Predictors of poor neurodevelopmental outcomes in neonates with clinically observed seizures: A prospective observational study in a tertiary care hospital of Bangladesh.

Neonatal seizures can lead to long-term neurodevelopmental problems. This study aims to identify predictors of poor developmental outcomes in neonates with seizures to aid in early intervention and referral for follow-up and rehabilitation. This observational study was conducted in the Department of Neonatology and Institute of Paediatric Neurodisorder and Autism, Bangabandhu Sheikh Mujib Medical University. Among 75 study cases of neonatal seizure, 23 died, and 46 were followed-up at 6 and 9 months after discharge. EEGs were performed on every patient. A comprehensive neurological examination and developmental evaluation were performed using Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III). Three-fourths of neonates were born at term (76.1 %), and over half were male (56.5 %). The majority were appropriate for gestational age (79.7 %) and had an average birth weight of 2607 ± 696 g (±SD). Over half of the neonates (52.2 %) had adverse neurodevelopmental outcomes, with global developmental delay being the most common. Recurrent seizures, the number of anticonvulsants needed to control seizures, and abnormal Electroencephalograms were identified as independent predictors of adverse neurodevelopmental outcomes. The study highlights the need for early referral for follow-up and rehabilitation of neonates with seizures having abnormal electroencephalograms, recurrent seizures and requiring more anticonvulsants to control seizures.

Patient self-referral patterns in a developing country: characteristics, prevalence, and predictors.

BACKGROUND: Efficient healthcare delivery and access to specialized care rely heavily on a well-established healthcare sector referral system. However, the referral system faces significant challenges in developing nations like Bangladesh. This study aimed to assess self-referral prevalence among patients attending tertiary care hospitals in Bangladesh and identify the associated factors. METHODS: This cross-sectional study was conducted at two tertiary care hospital, involving 822 patients visiting their outpatient or inpatient departments. A semi-structured questionnaire was used for data collection. The patients' mode of referral (self-referral or institutional referral) was considered the outcome variable. RESULTS: Approximately 58% of the participants were unaware of the referral system. Of all, 59% (485 out of 822) of patients visiting tertiary care hospitals were self-referred, while 41% were referred by other healthcare facilities. The primary reasons for self-referral were inadequate treatment (28%), inadequate facilities (23%), critical cases (14%), and lack of expert physicians (8%). In contrast, institutional referrals were mainly attributed to inadequate facilities to treat the patient (53%), inadequate treatment (47%), difficult-to-treat cases (44%), and lack of expert physicians (31%) at the time of referral. The private facilities received a higher proportion of self-referred patients compared to government hospitals (68% vs. 56%, p < 0.001). Among patients attending the study sites through institutional referral, approximately 10% were referred from community clinics, 6% from union sub-centers, 25% from upazila health complexes, 22% from district hospitals, 22% from other tertiary care hospitals, and 42% from private clinics. Patients visiting the outpatient department (adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 2.28-4.82, p < 0.001), residing in urban areas (aOR 1.29, 95% CI 1.04-1.64, p = 0.007), belonging to middle- and high-income families (aOR 1.34, 95% CI 1.03-1.62, p = 0.014, and aOR 1.98, 95% CI 1.54-2.46, p = 0.005, respectively), and living within 20 km of healthcare facilities (aOR 3.15, 95% CI 2.24-4.44, p-value < 0.001) exhibited a higher tendency for self-referral to tertiary care facilities. CONCLUSIONS: A considerable number of patients in Bangladesh, particularly those from affluent urban areas and proximity to healthcare facilities, tend to self-refer to tertiary care centers. Inadequacy of facilities in primary care centers significantly influences patients to opt for self-referral.

Health-care-seeking behaviour in patients with hypertension: experience from a dedicated hypertension centre in Bangladesh.

Objective: The study aimed to assess health-seeking behaviour (HSB) and associated factors among hypertensive patients in Bangladesh.Methods: This cross-sectional study was conducted in the Hypertension & Research Centre, Rangpur, Bangladesh, between January 2022 and June 2022. A total of 497 hypertensive adults were recruited consecutively. A pre-tested structured questionnaire was deployed by the research team for data collection. Multivariable logistic regression analysis was used to explore the predictors of HSB.Results: The mean age of the hypertensive patients was 52 ± 11 (SD) years. Most of them were aged between 51 and 60 years (33%), female (55%), came from rural areas (57%), and belonged to middle socioeconomic class (68%). One-fourth of the patients (27%) had chosen informal healthcare providers for their first consultation. Fear of stroke (244, 45%), headache (170, 36%), and neck pain (81, 17%) were the three most common compelling causes of their visit to the hypertension centre. Age (aOR 0.78, 95% CI 0.68 - 0.89), male sex (aOR: 1.79, 95% CI 1.05 - 3.10), living in semi-urban (aOR 4.68, 95% CI 1.45 - 15.10) and rural area (aOR 1.68, 95% CI 1.01 - 2.80), farmers as occupation (aOR: 3.24, 95%CI: 1.31 - 8.06) and belonging to lower social economic class (aOR 4.24, 95% CI 1.68 - 10.69) were predictors of visiting informal providers of hypertensive patient. One-fourth of the hypertensive patients received consultation from informal healthcare providers.Conclusions: Raising awareness among patients and proper referral to specialised hypertension centres could promulgate the patients towards appropriate behaviour.

Green synthesized silver nanoparticles of Terminalia bellirica leaves extract: synthesis, characterization, in-silico studies, and antimalarial activity.

Malaria is a mosquito-borne infectious disease that is caused by the Plasmodium parasite. Most of the available medication are losing their efficacy. Therefore, it is crucial to create fresh leads to combat malaria. Green silver nanoparticles (AgNPs) have recently attracted a lot of attention in biomedical research. As a result, green mediated AgNPs from leaves of Terminalia bellirica, a medicinal plant with purported antimalarial effects, were used in this investigation. Initially, cysteine-rich proteins from Plasmodium species were studied in silico as potential therapeutic targets. With docking scores between -9.93 and -11.25 kcal/mol, four leaf constituents of Terminalia bellirica were identified. The green mediated silver nanoparticles were afterward produced using leaf extract and were further examined using UV-vis spectrophotometer, DLS, Zeta potential, FTIR, XRD, and FESEM. The size of synthesized TBL-AgNPs was validated by the FESEM results; the average size of TBL-AgNPs was around 44.05 nm. The zeta potential study also supported green mediated AgNPs stability. Additionally, Plasmodium falciparum (3D7) cultures were used to assess the antimalarial efficacy, and green mediated AgNPs could effectively inhibit the parasitized red blood cells (pRBCs). In conclusion, this novel class of AgNPs may be used as a potential therapeutic replacement for the treatment of malaria.

SARS-CoV-2 infection induces adaptive NK cell responses by spike protein-mediated induction of HLA-E expression.

ABSTRACTHLA-E expression plays a central role for modulation of NK cell function by interaction with inhibitory NKG2A and stimulatory NKG2C receptors on canonical and adaptive NK cells, respectively. Here, we demonstrate that infection of human primary lung tissue with SARS-CoV-2 leads to increased HLA-E expression and show that processing of the peptide YLQPRTFLL from the spike protein is primarily responsible for the strong, dose-dependent increase of HLA-E. Targeting the peptide site within the spike protein revealed that a single point mutation was sufficient to abrogate the increase in HLA-E expression. Spike-mediated induction of HLA-E differentially affected NK cell function: whereas degranulation, IFN-γ production, and target cell cytotoxicity were enhanced in NKG2C+ adaptive NK cells, effector functions were inhibited in NKG2A+ canonical NK cells. Analysis of a cohort of COVID-19 patients in the acute phase of infection revealed that adaptive NK cells were induced irrespective of the HCMV status, challenging the paradigm that adaptive NK cells are only generated during HCMV infection. During the first week of hospitalization, patients exhibited a selective increase of early NKG2C+CD57- adaptive NK cells whereas mature NKG2C+CD57+ cells remained unchanged. Further analysis of recovered patients suggested that the adaptive NK cell response is primarily driven by a wave of early adaptive NK cells during acute infection that wanes once the infection is cleared. Together, this study suggests that NK cell responses to SARS-CoV-2 infection are majorly influenced by the balance between canonical and adaptive NK cells via the HLA-E/NKG2A/C axis.

Mitochondrial and microbial diversity of the invasive mosquito vector species Culex tritaeniorhynchus across its extensive inter-continental geographic range.

Background: Culex (Cx.) tritaeniorhynchus is an invasive mosquito species with an extensive and expanding inter-continental distribution, currently reported across Asia, Africa, the Middle East, Europe and now Australia. It is an important vector of medical and veterinary pathogens which cause significant morbidity and mortality in human and animal populations. Across regions endemic for Japanese encephalitis virus (JEV), Cx. tritaeniorhynchus is considered the major vector and has also been shown to contribute to the transmission of several other zoonotic arboviruses including Rift Valley fever virus (RVFV) and West Nile virus (WNV). Methods: In this study, we used laboratory vector competence experiments to determine if Cx. tritaeniorhynchus from a Southern European population were competent JEV vectors. We also obtained samples from multiple geographically dispersed Cx. tritaeniorhynchus populations from countries within Europe, Africa, Eurasia and Asia to perform phylogenetic analysis to measure the level of mitochondrial divergence using the cytochrome oxidase subunit 1 ( CO1) gene. We also undertook bacterial 16S rRNA gene amplicon sequencing to determine microbial diversity and used multi-locus sequence typing (MLST) to determine any evidence for the presence of strains of the naturally occurring endosymbiotic bacterium Wolbachia. Results: Cx. tritaeniorhynchus from a Greek population were shown be be competent vectors of JEV with high levels of virus present in saliva. We found a signficant level of mitochondrial genetic diversity using the mosquito CO1 gene between geographically dispersed populations. Furthermore, we report diverse microbiomes identified by 16S rRNA gene amplicon sequencing within and between geographical populations. Evidence for the detection of the endosymbiotic bacteria Wolbachia was confirmed using Wolbachia-specific PCR and MLST. Conclusions: This study enhances our understanding of the diversity of Cx. tritaeniorhynchus and the associated microbiome across its inter-continental range and highlights the need for greater surveillance of this invasive vector species in Europe.

The mosquito species Culex (Cx.) tritaeniorhynchus is expanding its range and is now present in over 50 countries across Asia, Africa, the Middle East, Europe and now Australasia. It can transmit human and animal pathogens, resulting in significant morbidity and mortality. This species transmits Japanese encephalitis virus in endemic areas of Asia, and it has also been shown to contribute to the transmission of several other viruses that can infect humans, including Rift Valley fever virus and West Nile virus. In this study, we firstly undertook some lab experiments to show that Cx. tritaeniorhynchus from a Southern European population are competent vectors of Japanese encephalitis virus. We also obtained field mosquitoes from countries within Europe, Africa, Eurasia and Asia and used phylogenetic analysis to demonstrate a high level of mitochondrial divergence within and between populations. In addition, we analysed the bacteria present within mosquitoes and found a high level of microbial diversity. Finally, we present evidence for the presence of Wolbachia endosymbiotic bacteria in some populations of this mosquito species. This study highlights the need for greater surveillance of this invasive vector species ­ particularly in Europe.

Microbiology of bloodstream infections in Ontario, Canada during COVID-19 pandemic.

Background: Bloodstream infections (BSI) caused by a wide range of bacterial and fungal pathogens are associated with high rates of morbidity and mortality. Based on an estimate in 2017, the number of BSI incidences in Ontario is 150 per 100,000 population. The epidemiology of BSIs may be affected by many factors, including the social and travel restrictions and increased rates of hospitalizations in Ontario during the coronavirus disease 2019 (COVID-19) pandemic. Objectives: This study aimed to assess the changes in the microbiology of BSIs in Ontario during the COVID-19 pandemic compared to the pre-pandemic period. Methods: Retrospective blood culture data (n=189,106) from LifeLabs Ontario (July 2018 to December 2021) were analyzed. Blood culture positivity rates for common bacterial pathogens were compared between pre-COVID-19 (July 2018 to March 2020) and COVID-19 (April 2020 to December 2021) periods in community and hospital settings, using the chi-square test for significance. Results: During the COVID-19 period, blood culture positivity rates in the community remained the same, while hospital rates increased by approximately threefold (p=0.00E-00). In the community, the isolation rates of most bacterial species remained unchanged, except for an increase in Enterococcus spp. and a decrease in Salmonella spp. The rates of antibiotic-resistant organisms (AROs) also significantly decreased in the community. In hospitals, all bacterial species, including AROs, showed significant increases in isolation rates during the COVID-19 period. Conclusion: The study revealed shifts in the microbiology of BSIs and suggests changes in the epidemiology of BSIs during the COVID-19 pandemic in Ontario, both in hospitals and in the community.

Effectiveness of two and three doses of COVID-19 mRNA vaccines against infection, symptoms, and severity in the pre-omicron era: A time-dependent gradient.

BACKGROUND: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities. METHODS: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death. RESULTS: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results. CONCLUSION: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster.

An investigation on the operational resilience of the Canadian electronic product stewardship program and the recycling business characteristics.

Electronic waste recycling companies have proliferated in many countries due to valuable materials present in end-of-life electronic and electrical equipment. This article examined the business characteristics and management performance of Electronic Products Recycling Association (EPRA), a Canadian nationwide electronic product stewardship organization. The organization's annual performance reports, from 2012 to 2020, for nine Canadian provinces in which it currently operates were aggregated and analyzed. Temporal analysis using regression and Mann-Kendall tests were employed, and five characteristics of EPRA's business were analyzed, including e-waste products collected, number of drop-off locations, efforts to build public awareness, operating expenses, and growth of e-waste stewardship. Results show a decline in the amount of e-waste collected across the provinces, except in New Brunswick, which started its program in 2017. The Mann-Kendall test revealed declining temporal trends in most provinces. Although the collection/drop off sites and stewardship organizations increased astronomically over the study period in Canada, the amounts of e-waste collected decreased. We found that public awareness generally did not increase the amount of e-waste collected, and these campaigns only appeared to be effective in jurisdictions with good accessibility of e-waste recycling. Processing cost accounted for the majority of the e-waste management budget in Canada, and different factors affected the financial success of the stewards differently.

Prophet time series modeling of waste disposal rates in four North American cities.

In this study, three different univariate municipal solid waste (MSW) disposal rate forecast models (SARIMA, Holt-Winters, Prophet) were examined using different testing periods in four North American cities with different socioeconomic conditions. A review of the literature suggests that the selected models are able to handle seasonality in a time series; however, their ability to handle outliers is not well understood. The Prophet model generally outperformed the Holt-Winters model and the SARIMA model. The MAPE and R2 of the Prophet model during pre-COVID-19 were 4.3-22.2% and 0.71-0.93, respectively. All three models showed satisfactory predictive results, especially during the pre-COVID-19 testing period. COVID-19 lockdowns and the associated regulatory measures appear to have affected MSW disposal behaviors, and all the univariate models failed to fully capture the abrupt changes in waste disposal behaviors. Modeling errors were largely attributed to data noise in seasonality and the unprecedented event of COVID-19 lockdowns. Overall, the modeling errors of the Prophet model were evenly distributed, with minimum modeling biases. The Prophet model also appeared to be versatile and successfully captured MSW disposal rates from 3000 to 39,000 tons/month. The study highlights the potential benefits of the use of univariate models in waste forecast.

Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance.

Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined. Here, we report that hepatocyte Cul3 knockout results in rapid resolution of steatosis in obese mice. However, the remarkable resistance of hepatocyte Cul3 knockout mice to developing steatosis does not lead to overall metabolic improvement but causes systemic metabolic disturbances. Liver transcriptomics analysis identifies that CRL3 inactivation causes persistent activation of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant defense pathway, which also reprograms the lipid transcriptional network to prevent TG storage. Furthermore, global metabolomics reveals that NRF2 activation induces numerous NAD+-consuming aldehyde dehydrogenases to increase the cellular NADH/NAD+ ratio, a redox imbalance termed NADH reductive stress that inhibits the glycolysis-citrate-lipogenesis axis in Cul3 knockout livers. As a result, this NRF2-induced cellular lipid storage defect promotes hepatic ceramide accumulation, elevates circulating fatty acids, and worsens systemic insulin resistance in a vicious cycle. Hepatic lipid accumulation is restored, and liver injury and hyperglycemia are attenuated when NRF2 activation and NADH reductive stress are abolished in hepatocyte Cul3/Nrf2 double-knockout mice. The resistance to hepatic steatosis, hyperglycemia, and NADH reductive stress are observed in hepatocyte Keap1 knockout mice with NRF2 activation. In summary, our study defines a critical role of CRL3 in hepatic metabolic regulation and demonstrates that the CRL3 downstream NRF2 overactivation causes hepatic metabolic maladaptation to obesity and insulin resistance.

Machine learning approach for predicting cardiovascular disease in Bangladesh: evidence from a cross-sectional study in 2023.

BACKGROUND: Cardiovascular disorders (CVDs) are the leading cause of death worldwide. Lower- and middle-income countries (LMICs), such as Bangladesh, are also affected by several types of CVDs, such as heart failure and stroke. The leading cause of death in Bangladesh has recently switched from severe infections and parasitic illnesses to CVDs. MATERIALS AND METHODS: The study dataset comprised a random sample of 391 CVD patients' medical records collected between August 2022 and April 2023 using simple random sampling. Moreover, 260 data points were collected from individuals with no CVD problems for comparison purposes. Crosstabs and chi-square tests were used to determine the association between CVD and the explanatory variables. Logistic regression, Naïve Bayes classifier, Decision Tree, AdaBoost classifier, Random Forest, Bagging Tree, and Ensemble learning classifiers were used to predict CVD. The performance evaluations encompassed accuracy, sensitivity, specificity, and area under the receiver operator characteristic (AU-ROC) curve. RESULTS: Random Forest had the highest precision among the five techniques considered. The precision rates for the mentioned classifiers are as follows: Logistic Regression (93.67%), Naïve Bayes (94.87%), Decision Tree (96.1%), AdaBoost (94.94%), Random Forest (96.15%), and Bagging Tree (94.87%). The Random Forest classifier maintains the highest balance between correct and incorrect predictions. With 98.04% accuracy, the Random Forest classifier achieved the best precision (96.15%), robust recall (100%), and high F1 score (97.7%). In contrast, the Logistic Regression model achieved the lowest accuracy of 95.42%. Remarkably, the Random Forest classifier achieved the highest AUC value (0.989). CONCLUSION: This research mainly focused on identifying factors that are critical in impacting patients with CVD and predicting CVD risk. It is strongly advised that the Random Forest technique be implemented in a system for predicting cardiac diseases. This research may change clinical practice by providing doctors with a new instrument to determine a patient's CVD prognosis.

Real-life experience on the effectiveness of conjunctival flap and amniotic membrane graft in the treatment of refractory fungal corneal ulcer.

PURPOSE: To evaluate and compare the results of the conjunctival flap (CF) and cryopreserved amniotic membrane graft (AMG) in the management of fungal corneal ulcers either with complications or non-responsive to medical treatment. STUDY DESIGN: A retrospective observational study. METHODS: Medical records of 30 patients with culture-positive fungal corneal ulcer treated with either CF or AMG (15 eyes in each group) in real world settings were retrieved for analysis. After the surgical procedure, patients were followed up on days 1, 7, 14, 21, 30, 60, 90, 120, and 180 to explore the outcomes of the operations along with complications. RESULTS: Infecting fungi were of genus Fusarium (n = 11), Aspergillus (n = 10), Mucor (n = 4) and Penicillium (n = 10). The most common indication was resistant ulcer with perforation. After the procedure, epithelization was completed in 11(73.33%) patients in the CF, and 13 patients in the (86.67%) AMG group. Visual acuity improvement was significantly better in the latter group (CF: 1 [6.67%] vs. AMG: 7 [46.67%], p = 0.023). Flap failure occurred in 4 patients (26.67%) from the CF and 2 (13.33%) from the AMG group. No significant differences were found between the two groups regarding success rate (p = 0.651), epithelialization time (p = 0.691), healing of corneal ulcer (p = 0.651), and postoperative stability (p = 0.651) of the flaps. CONCLUSIONS: CF and AMG are both effective for the management of refractory fungal corneal ulcers. However, AMG appears to improve visual acuity better than CF.

Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant.

Overall effectiveness of infection in preventing reinfection with SARS-CoV-2 JN.1 variant was estimated at 1.8% (95% CI: -9.3-12.6%), and demonstrated rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9 to 94.7%) within 3 to less than 6 months, to a negligible level after one year.

Isolation, characterization and pharmacological potentials of methanol extract of Cassia fistula leaves: Evidenced from mice model along with molecular docking analysis.

The purpose of the current investigation was to conduct a detailed analysis of the chemical components and medicinal properties of the methanolic crude extract derived from the leaves of Cassia fistula. This analysis was carried out using both experimental (in vivo) and computational (in silico) methods. Eleven chemicals were chromatographically isolated using GC-MS/MS, which utilizes a library of NIST and Wiley 2020 versions. FTIR analysis of the extract was performed to identify the functional group of the compounds. The glucose-lowering capacity, analgesic, and anti-diarrheal activities of methanolic crude extract were analyzed utilizing a well-known oral glucose tolerance test, tail immersion method, writhing assay, and castor oil-induced diarrheal mice methods, respectively. After 60 min, 120 min, and 180 min of loading the drugs, a significant reduction of blood glucose levels was examined (p < 0.05) in all the extracts of this plant (200 mg/kg, 400 mg/kg and 600 mg/kg) utilized in this research at a time-dependent manner. Similarly, all the crude extracts showed significant (p < 0.05) effects against pain centrally and peripherally compared to the standard drug morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw). Moreover, the methanol extract (400 mg/kg bw) manifested anti-diarrheal efficacy by inhibiting 72.0 % of the diarrheal episode in mice compared to the standard drug loperamide (inhibition = 80.0%). The results of the computational investigations corroborated existing in-vivo findings. Greater or close to equivalent binding affinity to the active binding sites of kappa opioid receptor, glucose transporter 3 (GLUT 3), and cyclooxygenase 2 was indicative of the potential anti-diarrheal, hypoglycemic, and analgesic characteristics of the isolated compounds (COX-2). Moreover, anticancer and antimicrobial potentiality was also found impressive through evaluation of binding affinity with epidermal growth factor receptor (EGFR) and dihydrofolate reductase (DHFR) receptors. Results from this study indicated that C. fistula might be a beneficial natural resource for treating diarrhea, hyperglycemia, and pain. However, additional research is required to conduct a comprehensive phytochemical screening and establish precise action mechanisms of the crude extract or the plant-derived compounds.

The 2023 Dengue Outbreak in Bangladesh: Exploring the Epidemiology in Hospitalized Patients.

For the past two decades, Bangladesh has faced recurrent dengue outbreaks, with the most recent occurring in 2023. We investigated the socioeconomic, clinical, and laboratory aspects of patients diagnosed with dengue during this outbreak. This observational study was conducted from July to September 2023 at Dhaka Medical College Hospital and Chittagong Medical College Hospital, and included 450 confirmed cases of dengue. Sociodemographic information was collected via face-to-face interviews, clinical examinations, and laboratory testing, which was done within 24 hours of admission. Dengue severity was classified according to the 2009 WHO dengue guidelines. Notably, 17% of patients experienced severe dengue, and 89% of those with nonsevere cases exhibited at least one warning sign. Most patients were young adults (mean age, 33 years), with a nearly equal male-to-female ratio. Common clinical presentations included fever (95%), myalgia (62%), and headache (58%), whereas warning signs such as vomiting (54%) and abdominal pain (39%) were prevalent. Plasma leakage indicators, including ascites, pleural effusion, and edema, were found predominantly in severe cases. Laboratory findings revealed leukopenia, thrombocytopenia, and elevated hepatic enzymes (alanine aminotransferase and aspartate aminotransferase) in nearly half the patients. An elevated hematocrit level was associated with severe dengue. We report that a substantial number of patients developed severe dengue during the epidemic in 2023, and provide detailed clinical-epidemiological profiles of the patients, offering valuable insight into management of dengue cases.

Acute hypothermia in a patient with COVID-19: a case report and summary of the evidence.

Introduction and importance: SARS-COV-2 has many presenting signs including a number of typical and atypical symptoms. However, having the enormous capacity of mutation, the virus is changing its genetic pattern continuously, giving rise to newer and rarer manifestations. Here, the authors report a case of adult COVID-19 along with features of hypothermia which is relatively rare and has future implications in clinical perspective. Case presentation: The patient presented with hypothermia and indicative symptoms of COVID-19 during admission. Comorbidities were assessed, potential differentials were ruled out thorough appropriate clinical examination and investigations. Insulation with a blanket and room heater was used to stabilize the normal body temperature (98.6°F) in the hospital setting, during this period vitals (Blood pressure, Pulse rate and oxygen saturation) were assessed regularly. On the sixth day of hospital admission, he was discharged from the hospital with advice. Clinical discussion: COVID-19 virus can enter into brain through olfactory tract and may cause dysfunction in the medial preoptic area of the hypothalamus containing warm sensitive neurons directly or via cytokine-induced release of prostaglandin E2 from endothelial cells, which acts through a paracrine mechanism that may provoke hypothermia in our case. Conclusions: This case highlights a rare presentation of COVID-19 infection that has not been thoroughly explored. The authors believe the case report holds particular importance especially in dealing with COVID-19 cases in both clinical and home settings.

Violence against physicians working in public tertiary care hospital of Bangladesh: a facility-based cross-sectional study.

BACKGROUND: Violence against physicians in the workplace is a prevalent global issue, and Bangladesh is no exception. Such violence significantly disrupts healthcare delivery and the attainment of universal health coverage. This study aimed to comprehensively evaluate the prevalence, nature and associated risk factors of workplace violence (WPV) against physicians in Bangladesh. METHODS: This descriptive cross-sectional study was conducted at a public tertiary care hospital involving 441 physicians with a minimum tenure of 6 months. Data were gathered through a structured self-reported questionnaire, and statistical analyses were performed by using SPSS V.25. RESULTS: Out of the surveyed physicians, 67.3% (n=297) reported experiencing violence, categorised as 84.5% psychological, 13.5% physical and 2% sexual in nature. Predominant forms of psychological violence included bullying (48.8%) and threats (40.1%). The mean age of exposed physicians was 32.5±4.3 (SD) years. Those working in the emergency unit (45.8%), surgery and allied departments (54.2%), engaging in rotating shift work (70%), morning shifts (59.6%) and postgraduate trainees (68%) were frequently subjected to violence. Factors significantly associated with WPV included placement in surgery and allied departments (p<0.001), working rotating shifts (p<0.001), marital status (p=0.011) and being a male physician (p=0.010). Perpetrators were primarily identified as relatives of patients (66%). Working in rotating shifts (adjusted OR(AOR):2.6, 95% CI:1.2 to 5.4) and surgery and allied departments (AOR:5.7, 95% CI:3.4 to 9.8) emerged as significant risk factors of violence against physicians. CONCLUSION: A higher proportion of physicians at the early to mid-level stages of their careers, especially those in rotating shifts and surgery-related departments, reported incidence of WPV. Urgent intervention from policy-makers and healthcare entities is imperative to implement preventive measures. Strengthening security measures, establishing antiviolence policies and providing comprehensive training programmes are crucial steps towards ensuring a safer work environment for healthcare professionals.

Addressing bias in the definition of SARS-CoV-2 reinfection: implications for underestimation.

Introduction: Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection. Methods: A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed. Results: The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results. Discussion: A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic.

Deletion of hepatocyte cysteine dioxygenase type 1, a bile acid repressed gene, enhances glutathione synthesis and ameliorates acetaminophen hepatotoxicity.

Liver is a major organ that metabolizes sulfur amino acids cysteine, which is the substrate for the synthesis of many essential cellular molecules including GSH, taurine, and coenzyme A. Bile acid-activated farnesoid x receptor (FXR) inhibits cysteine dioxygenase type 1 (CDO1), which mediates hepatic cysteine catabolism and taurine synthesis. To define the impact of bile acid inhibition of CDO1 on hepatic sulfur amino acid metabolism and antioxidant capacity, we developed hepatocyte-specific CDO1 knockout mice (Hep-CDO1 KO) and hepatocyte specific CDO1 transgenic mice (Hep-CDO1 Tg). Liver metabolomics revealed that genetic deletion of hepatic CDO1 reduced de novo taurine synthesis but had no impact on hepatic taurine abundance or bile acid conjugation. Consistent with reduced cysteine catabolism, Hep-CDO1 KO mice showed increased hepatic cysteine abundance but unaltered methionine cycle intermediates and coenzyme A synthesis. Upon acetaminophen overdose, Hep-CDO1 KO mice showed increased GSH synthesis capacity and alleviated liver injury. In contrast, hepatic CDO1 overexpression in Hep-CDO1 Tg mice stimulated hepatic cysteine to taurine conversion, resulting in reduced hepatic cysteine abundance. However, Hep-CDO1 Tg mice and WT showed similar susceptibility to acetaminophen-induced liver injury. Hep-CDO1 Tg mice showed similar hepatic taurine and coenzyme A compared to WT mice. In summary, these findings suggest that bile acid and FXR signaling inhibition of CDO1-mediated hepatic cysteine catabolism preferentially modulates hepatic GSH synthesis capacity and antioxidant defense, but has minimal effect on hepatic taurine and coenzyme A abundance. Repression of hepatic CDO1 may contribute to the hepatoprotective effects of FXR activation under certain pathologic conditions.