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Hypertensive rats serve as a good experimental model for studying the pathophysiology of cardiac hypertrophy and remodeling leading to heart failure. In this study, we aimed to analyze the effect of astaxanthin and possible mechanisms involved in alleviating oxidative stress, fibrosis and inflammation that triggers cardiac remodeling using male uninephrectomized Long Evans rats. Cardiac hypertrophy and hypertension were induced in rats termed as 'FCA-Salt rats' by an oral administration of fludrocortisone acetate (FCA) and 1 % NaCl in drinking water. Biochemical assays showed that FCA-Salt rats exhibited an upregulation of oxidative stress markers AOPP, MDA and downregulation of NO in heart and kidney, which was reversed by astaxanthin treatment. Astaxanthin further regularized the reduced activities of antioxidant enzymes GSH, SOD and CAT in these tissues. ELISA revealed that astaxanthin significantly reduced the inflammatory response by reducing the elevated levels of IL-1β, IL-17a, and TNF-α and pro-fibrotic marker TGF-β1 in plasma. Real-time qPCR depicted an upregulation of TNF-α, IL-1β, IL-6, IL-17A as well as signaling molecules TGF-β1, Smad2 and Smad3 in heart of FCA-Salt rats, which was reduced significantly by astaxanthin. Sirius red staining showed that the cardiac and renal fibrosis was significantly improved by astaxanthin treatment. Together, our results suggest that astaxanthin treatment is beneficial in protecting cardio-renal damage in hypertension through TGF-β/Smad signaling pathway, hence, this molecule may be considered for the maintenance of cardio-renal health., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Subcutaneous (SC) administration of chemotherapeutics combined with near-infrared (NIR) light activation can effectively target skin tumors by triggering localized drug release and enhancing cytotoxic effects. In this study, we developed NIR-responsive indocyanine green (ICG) and the chemotherapeutic agent doxorubicin (Dox) loaded into gelatin nanoparticles (NPs) for SC delivery in a skin tumor-bearing mouse model. Histological examination (hematoxylin and eosin staining) confirmed the successful delivery and swelling behavior of the Dox/ICG-loaded gelatin NPs at the SC site. In vitro and in vivo experiments demonstrated that NIR activation of the Dox/ICG-loaded gelatin NPs generated significant photothermal heat (48 and 46 °C), leading to targeted drug release and a substantial reduction in skin tumor size (from 15 to 3 mm 3 ). Our findings suggest that this dual-modality approach of SC chemotherapeutic administration and NIR-triggered photothermal therapy can concentrate cytotoxic drugs at the tumor site, offering a promising strategy for improving skin cancer treatment.

Importance: Rohingya refugees, forcibly displaced from Myanmar, face challenges adapting to Bangladesh. Examining their quality of life (QOL) is vital to identifying nuanced factors associated with their well-being, informing targeted interventions for an improved QOL., Objectives: To identify the QOL among Rohingya refugees 5 years after migration to Bangladesh, with a particular emphasis on understanding the complex interplay between sociodemographic factors and chronic illnesses., Design, Setting, and Participants: A cross-sectional study involving resettled Rohingya adults was conducted between May 18 and July 7, 2021, approximately 5 years after their resettlement in Bangladesh. Of the participants, 500 individuals were healthy, whereas 558 individuals were undergoing treatment for at least 1 chronic disease. Data were analyzed from January to February 2024., Main Outcomes and Measures: The study assessed QOL using the short version of the World Health Organization's QOL Questionnaire, covering 4 domains: physical, psychological, social, and environmental. Scores were transformed to a maximum of 100. Tobit linear regression, adjusted for potential confounders, was employed for analysis., Results: The study included a total of 1058 respondents, who were predominantly female (630 participants [59.5%]) and had a mean (SD) age of 42.5 (16.1) years. Despite being healthy, individuals without chronic illnesses had median QOL scores ranging from 44 to 56 out of 100, indicating a relatively poor QOL. A total of 260 participants (46.6%) with chronic diseases reported very poor or poor QOL, in contrast to 58 healthy individuals (11.6%) in the fifth year after displacement. Specifically, patients with cancer and those who had multimorbidity exhibited the lowest QOL scores across all domains, with significant reductions in the physical health (10.57 decrease; 95% CI, -12.97 to -8.17) and psychological domain scores (7.20 decrease; 95% CI, -9.71 to -5.93) according to Tobit regression analysis., Conclusions and Relevance: This study found that chronic illnesses were associated with all domains of QOL among Rohingya refugees, particularly those with musculoskeletal disorders, cancer, and multimorbid conditions. This heightened vulnerability may contribute to poor QOL in this population. By uncovering these disparities, the study lays the groundwork for targeted interventions and policies aligned with the United Nations' goal of leaving no one behind in sustainable development efforts.

Background: The differentiation between COVID-19 and post-COVID-19 syndromes is not properly defined as some patients remain asymptomatic for post-COVID-19. It can be characterized by several signs and symptoms. Risk factors related to post-COVID-19 remain unsolved. Here we aimed to differentiate post-COVID-19 patients among symptomatic and asymptomatic groups to check the percentage among them and the risk factors for post-COVID-19 and the association of different symptoms., Methods: This study was conducted in Chittagong division, Bangladesh at different hospitals. Data were collected from the participants either by in person interview or online (email) or mobile phone calls. Follow up was done after 3 months to check the development of post-COVID-19 syndromes. Relevant data were taken, and symptomatic and asymptomatic patients were divided based on the presence and severity of specific symptoms., Results: Our results showed that 41.88 % patients develop post-COVID-19 symptoms. Fever and Cough were classified as one of the factors of post-COVID-19, followed by dyspnea, fatigue, cough, rhinitis, sore throat, and muscular discomfort. On the other hand, age, respiratory distress, lethargy, duration of illness and severity were classified as risk factors for post-COVID-19. There was a significant difference between symptomatic and asymptomatic patients as only 16.3 % patients showed post-COVID-19 symptoms. Based on the severity grade, 80.7 % of patients had mild COVID-19. We also found that people with 'B' positive blood group had a higher chance of developing post-COVID-19 syndrome., Conclusion: It was concluded that age, duration of illness, presence of respiratory distress, blood group, and disease severity are major risk factors for the development of post-COVID-19 syndrome., 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., (© 2024 The Authors.)

Obesity is a known risk factor for many chronic diseases and a substantial threat to public health. We investigated the effects of figs sourced from Ficus hispida on a high fat-fed experimental rat model. We found that a 500-mg dose of ethanolic extract of figs (EFH) reduced oxidative stress markers nitric oxide (NO), malondialdehyde (MDA), and advanced oxidation protein products (AOPP), which were increased in high fat-fed rats. Antioxidant enzymes superoxide dismutase (SOD), catalase, reduced glutathione (GSH), and myeloperoxidase (MPO), found elevated in high fat-fed rats, were also normalized to nearly regular levels by fig treatment. Administration of EFH further reduced fat deposition and expression of adipogenic genes leptin, fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein-1c (SERBP-1c). Our results suggest that figs have significant effects on reducing oxidative stress and mitigating obesity-associated liver and adipose tissue abnormalities via suppressing adipogenesis. Thus, we propose that F. hispida has potential benefits in reducing obesity., 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., (© 2024 The Authors.)

Prostacyclin or prostaglandin I 2 (PGI 2 ), a metabolite of arachidonic cyclooxygenase pathway, has been demonstrated as an effector of adipocyte differentiation. However, due to its instability in biological fluid, it is difficult to evaluate the role of PGI 2 in regulating adipocyte differentiation in different stages in culture. Therefore, this study aimed to establish a simple and rapid method for the production of monoclonal antibody against 6-Keto PGF 1 α, a stable PGI 2 metabolite, and its quantification to determine the role of PGI 2 in culture medium. Eight-week-old female BALB/c mice were immunized with the hapten of 6-Keto PGF 1 α and BSA for several weeks until a higher antibody titer (absorbance value > 0.9 at 1000-times dilution) against 6-Keto PGF 1 α was found. Then, fusion of antibody-producing spleen lymphocytes with SP-2 myeloma cells and thymocytes was performed and cultured in HAT-medium supplemented with hypoxanthine, aminopterin, and thymine. Specific antibody-producing cells (M2-A4-B8-D10) against 6-Keto PGF 1 α were identified and separated. A standard ELISA calibration curve was developed with 100% reactivity for 6-Keto-PGF 1 α ranging from 0.26 pg to 6.44 ng corresponding to 90% and 10% of the maximum binding capacity for the immobilized antigen respectively. This method can easily be applied to monitor PGI 2 regulation in different stages of cultured adipocytes to reveal the regulatory roles of PGI 2 in maintaining homeostasis and adipocyte differentiation., 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., (© 2024 Published by Elsevier B.V.)

We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and in vivo mouse veins after intravenous administration. The trackable liposome delivery provides in vitro and in vivo photothermal heat (∼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.

Background: The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes., Methods: The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15-35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12-14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI) < 18.5 kg/m 2 and MMS for others; (4) targeted BEP for those with pre-pregnancy BMI < 18.5 kg/m 2 , MMS for others, and women with inadequate gestational weight gain switched from MMS to BEP until the end of pregnancy. Primary outcomes include birth weight, low birth weight (< 2500 g), and small for gestational age, defined using the 10 th percentile of the INTERGROWTH-21st reference, for live-born infants measured within 72 h of birth. Project-hired local female staff visit pregnant women monthly to deliver the assigned supplements, monitor adherence biweekly, and assess weight regularly during pregnancy. Trained data collectors conduct pregnancy outcome assessment and measure newborn anthropometry in the facility or home depending on the place of birth., Discussion: This study will assess the effectiveness of targeted balanced energy and protein supplementation to improve birth outcomes among pregnant women in rural Bangladesh and similar settings., Trial Registration: ClinicalTrials.gov NCT05576207. Registered on October 5th, 2022., (© 2024. The Author(s).)

This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)-induced hepatorenal complications in Wister albino rats. Additionally, it aims to detect polyphenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The rats were treated intraperitoneally with CP (7.5 mg/kg) to mediate hepatorenal damage. They were then treated with GP extract (75 and 150 mg/kg, P.O.) for 7 consecutive days. Although GP extract significantly ameliorated CP-mediated hepatorenal biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels in a dose-dependent manner, GP extract at 150 mg/kg dose normalized hepatorenal biomarkers ALP (45.11 U/L), ALT (34 U/L), AST (29 U/L), creatinine (10.3 mg/dl) and BUN (11.19 mg/dl) while comparing to control and disease group. Similarly, though it significantly reduced CP-induced oxidative stress inducers, including nitric oxide (NO) and advanced oxidative protein products (AOPP), higher dose (150 mg/kg) exhibited better activity in reducing NO (281.54 mmol/gm tissue in liver and 52.73 mmol/gm tissue in the kidney) and AOPP (770.95 mmol/mg protein in liver and 651.90 mmol/mg protein in the kidney). Besides, it showed better enhancement in the antioxidant enzymes superoxide dismutase, and glutathione levels at a higher dose (150 mg/kg). Histopathological studies showed that CP caused collagen accumulation in the liver and kidney tissues. GP extract drained the collagen mass and acted against hepatorenal damage. Ellagic acid, gallic acid, quercetin hydrate, kaempferol, and rutin hydrate were revealed in GP extract. In-silico modelling showed good docking scores of the polyphenolic compounds with molecular targets including CYP4502E1, NF-κB, caspase-3, and TNF-α. GP could be an effective therapeutic option for management of anticancer drugs' complications like CP-induced organ damage, although clinical studies are required to establish herbal formulation., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Global prevalence of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease is increasing gradually, whereas approvals of successful therapeutics for central nervous system disorders are inadequate. Accumulating evidence suggests pivotal roles of the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in modulating neuroinflammation and necroptosis. Discoveries of potent small molecule inhibitors for RIPK1 with favorable pharmacokinetic properties could thus address the unmet medical needs in treating neurodegeneration., Methods: In a structure-based virtual screening, we performed site-specific molecular docking of 4,858 flavonoids against the kinase domain of RIPK1 using AutoDock Vina. We predicted physicochemical descriptors of the top ligands using the SwissADME webserver. Binding interactions of the best ligands and the reference ligand L8D were validated using replicated 500-ns Gromacs molecular dynamics simulations and free energy calculations., Results: From Vina docking, we shortlisted the top 20 flavonoids with the highest binding affinities, ranging from -11.7 to -10.6 kcal/mol. Pharmacokinetic profiling narrowed down the list to three orally bioavailable and blood-brain-barrier penetrant flavonoids: Nitiducarpin, Pinocembrin 7-O-benzoate, and Paratocarpin J. Next, trajectories of molecular dynamics simulations of the top protein-ligand complexes were analyzed for binding interactions. The root-mean-square deviation (RMSD) was 1.191 Å (±0.498 Å), 1.725 Å (±0.828 Å), 1.923 Å (±0.942 Å), 0.972 Å (±0.155 Å) for Nitiducarpin, Pinocembrin 7-O-benzoate, Paratocarpin J, and L8D, respectively. The radius of gyration (Rg) was 2.034 nm (±0.015 nm), 2.0.39 nm (± 0.025 nm), 2.053 nm (±0.021 nm), 2.037 nm (±0.016 nm) for Nitiducarpin, Pinocembrin 7-O-benzoate, Paratocarpin J, and L8D, respectively. The solvent accessible surface area (SASA) was 159.477 nm 2 (±3.021 nm 2 ), 159.661 nm 2 (± 3.707 nm 2 ), 160.755 nm 2 (±4.252 nm 2 ), 156.630 nm 2 (±3.521 nm 2 ), for Nitiducarpin, Pinocembrin 7-O-benzoate, Paratocarpin J, and L8D complexes, respectively. Therefore, lower RMSD, Rg, and SASA values demonstrated that Nitiducarpin formed the most stable complex with the target protein among the best three ligands. Finally, 2D protein-ligand interaction analysis revealed persistent hydrophobic interactions of Nitiducarpin with the critical residues of RIPK1, including the catalytic triads and the activation loop residues, implicated in the kinase activity and ligand binding., Conclusion: Our target-based virtual screening identified three flavonoids as strong RIPK1 inhibitors, with Nitiducarpin exhibiting the most potent inhibitory potential. Future in vitro and in vivo studies with these ligands could offer new hope for developing effective therapeutics and improving the quality of life for individuals affected by neurodegeneration., Competing Interests: The authors declare that they have no competing interests., (© 2024 Bepari et al.)

Objectives: This study aims at exploring the effects of physicians' communication behaviors on patients' satisfaction in primary care medical consultations in Chattogram, Bangladesh. The study used a quantitative research approach designed with a cross-sectional survey., Methods: Data were collected using post-consultation and facilitator administered questionnaire from the patients who visited the physician for medical consultation in different hospitals and clinics in Chattogram city. Seven hundred patients were included as the study participants. A hierarchical linear regression analysis was performed to examine the factors contributing to the outcome variables., Results: A statistically significant difference ( P  < .001) appeared regarding patients' perception of adequate consultation, physicians' nonverbal behavior, inhibiting behavior and patients' participating behavior in private and public settings. However, R 2 value shows that physicians' patient-centered behaviors appeared as the stronger predictors of patient satisfaction toward medical interviews, followed by socioeconomic variables of patients and physicians and patients' participation during the consultation. Presence of a third person with patients during consultation (β = -.05, P  = .040), physicians' private setting of consultation (β = .16, P  < .001), physicians' seniority (β = .05, P  = .042), patients' participating behavior during consultation (β = .20, P  < .001), physicians' nonverbal behavior (β = .10, P  < .001), physicians' inhibiting behavior (β = -.39, P  < .001), and physicians' facilitating behavior with patients (β = .32, P  < .001) were reported as the influencing factors of patients' satisfaction with medical consultation., Conclusion: This study suggests the profound impact of physicians' patient-centered communication behaviors on patient satisfaction in primary care settings, overshadowing even socioeconomic factors and patient participation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Polymorphisms of the disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) are linked to pathophysiological changes in lung inflammation, cancer, Alzheimer's disease (AD), encephalopathy, liver fibrosis, and cardiovascular diseases. In this study, we predicted the pathogenicity of ADAM10 non-synonymous single nucleotide polymorphisms (nsSNPs) in a wide array of mutation analyzing bioinformatics tools. We retrieved 423 nsSNPs from dbSNP-NCBI for the analysis, and 13 were predicted deleterious by each of the ten tools: SIFT, PROVEAN, CONDEL, PANTHER-PSEP, SNAP2, SuSPect, PolyPhen-2, Meta-SNP, Mutation Assessor and Predict-SNP. Further assessment of amino acid sequences, homology models, conservation profiles, and inter-atomic interactions identified C222G, G361E and C639Y as the most pathogenic mutations. We validated this prediction through structural stability analysis using DUET, I-Mutant Suite, SNPeffect and Dynamut. Molecular dynamics simulations and principal component analysis also indicated considerable instability of the C222G, G361E and C639Y variants. Therefore, these ADAM10 nsSNPs could be candidates for diagnostic genetic screening and therapeutic molecular targeting.Communicated by Ramaswamy H. Sarma.

Lung cancer is responsible for causing one of the highest numbers of cancer deaths. In Bangladesh, both men and women are affected by lung cancer, and environmental contaminants are believed to be one of the main risk factors apart from smoking. The diagnosis of lung cancer is difficult due to the delicate structure and complexity of the lungs. Diagnosis in later stages results in a poor prognosis of the disease. Tissue biopsy is the most reliable way of identifying lung cancer, but it is invasive and requires identification of the primary neoplasm within the lungs. As inflammation is involved in carcinogenesis, circulating levels of cytokines might be elevated in patients during the early stages of cancer. Increased IL-6 levels have been associated with the promotion of tumor growth, and IL-17 is believed to aid metastasis of lung cancer. In this study, the use of IL-6 and IL-17 was investigated as diagnostic markers for lung cancer. IL-6 and IL-17 levels were compared between 35 lung cancer patients and 19 healthy individuals. IL-6 levels were markedly elevated (7.417 pg/mL) in lung cancer cases compared to the controls (0.970 pg/mL), indicating a positive correlation (p < 0.05). IL-17 levels were only slightly higher in lung cancer patients (9.400 pg/mL) compared to healthy individuals (8.922 pg/mL). Both IL-6 and IL-17 levels were higher in patients with adenocarcinoma compared with other subtypes of lung cancer. Treatment with chemotherapy and radiotherapy did not significantly affect IL-6 levels. However, IL-17 levels were reduced due to cancer treatment. Further studies with larger sample sizes assessing the IL-6 and IL-17 in lung cancer patients are needed to establish the diagnostic role of the two cytokines., 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.)

Previously, we observed curcumin improves aging-associated memory impairment in D-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders., (© 2023. Springer Nature Limited.)

The human receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical necroptosis regulator implicated in cancer, psoriasis, ulcerative colitis, rheumatoid arthritis, Alzheimer's disease, and multiple sclerosis. Currently, there are no specific RIPK1 antagonists in clinical practice. In this study, we took a target-based computational approach to identify blood-brain-barrier-permeable potent RIPK1 ligands with novel chemotypes. Using molecular docking, we virtually screened the Marine Natural Products (MNP) library of 14,492 small molecules. Initial 18 hits were subjected to detailed ADMET profiling for bioavailability, brain penetration, druglikeness, and toxicities and eventually yielded 548773-66-6 as the best ligand. RIPK1 548773-66-6 binding was validated through duplicated molecular dynamics (MD) simulations where the co-crystallized ligand L8D served as a reference. Trajectory analysis indicated negligible Root-Mean-Square-Deviations (RMSDs) of the best ligand 548773-66-6 relative to the protein backbone: 0.156 ± 0.043 nm and 0.296 ± 0.044 nm (mean ± standard deviations) in two individual simulations. Visual inspection confirmed that 548773-66-6 occupied the RIPK1 ligand-binding pocket associated with the kinase activation loop. Further computations demonstrated consistent hydrogen bond interactions of the ligand with the residue ASP156. Binding free energy estimation also supported stable interactions of 548773-66-6 and RIPK1. Together, our in silico analysis predicted 548773-66-6 as a novel ligand for RIPK1. Therefore, 548773-66-6 could be a viable lead for inhibiting necroptosis in central nervous system inflammatory disorders.Communicated by Ramaswamy H. Sarma.

Introduction: Inappropriate antibiotic use in community settings significantly contributes to antimicrobial resistance (AMR) globally, compromising the quality of life and threatening public health. This study aimed to identify AMR contributing factors by analyzing the knowledge, attitude, and practice (KAP) of the unqualified village medical practitioners and pharmacy shopkeepers in rural Bangladesh., Methods: We performed a cross-sectional study where the participants were pharmacy shopkeepers and unqualified village medical practitioners aged ≥ 18 years and living in Sylhet and Jashore districts in Bangladesh. Primary outcome variables were knowledge, attitude, and practice of antibiotic use and AMR., Results: Among the 396 participants, all were male aged between 18 and 70 years, 247 were unqualified village medical practitioners, and 149 were pharmacy shopkeepers, and the response rate was 79%. Participants showed moderate to poor knowledge (unqualified village medical practitioners, 62.59%; pharmacy shopkeepers, 54.73%), positive to neutral attitude (unqualified village medical practitioners, 80.37%, pharmacy shopkeepers, 75.30%), and moderate practice (unqualified village medical practitioners, 71.44%; pharmacy shopkeepers, 68.65%) scores regarding antibiotic use and AMR. The KAP score range was 40.95-87.62%, and the mean score was statistically significantly higher for unqualified village medical practitioners than pharmacy shopkeepers. Multiple linear regression analysis suggested that having a bachelor's degree, pharmacy training, and medical training were associated with higher KAP scores., Conclusion: Our survey results demonstrated that unqualified village medical practitioners and pharmacy shopkeepers in Bangladesh possess moderate to poor knowledge and practice scores on antibiotic use and AMR. Therefore, awareness campaigns and training programs targeting unqualified village medical practitioners and pharmacy shopkeepers should be prioritized, antibiotic sales by pharmacy shopkeepers without prescriptions should be strictly monitored, and relevant national policies should be updated and implemented., (© 2023. The Author(s).)

We describe the synthesis of a nanostructured dermal patch composed of chitosan-tannic acid (CT) that can carry near-infrared (NIR) active Indocyanine green (ICG) dye for performing photothermal heat conversion activity. The NIR-responsive CT-I dermal patch can deliver topical antibiotic drugs (Neomycin). The CT-I and drug-loaded CT-I/N patches have been demonstrated by FTIR, SEM/EDX, TGA, and DSC analysis. The in vitro drug release from the CT-I/N patch are favorable in the dermal environment (pH = 5.5) and significantly increases 25 % more at higher temperatures of 40 to 45 °C. The CT-I/N showed increasing photothermal heat in response to NIR (808 nm) light. The in vivo thermograph demonstrated that the CT-I/N patch can generate >45 °C within 5 min NIR irradiation. As a result, sustained wound healing was shown in H&E (hematoxylin and eosin) staining dermal tissue. Such NIR-active nanostructure film/patch is promising for the future of any sustained on-demand drug delivery 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 B.V. All rights reserved.)

Liver disease is a serious health problem affecting people worldwide at an alarming rate. The present study aimed to investigate the protective effects of Ganoderma lucidum against CCl 4 -induced liver toxicity in rats. The experimental Long Evans rats were divided into five groups, of which four groups were treated with carbon tetrachloride (CCl 4 ). Among the CCl 4 treated groups, one of the groups was treated with silymarin and two of them with ethanolic extract of G. lucidum at 100 and 200 mg/Kg body weight. The oxidative stress parameters and endogenous antioxidant enzyme concentrations were assessed by biochemical tests. Liver enzymes ALT, AST, and ALP were determined spectrophotometrically. Histopathological examinations were carried out to assess hepatic tissue damage and fibrosis. Reverse transcription PCR (RT-PCR) was performed to determine the expression of IL-1β, IL-6, IL-10, TNF-α, and TGF-β genes. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis revealed that G. lucidum is rich in several phytochemicals including 6-Octadecanoic acid (55.81%), l-( +)-Ascorbic acid 2,6-dihexadecanoate (18.72%), Cis-11-Eicosenamide (5.76%), and Octadecanoic acid (5.26%). Treatment with the G. lucidum extract reduced the elevated ALT, AST, ALP levels, and cellular oxidative stress markers and increased the endogenous antioxidant levels. Histopathology observations revealed that the inflammation, infiltration of immune cells, and aberration of collagen fibers in the hepatocytes were altered by the G. lucidum treatment. The increased expression of inflammatory cytokines TNF-α, TGF-β, IL-1 β, and IL-6 were markedly suppressed by G. lucidum extract treatment. G. lucidum also prevented the suppression of protective IL-10 expression by CCl 4 . This study strongly suggests that G. lucidum extract possesses significant hepatoprotective activity as evidenced by reduced oxidative stress and inflammation mediated by suppression in inflammatory cytokine expression and increased protective IL-10 cytokine expression., (© 2023. The Author(s).)

Antibiotic resistance has been recognized as a public health threat in recent years, and mortality due to resistance is increasing alarmingly every year. Antibiotic resistance, among many factors, may arise due to the consumption of substandard antibiotic brands that provide subnormal levels of the drug in the blood. Post-market evaluation can provide important information in assessing pharmaceutical products in terms of quality, purity, and therapeutic aspects. Ciprofloxacin, a broad-spectrum antibiotic, has been used against a wide range of infectious diseases in Bangladesh. The present study aimed to determine the quality attributes of twenty-two commonly prescribed brands of ciprofloxacin 500 mg tablet collected from Dhaka city and the rural regions of Jessore. RP-HPLC coupled with UV-visible spectrophotometry was used to determine the potency of ciprofloxacin in tablets, and the zone of inhibition was determined using Kirby-Bauer's disc diffusion method to assess the antimicrobial efficacy against different strains of microorganisms. We found that 95.45% of brands (21 out of 22 brands) of ciprofloxacin tablets met United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) specified potency, whereas one brand failed. From dissolution studies, we observed that 68.2% of brands (15 out of 22 brands) followed USP/NF dissolution test specifications, whereas 31.8% (7 out of 22 brands) failed to release 80% of the labeled amount of drug within 30 min. Drug release kinetics data showed that most brands followed the Weibull drug release kinetic model. Fit factor analysis exhibited that 8 brands out of 22 (36.4%) failed to comply similar dissolution profiles with the reference product. Minimum inhibitory concentrations, assessed against five bacterial strains, further showed good antimicrobial sensitivity by all brands., 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 Author(s).)

Background and Aims: Cervical cancer is characterized by abnormal cell growth in the lining of cervix and it is the second major cause of cancer-related deaths among females in Bangladesh. Interleukin-6 ( IL-6 ) is a multifunctional cytokine that has been heavily linked with cervical cancer. Our aim was to investigate the association of two promoter single-nucleotide polymorphisms (SNPs) of IL-6 (rs1800795 and rs1800797) with the susceptibility of cervical cancer in Bangladeshi women., Methods: DNA was extracted from venous blood samples from cervical cancer patients ( n  = 126) and healthy controls ( n  = 120). Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping of the selected SNPs. Logistic regression was performed to calculate the odds ratio (OR) with 95% confidence interval (CI) and p values., Results: We found a significant association between rs1800795 and rs1800797 polymorphisms and cervical cancer. For, rs1800795 (G > C) the GC heterozygous genotype (OR = 2.80, 95% CI = 1.55-5.07, p  = 0.0007) and CC mutant homozygous genotype (OR = 3.5, 95% CI = 1.29-9.51, p  = 0.014) conferred an increased risk of cervical cancer. In case of rs1800797 (G > A) polymorphism, the AG heterozygous genotype (OR = 6.94, 95% CI = 3.76-12.81, p  < 0.0001) and AA mutant homozygous genotype (OR = 3.88, 95% CI = 1.12-13.51, p  = 0.0332) also exhibited an elevated risk of cervical cancer. Use of contraceptives was found as risk factor and patients who smoke were carriers of both the risk alleles and thus had an increased risk of cervical cancer., Conclusion: Our findings suggest that polymorphism of rs1800795 and rs1800797 of the IL-6 gene play a significant role in cervical cancer susceptibility in Bangladeshi women., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Competing Interests: None.

Carbofuran is a widely used poisonous pesticide around the world that helps to control insects during farming. Upon oral ingestion to humans, it exaggerates oxidative stress in various organs like the liver, brain, kidney, and heart. Several studies reported that oxidative stress in the liver initiates and propagates hepatic cell necrosis, ultimately resulting in hepatotoxicity. It also reported that coenzyme Q10 (CoQ10) can neutralize oxidative stress due to its antioxidant properties. However, the hepatoprotective and nephroprotective role of CoQ10 against carbofuran toxicity has not been investigated. Therefore, the present study aimed to evaluate the hepatoprotective and nephroprotective role of CoQ10 in carbofuran-induced hepatotoxicity and nephrotoxicity in a mouse model for the first time. We determined the blood serum diagnostic markers, oxidative stress parameters, antioxidant system, and histopathological characteristics of liver and kidney tissues. The administration of 100 mg/kg of CoQ10 in carbofuran-treated rats significantly attenuated AST, ALT, ALP, serum creatinine, and BUN levels. Moreover, CoQ10 (100 mg/kg) remarkably altered the level of NO, MDA, AOPP, GSH, SOD, and CAT in both the liver and kidney. The histopathological data also unveiled that CoQ10 treatment prevented inflammatory cell infiltration in carbofuran-exposed rats. Therefore, our findings infer that CoQ10 may effectively protect liver and kidney tissues against carbofuran-induced oxidative hepatotoxicity and nephrotoxicity., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 Published by Elsevier Ltd.)

Background: Urinary tract infection (UTI) is one of the most recurrent infections in the community and healthcare settings. Although many studies related with microbial sensitivity (MS) of uropathogens (UPs) to antibiotics have been done in Bangladesh, no conclusive study has compared antibiotic sensitivity (AS) to UPs in diabetic and non-diabetic patients. The aim of the study is to find out whether there is a difference in AS in common UPs between diabetic and non-diabetic UTI patients., Methods: A retrospective review was conducted on 833 patients. The data was collected from different diagnostic centers located within Dhaka city in Bangladesh, and the data was analyzed using convenient statistical tools., Results: We have studied a total of 833 UTI patients. Out of 833 patients, 664 were diabetic and 169 were non-diabetic patients respectively. Among the studied population, females were found to be more inclined to have UTIs as compared to males. E. coli was found to be the leading UPs in our study. Patients within the age of 20-34 were more vulnerable to UTI in both groups. Imipenem and meropenem showed 100% sensitivity against E. coli , Staphylococcus and Klebsiella in non-diabetic patients, while both antibiotics showed lower sensitivity to the same organisms in diabetic patients. Antibiotics like nitrofurantoin (p ≤ 0.0002), ceftazidime (p ≤ 0.0124) and ceftriaxone (p ≤ 0.0168) showed less sensitivity to E. coli in diabetic UTI patients as compared to non-diabetic UTI patients. Overall sensitivity patterns elucidated that all the studied antibiotics, except ciprofloxacin and levofloxacin, showed lower sensitivity against UPs in diabetic while compared to non-diabetic UTI patients (p= <0.05 to 0.0001)., Conclusion: We found significant difference in microbial sensitivity in patients with diabetes compared to non-diabetic UTI patients. Diabetes changes the pathophysiological state of the uropathogens leading to the declining sensitivity of the antibiotics in diabetic patients with UTIs., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Much scholarly debate has centered on Bangladesh's family planning program (FPP) in lowering the country's fertility rate. This study aimed to investigate the prevalence of using modern and traditional contraceptive methods and to determine the factors that explain the contraceptive methods use., Methods: The study used data from the 2017-18 Bangladesh Demographic and Health Survey (BDHS), which included 11,452 (weighted) women aged 15-49 years in the analysis. Multilevel multinomial logistic regression was used to identify the factors associated with the contraceptive method use., Results: The prevalence of using modern contraceptive methods was 72.16%, while 14.58% of women used traditional methods in Bangladesh. In comparison to women in the 15-24 years age group, older women (35-49 years) were more unwilling to use modern contraceptive methods (RRR: 0.28, 95% CI: 0.21-0.37). Women who had at least a living child were more likely to use both traditional and modern contraceptive methods (RRR: 4.37, 95% CI: 3.12-6.11). Similarly, given birth in the previous 5 years influenced women 2.41 times more to use modern method compared to those who had not given birth (RRR: 2.41, 95% CI: 1.65-3.52). Husbands'/partners' decision for using/not using contraception were positively associated with the use of both traditional (RRR: 4.49, 95% CI: 3.04-6.63) and modern methods (RRR: 3.01, 95% CI: 2.15-4.17) rather than using no method. This study suggests rural participants were 21% less likely to utilize modern methods than urban participants (RRR: 0.79, 95% CI: 0.67-0.94)., Conclusion: Bangladesh remains a focus for contraceptive use, as it is one of the most populous countries in South Asia. To lower the fertility rate, policymakers may design interventions to improve awareness especially targeting uneducated, and rural reproductive women in Bangladesh. The study also highlights the importance of male partners' decision-making regarding women's contraceptive use., (© 2022. The Author(s).)

Functional foods such as mushrooms are rich in polyphenolic compounds and secondary metabolites with health-promoting properties such as antioxidant, antimicrobial, antidiabetic and immunostimulatory effects. The present study is aimed to investigate the ethanolic extracts of three varieties of mushrooms, namely, G. lucidum , G. tropicum , and C. indica grown in Bangladesh for phenolic and flavonoid content and their antioxidant properties. Moreover, the phenolic composition of the extracts was analyzed by using the HPLC-DAD system. G. lucidum extract exhibited the highest antioxidant potential as evidenced by its lowest IC 50 value in all the tested assay models (40.44 ± 2.09  μ g/mL, 151.32 ± 0.35  μ g/mL, 137.89 ± 1.85  μ g/mL in DPPH, H 2 O 2, and NO scavenging assay, respectively) along with the highest phenolic content (81.34 ± 0.68 GAE g -1 extract). G. tropicum and C. indica extracts also showed significant antioxidant properties and a good amount of phenolic content, 52.16 ± 0.25 GAE g -1 extract, and 47.1 ± 0.26 GAE g -1 extract, respectively. The scavenging activity increased with the increasing concentration of extracts in all cases. The total phenolic content of the ethanolic extracts of mushroom species was highly correlated with antioxidant effects with Pearson's correlation coefficient ( r ) values ranging from 0.8883-0.9851. The α -amylase inhibitory and antibacterial activity of G. lucidum was evaluated by using 3,5-dinitrosalicylic acid and disc diffusion method, respectively. The maximum inhibitory activity recorded against α -amylase was 70.98 ± 0.042% at a concentration of 500  μ g/mL. G. lucidum extract exhibited the highest antibacterial activity against Pseudomonas aeruginosa with 23.00 ± 1.00 mm clear zone of inhibition and an MIC value of 3.5 mg/mL. The results indicate that the mushroom species tested in this study could serve as a potential source of natural antioxidants in the development of nutraceuticals and herbal drugs for the management of oxidative stress-associated diseases as well as infectious diseases., 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., (Copyright © 2022 Anika Tabassum Bristy et al.)

Wastewater-based epidemiology (WBE) has emerged as a valuable approach for forecasting disease outbreaks in developed countries with a centralized sewage infrastructure. On the other hand, due to the absence of well-defined and systematic sewage networks, WBE is challenging to implement in developing countries like Bangladesh where most people live in rural areas. Identification of appropriate locations for rural Hotspot Based Sampling (HBS) and urban Drain Based Sampling (DBS) are critical to enable WBE based monitoring system. We investigated the best sampling locations from both urban and rural areas in Bangladesh after evaluating the sanitation infrastructure for forecasting COVID-19 prevalence. A total of 168 wastewater samples were collected from 14 districts of Bangladesh during each of the two peak pandemic seasons. RT-qPCR commercial kits were used to target ORF1ab and N genes. The presence of SARS-CoV-2 genetic materials was found in 98% (165/168) and 95% (160/168) wastewater samples in the first and second round sampling, respectively. Although wastewater effluents from both the marketplace and isolation center drains were found with the highest amount of genetic materials according to the mixed model, quantifiable SARS-CoV-2 RNAs were also identified in the other four sampling sites. Hence, wastewater samples of the marketplace in rural areas and isolation centers in urban areas can be considered the appropriate sampling sites to detect contagion hotspots. This is the first complete study to detect SARS-CoV-2 genetic components in wastewater samples collected from rural and urban areas for monitoring the COVID-19 pandemic. The results based on the study revealed a correlation between viral copy numbers in wastewater samples and SARS-CoV-2 positive cases reported by the Directorate General of Health Services (DGHS) as part of the national surveillance program for COVID-19 prevention. The findings of this study will help in setting strategies and guidelines for the selection of appropriate sampling sites, which will facilitate in development of comprehensive wastewater-based epidemiological systems for surveillance of rural and urban areas of low-income countries with inadequate sewage infrastructure., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Wastewater-Based Epidemiological Monitoring (WBEM) is an efficient surveillance tool during the COVID-19 pandemic as it meets all requirements of a complete monitoring system including early warning, tracking the current trend, prevalence of the disease, detection of genetic diversity as well asthe up-surging SARS-CoV-2 new variants with mutations from the wastewater samples. Subsequently, Clinical Diagnostic Test is widely acknowledged as the global gold standard method for disease monitoring, despite several drawbacks such as high diagnosis cost, reporting bias, and the difficulty of tracking asymptomatic patients (silent spreaders of the COVID-19 infection who manifest nosymptoms of the disease). In this current reviewand opinion-based study, we first propose a combined approach) for detecting COVID-19 infection in communities using wastewater and clinical sample testing, which may be feasible and effective as an emerging public health tool for the long-term nationwide surveillance system. The viral concentrations in wastewater samples can be used as indicatorsto monitor ongoing SARS-CoV-2 trends, predict asymptomatic carriers, and detect COVID-19 hotspot areas, while clinical sampleshelp in detecting mostlysymptomaticindividuals for isolating positive cases in communities and validate WBEM protocol for mass vaccination including booster doses for COVID-19., 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., (© 2022 The Author(s).)

Objectives: Despite having profound therapeutic value, the clinical application of resveratrol is restrained due to its <1% bioavailability, arising from the extensive fast-pass effect along with enterohepatic recirculation. This study aimed to develop a self-emulsifying formulation capable of increasing the bioavailability of resveratrol via lymphatic transport. Methods: The resveratrol−phospholipid complex (RPC) was formed by the solvent evaporation method and characterized by FTIR, DSC, and XRD analyses. The RPC-loaded self-emulsifying drug delivery system (SEDDS) was designed, developed, and optimized using the QbD approach with an emphasis on resveratrol transport through the intestinal lymphatic pathway. The in vivo pharmacokinetic study was investigated in male Wister Albino rats. Results: The FTIR, DSC, and XRD analyses confirmed the RPC formation. The obtained design space provided robustness of prediction within the 95% prediction interval to meet the CQA specifications. An optimal formulation (desirability value of 7.24) provided Grade-A self-emulsion and exhibited a 48-fold bioavailability enhancement compared to the pure resveratrol. The cycloheximide-induced chylomicron flow blocking approach demonstrated that 91.14% of the systemically available resveratrol was transported through the intestinal lymphatic route. Conclusions: This study suggests that an optimal self-emulsifying formulation can significantly increase the bioavailability of resveratrol through lymphatic transport to achieve the desired pharmacological effects.

Objectives: Bangladesh reports one of the highest rates of child marriage (CM) (59%) in the world and the highest rate within South Asia. Age at marriage of girls is a critical human rights and developmental issue in Bangladesh. Migration has been documented to be positively associated with age at marriage. Bangladesh experiences one of the highest rates of rural to urban migration in the world. An increase in rural-urban migration of adolescent girls has been observed over the last few decades in Bangladesh with the expansion of employment opportunities particularly in the ready-made garment industry (RMG). This analysis explores the effect of migration on age at marriage and CM among adolescent girls living in urban slums of Dhaka., Methods: The sample was selected from icddr,b's Urban Health and Demographic Surveillance System (UHDSS) and comprises of never-married adolescent girls aged 15-19, who migrated in from rural Bangladesh to slums in and around Dhaka during 2015-2019. These in-migrants were matched with their rural counterparts from icddr,b's Matlab HDSS (MHDSS), using one to one nearest neighbor matching with caliper 0.1 using propensity score matching (PSM) method. The sample derived included a total of 2,700 never-married adolescent girls from Dhaka and Matlab. The association between migration and age at first marriage was estimated using a linear regression model and the effect of migration on CM was explored using logistic regression analyses., Results: The in-migrants perfectly matched with their rural peers in terms of age, household wealth and religion. However, their income earning status was hugely different. Urban migrants had significantly higher age at marriage than the rural non-migrants for both 15-19 (Coefficient, 1.77; 95% CI, 1.07-2.46) and 20-24 years age group (Coefficient, 2.87; 95% CI, 2.18-3.55). The migrant girls aged 20-24 years were 71% (aOR, 0.29; 95% CI, 0.12-0.69) less likely to get married before CM age bar in Bangladesh compared to their rural counterparts., Conclusion: Migration has a positive effect on delaying marriage and reducing CM among adolescent girls. Findings from this study suggest that CM can be reduced by creating educational and economic opportunities for females., 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 © 2022 Antu, Parvin, Sujan, Mamun and Naved.)

Aging-induced memory impairment is closely associated with oxidative stress. D-Galactose (D-gal) evokes severe oxidative stress and mimics normal aging in animals. Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. There are several proteins like glutathione S-transferase A1 (GSTA1), glutathione S-transferase omega-1 (GSTO1), kelch-like ECH-associated protein 1 (KEAP1), beta-secretase 1 (BACE1), and amine oxidase [flavin-containing] A (MAOA) are commonly involved in oxidative stress and aging. This study aimed to investigate the interaction of curcumin to these proteins and their subsequent effect on aging-associated memory impairment in two robust animal models: D-Gal and normal aged (NA) mice. The aging mice model was developed by administering D-gal intraperitoneally (i.p). Mice (n = 64) were divided into the eight groups (8 mice in each group): Vehicle, Curcumin-Control, D-gal (100mg/kg; i.p), Curcumin + D-gal, Astaxanthin (Ast) + D-gal, Normal Aged (NA), Curcumin (30mg/kg Orally) + NA, Ast (20mg/kg Orally) + NA. Retention and freezing memories were assessed by passive avoidance (PA) and contextual fear conditioning (CFC). Molecular docking was performed to predict curcumin binding with potential molecular targets. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA., Competing Interests: Author Mohammed Uddin is employed by Cellular Intelligence (Ci) Lab, GenomeArc Inc., Toronto, ON, Canada. 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.

Ageing is one of the greatest risk factors for chronic non-communicable diseases, and cellular senescence is one of the major causes of ageing and age-related diseases. The persistent presence of senescent cells in late life seems to cause disarray in a tissue-specific manner. Ageing disrupts the circadian clock system, which results in the development of many age-related diseases such as metabolic syndrome, cancer, cardiac diseases and sleep disorders and an increased susceptibility to infections. In this review, we first discuss cellular senescence and some of its basic characteristics and detrimental roles. Then, we discuss a relatively unexplored topic on the link between cellular senescence and the circadian clock and attempt to determine whether cellular senescence could be the underlying factor for circadian clock disruption., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

The high temperature requirement factor A1 (HTRA1) is a serine protease which modulates an array of signalling pathways driving basal biological processes. HTRA1 plays a significant role in cell proliferation, migration and fate determination, in addition to controlling protein aggregates through refolding, translocation or degradation. The mutation of HTRA1 has been implicated in a plethora of disorders and this has also led to its growing interest as drug therapy target. This review details the involvement of HTRA1 in certain signalling pathways, namely the transforming growth factor beta (TGF-β), canonical Wingless/Integrated (WNT) and NOTCH signalling pathways during organogenesis and various disease pathogenesis such as preeclampsia, age-related macular degeneration (AMD), small vessel disease and cancer. We have also explored possible avenues of exploiting the serine proteases for therapeutic management of these disorders., 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., (© 2021 The Author(s).)

Variance components and heritabilities for daily weight gain (DWG) were estimated for Nile tilapia farmed in cages across nine generations (G1-G9) of selection in a breeding program in Brazil. DWG was measured in 16,272 accumulated tagged animals representing 535 full- and half-sib families of Nile tilapia under cage farming. The additive genetic variance showed a slight variation (0.051-0.066), and heritability estimates ranged from 0.20 to 0.33. The common environmental effect accounted for a higher proportion of the total variance in DWG, especially in the last generations (6%-24%). A genetic trend based on all data available showed a substantial increase in the DWG (about 3.3% per generation) of Nile tilapia across nine generations of selection. Furthermore, our results demonstrate ample scope for further genetic improvement., (© 2021 Wiley-VCH GmbH.)

Flutamide which is used to treat prostate cancer and other diseases induces liver damage during and after the therapy. The aim of this study was to develop a flutamide/piperineco-loaded self-emulsifying drug delivery system (FPSEDDS) to inhibit flutamide-induced liver injury by utilizing piperine as a metabolic inhibitor. The development of SEDDS was carried out following a quality by design (QbD) approach. The risk assessment study was performed to identify critical quality attributes (CQAs) and critical material attributes (CMAs)/critical process parameters (CPPs). I-optimal mixture design was executed with three CMAs as the independent variables and CQAs as the dependable variables. The effectiveness of optimized SEDDS to circumvent flutamide-induced hepatotoxicity was assessed in mice. The numerical optimization suggested an optimal formulation with a desirability value of 0.621, using CQAs targets as optimization goals with 95% prediction intervals (α = 0.05). The optimal formulation exhibited the grade A SEDDS characteristics with the guarantee of high payloads in self-formed oily droplets. The design space was also obtained from the same optimization goals. All CQA responses of verification points were found within the 95% prediction intervals of the polynomial models, indicating a good agreement between actual versus predicted responses within the design space. These obtained responses also passed CQAs acceptance criteria. Finally, hematoxylin-eosin staining revealed the minimal flutamide-induced hepatotoxicity from the optimal SEDDS formulation as compared to the control and flutamide/piperine normal suspension. We demonstrate that the piperine containing optimized SEDDS formulation developed by QbD significantly reduces the flutamide-induced liver injury in mice., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

We conducted a cluster-randomized trial to measure the effect of community-level mask distribution and promotion on symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in rural Bangladesh from November 2020 to April 2021 ( N = 600 villages, N = 342,183 adults). We cross-randomized mask type (cloth versus surgical) and promotion strategies at the village and household level. Proper mask-wearing increased from 13.3% in the control group to 42.3% in the intervention arm (adjusted percentage point difference = 0.29; 95% confidence interval = [0.26, 0.31]). The intervention reduced symptomatic seroprevalence (adjusted prevalence ratio = 0.91 [0.82, 1.00]), especially among adults ≥60 years old in villages where surgical masks were distributed (adjusted prevalence ratio = 0.65 [0.45, 0.85]). Mask distribution with promotion was a scalable and effective method to reduce symptomatic SARS-CoV-2 infections.

Background: There is evidence on benefits of psychosocial stimulation (PS) and cash transfer programmes in low- and middle-income countries on children's development. We integrated PS into an unconditional cash transfer (UCT) programme for poor Bangladeshi mothers to examine the effects on children's development., Methods: This cluster randomized controlled trial was conducted in rural Bangladesh from July 2017 to December 2018 in 33 clusters, with 11 clusters randomly assigned to each of the three arms, namely i) PS + UCT ii) UCT-only and iii) Comparison. We enrolled poor mothers and child (6-16 months) dyads eligible to receive maternity allowance by the Government of Bangladesh. Trained local women imparted training to mothers to provide psychosocial stimulation to their children for one year. Children's cognitive, language and motor development were measured with Bayley-III, behaviour with Wolke's ratings and maternal self-esteem with Rosenberg self-esteem scale. The analysis was intention-to-treat., Results: Of the 594 mother-child dyads, 40 (6·8%) were lost to follow-up. Compared to UCT-only, children in the PS + UCT had significant improvement in cognitive (B = 2.96, 95% CI: 0.46-5.47, Effect Size [ES] 0.24SD) and language (2.73, 0.39-5.00, ES 0.21SD) scores and were more responsive to examiner (0.30, 0.06-0.52, ES 0.27SD), while compared to comparison group, they had significantly higher cognitive (3.37, 1.27-6.19, ES 0.32SD), language (2.82, 0.53-5.10, ES 0.24SD) and motor (2.65, 0.24-5.06, ES 0.22SD) scores and were more responsive to examiner (0.30, 0.08-0.52, ES 0.26 SD). The mothers' self-esteem was significantly higher in PS + UCT (2.46, 0.94-3.98, ES 0.48 SD) and UCT-only (1.67, 0.02-3.20, ES 0.32 SD) compared to the comparison group., Conclusion: PS integrated into an UCT programme benefited children's neurodevelopment and UCT improved mother's self-esteem. UCT programme may be an important platform for child stimulation programmes for rural poor populations., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Differential expression of p53 has been reported in cervical cancer, primarily in tumor tissue biopsies. In this study, we examined the association of TP53 codon 47 and codon 72 polymorphisms and serum level expression of p53 in cervical cancer patients (n = 129) and healthy controls (n = 122). We found elevated levels of serum p53 protein levels in cervical cancer patients (p = 0.0442) compared to healthy controls. Moreover, we found higher levels of serum p53 in patients with grade-III tumor (p = 0.001) compared to healthy controls. Examination of SNPs showed TP53 Arg/Pro heterozygosity (adjusted OR = 2.126, 95% CI = 1.181-3.827, p = 0.012), Pro/Pro mutant homozygosity (adjusted OR = 3.564, 95% CI = 1.647-7.713, p = 0.001), along with the combined genotype (Arg/Pro+Pro/Pro) (adjusted OR 2.542, 95% CI = 1.517-4.260, p<0.001) significantly increases the risk of cervical cancer. Expression quantitative trait analysis revealed no significant association with protein expression. Our results represent for the first time the upregulation of serum p53 in cervical cancer in Bangladeshi women and supports the association of TP53 codon 72 polymorphisms with cervical cancer., Competing Interests: The authors have declared that no competing interests exist.

Multi-drug-resistance (MDR) is a severe public health concern worldwide, and its containment is more challenging in developing countries due to poor antimicrobial resistance (AMR) surveillance and irrational use of antibiotics. The current study investigated 100 clinical E. coli isolates and revealed that 98% of them were MDR. PCR analysis using 25 selected isolates showed the predominance of metallo-β-lactamase gene bla NDM (80%) and ESBL genes bla OXA (48%) and bla CTX-M-15 (32%). The AmpC gene was detected in 68% of the isolates, while 32% was tetC positive. Notably, 34% of the isolates were resistant to carbapenem. Whole genome sequence (WGS) analysis of an extensively drug-resistant (XDR) isolate (L16) revealed the presence of the notorious sequence type 131 responsible for multi-drug-resistant infections, multiple antibiotic resistance genes (ARGs), virulence genes, and mobile genetic elements that pose risks to environmental transmission. Our results indicate that MDR is alarmingly increasing in Bangladesh that critically limits the treatment option against infections and contributes to further aggravation to the prevailing situation of MDR worldwide. The findings of this study will be valuable in designing sustainable strategies to contain MDR in the region., (© 2021. The Author(s).)

Brief Introduction: Myocardial infarction (MI) is a common manifestation of certain cardiac diseases where oxidative stress and fibrosis aggravate the condition markedly., Main Objective of the Study: Investigation of L-carnitine's cardioprotective roles and mechanism of action in a rat model of MI., Methods: To develop a MI animal model, Isoproterenol (ISO) was administered in male Long Evans rats where animals were divided into five groups (six rats/group). The oxidative stress and antioxidant enzyme activities were determined by different biochemical tests. The real-time PCR was performed to determine the expression of TNF-α and Il-1β. Histopathological observations by hematoxylin-eosin and Masson trichrome were made to observe the tissue damage and fibrosis in heart and kidney., Significant Findings From the Study: The ISO-treated rats showed increased levels of troponin I and lipid peroxidation and lower antioxidant enzyme activity in heart and kidney tissues. The levels of TNF-α and IL-1β were also increased in ISO-rats. Co-administration of L-carnitine with ISO reversed all these parameters. The elevated levels of uric acid and creatinine kinase and ALP, AST and ALT activities in ISO-rats were also significantly reduced by L-carnitine administration. L-carnitine markedly decreased the infiltration of inflammatory cells and improved the tissue architecture in heart and kidney. Control animals did not show any appreciable response upon L-carnitine administration., Relevant Contribution to Knowledge: These results suggest that L-carnitine plays a defensive role against cardiac and renal damage in ISO-treated MI rat model via suppressing oxidative stress and increasing antioxidant enzyme functions through inhibition of TNF-α and IL-1β., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Oral polio vaccine (OPV) campaigns, but not other campaigns, have been associated with major reductions in child mortality. Studies have shown that OPV reduces the risk of respiratory infections. We analysed the causes of death at 0-2 years of age in Chakaria, a health and demographic surveillance Systems in Bangladesh, in the period 2012-2019 where 13 national campaigns with combinations of OPV ( n = 4), vitamin A supplementation ( n = 9), measles vaccine (MV) ( n = 2), and albendazole ( n = 2) were implemented. OPV-only campaigns reduced overall mortality by 30% (95% confidence interval: -10-56%). Deaths from respiratory infections were reduced by 62% (20-82%, p = 0.01) in the post-neonatal period (1-35 months), whereas there was as slight increase of 19% (-37-127%, p = 0.54) for deaths from other causes. There was no benefit of other types of campaigns. Hence, the hypothesis that OPV may have beneficial non-specific effects, protecting particularly against respiratory infections, was confirmed.

The development of externally controlled drug delivery systems that can rapidly trigger drug release is widely expected to change the landscape of future drug carriers. In this study, a drug delivery system was developed for on-demand therapeutic effects. The thermoresponsive paraffin film can be loaded on the basis of therapeutic need, including local anesthetic (lidocaine) or topical antibiotic (neomycin), controlled remotely by a portable mini-heater. The application of mild temperature (45 °C) to the drug-loaded paraffin film allowed a rapid stimulus response within a short time (5 min). This system exploits regular drug release and the rapid generation of mild heat to trigger a burst release of 80% within 6 h of any locally administered drug. The in vitro drug release studies and in vivo therapeutic activity were observed for local anesthesia and wound healing using a neomycin-loaded film. The studies demonstrated on-demand drug release with minimized inflammation and microbial infection. This temperature-responsive drug-loaded film can be triggered remotely to provide flexible control of dose magnitude and timing. Our preclinical studies on these remotely adjustable drug delivery systems can significantly improve patient compliance and medical practice.

All governments, regulatory authorities, and vaccine-related committees are under tremendous pressure to roll out vaccines to safeguard the people against COVID-19. To be noted that all COVID-19 vaccines have been developed hurriedly, some with new technologies being used on humans for the first time ever. Most clinical trials did not include elderly patients with comorbidities, hence a careful and logical rollout planning, especially for elderly people, is necessary., Competing Interests: Conflict of interest: None., (© 2021 Razmin Bari et al., published by De Gruyter.)