgG antibody titers were recorded against CP and PP at 28 days after infection. The highest serum IgG antibody titers were recorded at 42 days after infection against WCA and 90 days after infection only against OMP. WB assay revealed a wide array of protein bands between molecular weight of 13 and 95 kDa for WCA, 13 and 95 kDa for OMP, 15 and 65 kDa for PP, and 12 and 85 kDa for CP. Proteins bands of 10, 13, 20, 24, 46, and 76 kDa for WCA; 28, 35, 39, 85, and 95 for OMP; 20, 30, 40, 43, 46, and 65 kDa for PP, and 12, 23, 68, and 85 for CP were intensely recognized. Conclusion: Data of this study indicated that WCA, CP, and PP of B. abortus could be useful for diagnosis of acute and subacute brucellosis in SD rat model. OMP of B. abortus could be useful for differential diagnosis of subacute brucellosis.

The role of vaccination and environmental factors on outbreaks of high pathogenicity avian influenza H5N1 in Bangladesh.

High Pathogenicity Avian Influenza (HPAI) H5N1 outbreaks continue to wreak havoc on the global poultry industry and threaten the health of wild bird populations, with sporadic spillover in humans and other mammals, resulting in widespread calls to vaccinate poultry. Bangladesh has been vaccinating poultry since 2012, presenting a prime opportunity to study the effects of vaccination on HPAI H5N1circulation in both poultry and wild birds. We investigated the efficacy of vaccinating commercial poultry against HPAI H5N1 along with climatic and socio-economic factors considered potential drivers of HPAI H5N1 outbreak risk in Bangladesh. Using a multivariate modeling approach, we estimated that the rate of outbreaks was 18 times higher before compared to after vaccination, with winter months having a three times higher chance of outbreaks than summer months. Variables resulting in small but significant increases in outbreak rate were relatively low ambient temperatures for the time of year, literacy rate, chicken and duck density, crop density, and presence of highways; this may be attributable to low temperatures supporting viral survival outside the host, higher literacy driving reporting rate, density of the host reservoir, and spread of the virus through increased connectivity. Despite the substantial impact of vaccination on outbreaks, we note that HPAI H5N1 is still enzootic in Bangladesh; vaccinated poultry flocks have high rates of H5N1 prevalence, and spillover to wild birds has increased. Vaccination in Bangladesh thus bears the risk of supporting "silent spread," where the vaccine only provides protection against disease and not also infection. Our findings underscore that poultry vaccination can be part of holistic HPAI mitigation strategies when accompanied by monitoring to avoid silent spread.

Determinants for the presence of avian influenza virus in live bird markets in Bangladesh: Towards an easy fix of a looming one health issue.

Highly pathogenic avian influenza virus subtype H5N1 endangers poultry, wildlife, and human health and is enzootic in large parts of Asia, with live bird markets (LBMs) as putative hotspots for their maintenance, amplification, and spread. To mitigate the extent of these and other avian influenza viruses (AIV) of concern, we aimed to increase our quantitative understanding of the factors determining the presence of avian influenza virus in LBM stalls. Between 2016 and 2017, we collected fecal or offal samples from 1008 stalls in 113 LBMs across the Dhaka and Rajshahi districts in Bangladesh. For each stall, samples were pooled and tested for the AIV matrix gene, followed by H5 and H9 subtyping using rRT-PCR. We detected Influenza A viral RNA in 49% of the stalls. Of the AIV positive samples, 52% and 24% were determined to be H5 and H9 viruses, respectively, which are both subtypes of considerable health concern. We used generalized linear mixed effect modelling to study AIV presence in individual stalls within LBMs as a function of 13 out of the 20 risk factors identified by FAO. We found that small and feasible improvements in cleaning and disinfection frequency, installing running water in stalls, and not mixing different breeds of chicken in the same cages had large impacts on the presence of AIV in stalls (Odds ratios 0.03-0.05). Next, cleaning vehicles used in poultry transport, not selling waterfowl with chickens in the same stall, buying stock directly from commercial farms, separating sick birds from healthy ones, and avoiding access by wild birds like house crows, also had major effects on lowering the risk of stalls having AIV (Odds ratios 0.16-0.33). These findings can be directly used in developing practical and affordable measures to reduce the prevalence of AIV in LBMs. Also, in settings with limited resources like Bangladesh, such mitigation may significantly contribute to reducing AIV circulation amongst poultry and spillover to wildlife and humans.

Potential risk zones and climatic factors influencing the occurrence and persistence of avian influenza viruses in the environment of live bird markets in Bangladesh.

Live bird markets (LBMs) are critical for poultry trade in many developing countries that are regarded as hotspots for the prevalence and contamination of avian influenza viruses (AIV). Therefore, we conducted weekly longitudinal environmental surveillance in LBMs to determine annual cyclic patterns of AIV subtypes, environmental risk zones, and the role of climatic factors on the AIV presence and persistence in the environment of LBM in Bangladesh. From January 2018 to March 2020, we collected weekly fecal and offal swab samples from each LBM and tested using rRT-PCR for the M gene and subtyped for H5, H7, and H9. We used Generalized Estimating Equations (GEE) approaches to account for repeated observations over time to correlate the AIV prevalence and potential risk factors and the negative binomial and Poisson model to investigate the role of climatic factors on environmental contamination of AIV at the LBM. Over the study period, 37.8% of samples tested AIV positive, 18.8% for A/H5, and A/H9 was, for 15.4%. We found the circulation of H5, H9, and co-circulation of H5 and H9 in the environmental surfaces year-round. The Generalized Estimating Equations (GEE) model reveals a distinct seasonal pattern in transmitting AIV and H5. Specifically, certain summer months exhibited a substantial reduction of risk up to 70-90% and 93-94% for AIV and H5 contamination, respectively. The slaughtering zone showed a significantly higher risk of contamination with H5, with a three-fold increase in risk compared to bird-holding zones. From the negative binomial model, we found that climatic factors like temperature and relative humidity were also significantly associated with weekly AIV circulation. An increase in temperature and relative humidity decreases the risk of AIV circulation. Our study underscores the significance of longitudinal environmental surveillance for identifying potential risk zones to detect H5 and H9 virus co-circulation and seasonal transmission, as well as the imperative for immediate interventions to reduce AIV at LBMs in Bangladesh. We recommend adopting a One Health approach to integrated AIV surveillance across animal, human, and environmental interfaces in order to prevent the epidemic and pandemic of AIV.

In silico prediction of interaction between Nipah virus attachment glycoprotein and host cell receptors Ephrin-B2 and Ephrin-B3 in domestic and peridomestic mammals.

Nipah virus (NiV) is a lethal bat-borne zoonotic virus that causes mild to acute respiratory distress and neurological manifestations in humans with a high mortality rate. NiV transmission to humans occurs via consumption of bat-contaminated fruit and date palm sap (DPS), or through direct contact with infected individuals and livestock. Since NiV outbreaks were first reported in pigs from Malaysia and Singapore, non-neutralizing antibodies against NiV attachment Glycoprotein (G) have also been detected in a few domestic mammals. NiV infection is initiated after NiV G binds to the host cell receptors Ephrin-B2 and Ephrin-B3. In this study, we assessed the degree of NiV host tropism in domestic and peridomestic mammals commonly found in Bangladesh that may be crucial in the transmission of NiV by serving as intermediate hosts. We carried out a protein-protein docking analysis of NiV G complexes (n = 52) with Ephrin-B2 and B3 of 13 domestic and peridomestic species using bioinformatics tools. Protein models were generated by homology modelling and the structures were validated for model quality. The different protein-protein complexes in this study were stable, and their binding affinity (ΔG) scores ranged between -8.0 to -19.1 kcal/mol. NiV Bangladesh (NiV-B) strain displayed stronger binding to Ephrin receptors, especially with Ephrin-B3 than the NiV Malaysia (NiV-M) strain, correlating with the observed higher pathogenicity of NiV-B strains. From the docking result, we found that Ephrin receptors of domestic rat (R. norvegicus) had a higher binding affinity for NiV G, suggesting greater susceptibility to NiV infections compared to other study species. Investigations for NiV exposure to domestic/peridomestic animals will help us knowing more the possible role of rats and other animals as intermediate hosts of NiV and would improve future NiV outbreak control and prevention in humans and domestic animals.

Unveiling Neuroprotective Potential of Spice Plant-Derived Compounds against Alzheimer's Disease: Insights from Computational Studies.

Alzheimer's disease (AD) is a serious threat to the global health care system and is brought on by a series of factors that cause neuronal dysfunction and impairment in memory and cognitive decline. This study investigated the therapeutic potential of phytochemicals that belong to the ten regularly used spice plants, based on their binding affinity with AD-associated proteins. Comprehensive docking studies were performed using AutoDock Vina in PyRx followed by molecular dynamic (MD) simulations using AMBER 14. The docking study of the chosen molecules revealed the binding energies of their interactions with the target proteins, while MD simulations were carried out to verify the steadiness of bound complexes. Through the Lipinski filter and admetSAR analysis, the chosen compounds' pharmacokinetic characteristics and drug likeness were also examined. The pharmacophore mapping study was also done and analyzed for best selected molecules. Additionally, principal component analysis (PCA) was used to examine how the general motion of the protein changed. The results showed quercetin and myricetin to be potential inhibitors of AChE and alpha-amyrin and beta-chlorogenin to be potential inhibitors of BuChE, exhibiting best binding energies comparable to those of donepezil, used as a positive control. The multiple descriptors from the simulation study, root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bond, radius of gyration (Rg), and solvent-accessible surface areas (SASA), confirm the stable nature of the protein-ligand complexes. Molecular mechanic Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations indicated the energetically favorable binding of the ligands to the protein. Finally, according to pharmacokinetic properties and drug likeness, characteristics showed that quercetin and myricetin for AChE and alpha-amyrin and beta-chlorogenin for BuChE were found to be the most effective agents for treating the AD.

Lipid Polyunsaturated Fatty Acid Chains in Mouse Kidneys Were Increased within 5 min of a Single High Dose Whole Body Irradiation.

To understand the ultra-early reaction of normal organ lipids during irradiation, we investigated the response of lipids, including polyunsaturated fatty acid (PUFA) chains, which are particularly susceptible to damage by ROS, in mice's kidneys, lungs, brains, and livers within 5 min of single high-dose irradiation. In this study, we set up three groups of C56BL/6 male mice and conducted whole-body irradiation with 0 Gy, 10 Gy, and 20 Gy single doses. Kidney, lung, brain, and liver tissues were collected within 5 min of irradiation. PUFA-targeted and whole lipidomic analyses were conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that PUFA chains of kidney phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG) significantly increased within 5 min of 10 Gy and 20 Gy irradiation. The main components of increased PUFA chains in PC and PE were C18:2, C20:4, and C22:6, and in TG the main component was C18:2. The kidney lipidomes also showed significant changes from the perspective of lipid species, mainly dominated by an increase in PC, PE, TG, and signal lipids, while lipidomes of the lung, brain, and liver were slightly changed. Our results revealed that acute PUFA chains increase and other lipidomic changes in the kidney upon whole-body irradiation within 5 min of irradiation. The significantly increased lipids also showed a consistent preference for possessing PUFA chains. The lipidomic changes varied from organ to organ, which indicates that the response upon irradiation within a short time is tissue-specific.

Machine learning approaches for predicting suicidal behaviors among university students in Bangladesh during the COVID-19 pandemic: A cross-sectional study.

Psychological and behavioral stress has increased enormously during Coronavirus Disease 2019 (COVID-19) pandemic. However, early prediction and intervention to address psychological distress and suicidal behaviors are crucial to prevent suicide-related deaths. This study aimed to develop a machine algorithm to predict suicidal behaviors and identify essential predictors of suicidal behaviors among university students in Bangladesh during the COVID-19 pandemic. An anonymous online survey was conducted among university students in Bangladesh from June 1 to June 30, 2022. A total of 2391 university students completed and submitted the questionnaires. Five different Machine Learning models (MLMs) were applied to develop a suitable algorithm for predicting suicidal behaviors among university students. In predicting suicidal behaviors, the most crucial background and demographic features were relationship status, friendly environment in the family, family income, family type, and sex. In addition, features related to the impact of the COVID-19 pandemic were identified as job loss, economic loss, and loss of family/relatives due to COVID-19. Moreover, factors related to mental health include depression, anxiety, stress, and insomnia. The performance evaluation and comparison of the MLM showed that all models behaved consistently and were comparable in predicting suicidal risk. However, the Support Vector Machine was the best and most consistent performing model among all MLMs in terms of accuracy (79%), Kappa (0.59), receiver operating characteristic (0.89), sensitivity (0.81), and specificity (0.81). Support Vector Machine is the best-performing model for predicting suicidal risks among university students in Bangladesh and can help in designing appropriate and timely suicide prevention interventions.

Epidemiology and phylodynamics of multiple clades of H5N1 circulating in domestic duck farms in different production systems in Bangladesh.

Waterfowl are considered to be natural reservoirs of the avian influenza virus (AIV). However, the dynamics of transmission and evolutionary patterns of AIV and its subtypes within duck farms in Bangladesh remain poorly documented. Hence, a cross-sectional study was conducted in nine districts of Bangladesh between 2019 and 2021, to determine the prevalence of AIV and its subtypes H5 and H9, as well as to identify risk factors and the phylodynamics of H5N1 clades circulating in domestic duck farms. The oropharyngeal and cloacal swab samples were tested for the AIV Matrix gene (M-gene) followed by H5, H7, and H9 subtypes using rRT-PCR. The exploratory analysis was performed to estimate AIV and its subtype prevalence in different production systems, and multivariable logistic regression model was used to identify the risk factors that influence AIV infection in ducks. Bayesian phylogenetic analysis was conducted to generate a maximum clade credibility (MCC) tree and the maximum likelihood method to determine the phylogenetic relationships of the H5N1 viruses isolated from ducks. AIV was detected in 40% (95% CI: 33.0-48.1) of the duck farms. The prevalence of AIV was highest in nomadic ducks (39.8%; 95% CI: 32.9-47.1), followed by commercial ducks (24.6%; 95% CI: 14.5-37.3) and backyard ducks (14.4%; 95% CI: 10.5-19.2). The H5 prevalence was also highest in nomadic ducks (19.4%; 95% CI: 14.0-25.7). The multivariable logistic regression model revealed that ducks from nomadic farms (AOR: 2.4; 95% CI: 1.45-3.93), juvenile (AOR: 2.2; 95% CI: 1.37-3.61), and sick ducks (AOR: 11.59; 95% CI: 4.82-32.44) had a higher risk of AIV. Similarly, the likelihood of H5 detection was higher in sick ducks (AOR: 40.8; 95% CI: 16.3-115.3). Bayesian phylogenetic analysis revealed that H5N1 viruses in ducks belong to two distinct clades, 2.3.2.1a, and 2.3.4.4b. The clade 2.3.2.1a (reassorted) has been evolving silently since 2015 and forming at least nine subgroups based on >90% posterior probability. Notably, clade 2.3.4.4b was introduced in ducks in Bangladesh by the end of the year 2020, which was genetically similar to viruses detected in wild birds in Japan, China, and Africa, indicating migration-associated transmission of an emerging panzootic clade. We recommend continuing AIV surveillance in the duck production system and preventing the intermingling of domestic ducks with migratory waterfowl in wetlands.

The royal food of termites shows king and queen specificity.

Society in eusocial insects is based on the reproductive division of labor, with a small number of reproductive individuals supported by a large number of nonreproductive individuals. Because inclusive fitness of all colony members depends on the survival and fertility of reproductive members, sterile members provide royals with special treatment. Here, we show that termite kings and queens each receive special food of a different composition from workers. Sequential analysis of feeding processes demonstrated that workers exhibit discriminative trophallaxis, indicating their decision-making capacity in allocating food to the kings and queens. Liquid chromatography tandem-mass spectrometry analyses of the stomodeal food and midgut contents revealed king- and queen-specific compounds, including diacylglycerols and short-chain peptides. Desorption electrospray ionization mass spectrometry imaging analyses of 13C-labeled termites identified phosphatidylinositol and acetyl-l-carnitine in the royal food. Comparison of the digestive tract structure showed remarkable differences in the volume ratio of the midgut-to-hindgut among castes, indicating that digestive division of labor underlies reproductive division of labor. Our demonstration of king- and queen-specific foods in termites provides insight into the nutritional system that underpins the extraordinary reproduction and longevity of royals in eusocial insects.

Annual trading patterns and risk factors of avian influenza A/H5 and A/H9 virus circulation in turkey birds (Meleagris gallopavo) at live bird markets in Dhaka city, Bangladesh.

The impacts of the avian influenza virus (AIV) on farmed poultry and wild birds affect human health, livelihoods, food security, and international trade. The movement patterns of turkey birds from farms to live bird markets (LBMs) and infection of AIV are poorly understood in Bangladesh. Thus, we conducted weekly longitudinal surveillance in LBMs to understand the trading patterns, temporal trends, and risk factors of AIV circulation in turkey birds. We sampled a total of 423 turkeys from two LBMs in Dhaka between May 2018 and September 2019. We tested the swab samples for the AIV matrix gene (M-gene) followed by H5, H7, and H9 subtypes using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We used exploratory analysis to investigate trading patterns, annual cyclic trends of AIV and its subtypes, and a generalized estimating equation (GEE) logistic model to determine the factors that influence the infection of H5 and H9 in turkeys. Furthermore, we conducted an observational study and informal interviews with traders and vendors to record turkey trading patterns, demand, and supply and turkey handling practices in LBM. We found that all trade routes of turkey birds to northern Dhaka are unidirectional and originate from the northwestern and southern regions of Bangladesh. The number of trades from the source district to Dhaka depends on the turkey density. The median distance that turkey was traded from its source district to Dhaka was 188 km (Q1 = 165, Q3 = 210, IQR = 45.5). We observed seasonal variation in the median and average distance of turkey. The qualitative findings revealed that turkey farming initially became reasonably profitable in 2018 and at the beginning of 2019. However, the fall in demand and production in the middle of 2019 may be related to unstable market pricing, high feed costs, a shortfall of adequate marketing facilities, poor consumer knowledge, and a lack of advertising. The overall prevalence of AIV, H5, and H9 subtypes in turkeys was 31% (95% CI: 26.6-35.4), 16.3% (95% CI: 12.8-19.8), and 10.2% (95% CI: 7.3-13.1) respectively. None of the samples were positive for H7. The circulation of AIV and H9 across the annual cycle showed no seasonality, whereas the circulation of H5 showed significant seasonality. The GEE revealed that detection of AIV increases in retail vendor business (OR: 1.71; 95% CI: 1.12-2.62) and the bird's health status is sick (OR: 10.77; 95% CI: 4.31-26.94) or dead (OR: 11.33; 95% CI: 4.30-29.89). We also observed that winter season (OR: 5.83; 95% CI: 2.80-12.14) than summer season, dead birds (OR: 61.71; 95% CI: 25.78-147.75) and sick birds (OR 8.33; 95% CI: 3.36-20.64) compared to healthy birds has a higher risk of H5 infection in turkeys. This study revealed that the turkeys movements vary by time and season from the farm to the LBM. This surveillance indicated year-round circulation of AIV with H5 and H9 subtypes in turkey birds in LBMs. The seasonality and health condition of birds influence H5 infection in birds. The trading pattern of turkey may play a role in the transmission of AIV viruses in the birds. The selling of sick turkeys infected with H5 and H9 highlights the possibility of virus transmission to other species of birds sold at LBMs and to people.

Occurrence of tuberculosis among people exposed to cattle in Bangladesh.

BACKGROUND: Tuberculosis (TB) has been an important public health concern in Bangladesh. The most common cause of human TB is Mycobacterium tuberculosis, while bovine TB is caused by Mycobacterium bovis. OBJECTIVE: The objective of this study was to determine the frequency of TB in individuals with occupational exposure to cattle and to detect Mycobacterium bovis among cattle in slaughterhouses in Bangladesh. METHODS: Between August 2014 and September 2015, an observational study was conducted in two government chest disease hospitals, one cattle market, and two slaughterhouses. [Correction added on 27 June 2023, after first online publication: In the preceding sentence, the year "2014" has been added after the word "August".] Sputum samples were collected from individuals who met the criteria for suspected TB and had been exposed to cattle. Tissue samples were collected from cattle that had low body condition score(s). Both humans and cattle samples were screened for acid-fast bacilli (AFB) by Ziehl-Neelsen (Z-N) staining and cultured for Mycobacterium tuberculosis complex (MTC). Region of difference (RD) 9-based polymerase chain reaction (PCR) was also performed to identify Mycobacterium spp. We also conducted Spoligotyping to identify the specific strain of Mycobacterium spp. RESULTS: Sputum was collected from a total of 412 humans. The median age of human participants was 35 (IQR: 25-50) years. Twenty-five (6%) human sputum specimens were positive for AFB, and 44 (11%) were positive for MTC by subsequent culture. All (N = 44) culture-positive isolates were confirmed as Mycobacterium tuberculosis by RD9 PCR. Besides, 10% of cattle workers were infected with Mycobacterium tuberculosis in the cattle market. Of all TB (caused by Mycobacterium tuberculosis) infected individuals, 6.8% of individuals were resistant to one or two anti-TB drugs. The majority of the sampled cattle (67%) were indigenous breeds. No Mycobacterium bovis was detected in cattle. CONCLUSIONS: We did not detect any TB cases caused by Mycobacterium bovis in humans during the study. However, we detected TB cases caused by Mycobacterium tuberculosis in all humans, including cattle market workers.

Detection of Distinct Distributions of Acetaminophen and Acetaminophen-Cysteine in Kidneys up to 10 µm Resolution and Identification of a Novel Acetaminophen Metabolite Using an AP-MALDI Imaging Mass Microscope.

Drug distribution studies in tissue are crucial for understanding the pharmacokinetics and potential toxicity of drugs. Recently, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) has gained attention for drug distribution studies due to its high sensitivity, label-free nature, and ability to distinguish between parent drugs, their metabolites, and endogenous molecules. Despite these advantages, achieving high spatial resolution in drug imaging is challenging. Importantly, many drugs and metabolites are rarely detectable by conventional vacuum MALDI-MSI because of their poor ionization efficiency. It has been reported that acetaminophen (APAP) and one of its major metabolites, APAP-Cysteine (APAP-CYS), cannot be detected by vacuum MALDI-MSI without derivatization. In this context, we showed the distribution of both APAP and APAP-CYS in kidneys at high spatial resolution (25 and 10 µm) by employing an atmospheric pressure-MALDI imaging mass microscope without derivatization. APAP was highly accumulated in the renal pelvis 1 h after drug administration, while APAP-CYS exhibited characteristic distributions in the outer medulla and renal pelvis at both 30 min and 1 h after administration. Interestingly, cluster-like distributions of APAP and APAP-CYS were observed in the renal pelvis at 10 µm spatial resolution. Additionally, a novel APAP metabolite, tentatively coined as APAP-butyl sulfate (APAP-BS), was identified in the kidney, brain, and liver by combining MSI and tandem MSI. For the first time, our study revealed differential distributions of APAP, APAP-CYS (in kidneys), and APAP-BS (in kidney, brain, and liver) and is believed to enhance the understanding of the pharmacokinetics and potential nephrotoxicity of this drug.

Prevalence and risk factors for avian influenza virus (H5 and H9) contamination in peri-urban and rural live bird markets in Bangladesh.

Avian influenza viruses (AIV) have been frequently detected in live bird markets (LBMs) around the world, primarily in urban areas, and have the ability to spillover to other species, including humans. Despite frequent detection of AIV in urban LBMs, the contamination of AIV on environmental surfaces in rural and peri-urban LBMs in Bangladesh is poorly documented. Therefore, we conducted this study to determine the prevalence of AIV subtypes within a subset of peri-urban and rural LBMs in Bangladesh and to further identify associated risk factors. Between 2017 and 2018, we collected faecal and offal samples from 200 stalls in 63 LBMs across four sub-districts. We tested the samples for the AIV matrix gene (M-gene) followed by H5, H7, and H9 subtypes using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We performed a descriptive analysis of market cleanliness and sanitation practices in order to further elucidate the relationship between LBM biosecurity and AIV subtypes by species, sample types, and landscape. Subsequently, we conducted a univariate analysis and a generalized linear mixed model (GLMM) to determine the risk factors associated with AIV contamination at individual stalls within LBMs. Our findings indicate that practices related to hygiene and the circulation of AIV significantly differed between rural and peri-urban live bird markets. 42.5% (95% CI: 35.56-49.67) of stalls were positive for AIV. A/H5, A/H9, and A HA/Untyped were detected in 10.5% (95% CI: 6.62-15.60), 9% (95% CI: 5.42-13.85), and 24.0% (95% CI: 18.26-30.53) of stalls respectively, with no detection of A/H7. Significantly higher levels of AIV were found in the Sonali chicken strain compared to the exotic broiler, and in offal samples compared to fecal samples. In the GLMM analysis, we identified several significant risk factors associated with AIV contamination in LBMs at the stall level. These include: landscape (AOR: 3.02; 95% CI: 1.18-7.72), the number of chicken breeds present (AOR: 2.4; 95% CI: 1.01-5.67), source of birds (AOR: 2.35; 95% CI: 1.0-5.53), separation of sick birds (AOR: 3.04; 95% CI: 1.34-6.92), disposal of waste/dead birds (AOR: 3.16; 95% CI: 1.41-7.05), cleaning agent (AOR: 5.99; 95% CI: 2.26-15.82), access of dogs (AOR: 2.52; 95% CI: 1.12-5.7), wild birds observed on site (AOR: 2.31; 95% CI: 1.01-5.3). The study further revealed a substantial prevalence of AIV with H5 and H9 subtypes in peri-urban and rural LBMs. The inadequate biosecurity measures at poultry stalls in Bangladesh increase the risk of AIV transmission from poultry to humans. To prevent the spread of AIV to humans and wild birds, we suggest implementing regular surveillance at live bird markets and enhancing biosecurity practices in peri-urban and rural areas in Bangladesh.