Emergence of multidrug-resistant Bacillus spp. derived from animal feed, food and human diarrhea in South-Eastern Bangladesh.

BACKGROUND: Antimicrobial resistance poses a huge risk to human health worldwide, while Bangladesh is confronting the most severe challenge between the food supply and the huge consumption of antibiotics annually. More importantly, probiotics containing Bacillus spp. are claimed to be an alternative to antimicrobial stewardship programs. However, their antibiotic resistance remains elusive. Thus, we employed the antimicrobial susceptibility test and PCR to assess the prevalence of resistance, including multidrug resistance (MDR) and resito-genotyping of isolated Bacillus spp. RESULTS: The phenotypic profile showed that Bacillus spp. were 100% sensitive to gentamicin (2 µg/mL), whereas lowered sensitivity to levofloxacin (67.8%, 0.5-1 µg/mL), ciprofloxacin (62.3%, 0.5-1 µg/mL), clindamycin (52.2%, 0.25-0.5 µg/mL), amoxicillin-clavulanic acid (37.6%, 0.06 µg/mL), azithromycin (33.4%, 1-2 µg/mL), tetracycline (25.6%, 2-4 µg/mL), nitrofurantoin (21.1%, 16-32 µg/mL), co-trimoxazole (19.2%, 2 µg/mL), and erythromycin (18.8%, 0.25-0.5 µg/mL). The strains were completely resistant to penicillin, amoxicillin-clavulanic acid, cefixime, ceftriaxone, vancomycin, and co-trimoxazole, and a species-specific trend was seen in both phenotypic and genotypic resistance patterns. Genotypic resistance indicated prevalence of the bla1 (71.5%), tetA (33%), erm1 (27%), blaTEM (13.1%), blaCTX-M-1/blaCTX-M-2 /sul1 (10.1%), blaSHV (9.6%), and qnrS (4.1%) genes. The ß-lactamase resistance gene bla1 was found in all penicillin-resistant (MIC ≥ 32 µg/mL) Bacillus spp. One hundred ninety-one isolates (89.6%) were MDR, with 100% from diarrhea, 90.3% from food, and 88.7% from animal feed. CONCLUSION: Based on the MIC value and profile analysis of antibiotic resistance genes, this is the first study that Bacillus spp. antimicrobial susceptibilities have been identified in Bangladesh, and our study will shed light on the adverse effects of feed-borne Bacillus spp. emerging from animal feed to the food chain. A comprehensive investigation is urgently needed by policymakers on tolerance limits and harmful effects in the animal industry.

Deciphering KDM8 dysregulation and CpG methylation in hepatocellular carcinoma using multi-omics and machine learning.

Aim: This study investigates the altered expression and CpG methylation patterns of histone demethylase KDM8 in hepatocellular carcinoma (HCC), aiming to uncover insights and promising diagnostics biomarkers. Materials & methods: Leveraging TCGA-LIHC multi-omics data, we employed R/Bioconductor libraries and Cytoscape to analyze and construct a gene correlation network, and LASSO regression to develop an HCC-predictive model. Results: In HCC, KDM8 downregulation is correlated with CpGs hypermethylation. Differential gene correlation analysis unveiled a liver carcinoma-associated network marked by increased cell division and compromised liver-specific functions. The LASSO regression identified a highly accurate HCC prediction signature, prominently featuring CpG methylation at cg02871891. Conclusion: Our study uncovers CpG hypermethylation at cg02871891, possibly influencing KDM8 downregulation in HCC, suggesting these as promising biomarkers and targets.

Changes in gene function can play a role in causing cancer. In this study, we looked at how a specific gene called KDM8 behaves in liver cancer. By analyzing a large set of liver cancer samples, we investigated how gene interactions are different in this disease and if they can help predict liver cancer risk. Our results show that the KDM8 gene is less active, and its DNA gets chemically modified more often in liver cancer. We also found a group of genes and DNA changes, which are linked to the disease. Using this information, we identified 16 important markers and built a computer model that can accurately predict liver cancer. We found that DNA methylation at a specific spot called cg02871891 is especially important for predicting liver cancer. Overall, our study suggests that high levels of DNA methylation may lead to reduced KDM8 activity in liver cancer, which could be important for future research and better diagnostic tools.

Migraine among women with endometriosis: a hospital-based case-control study in Bangladesh.

BACKGROUND: Endometriosis is a disease among women of reproductive age, which causes several health problems, such as dysmenorrhea, dyspareunia, and subfertility. In addition, it increases psychological stress and often results in marital disharmony. Similarly, migraine is more frequent among this group of women. Several studies have shown an association between endometriosis and migraine among groups of populations completely different from Bangladesh. OBJECTIVE: This study aimed to identify the association between endometriosis and migraine among the Bangladeshi population. STUDY DESIGN: This nonrandomized case-control study was conducted with cases of endometriosis and controls without endometriosis who were confirmed by laparoscopy or laparotomy. Among the study participants, cases of migraine in 1 group of respondents who were already diagnosed as patients of migraine were identified, and the others with complaints of headaches were further confirmed by a medicine specialist. Patients were recruited from the Department of Obstetrics and Gynecology at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders General Hospital and Ibrahim Medical College. The study was approved by the ethical review committee of the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders General Hospital. Multivariate logistic regression was used to identify the association between endometriosis and migraine using odds ratios and 95% confidence intervals. RESULTS: Of 1496 patients who underwent laparoscopy or laparotomy during the study period, the frequency of endometriosis was found to be 12.7%. A total of 190 patients with confirmed endometriosis cases and an equal number of controls without endometriosis were enrolled, maintaining the age distribution of the controls similar to that of the cases. Compared with controls, the distribution of age, body mass index, education, and marital status of the patients with endometriosis were similar. The average ages of respondents were 30.6 years in both the case and control groups. Regarding occupation, cases included more students than controls (12% vs 0%, respectively). The odds of suffering from dysmenorrhea and dyspareunia among the cases were 3.3 (95% confidence interval, 2.66-4.15; P<.001) and 9.5 (95% confidence interval, 5.3-17.9; P<.001) times higher than that of controls, respectively. In addition, the odds of menstrual irregularity was 60% lower among the cases than among controls (odds ratio, 0.4; 95% confidence interval, 0.24-0.64; P<.001). No significant difference was observed in having primary subfertility and secondary subfertility among the 2 groups of respondents. Univariate regression analysis showed that patients with endometriosis have 6.13 times higher odds (95% confidence interval, 2.50-18.40; P<.001) of having a migraine and 2.00 times higher odds (95% confidence interval, 1.2-3.2; P=.01) of having a headache than controls. Furthermore, the age- and body mass index-adjusted multivariate model showed that patients with endometriosis have 5.4 times higher odds of having migraine than patients without endometriosis (95% confidence interval, 2.11-16.4; P<.001). In addition, the higher the age of reproductive-age women, the higher the odds of having migraine. A 1-year increase in age increases the odds of having migraine by 23% (odds ratio, 1.23; 95% confidence interval, 1.13-1.16; P<.001). CONCLUSION: Our results support the association between endometriosis and migraine among the Bangladeshi population, which is similar to relevant studies conducted in other geographic locations. The groups of physicians who treat patients suffering from the 2 diseases, endometriosis and migraine, should keep this interrelationship in mind to ensure a better quality of life for the patient.

Adsorbents from rice husk and shrimp shell for effective removal of heavy metals and reactive dyes in water.

Widespread contamination by heavy metals (HMs) and dyes poses a major health risk to people and ecosystems requiring effective treatment. In this work, rice husk (RH) and shrimp shells were extracted to obtain amorphous silica and chitosan, respectively, which were utilized to produce nano-chitosan-coated silica (NCCS). To ensure the stability of the nanoparticles, silica was freeze-dried after being coated with nano-chitosan. Functional groups (-NH2, -OH, P]O) from chitosan nanoparticles (CNPs) were introduced to the surface of silica during this process. Dyes such as brilliant green (BG), methylene blue (MB) and reactive brown (RB) as well as HMs (Cr6+, Pb2+, Cd2+, Ni2+) were removed by adsorbents. CNPs showed the highest adsorption capacity for RB (59.52 mg/g) among dyes and Cr6+ (42.55 mg/g) among HMs. CNPs showed the highest adsorption capacity for HMs among different adsorbents. Although NCCS and CNPs showed similar adsorption capabilities for HMs and dyes, NCCS showed the best stability. The adsorption performance decreased as RB > Cr6+ > MB > BG > Pb2+ > Cd2+ > Ni2+. The adsorption reactions followed both pseudo-first-order and second-order kinetics, and was spontaneous from thermodynamic analysis. In summary, the waste-derived adsorbents demonstrated excellent potential for removing HMs and dyes from water, while supporting effective management solid waste.

Antiviral Activity, Pharmacoinformatics, Molecular Docking, and Dynamics Studies of Azadirachta indica Against Nipah Virus by Targeting Envelope Glycoprotein: Emerging Strategies for Developing Antiviral Treatment.

The Nipah virus (NiV) belongs to the Henipavirus genus is a serious public health concern causing numerous outbreaks with higher fatality rate. Unfortunately, there is no effective medication available for NiV. To investigate possible inhibitors of NiV infection, we used in silico techniques to discover treatment candidates in this work. As there are not any approved treatments for NiV infection, the NiV-enveloped attachment glycoprotein was set as target for our study, which is responsible for binding to and entering host cells. Our in silico drug design approach included molecular docking, post-docking molecular mechanism generalised born surface area (MM-GBSA), absorption, distribution, metabolism, excretion/toxicity (ADME/T), and molecular dynamics (MD) simulations. We retrieved 418 phytochemicals associated with the neem plant (Azadirachta indica) from the IMPPAT database, and molecular docking was used to ascertain the compounds' binding strength. The top 3 phytochemicals with binding affinities of -7.118, -7.074, and -6.894 kcal/mol for CIDs 5280343, 9064, and 5280863, respectively, were selected for additional study based on molecular docking. The post-docking MM-GBSA of those 3 compounds was -47.56, -47.3, and -43.15 kcal/mol, respectively. As evidence of their efficacy and safety, all the chosen drugs had favorable toxicological and pharmacokinetic (Pk) qualities. We also performed MD simulations to confirm the stability of the ligand-protein complex structures and determine whether the selected compounds are stable at the protein binding site. All 3 phytochemicals, Quercetin (CID: 5280343), Cianidanol (CID: 9064), and Kaempferol (CID: 5280863), appeared to have outstanding binding stability to the target protein than control ribavirin, according to the molecular docking, MM-GBSA, and MD simulation outcomes. Overall, this work offers a viable approach to developing novel medications for treating NiV infection.

Effects of examination-induced stress on memory and blood pressure.

Stress has been defined in many ways as a state of psychological arousal that results when the external demand is beyond what one can cope with. Stress is caused by various factors called stressors. Medical students are subjected to different kinds of stressors, such as pressure of academics with obligation to succeed, an uncertain future and difficulties of integrating into the system and different teaching protocols, which may affect their learning ability and performance. Stress has a great impact on brain mainly in the form of impaired memory and on cardiovascular function in the form of increased heart rate and blood pressure. The study was planned to assess the effects of examination induced stress on memory and blood pressure. The study was longitudinal in nature conducted at Department of Physiology, Santosh Medical College, Ghaziabad, India. Initially 100 subjects were selected from 17-24 years of age group then all the subjects were divided into two groups of 'slow-learners' and 'fast-learners' based upon their past academic performances. Readings were taken at two stages of academic year, 05 months before pre-prof examination and 03 days before pre-prof examination. Blood Pressure were measured and the memory assessments were done by using 10 subtests of PGI memory scale. We found a significant increase in stress level 3 days before the examination, compared to 5 months before the examination which in turn affected both blood pressure and memory functions. But, slow-learners were affected more compared to fast-learners.

Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase.

The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular growth and survival, and its dysregulation is implicated in various cancers, making it a prime target for cancer therapy. Natural compounds known as catechins have garnered attention as promising anticancer agents. These compounds exert their anticancer effects through diverse mechanisms, primarily by inhibiting receptor tyrosine kinases (RTKs), a protein family that includes the notable member EGFR. Catechins, characterized by two chiral centers and stereoisomerism, demonstrate variations in chemical and physical properties due to differences in the spatial orientation of atoms. Although previous studies have explored the membrane fluidity effects and transport across cellular membranes, the stereo-selectivity of catechins concerning EGFR kinase inhibition remains unexplored. In this study, we investigated the stereo-selectivity of catechins in inhibiting EGFR kinase, both in its wild-type and in the prevalent L858R mutant. Computational analyses indicated that all stereoisomers, including the extensively studied catechin (-)-EGCG, effectively bound within the ATP-binding site, potentially inhibiting EGFR kinase activity. Notably, gallated catechins emerged as superior EGFR inhibitors to their non-gallated counterparts, revealing intriguing binding trends. The top four stereoisomers exhibiting high dock scores and binding energies with wild-type EGFR comprise (-)-CG (-)-GCG (+)-CG, and (-)-EGCG. To assess dynamic behavior and stability, molecular dynamics simulations over 100 ns were conducted for the top-ranked catechin (-)-CG and the widely investigated catechin (-)-EGCG with EGFR kinase. This study enhances our understanding of how the stereoisomeric nature of a drug influences inhibitory potential, providing insights that could guide the selection of specific stereoisomers for improved efficacy inexisting drugs.

Exposure to Brucella spp. in Humans and Cows in a High Milk-Producing Area of Bangladesh.

Brucellosis is a zoonotic disease, caused by some species within the Brucella genus. The primary and secondary objectives of this cross-sectional study were to determine the seroprevalence of Brucella antibodies in humans and cows and identify risk factors for exposure to Brucella spp. among people in Shahjadpur sub-district, Bangladesh. Twenty-five villages were randomly selected from the 303 milk-producing villages in the sub-district. We randomly selected 5% of the total households from each village. At each household, we collected demographic information and history of potential exposure to Brucella spp. in humans. In addition, we collected serum from household participants and serum and milk from cattle and tested to detect antibodies to Brucella sp. Univariate analysis was performed to detect associations between seropositivity and demographics, risk factors, and behaviors in households. We enrolled 647 households, 1313 humans, and 698 cows. Brucella antibodies were detected in sera from 27 household participants (2.1%, 95% confidence interval [95%CI]: 1.2-2.9%). Eleven (1.6%, 95%CI 0.6-2.4%) cows had detectable Brucella antibodies in either milk or serum. About half (53%) of the 698 cows exhibited more than one reproductive problem within the past year; of these, seven (2%) had Brucella antibodies. Households with seropositive individuals more frequently reported owning cattle (78% vs. 32%, P < 0.001). Despite a low prevalence of Brucella seropositivity in the study, the public health importance of brucellosis cannot be ruled out. Further studies would help define Brucella prevalence and risk factors in this region and nationally.