Human Immunodeficiency Virus Preexposure Prophylaxis Awareness and Acceptability among Men Who Have Sex with Men and Transgender Persons in India: Systematic Review and Meta-analysis.

With increasing importance being given to preexposure prophylaxis (PrEP) for human immunodeficiency virus prevention among men who have sex with men (MSM) and transgender persons (TG), we undertook a systematic review and meta-analysis of PrEP awareness and acceptability among these key populations in India, and their sociodemographic and behavioral determinants. The systematic review was registered with PROSPERO (CRD42023390508). Studies were included if they provided quantitative data on PrEP awareness or acceptability among MSM or TG in India. MEDLINE, Scopus, Web of Science, and Embase were searched from inception to February 29, 2024, using keywords and database-specific terms. Relevant websites were also searched. Critical appraisal was done using the Joanna Briggs Institute Checklist for Prevalence Studies. Random-effects meta-analysis was done for common outcomes reported by the studies. Reporting was as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement. Ten studies providing cross-sectional data, mostly from South West India, were included for qualitative synthesis. All were conducted in settings where PrEP was not available. The pooled prevalence among MSM and TG was 18.7% (95% confidence interval [CI] 8.7%, 28.7%) for awareness and 79.8% (95% CI 57.4%, 100.0%) for willingness to use daily oral PrEP. This review highlights the felt need for PrEP among MSM and TG in India. Further research is needed to understand user attitudes in different parts of the country.

Engineering a 3-dimensional tissue construct with adipose-derived stem cells for healing bone defect: An ex vivo study with femur head.

The compatibility of bone graft substitutes (BGS) with mesenchymal stem cells (MSCs) is an important parameter to consider for their use in repairing bone defects as it eventually affects the clinical outcome. In the present study, a few commercially available BGS - ß-tricalcium phosphate (ß-TCP), calcium sulfate, gelatin sponge, and different forms of hydroxyapatite (HAP) were screened for their interactions with MSCs from adipose tissue (ADSCs). It was demonstrated that HAP block favorably supported ADSC viability, morphology, migration, and differentiation compared to other scaffolds. The results strongly suggest the importance of preclinical evaluation of bone scaffolds for their cellular compatibility. Furthermore, the bone regenerative potential of HAP block with ADSCs was evaluated in an ex vivo bone defect model developed using patient derived trabecular bone explants. The explants were cultured for 45 days in vitro and bone formation was assessed by expression of osteogenic genes, ALP secretion, and high resolution computed tomography. Our findings confirmed active bone repair process in ex vivo settings. Addition of ADSCs significantly accelerated the repair process and improved bone microarchitecture. This ex vivo bone defect model can emerge as a viable alternative to animal experimentation and also as a potent tool to evaluate patient specific bone therapeutics under controlled conditions.

Social support and economic conditions among older migrants in India: do distance, duration, and streams of migration play a role in later life?

BACKGROUND: Being older and having a migrant feature might cause a double risk of vulnerability in poor economic, social support, and health status at the place of destination. This study examines the association of migration on the social support and economic condition of older persons in India. METHODS: Longitudinal Ageing Study in India (LASI) wave-I (2017-2018) data with total samples of 66,156 older adults aged 45 + with 30,869 and 35,287 male and female samples, respectively, used in this study. Descriptive and bivariate analyses have been performed to examine the pattern of older migrants, and multinomial logistic regression analysis has been used to establish the associations between migration, social support, and economic condition. RESULTS: Over half (57.5%) of the population aged 45 + in India had migrant characteristics; 80% migrated before 25 years. Of all migrants, about 90% migrated within one state (Intrastate), and 9% migrated to another (Interstate). The association between social support and migration by distance and the adjusted result showed that immigrants were less likely to have medium [RRR = 0.56 (CI; 0.46-0.68)] and high [RRR = 0.39 (CI; 0.30-0.50)] social support. The interstate migrants were also less likely to have high [RRR = 0.90 (CI; 0.83-0.98)] social support. The migrants with 0-9 years of duration were less likely to have high social support, and the urban to rural stream migrants were more likely to have high social support. The association between economic status and migration by distance and the adjusted result showed that more affluent immigrants were likelier to have [RRR = 1.41 (CI; 1.14-1.73)] better economic conditions than affluent non-migrants. Migrants with 0-9-year duration and urban to rural stream were found to be likelier to have better economic conditions. CONCLUSIONS: The findings of this study suggest that distance, duration, and migration stream have a significant association with social support and economic conditions in later life. In exploring migration's effect on social and economic status, policymakers should prioritize migrants in their agenda to maintain socio-economic and social support for older persons in India to achieve the sustainable goal of active and healthy ageing.

The burden of chronic kidney disease of undetermined etiology (CKDu) in a tertiary care public hospital in north India.

INTRODUCTION: Chronic kidney disease of undetermined aetiology (CKDu) is an important public health problem. Indian data is mostly based on studies from rural regions in south and eastern India. We examined the burden and profile of CKDu in patients attending a tertiary care hospital in north India. METHODS: We assessed records of consecutive new CKD patients registered in nephrology clinic from January 2015 till June 2022. Patients were classified as CKDu based on predefined inclusion and exclusion criteria. Clinical and laboratory parameters at presentation and kidney biopsy when done were noted. RESULTS: Records of 32369 patients with CKD were screened, 29663 were included (2706 excluded due to inadequate data). 370 (1.2%) patients were categorized as CKDu. Mean age was 41±14.7 years, 58.1% being males. 158 (42.7%) patients were in CKD stage 3, 89 (24.1%) in stage 4, 84(22.7%) in stage 5 and 39(10.5%) were dialysis dependent at presentation. 232(62.7%) patients had proteinuria <0.5gm/day and 138(37.3%) between 0.5-1 gm/day. Renal histology was available for 65 CKDu patients :62 had chronic tubulointerstitial nephritis (CTIN) and 3 had non-specific changes. CONCLUSION: When defined using strict criteria with intensive diagnostic work-up, burden of CKDu is low in our hospital-based cohort of CKD patients. CTIN is the predominant histopathological finding in kidney biopsy.

The LIDPAD Mouse Model Captures the Multisystem Interactions and Extrahepatic Complications in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.

A hybrid SWAT-ANN model approach for analysis of climate change impacts on sediment yield in an Eastern Himalayan sub-watershed of Brahmaputra.

The current study focuses on analyzing the impacts of climate change and land use/land cover (LULC) changes on sediment yield in the Puthimari basin, an Eastern Himalayan sub-watershed of the Brahmaputra, using a hybrid SWAT-ANN model approach. The analysis was meticulously segmented into three distinct time spans: 2025-2049, 2050-2074, and 2075-2099. This innovative method integrates insights from multiple climate models under two Representative Concentration Pathways (RCP4.5 and RCP8.5), along with LULC projections generated through the Cellular Automata Markov model. By combining the strengths of the Soil and Water Assessment Tool (SWAT) and artificial neural network (ANN) techniques, the study aims to improve the accuracy of sediment yield simulations in response to changing environmental conditions. The non-linear autoregressive with external input (NARX) method was adopted for the ANN component of the hybrid model. The adoption of the hybrid SWAT-ANN approach appears to be particularly effective in improving the accuracy of sediment yield simulation compared to using the SWAT model alone, as evidenced by the higher coefficient of determination value of 0.74 for the hybrid model compared to 0.35 for the standalone SWAT model. In the context of the RCP4.5 scenario, during 2075-99, the study noted a 29.34% increase in sediment yield, accompanied by simultaneous rises of 42.74% in discharge and 27.43% in rainfall during the Indian monsoon season, spanning from June to September. In contrast, under the RCP8.5 scenario, for the same period, the increases in sediment yield, discharge, and rainfall for the monsoon season were determined to be 116.56%, 103.28%, and 64.72%, respectively. The present study's comprehensive analysis of the factors influencing sediment supply in the Puthimari River basin fills an important knowledge gap and provides valuable insights for designing proactive flood and erosion management strategies. The findings from this research are crucial for understanding the vulnerability of the Puthimari basin to climate and land use changes, and by incorporating these findings into policy and decision-making processes, stakeholders can work towards enhancing resilience and sustainability in the face of future hydrological and environmental challenges.

Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients with Positive Nodes Using Low-Cost Dual Dye Technique: Identifying Factors Associated with Adequate False Negative Rate Threshold.

Background: In this study, we evaluated the feasibility of the sentinel lymph node (SLN) identification rate (SLN-IR) of fluorescein-guided sentinel lymph node biopsy (SLNB) in combination with methylene blue dye (MBD) and factors which can lead to a false negative rate (FNR) threshold of 10%. Methods: This was a prospective cross-sectional non-randomized validation study in patients with post-neoadjuvant chemotherapy (NACT) clinically node negative axilla who were node positive prior to start of NACT. Patients underwent validation of SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and FNR were assessed and compared with various molecular subtypes. Results: The SLNs were identified in 102 out of 120 (85%) post-NACT patients. The median number of sentinel lymph nodes identified was 2 (range 1-3). The SLN-IR using MBD was 85%, FD was 82.5%, and combined MBD FD was 85%. Two or more SLNs were removed in 72 patients and 11 patients had tumor in the rest of the axilla, resulting in an FNR of 17.4%. An FNR was 25% in case only one SLN was found, and it was 11.42% if two or more than two SLNs were excised. Conclusions: This cohort study found that use of low-cost dual dyes in patients with positive axillary disease, rendered cN0 with NACT, with 2 or more negative SLNs with SLNB alone, results in an FNR of 11.4%. Her 2 positive and TNBC with 2 or more negative SLNs are associated with an FNR of <10%. However, the number of such patients was small and further studies with larger sample size are warranted to confirm these findings.

Fabrication of magnetite/GO/potassium copper hexacyanoferrate nanocomposite for removal of radioactive cesium ions.

Metal hexacyanoferrates (MHCF) are a class of inorganic adsorbents used for wastewater management due to the presence of interstitial sites for capturing heavy metal ions. In present work, we are reporting the synthesis of magnetic nanocomposite of Fe3O4/graphene oxide/potassium copper hexacyanoferrate via wet chemical and coprecipitation approach. Potassium copper hexacyanoferrate (KCuHCF) and Graphene oxide (GO) both are marvelous adsorbents but their nano-size becomes a major obstacle in their separation process after the adsorption of the radionuclides. Thus, our synthesized nanocomposite Fe3O4/GO/KCuHCF enhances the recovery of KCuHCF even after radioactive Cs+ adsorption with adsorption capacity of 18 mg g-1 coinciding well with the Langmuir adsorption isotherm mechanism. The synthesized adsorbent is characterized thoroughly using UV-Visible spectroscopy, FT-IR, TGA, XPS, Raman spectroscopy, TEM-EDAX and XRD. This synthesized nanocomposite is used for the batch extraction of radioactive Cs+ from low level radioactive waste (LLW). The extraction kinetics followed pseudo-second-order kinetics mechanism.

A novel framework based on explainable AI and genetic algorithms for designing neurological medicines.

The advent of the fourth industrial revolution, characterized by artificial intelligence (AI) as its central component, has resulted in the mechanization of numerous previously labor-intensive activities. The use of in silico tools has become prevalent in the design of biopharmaceuticals. Upon conducting a comprehensive analysis of the genomes of many organisms, it has been discovered that their tissues can generate specific peptides that confer protection against certain diseases. This study aims to identify a selected group of neuropeptides (NPs) possessing favorable characteristics that render them ideal for production as neurological biopharmaceuticals. Until now, the construction of NP classifiers has been the primary focus, neglecting to optimize these characteristics. Therefore, in this study, the task of creating ideal NPs has been formulated as a multi-objective optimization problem. The proposed framework, NPpred, comprises two distinct components: NSGA-NeuroPred and BERT-NeuroPred. The former employs the NSGA-II algorithm to explore and change a population of NPs, while the latter is an interpretable deep learning-based model. The utilization of explainable AI and motifs has led to the proposal of two novel operators, namely p-crossover and p-mutation. An online application has been deployed at https://neuropred.anvil.app for designing an ideal collection of synthesizable NPs from protein sequences.

PIM kinase inhibitors: an updated patent review (2016-present).

INTRODUCTION: PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer. AREAS COVERED: A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted. EXPERT OPINION: Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.

Monte Carlo-based dosimetry of proposed bi-radionuclide (125I and 106Ru/106Rh) eye plaque: A feasibility study.

BACKGROUND: Combining the sharp dose fall off feature of beta-emitting 106Ru/106Rh radionuclide with larger penetration depth feature of photon-emitting125I radionuclide in a bi-radionuclide plaque, prescribed dose to the tumor apex can be delivered while maintaining the tumor dose uniformity and sparing the organs at risk. The potential advantages of bi-radionuclide plaque could be of interest in context of ocular brachytherapy. PURPOSE: The aim of the study is to evaluate the dosimetric advantages of a proposed bi-radionuclide plaque for two different designs, consisting of indigenous 125I seeds and 106Ru/106Rh plaque, using Monte Carlo technique. The study also explores the influence of other commercial 125I seed models and presence or absence of silastic/acrylic seed carrier on the calculated dose distributions. The study further included the calculation of depth dose distributions for the bi-radionuclide eye plaque for which experimental data are available. METHODS: The proposed bi-radionuclide plaque consists of a 1.2-mm-thick silver (Ag) spherical shell with radius of curvature of 12.5 mm, 20 µm-thick-106Ru/106Rh encapsulated between 0.2 mm Ag disk, and a 0.1-mm-thick Ag window, and water-equivalent gel containing 12 symmetrically arranged 125I seeds. Two bi-radionuclide plaque models investigated in the present study are designated as Design I and Design II. In Design I, 125I seeds are placed on the top of the plaque, while in Design II 106Ru/106Rh source is positioned on the top of the plaque. In Monte Carlo calculations, the plaque is positioned in a spherical water phantom of 30 cm diameter. RESULTS: The proposed bi-radionuclide eye plaque demonstrated superior dose distributions as compared to 125I or 106Ru plaque for tumor thicknesses ranges from 5 to 10 mm. Amongst the designs, dose at a given voxel for Design I is higher as compared to the corresponding voxel dose for Design II. This difference is attributed to the higher degree of attenuation of 125I photons in Ag as compared to beta particles. Influence of different 125I seed models on the normalized lateral dose profiles of Design I (in the absence of carrier) is negligible and within 5% on the central axis depth dose distribution as compared to the corresponding values of the plaque that has indigenous 125I seeds. In the presence of a silastic/acrylic seed carrier, the normalized central axis dose distributions of Design I are smaller by 3%-12% as compared to the corresponding values in the absence of a seed carrier. For the published bi-radionuclide plaque model, good agreement is observed between the Monte Carlo-calculated and published measured depth dose distributions for clinically relevant depths. CONCLUSION: Regardless of the type of 125I seed model utilized and whether silastic/acrylic seed carrier is present or not, Design I bi-radionuclide plaque offers superior dose distributions in terms of tumor dose uniformity, rapid dose fall off and lesser dose to nearby critical organs at risk over the Design II plaque. This shows that Design I bi-radionuclide plaque could be a promising alternative to 125I plaque for treatment of tumor sizes in the range 5 to 10 mm.

The Alk receptor tyrosine kinase regulates Sparkly, a novel activity regulating neuropeptide precursor in the Drosophila central nervous system.

Numerous roles for the Alk receptor tyrosine kinase have been described in Drosophila, including functions in the central nervous system (CNS), however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analyzed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk and scRNA-seq datasets from larval brains in which Alk signaling was manipulated identified a previously uncharacterized Drosophila neuropeptide precursor encoded by CG4577 as an Alk signaling transcriptional target. CG4577, which we named Sparkly (Spar), is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of the Drosophila Alk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (clock) neurons, and flies lacking Spar exhibit defects in sleep and circadian activity control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in the Drosophila CNS.

Hypogonadotropic hypogonadism with Zinner syndrome: a coincidence or a consequence?

This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also exhibited hyposmia, eunuchoid stature and gynecomastia. Biochemical investigations revealed low levels of testosterone, luteinising hormone and follicle-stimulating hormone. Hence, he was diagnosed with Kallmann syndrome. Imaging studies showed an absent right kidney and cystic dilatation of the distal ureteric bud, seminal vesicle and absent/hypoplastic ejaculatory duct. The association of hypogonadotropic hypogonadism with Zinner syndrome, a rare condition characterised by renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction, was noted.

Unveiling novel metabolic alterations in postmenopausal osteoporosis and type 2 diabetes mellitus through NMR-based metabolomics: A pioneering approach for identifying early diagnostic markers.

BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.

Like Father, Like Daughter - Ectodermal Dysplasia-Syndactyly Syndrome: A Case Report.

Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) is an exceedingly rare condition associated with mutations in the PVL4 gene. It is characterised by sparse, brittle hair, eyebrows and eyelashes, abnormal dentition and nails, along with bilateral cutaneous syndactyly involving the fingers and toes. We report a 2-year-old girl who presented to us with bilateral complete simple syndactyly of the third and fourth web spaces of the hands, along with bilateral syndactyly of both feet involving the second to fourth toes. Upon examination, sparse hair and eyebrows, along with abnormal dentition, were noted. Thorough clinical examination and genetic analysis were conducted on the affected child and her father, who exhibited similar clinical features. Genetic analysis revealed a homozygous nonsense mutation in the PVL4 gene in both individuals. According to the literature, EDSS1 has been reported in only 10 families worldwide, and there are no reported cases from India. Level of Evidence: Level V (Therapeutic).

Green Synthesized Chitosan Nanoparticles for Controlling Multidrug-Resistant mecA- and blaZ-Positive Staphylococcus aureus and aadA1-Positive Escherichia coli.

Antimicrobial resistance has recently been considered an emerging catastrophe globally. The public health and environmental threats were aggravated by the injudicious use of antibiotics in animal farming, aquaculture, and croup fields, etc. Consequently, failure of antibiotic therapies is common because of the emergence of multidrug-resistant (MDR) bacteria in the environment. Thus, the reduction in antibiotic spillage in the environment could be an important step for overcoming this situation. Bear in mind, this research was focused on the green synthesis of chitosan nanoparticles (ChiNPs) using Citrus lemon (Assam lemon) extract as a cross-linker and application in controlling MDR bacteria to reduce the antibiotic spillage in that sector. For evaluating antibacterial activity, Staphylococcus aureus and Escherichia coli were isolated from environmental specimens, and their multidrug-resistant pattern were identified both phenotypically by disk diffusion and genotypically by detecting methicillin- (mecA), penicillin- (blaZ), and streptomycin (aadA1)-resistance encoding genes. The inhibitory zone's diameter was employed as a parameter for determining the antibacterial effect against MDR bacteria revealing 30 ± 0.4 mm, 34 ± 0.2 mm, and 36 ± 0.8 mm zones of inhibition against methicillin- (mecA) and penicillin (blaZ)-resistant S. aureus, and streptomycin (aadA1)-resistant E. coli, respectively. The minimum inhibitory concentration at 0.31 mg/mL and minimum bactericidal concentration at 0.62 mg/mL of yielded ChiNPs were used as the broad-spectrum application against MDR bacteria. Finally, the biocompatibility of ChiNPs was confirmed by showing a negligible decrease in BHK-21 cell viability at doses less than 2 MIC, suggesting their potential for future application in antibiotic-free farming practices.

Prevalence of opportunistic pathogens and anti-microbial resistance in urban aquaculture ponds.

Bacterial antimicrobial resistance (AMR) has emerged as a significant concern worldwide. The microbial community profile and potential AMR level in aquaculture ponds are often undervalued and attract less attention than other aquatic environments. We used amplicon and metagenomic shotgun sequencing to study microbial communities and AMR in six freshwater polyculture ponds in rural and urban areas of Bangladesh. Amplicon sequencing revealed different community structures between rural and urban ponds, with urban ponds having a higher bacterial diversity and opportunistic pathogens including Streptococcus, Staphylococcus, and Corynebacterium. Despite proteobacterial dominance, Firmicutes was the most interactive in the community network, especially in the urban ponds. Metagenomes showed that drug resistance was the most common type of AMR found, while metal resistance was only observed in urban ponds. AMR and metal resistance genes were found mainly in beta and gamma-proteobacteria in urban ponds, while AMR was found primarily in alpha-proteobacteria in rural ponds. We identified potential pathogens with a high profile of AMR and metal resistance in urban aquaculture ponds. As these ponds provide a significant source of protein for humans, our results raise significant concerns for the environmental sustainability of this food source and the dissemination of AMR into the food chain.

Microbes vary strategically in their metalation of mononuclear enzymes.

Studies have determined that nonredox enzymes that are cofactored with Fe(II) are the most oxidant-sensitive targets inside Escherichia coli. These enzymes use Fe(II) cofactors to bind and activate substrates. Because of their solvent exposure, the metal can be accessed and oxidized by reactive oxygen species, thereby inactivating the enzyme. Because these enzymes participate in key physiological processes, the consequences of stress can be severe. Accordingly, when E. coli senses elevated levels of H2O2, it induces both a miniferritin and a manganese importer, enabling the replacement of the iron atom in these enzymes with manganese. Manganese does not react with H2O2 and thereby preserves enzyme activity. In this study, we examined several diverse microbes to identify the metal that they customarily integrate into ribulose-5-phosphate 3-epimerase, a representative of this enzyme family. The anaerobe Bacteroides thetaiotaomicron, like E. coli, uses iron. In contrast, Bacillus subtilis and Lactococcus lactis use manganese, and Saccharomyces cerevisiae uses zinc. The latter organisms are therefore well suited to the oxidizing environments in which they dwell. Similar results were obtained with peptide deformylase, another essential enzyme of the mononuclear class. Strikingly, heterologous expression experiments show that it is the metal pool within the organism, rather than features of the protein itself, that determine which metal is incorporated. Further, regardless of the source organism, each enzyme exhibits highest turnover with iron and lowest turnover with zinc. We infer that the intrinsic catalytic properties of the metal cannot easily be retuned by evolution of the polypeptide.

Basal and FSH-stimulated Inhibin B in Precocious Puberty.

OBJECTIVE: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B to differentiate premature thelarche from gonadotropin-dependent precocious puberty (GDPP). METHOD: This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age (n = 10), healthy girls with normal pubertal development (pubertal control) (n = 8) and healthy prepubertal girls (prepubertal control) (n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test. RESULTS: Median (IQR) basal inhibin B in premature thelarche was 5.42 (2.91, 30.58) pg/mL and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) pg/mL (P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11-1266.18) pg/mL (P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche (P = 0.032). Median (IQR) basal inhibin B in prepubertal and prepubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively. CONCLUSIONS: Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size.