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Dengue, a rapidly spreading mosquito-borne human viral disease caused by dengue virus (DENV), is a public health concern in tropical and subtropical areas due to its expanding geographical range. DENV can cause a wide spectrum of illnesses in humans, ranging from asymptomatic infection or mild dengue fever (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is caused by four DENV serotypes; however, dengue pathogenesis is complex and poorly understood. Establishing a useful animal model that can exhibit dengue-fever-like signs similar to those in humans is essential to improve our understanding of the host response and pathogenesis of DENV. Although several animal models, including mouse models, non-human primate models, and a recently reported tree shrew model, have been investigated for DENV infection, animal models with clinical signs that are similar to those of DF in humans have not yet been established. Although animal models are essential for understanding the pathogenesis of DENV infection and for drug and vaccine development, each animal model has its own strengths and limitations. Therefore, in this review, we provide a recent overview of animal models for DENV infection and pathogenesis, focusing on studies of the antibody-dependent enhancement (ADE) effect in animal models.

The present study sought to evaluate the central nervous system (CNS) depressant, antioxidant, and cytotoxicity activity of methanol and aqueous extract of Trametes versicolor (METV and AETV). The CNS activity was assessed by the open field, hole-cross, forced swimming, thiopental sodium-induced sleeping time, hole-board, and rotarod tests in Swiss albino mice. For both extracts, a substantial decrease in locomotion was observed in open field and hole-cross tests. In addition, the molecular docking study has been implemented through Maestro V11.1. The higher dose of METV (400 mg/kg) and the lower dose of AETV (200 mg/kg) exhibited a significant decrease in immobility time in forced swimming test and increased prolongation of sleep in thiopental sodium-induced sleeping time test, respectively. In contrast, a moderate finding was observed for the hole-board and rotarod tests. Additionally, a significant DPPH scavenging assay and a high toxicity effect in brine shrimp lethality assay were observed. Besides, five phenolic compounds, namely baicalin, quercetin, catechin, p-hydroxybenzoic acid, and quinic acid, were used for the molecular docking study, whereas catechin demonstrated the highest binding affinity towards the targets. The findings conclude that the T. versicolor could be an alternative source for CNS anti-depressant and antioxidant activity.

Hepatitis B Virus (HBV) is the most common cause of chronic liver disease worldwide. The mechanisms that regulate HBV viral replication remain poorly defined. Here, we show that blocking of the neddylation elicits antiviral effect against HBV replication, indicating that NEDD8 supports viral production. To explore role of neddylation, HBV-replicating HepG2.2.15.7 cells and HBV-infected HepG2-hNTCP-30 cells were treated with siNEDD8 and MLN4924, a potent and selective NEDD8-activating enzyme inhibitor. Cell viability, intracellular and extracellular HBV DNA, covalently closed circular DNA (cccDNA), HBsAg, HBeAg, and HBcrAg were measured to assess the consequences of the various treatments on viral replication. Our data showed that HBV infection increased NEDD8 expression in human liver cell lines. Symmetrically, NEDD8 knockdown by siRNA or MLN4924 treatments decreased HBV replication in HepG2.2.15.7 and HepG2-hNTCP-30 cells. Notably, HBsAg, and HBeAg secretions were strongly suppressed in the culture supernatants, but not the HBcrAg. These results indicate that the suppression of NEDD8 decreases HBV replication. However, cccDNA steady level confirms once again its persistence and longevity in chronic infection. The manipulation of the neddylation pathway can thus provide new tools interfering with HBV persistence as well as novel therapeutic strategies against chronic hepatitis B.

Muhammad Shah Alam,1 ABM Kamrul-Hasan,2 Syeda Tanzina Kalam,3 SM Mizanur Rahman,4 Mohammad Izazul Hoque,5 Md Belalul Islam,6 Ajit Kumar Paul7 1Department of Medicine, Army Medical College, Comilla, Bangladesh; 2Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh; 3Department of Psychiatry, Comilla Medical College Hospital, Comilla, Bangladesh; 4Department of Medicine, CMH and Army Medical College, Comilla, Bangladesh; 5Department of Hepatology, Comilla Medical College, Comilla, Bangladesh; 6Department of Medicine, Comilla Medical College, Comilla, Bangladesh; 7Department of Endocrinology, Maynamati Medical College, Comilla, BangladeshCorrespondence: ABM Kamrul-HasanDepartment of Endocrinology, Mymensingh Medical College, Charpara, Mymensingh, 2207, BangladeshTel +8801711103905Email rangassmc@gmail.comPurpose: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD), and the presence of T2DM tremendously drives NAFLD progression. The use of transient elastography (TE) for assessment of NAFLD has been increasing due to its high sensitivity and specificity. This study aimed to measure liver stiffness in patients with T2DM and ultrasonography (USG)-diagnosed NAFLD and assess the correlations between liver stiffness and other clinical and biochemical parameters.Patients and Methods: This cross-sectional study assessed 205 adult patients with T2DM and USG-diagnosed NAFLD who were being treated at a specialized endocrine private practice in Bangladesh. All subjects underwent TE for hepatic fibrosis assessment, which was performed using a FibroScan® 402 device. A fibrosis score ≥ 9.7 kilopascals (kPa) was used to define advanced fibrosis (≥F3).Results: Out of 205 (65.9% female, mean age 45 ± 27 years, 67.3% obese) patients, the frequencies of Grade 1, Grade 2, and Grade 3 fatty liver on USG were 46.3%, 51.2%, and 2.4%, respectively. According to the TE results, 41 (20%) had advanced fibrosis (≥F3). Subjects with advanced fibrosis had a higher body mass index (BMI), higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and higher frequencies of individuals with elevated ALT and AST and advanced fatty liver grades on USG. The fibrosis score (kPa) was strongly and positively correlated with age, BMI, waist circumference, obesity, serum ALT and AST levels, and the fatty liver grade in USG; the AST:ALT ratio did not correlate with kPa.Conclusion: The data showed that 20% of the subjects with T2DM having NAFLD on USG exhibited advanced fibrosis, demonstrating the need for early diagnosis and treatment of NAFLD in T2DM. The use of TE with other serum markers can be helpful for the diagnosis of advanced fibrosis.Keywords: type 2 diabetes, NAFLD, transient elastography, advanced fibrosis, AST:ALT ratio

This study was undertaken to evaluate the antidiabetic, hypolipidemic, and hepatoprotective effects of methanol and aqueous extracts of Ganoderma applanatum (MEGA, AEGA) in alloxan‐induced diabetic rats. The antidiabetic study was implemented by the induction of alloxan to the rats. The analysis of the hypolipidemic and liver‐protective effects of fungus extracts was studied by estimating the lipid profile and the liver marker enzymes. Besides, in silico screening of the compounds of Ganoderma applanatum has been incorporated thus to check the binding affinity of compounds and enzymes affinity. The Discovery Studio 2020, UCSF Chimera, and PyRx AutoDock Vina have been used to implement the docking analysis. Nine days of oral feeding of MEGA and AEGA of Ganoderma applanatum resulted in a significant (p, This study aggregates, consolidates, and validates the use of mushroom for the treatment of diabetes, hyperlipidemia, and hepatic degenerations, Besides, the bioactive compounds have been accelerated to investigate the binding reactions with diabetes, hyperlipidemia, and hepatic receptors.

Koala retrovirus (KoRV), a major pathogen of koalas, exists in both endogenous (KoRV-A) and exogenous forms (KoRV-B to J). However, the impact of infection with multiple subtypes is not well understood. Accordingly, in this study, we surveyed a representative sample from a Japanese zoo population to determine the infection status for three KoRV subtypes (KoRV-A, B, and C) and to investigate the proviral and RNA load profiles in animals with single- and multiple-subtype infections, using peripheral blood mononuclear cells (PBMCs) and plasma. Six koalas were evaluated in the study; all were infected with KoRV-A, and two koalas were coinfected with non-A subtypes (KoRV-B and/or KoRV-C). The highest KoRV total RNA and viral loads in PBMCs and plasma were found in a koala infected with multiple subtypes (KoRV-A, -B and -C). The other koala infected with multiple subtypes (KoRV-A and B) showed the highest proviral PBMC load but the lowest RNA copy number in PBMC and plasma. PBMCs from this animal were cultured for further investigation, and KoRV RNA was detected in the cells and culture supernatant after 7 and/or 14 days. The koalas harboring multiple subtypes had a higher white blood cell count than those harboring only KoRV-A and were judged to be leukemic, and they subsequently died due to lymphoma. Accordingly, we conclude that coinfection with multiple KoRV subtypes may be linked to more-severe disease. In a sequence alignment, the detected KoRV-A env gene showed 100% sequence identity to the reference gene, whereas the KoRV-B and -C env genes varied from their reference sequences.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a global health burden having systemic and extrapulmonary manifestations. Among them cardiovascular changes are the major comorbidity associated with COPD, responsible for significant morbidity and mortality. Echocardiography is one of the simplest and noninvasive tools in assessing these changes. Objective: To evaluate the echocardiographic changes in patients with chronic obstruction palmonary disease. Methods: A cross sectional observational study was carried out in Department of Cardiology and Department of Respiratory Medicine, Dhaka Medical College Hospital from July, 2018 to June, 2019. Total 98 COPD patients were included in the study. They underwent spirometry in Department of Respiratory Medicine and echocardiography in Department of Cardiology. Data was collected from the patients and recorded in a structured report form. Results: Significant echocardiographic abnormalities were present in 51.02% patients. Most common echocardiographic change was pulmonary hypertension (43.9%). Other echocardiographic findings were dilated RA & RV (36.7%), RVH (35.7%), LV diastolic dysfunction (30.6%) and RV systolic dysfunction (9.2%). Echocardiographic signs of pulmonary hypertension, dilated RA & RV, RVH, RV systolic dysfunction and LV diastolic dysfunction were correlated with the severity of the disease. Though echocardiographic change of pulmonary hypertension was uncommon in COPD stage 1 & 2, but it was very common in stage 3(45.7%) & stage 4(92.9%). Conclusion: This study showed that echocardiographic changes were very common among the COPD GOLD stage 3 & 4 patients. Though these changes were infrequent among mild COPD patients but their severity increased with increasing stage of COPD. Bangladesh Med Res Counc Bull 2020; 46(3): 204-210

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system has considerable therapeutic potential for use in treating a wide range of intractable genetic and infectious diseases including hepatitis B virus (HBV) infections. While non-viral delivery technologies for the CRISPR/Cas system are expected to have clinical applications, difficulties associated with the clinically relevant synthesis of formulations and the poor efficiency of delivery severely hinder therapeutic genome editing. We report herein on the production of a lipid nanoparticle (LNP)-based CRISPR/Cas ribonucleoprotein (RNP) delivery nanoplatform synthesized using a clinically relevant mixer-equipped microfluidic device. DNA cleavage activity and the aggregation of Cas enzymes was completely avoided under the optimized synthetic conditions. The optimized formulation, which was identified through 2 steps of design of experiments, exhibited excellent gene disruption (up to 97%) and base substitution (up to 23%) without any apparent cytotoxicity. The addition of negative charges to the RNPs by complexing single-stranded oligonucleotide (ssON) significantly enhanced the delivery of both Cas9 and Cpf1 RNPs. The optimized formulation significantly suppressed both HBV DNA and covalently closed circular DNA (cccDNA) in HBV-infected human liver cells compared to adeno-associated virus type 2 (AAV2). These findings represent a significant contribution to the development of CRISPR/Cas RNP delivery technology and its practical applications in genome editing therapy.

Pre -eclampsia is a disorder of 2nd half of pregnancy, which is characterized by a combination of hypertension, proteinuria and edema, secondary to decreased placental perfusion. Clinical studies suggest that antioxidant vitamins, such as Vit C and Vit. E can stabilize reactive free radicals, which are produced due to placental hypo perfusion, thereby preventing the development of pre-eclampsia. Pre-eclampsia remain a major cause of infant and maternal mortality and morbidity. In developing countries, pre-eclampsia causes an estimated 50,000 maternal deaths per year. Only a small number of studies have however, been conducted in Bangladesh. Objective: To compare the serum levels of antioxidants in selected pre-eclamptic and normotensive pregnant women. Methods: 220 pregnant women were selected with inclusion and exclusion criteria from 3 different medical colleges and divided into 2 groups – A study group, consisting of 110 pre-eclamptic women and a control group consisting of 110 normotensive pregnant women. Dietary information was collected by 7 days food frequency questionnaire and food score was determined. Anthropometric and biochemical tests were performed. Biochemical analysis such as serum vitamin C levels were measured by spectrophotometric method, and serum vitamin E levels were measured by HPLC (High Performance Liquid Chromatography) method. Results: The mean serum levels of Vit. C and Vit E were found to be significantly lower in the study group, compared to the control group. Anthropometric study revealed that the babies born to pre-eclamptic mothers had lower birth weight than those born to normotensive mothers. Conclusion: Therefore, low antioxidant levels do play a key role in the development of preeclampsia in pregnant women. J Dhaka Medical College, Vol. 29, No.1, April, 2020, Page 53-58

Penetrating injuries to the subclavian arteries as well as post traumatic pseudoaneurysm involving Subclavian artery (SCA) are very much uncommon. We present one case of a 21 year-old male sustained a physical assault with a post stab injury left subclavian artery pseudoaneurysm. He was referred to our facility, two days after sustaining a penetrating chest trauma over left infraclavicular area of the chest. The presentation, diagnostic procedures and surgical approach for management of this very rare injury are discussed.

North Borneo (NB) is home to more than 40 native populations. These natives are believed to have undergone local adaptation in response to environmental challenges such as the mosquito-abundant tropical rainforest. We attempted to trace the footprints of natural selection from the genomic data of NB native populations using a panel of ∼2.2 million genome-wide single nucleotide polymorphisms. As a result, an ∼13-kb haplotype in the Major Histocompatibility Complex Class II region encompassing candidate genes TSBP1–BTNL2–HLA-DRA was identified to be undergoing natural selection. This putative signature of positive selection is shared among the five NB populations and is estimated to have arisen ∼5.5 thousand years (∼220 generations) ago, which coincides with the period of Austronesian expansion. Owing to the long history of endemic malaria in NB, the putative signature of positive selection is postulated to be driven by Plasmodium parasite infection. The findings of this study imply that despite high levels of genetic differentiation, the NB populations might have experienced similar local genetic adaptation resulting from stresses of the shared environment.

Immunohistochemical stains have been suggested to aid in diagnostically challenging cases of urothelial carcinoma in-situ (CIS). Although full thickness immunostaining for CK20 is supportive of CIS, a subset of CIS cases is CK20(-), the clinical significance of which was unknown. This study included 43 patients with primary diagnosis of bladder CIS including 32 with only CIS, 5 with CIS and separate noninvasive high-grade papillary urothelial carcinoma, and 6 with CIS and separate high-grade urothelial carcinoma with lamina propria invasion. Digital morphometric image analysis showed that the average nuclear areas of enlarged nuclei were similar in CK20(+) and CK20(-) CIS (26.9 vs. 24.5 µM2; P=0.31). Average Ki67 index for CK20(+) CIS was higher than CK20(-) CIS (31.1% vs. 18.3%; P=0.03). Patients with CK20(+) CIS [28 (65%)] and patients with CK20(-) CIS [15 (35%)] had the same rates of Bacillus Calmete-Guerin (BCG) failure but patients with CK20(-) CIS had higher stage progression [3 CK20(+) (11%) vs. 6 CK20(-) (40%); P=0.02]. Given recent approval of immune checkpoint inhibitors in patients with CIS refractory to BCG, programmed death ligand-1 expression and colocalization with CD8(+) lymphocytes was investigated as signature of adaptive immune response and was seen in 8 patients regardless of CK20 status and exclusively among patients who failed BCG. Our results confirm that negative CK20 IHC does not exclude CIS and that those patients have similar clinical outcomes as patients with CK20(+) CIS. Programmed death ligand-1 and CD8 colocalization seen among patients who failed BCG therapy is an easy assay to perform to identify patients who could potentially benefit from combined BCG therapy and immune checkpoint inhibition.

Cattle are one of the indices of civilization, sources of wealth, health and prosperity for the nation. Cattle provide us food, cash as well as mechanical power. The production of cattle is low due to their poor genetic makeup, indigenous and large incidence of diseases. Artificial Insemination (AI) is the first generation reproductive biotechnology that has made a profound contribution to the genetic improvement as well as recognized breeding tool of the cattle. But the farmers in Bangladesh are yet to adopt it perfectly. For these, the principle objective of the study was to determine the extent of problems faced by the farmers in adopting AI of cattle. Problem confrontation was measured based on 18 different aspects of AI using four point scale where 3 indicates high problem, 2 medium, 1 low and 0 no problem at all. The study was conducted in Kishoreganj Sadar Upazila under Kishoreganj district. Data were collected from randomly selected 100 farmers out of 340 farmers using an interview schedule. The majority of the farmers (58%) had medium problems while 39% had high and only 3% had low problems in adopting artificial insemination. Among the problems, inseminator problem and heat stage were considered the most critical problems in the survey area.

Background: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) is in Pandemic form and has affected people of 215 countries. It produces symptoms like fever, cough, shortness of breath, sore throat, headache, loss of taste, smell or appetite and many other rare symptoms. But the most important symptom is shortness of breath due to hypoxia. In a normal individual oxygen saturation (SpO2) is at least 95% and patient feels shortness of breath when SpO2 falls below 90% with some exception. SARS-CoV-2, a newly emergent coronavirus has the peculiarity to produce silent hypoxia, meaning SpO2< 90% or less like 80%, 70%, 60% without shortness of breath. Silent hypoxia can be diagnosed by monitoring SpO2 with pulse oximeter. For management of COVID-19, early symptoms like fever & cough, SpO2 should be monitored by pulse oximeter, followed by immediate correction of hypoxia by O2 supplementation and prophylactic oral or injectable anticoagulant to prevent thromboembolism and thus death rate can be reduced. Case summary: A 72-year-old man presented with the complaints of fever and headache followed by cough, fatigue, anorexia, loss of taste and appetite in next few days but no shortness of breath. The patient was clinically diagnosed as a case of COVID-19 & positive result of Real time-Polymerase Chain Reaction (RT-PCR) test confirmed the diagnosis. From the first day, SpO2 was regularly monitored with pulse oximeter and SpO2 on day 1, it was 96-98%. On day 8, SpO2 fell to 89-93%, pulse 96/min, respiratory rate>30/min, temperature 101o F, taste sensation was reduced. According to sign and symptoms, the patient was diagnosed as COVID-19 with severe pneumonia. Management was started at home with continuous monitoring, lying in prone position for 5-6 hours/day, supplemental oxygenation to maintain level of SpO2 between 94-96%, injectable anticoagulant enoxaparin to prevent venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) was given. Prophylactic antibiotics and symptomatic treatment were also given. Results: According to this case report, patient’s SpO2 was monitored by pulse oximeter on first day; on day 08, SpO2 fell to 89-93% & on day 10, further dropped to 85-88% which indicated severe pneumonia but there was no complaint of breathlessness as it was silent hypoxia. Sometimes the patient spent 30 minutes or more in toilet and SpO2 used to fall to 82-83% without any subjective shortness of breath but with only mild heaviness of chest and cough. Therefore SpO2 monitoring by pulse oximeter is essential in early diagnosis of silent hypoxia. Correction of hypoxia by supplemental oxygenation and prevention of VTE and DIC by using anticoagulant was the mainstay of treatment and patient had significant improvement on day 14. The patient was managed completely at home except X-ray being done in a hospital. Conclusion: Fall of SpO2 in COVID-19 i.e. hypoxia (usually present as shortness of breath) or silent hypoxia can be diagnosed early by pulse oximeter or smart phone pulse oximetry apps. Early management by isolation, supplemental oxygenation and oral/injectable anticoagulation can prevent further events like Acute Respiratory Distress Syndrome (ARDS), respiratory failure followed by multiple organ failure (that may cause death). The authors advocate further clinical trial and research. Bangladesh J Otorhinolaryngol; April 2020; 26(1): 55-67

Background Access to oxytocin for prevention of postpartum haemorrhage (PPH) in resource-poor settings is limited by the requirement for a consistent cold chain and for a skilled attendant to administer the injection. To overcome these barriers, heat-stable, non-injectable formulations of oxytocin are under development, including oxytocin for inhalation. This study modelled the cost-effectiveness of an inhaled oxytocin product (IHO) in Bangladesh and Ethiopia. Methods A decision analytic model was developed to assess the cost-effectiveness of IHO for the prevention of PPH compared to the standard of care in Bangladesh and Ethiopia. In Bangladesh, introduction of IHO was modelled in all public facilities and home deliveries with or without a skilled attendant. In Ethiopia, IHO was modelled in all public facilities and home deliveries with health extension workers. Costs (costs of introduction, PPH prevention and PPH treatment) and effects (PPH cases averted, deaths averted) were modelled over a 12-month program. Life years gained were modelled over a lifetime horizon (discounted at 3%). Cost of maintaining the cold chain or effects of compromised oxytocin quality (in the absence of a cold chain) were not modelled. Results In Bangladesh, IHO was estimated to avert 18,644 cases of PPH, 76 maternal deaths and 1954 maternal life years lost. This also yielded a cost-saving, with the majority of gains occurring among home deliveries where IHO would replace misoprostol. In Ethiopia, IHO averted 3111 PPH cases, 30 maternal deaths and 767 maternal life years lost. The full IHO introduction program bears an incremental cost-effectiveness ratio (ICER) of between 2 and 3 times the per-capita Gross Domestic Product (GDP) ($1880 USD per maternal life year lost) and thus is unlikely to be considered cost-effective in Ethiopia. However, the ICER of routine IHO administration considering recurring cost alone falls under 25% of per-capita GDP ($175 USD per maternal life-year saved). Conclusions IHO has the potential to expand access to uterotonics and reduce PPH-associated morbidity and mortality in high burden settings. This can facilitate reduced spending on PPH management, making the product highly cost-effective in settings where coverage of institutional delivery is lagging.

Introduction: Corona Virus Disease 2019 (COVID-19) is caused by SARS-CoV-2, a newly emergent virus. World Health Organization declared COVID-19 as pandemic on March 11, 2020 for its rapid spreading. Not only to diagnose the disease (confirm case) but also to control and contain the transmission; test, trace and isolation are fundamental. RT-PCR for SARS-CoV-2 is used to detect and diagnose COVID-19 which started in Dhaka Medical College Hospital (DMCH) on 2nd April 2020. In this study we described our observation of RT-PCR done in patients presented in DMCH in the first month after starting the test. Methods: This observational, cross sectional study was done to find out the rate of RT-PCR positivity in suspected COVID -19 patients presented to DMCH from 2nd April to 3rd May, 2020 by the Department of Medicine in association with the Department of Virology. Data was collected from the registry book of the Department of Virology. The rate of RT-PCR for SARS-CoV-2 positivity among the suspected COVID-19 patients and demographical variable was observed. Results: Among the total studied patients (n=3206), 58.8% (n=1886) was male and mean age was 37.7(±14.38784) years. RT-PCR for SARS- CoV-2 was positive in 26.9% (n=864). Mean age was higher in patients positive for test (39.6± 15.9 year vs. 37±14.4 year). Male predominance was more marked in patients with positive PCR test (68.4 vs. 55.9). Conclusion: High rate of positivity of RT PCR for SARSCoV- 2 among the suspected patient for COVID 19 indicated high disease burden and transmission in this highly populated area in the early period of pandemic which should be considered as was alarming. J Bangladesh Coll Phys Surg 2020; 38(0): 67-70

Introduction: The outbreak of COVID-19 is taking an unprecedented mental toll on health workers worldwide. So it comes as no surprise that the mental well-being of health care workers of Bangladesh too is in serious jeopardy. This survey was aimed to assess the immediate psychological impact on doctors working in largest Covid-19 dedicated facility in Bangladesh, Dhaka Medical College Hospital. Methods: This cross sectional study was conducted in a single-centre with response received from participating doctors between 31st May to 3rd June, 2020. Mental health variables were assessed via the Athens Insomnia Scale (AIS) and Hospital Anxiety Depression Score (HADS). Results: We received 192 completed questionnaires (response rate, 64.43%) among whom around 50% of the participating doctors reportedly have depression and anxiety symptoms respectively. Among them 104 doctors (54.17%) responded to have insomnia. Around 56% of the responding subjects perceived the highly contagious nature of the SARS-CoV-2 as the most striking threat of COVID-19. Conclusion: Agonizing disease process, high death toll, highly contagious nature of the responsible virus is taking a serious mental toll on physicians in the background of their heightened concern about personal health and family health, scarcity in PPE and adequate hospital facility. Psychological protective measures implemented by the hospital could be helpful. J Bangladesh Coll Phys Surg 2020; 38(0): 50-55

To estimate the pooled prevalence of smokeless tobacco consumption (STC) by gender and location in Bangladesh, India and Myanmar and to identify periodic changes in STC prevalence using data extracted from published studies.We searched for a combination of keywords in electronic databases and used a standard form to extract data from each article. We undertook a meta-analysis to estimate pooled prevalence and confidence intervals within these countries. To compare periodic changes in STC prevalence, we grouped studies into five-year periods (2000-2004, 2005-2009, 2010-2014 and 2015-2019).The pooled estimates of STC prevalence were 25% (95% CI: 22-28%), 22% (95% CI: 15-28%) and 21% (95% CI: 14-28%) for Bangladesh, India and Myanmar, respectively. In pooled estimates across these countries, we found higher STC prevalence for men (30%; 95% CI: 24-35%) than women (16%; 95% CI: 10-23%) and for rural dwellings (24%; 95% CI: 18-31%) than urban dwellings (17%; 95% CI: 10-24%). We found significant decrease in STC in Bangladesh and India in the period 2010-2014 and 2015-2019, respectively. In Myanmar, STC prevalence increased significantly and substantially in 2010-2014, to levels higher than in Bangladesh and India.The prevalence of STC in Bangladesh, India and Myanmar is highest in rural areas and among men. Public health prevention strategies are needed to maintain decrease in STC in Bangladesh and India, and to reverse the increased use in Myanmar.Estimer la prévalence poolée de la consommation de tabac sans fumée (CTSF) par sexe et lieu au Bangladesh, en Inde et au Myanmar et identifier les changements périodiques de la prévalence des CTSF à l'aide de données extraites d'études publiées. MÉTHODES: Nous avons recherché une combinaison de mots-clés dans les bases de données électroniques et utilisé un formulaire standard pour extraire les données de chaque article. Nous avons entrepris une méta-analyse pour estimer la prévalence poolée et les intervalles de confiance dans ces pays. Pour comparer les changements périodiques de la prévalence des CTSF, nous avons regroupé les études en périodes de cinq ans (2000-2004, 2005-2009, 2010-2014, 2015-2019). RÉSULTATS: Les estimations poolées de la prévalence des CTSF étaient de 25% (IC95%: 22-28%), 22% (IC95%: 15-28%) et 21% (IC95%: 14-28%) pour le Bangladesh, l'Inde et le Myanmar, respectivement. Dans les estimations poolées de ces pays, nous avons constaté une prévalence des CTSF plus élevée pour les hommes (30%; IC95%: 24-35%) que pour les femmes (16%; IC95%: 10-23%) et pour les habitations rurales (24%; IC95%: 18-31%) que les habitations urbaines (17%; IC95%: 10-24%). Nous avons constaté une diminution significative des CTSF au Bangladesh et en Inde au cours de la période 2010-2014 et 2015-2019 respectivement. Au Myanmar, la prévalence des CTSF a augmenté de manière significative et substantielle en 2010-2014, à des niveaux plus élevés qu'au Bangladesh et en Inde.La prévalence des CTSF au Bangladesh, en Inde et au Myanmar est la plus élevée dans les zones rurales et chez les hommes. Des stratégies de prévention de la santé publique sont nécessaires pour maintenir la diminution des CTSF au Bangladesh et en Inde et pour inverser l'augmentation de la consommation au Myanmar.

In the present study, nutritional status was assessed using dietary diversity of fish and non-fish farming households in Mymensingh district of Bangladesh. It has determined the incidence of poverty in fish and non-fish farm households through a comparative analysis of family profile, food consumption, calories, and protein intake. A total of 420 farms were selected for data collection using structured questionnaires with 210 fish and 210 non-fish farm families. The study using both descriptive and functional analysis revealed that the respondent age of both farms was 45.10 years, family size was 5.70, average education was 4.64 schooling years, and average farm size was 0.514 hectares. As a result, due to the increase in household income, fish farm families improved their food consumption, calories, and protein intake in comparison with non-fish farms. On a direct calorie intake (DCI) basis, the overall absolute and hardcore poverty levels of fish farm households were 32 percent and 18 percent, respectively, while those of non-fish farm households were 22 percent and 10 percent, respectively. Therefore, the incidence of poverty was higher in non-fish farming families than in fish farming families. In principle, provision of various forms of government assistance through the Department of Fisheries (DOF) will further intensify and strengthen fish farming, which will easily bring fallow and uncultivated lands of the area under fish farming. Moreover, it is possible to inspire the younger generation through this research that will help them to become a fish farm-based entrepreneur. The main conclusion of the present study is that fish farming is more positively related to household income, family food intake, and nutritional status than any other type of farming.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to coronavirus disease (COVID-19), a global health pandemic causing millions of deaths worldwide. However, the immunopathogenesis of COVID-19, particularly the interaction between SARS-CoV-2 and host innate immunity, remains unclear. The innate immune system acts as the first line of host defense, which is critical for the initial detection of invading pathogens and the activation and shaping of adaptive immunity. Toll-like receptors (TLRs) are key sensors of innate immunity that recognize pathogen-associated molecular patterns and activate downstream signaling for pro-inflammatory cytokine and chemokine production. However, TLRs may also act as a double-edged sword, and dysregulated TLR responses may enhance immune-mediated pathology, instead of providing protection. Therefore, a proper understanding of the interaction between TLRs and SARS-CoV-2 is of great importance for devising therapeutic and preventive strategies. The use of TLR agonists as vaccine adjuvants for human disease is a promising approach that could be applied in the investigation of COVID-19 vaccines. In this review, we discuss the recent progress in our understanding of host innate immune responses in SARS-CoV-2 infection, with particular focus on TLR response. In addition, we discuss the use of TLR agonists as vaccine adjuvants in enhancing the efficacy of COVID-19 vaccine.

There are a number of gastrointestinal symptoms and complications of COVID-19. Asymptomatic increase in pancreatic enzymes and rarely symptomatic pancreatitis are observed in this disease. This article describes a 37-year-old male suffering from mildly symptomatic COVID-19 infection, who received tablet favipiravir for his management. His condition was improving, when he developed acute pancreatitis, diagnosed clinically, biochemically and also with help of abdominal ultrasound. When he developed this, all typical symptoms of COVID-19 were improved. As a result, role of favipiravir in the development of this pancreatitis was suspected. J MEDICINE JAN 2021; 22 (1) : 69-71

Mutations in mitochondrial DNA (mtDNA) have been linked to risk, progression, and treatment response of head and neck squamous cell carcinoma (HNSCC). Due to their clonal nature and high copy number, mitochondrial mutations could serve as powerful molecular markers for detection of cancer cells in bodily fluids, surgical margins, biopsies and lymph node (LN) metastasis, especially at sites where tumor involvement is not histologically apparent. Despite a pressing need for high-throughput, cost-effective mtDNA mutation profiling system, current methods for library preparation are still imperfect for detection of low prevalence heteroplasmic mutations. To this end, we have designed an ultra-deep amplicon-based sequencing library preparation approach that covers the entire mitochondrial genome. We sequenced mtDNA in 28 HNSCCs, matched LNs, surgical margins and bodily fluids, and applied multiregional sequencing approach on 14 primary tumors. Our results demonstrate that this quick, sensitive and cost-efficient method allows obtaining a snapshot on the mitochondrial heterogeneity, and can be used for detection of low frequency tumor-associated mtDNA mutations in LNs, sputum and serum specimens. These findings provide the foundation for using mitochondrial sequencing for risk assessment, early detection, and tumor surveillance.

Introduction: To determine the clinical types and etiological factors and to assess the biochemical abnormalities in neonates with seizure. Materials and Methods: This was a Cross-sectional, comparative hospital based study. Ninety neonates, age up to 28 days of both sexes were evaluated for clinical types, etiological factors and biochemical abnormalities with seizure and compared with those having no seizures. The variables were analyzed using student t- test. All the data was processed and analyzed by computer software SPSS version 15.0. Level of significance was considered as p value less than 0.05. Results: Most of the neonates having seizures (72%) within 3 days of life. The seizures were common in male babies (62%). 35% of the mother of baby with seizure gave history of prolonged labour. HIE was diagnosed 56.67% neonates with seizure whereas infection were found in 25% cases with seizure. Among the seizure subtypes, subtle seizures were 58% followed by clonic seizures 30%. Significant biochemical changes we found in 43.34% of neonates with seizures. Hypocalcemia (46%) was most common followed by hypoglycemia(38%). Conclusion: Hypoxic ischemic encephalopathy was the commonest cause of neonatal seizure followed by neonatal infections including meningitis and sepsis.. Biochemical abnormalities are more common in neonates with seizure than neonates free from seizure. Among the biochemical abnormalities hypocalcaemia and hypoglycemia occurs most commonly followed by hyponatraemia and hypomagnesaemia. Medicine Today 2020 Vol.32(1): 37-41

Background: Stroke in young age is less frequent than in older populations but has a major impact on the individual and society. This study was done to find out aetiological pattern and associated risk factors of stroke in young adults. Methods: This descriptive cross-sectional observational study was conducted in the Department of Medicine and Neurology, Dhaka Medical College, Dhaka, during the period of April to October 2016. We studied consecutive 100 stroke patients between the age of 15-45 years. Results: In this study 62% patients were male and 38% were female, male incidence is 24% higher than female and ratio is 1. 38. Infarction was found in 65% cases. Haemorrhage was in 35% cases. Dyslipidaemia was mostly associated risk factor in both infarction (76. 91%) and in haemorrhage (85. 71%). High prevalence of dyslipidaemia as associated risk factor may indicate premature atherosclerosis. Conclusion: Stroke in young requires a different approach to investigation and management than stroke in the elderly due to differences in the relative frequencies of possible underlying causes. It remains the case, however, that atherosclerosis contributes to a large proportion of stroke in young patients, thus conventional risk factors must be targeted aggressively. J MEDICINE JAN 2020; 21 (1) : 26-30

Koala retrovirus (KoRV) is unique among endogenous retroviruses because its endogenization is still active. Two major KoRV subtypes, KoRV-A and B, have been described, and KoRV-B is associated with disease and poses a health threat to koalas. Here, we investigated the co-prevalence of KoRV-A and KoRV-B, detected by type-specific PCR and sequencing, and their impact on the health of koalas in three Japanese zoos. We also investigated KoRV proviral loads and found varying amounts of genomic DNA (gDNA) in peripheral blood mononuclear cells (PBMCs). We found that 100% of the koalas examined were infected with KoRV-A and 60% (12/20) were coinfected with KoRV-B. The KoRV-A sequence was highly conserved, whereas the KoRV-B sequence varied among individuals. Interestingly, we observed possible vertical transmission of KoRV-B in one offspring in which the KoRV-B sequence was similar to that of the father but not the mother. Moreover, we characterized the KoRV growth patterns in concanavalin-A-stimulated PBMCs isolated from KoRV-B-coinfected or KoRV-B-uninfected koalas. We quantified the KoRV provirus in gDNA and the KoRV RNA copy numbers in cells and culture supernatants by real-time PCR at days 4, 7, and 14 post-seeding. As the study population is housed in captivity, a longitudinal study of these koalas may provide an opportunity to study the transmission mode of KoRV-B. In addition, we characterized KoRV isolates by infecting tupaia cells. The results suggested that tupaia may be used as an infection model for KoRV. Thus, this study may enhance our understanding of KoRV-B coinfection and transmission in the captive koalas.

Objectives In this study we describe the tumor microenvironment, the signaling pathways and genetic alterations associated with the presence or absence of CD8+ T-cell infiltration in primary squamous cell carcinoma of the head and neck (SCCHN) tumors. Materials and Methods Two SCCHN multi-analyte cohorts were utilized, the Cancer Genome Atlas (TCGA) and the Chicago Head and Neck Genomics (CHGC) cohort. A well-established chemokine signature classified SCCHN tumors into high and low CD8+ T-cell inflamed phenotypes (TCIP-H, TCIP-L respectively). Gene set enrichment and iPANDA analyses were conducted to dissect differences in signaling pathways, somatic mutations and copy number aberrations for TCIP-H versus TCIP-L tumors, stratified by HPV status. Results TCIP-H SCCHN tumors were enriched in multiple immune checkpoints irrespective of HPV-status. HPV-positive tumors were enriched in markers of T-regulatory cells (Tregs) and HPV-negative tumors in protumorigenic M2 macrophages. TCIP-L SCCHN tumors were enriched for the β-catenin/WNT and Hedgehog signaling pathways, had frequent mutations in NSD1, amplifications in EGFR and YAP1, as well as CDKN2A deletions. TCIP-H SCCHN tumors were associated with the MAPK/ERK, JAK/STAT and mTOR/AKT signaling pathways, and were enriched in CASP8, EP300, EPHA2, HRAS mutations, CD274, PDCD1LG2, JAK2 amplifications. Conclusions Our findings support that combinatorial immune checkpoint blockade and depletion strategies targeting Tregs in HPV-positive and M2 macrophages in HPV-negative tumors may lead to improved antitumor immune responses in patients with TCIP-H SCCHN. We highlight novel pathways and genetic events that may serve as candidate biomarkers and novel targeted therapies to enhance the efficacy of immunotherapy in SCCHN patients.

The safety of distracted pedestrians presents a significant public health challenge in the United States and worldwide. An estimated 6,704 American pedestrians died and over 200,000 pedestrians were injured in traffic crashes in 2018, according to the Centers for Disease Control and Prevention (CDC) [1]. This number is increasing annually and many researchers posit that distraction by smartphones is a primary reason for the increasing number of pedestrian injuries and deaths. One strategy to prevent pedestrian injuries and death is to use intrusive interruptions that warn distracted pedestrians directly on their smartphones. To this end, we developed StreetBit, a Bluetooth beacon-based mobile application that alerts distracted pedestrians with a visual and/or audio interruption when they are distracted by their smartphones and are approaching a potentially-dangerous traffic intersection. In this paper, we present the background, architecture, and operations of the StreetBit Application.

Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease caused by dengue virus (DENV). Recently, DENV has been affecting humans within an expanding geographic range due to the warming of the earth. Innate immune responses play a significant role in antiviral defense, and Toll-like receptors (TLRs) are key regulators of innate immunity. Therefore, a detailed understanding of TLR and DENV interactions is important for devising therapeutic and preventive strategies. Several studies have indicated the ability of DENV to modulate the TLR signaling pathway and host immune response. Vaccination is considered one of the most successful medical interventions for preventing viral infections. However, only a partially protective dengue vaccine, the first licensed dengue vaccine CYD-TDV, is available in some dengue-endemic countries to protect against DENV infection. Therefore, the development of a fully protective, durable, and safe DENV vaccine is a priority for global health. Here, we demonstrate the progress made in our understanding of the host response to DENV infection, with a particular focus on TLR response and how DENV avoids the response toward establishing infection. We also discuss dengue vaccine candidates in late-stage development and the issues that must be overcome to enable their success.

Simple Summary Effective cancer treatment hinges upon overcoming therapeutic resistance mechanisms that allow for the continued proliferation of cancer cell subpopulations. Exposure to pharmacotherapy invariably leads to resistance as tumor cells with selected advantageous features evade destruction and alter the tumor composition. Cancer stem cells (CSCs) with features of plasticity that allow for regeneration and differentiation are particularly responsible for this phenomenon. Advances in tumor biology and molecular signaling have highlighted their role in neoplastic initiation, invasion, and maintenance. Novel strategies to direct therapy against these tumor cell subpopulations have the potential to dramatically alter tumor response and change the course of cancer care. Abstract Resistance to cancer therapy remains a significant obstacle in treating patients with various solid malignancies. Exposure to current chemotherapeutics and targeted agents invariably leads to therapy resistance, heralding the need for novel agents. Cancer stem cells (CSCs)—a subpopulation of tumor cells with capacities for self-renewal and multi-lineage differentiation—represent a pool of therapeutically resistant cells. CSCs often share physical and molecular characteristics with the stem cell population of the human body. It remains challenging to selectively target CSCs in therapeutically resistant tumors. The generation of CSCs and induction of therapeutic resistance can be attributed to several deregulated critical growth regulatory signaling pathways such as WNT/β-catenin, Notch, Hippo, and Hedgehog. Beyond growth regulatory pathways, CSCs also change the tumor microenvironment and resist endogenous immune attack. Thus, CSCs can interfere with each stage of carcinogenesis from malignant transformation to the onset of metastasis to tumor recurrence. A thorough review of novel targeted agents to act against CSCs is fundamental for advancing cancer treatment in the setting of both intrinsic and acquired resistance.

Chronic hepatitis B virus (HBV) infection remains a major global health problem. The immunopathology of the disease, especially the interplay between HBV and host innate immunity, is poorly understood. Moreover, inconsistent literature on HBV and host innate immunity has led to controversies. However, recently, there has been an increase in the number of studies that have highlighted the link between innate immune responses, including Toll-like receptors (TLRs), and chronic HBV infection. TLRs are the key sensing molecules that detect pathogen-associated molecular patterns and regulate the induction of pro- and anti-inflammatory cytokines, thereby shaping the adaptive immunity. The suppression of TLR response has been reported in patients with chronic hepatitis B (CHB), as well as in other models, including tree shrews, suggesting an association of TLR response in HBV chronicity. Additionally, TLR agonists have been reported to improve the host innate immune response against HBV infection, highlighting the potential of these agonists as immunomodulators for enhancing CHB treatment. In this study, we discuss the current understanding of host innate immune responses during HBV infection, particularly focusing on the TLR response and TLR agonists as immunomodulators.

Viral infection is a global public health threat causing millions of deaths. A suitable small animal model is essential for viral pathogenesis and host response studies that could be used in antiviral and vaccine development. The tree shrew (Tupaia belangeri or Tupaia belangeri chinenesis), a squirrel-like non-primate small mammal in the Tupaiidae family, has been reported to be susceptible to important human viral pathogens, including hepatitis viruses (e.g., HBV, HCV), respiratory viruses (influenza viruses, SARS-CoV-2, human adenovirus B), arboviruses (Zika virus and dengue virus), and other viruses (e.g., herpes simplex virus, etc.). The pathogenesis of these viruses is not fully understood due to the lack of an economically feasible suitable small animal model mimicking natural infection of human diseases. The tree shrew model significantly contributes towards a better understanding of the infection and pathogenesis of these important human pathogens, highlighting its potential to be used as a viable viral infection model of human viruses. Therefore, in this review, we summarize updates regarding human viral infection in the tree shrew model, which highlights the potential of the tree shrew to be utilized for human viral infection and pathogenesis studies.

Objective We evaluated whether ivermectin combined with doxycycline reduced the clinical recovery time in adults with COVID-19 infection. Methods This was a randomized, blinded, placebo-controlled trial in patients with mild-to-moderate COVID-19 symptoms randomly assigned to treatment (n = 200) and placebo (n = 200) groups. The primary outcome was duration from treatment to clinical recovery. Secondary outcomes were disease progression and persistent COVID-19 positivity by RT-PCR. Results Among 556 screened patients, 400 were enrolled and 363 completed follow-up. The mean patient age was 40 years, and 59% were men. The median recovery time was 7 (4–10, treatment group) and 9 (5–12, placebo group) days (hazard ratio, 0.73; 95% confidence interval, 0.60–0.90). The number of patients with a ≤7-day recovery was 61% (treatment group) and 44% (placebo groups) (hazard ratio, 0.06; 95% confidence interval, 0.04–0.09). The proportion of patients who remained RT-PCR positive on day 14 and whose disease did not progress was significantly lower in the treatment group than in the placebo group. Conclusions Patients with mild-to-moderate COVID-19 infection treated with ivermectin plus doxycycline recovered earlier, were less likely to progress to more serious disease, and were more likely to be COVID-19 negative by RT-PCR on day 14. Trial Registration ClinicalTrials.gov Identifier: NCT04523831. Data Repository ID Dryad. doi:10.5061/dryad.qjq2bvqf6

Koala retrovirus (KoRV) poses a major threat to koala health and conservation, and currently has 10 identified subtypes: an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). However, subtype-related variations in koala immune response to KoRV are uncharacterized. In this study, we investigated KoRV-related immunophenotypic changes in a captive koala population (Hirakawa zoo, Japan) with a range of subtype infection profiles (KoRV-A only vs. KoRV-A with KoRV-B and/or -C), based on qPCR measurements of CD4, CD8b, IL-6, IL-10 and IL-17A mRNA expression in unstimulated and concanavalin (Con)-A-stimulated peripheral blood mononuclear cells (PBMCs). Although CD4, CD8b, and IL-17A expression did not differ between KoRV subtype infection profiles, IL-6 expression was higher in koalas with exogenous infections (both KoRV-B and KoRV-C) than those with the endogenous subtype only. IL-10 expression did not significantly differ between subtype infection profiles but did show a marked increase&mdash, accompanying decreased CD4:CD8b ratio&mdash, in a koala with lymphoma and co-infected with KoRV-A and -B, thus suggesting immunosuppression. Taken together, the findings of this study provide insights into koala immune response to multiple KoRV subtypes, which can be exploited for the development of prophylactic and therapeutic interventions for this iconic marsupial species.

Disruption of the KEAP1-NRF2 pathway results in the transactivation of NRF2 target genes, consequently inducing cell proliferation and other phenotypic changes in cancer cells. Here, we demonstrated that GULP1 was a KEAP1-binding protein that maintained actin cytoskeleton architecture and helped KEAP1 to sequester NRF2 in the cytoplasm. In urothelial carcinoma of the bladder (UCB), silencing of GULP1 facilitated the nuclear accumulation of NRF2, led to constitutive activation of NRF2 signaling, and conferred resistance to the platinum drug cisplatin. Knockdown of GULP1 in UCB cells promoted tumor cell proliferation in vitro and enhanced tumor growth in vivo. In primary UCB, GULP1 silencing was more prevalent in muscle-invasive UCB compared to nonmuscle-invasive UCB. GULP1 knockdown cells showed resistance to cisplatin treatment. In parallel with decreased GULP1 expression, we observed increased expression of NRF2, HMOX1, and other candidate antioxidant genes in cisplatin-resistant cells. Furthermore, low or no expression of GULP1 was observed in most cisplatin nonresponder cases. Silencing of GULP1 was associated with GULP1 promoter hypermethylation in cell lines and primary tumors, and a high frequency of GULP1 promoter methylation was observed in multiple sets of primary clinical UCB samples. Together, our findings demonstrate that GULP1 is a KEAP1-binding protein that regulates KEAP1-NRF2 signaling in UCB and that promoter hypermethylation of GULP1 is a potential mechanism of GULP1 silencing.

Chronic hepatitis B virus (HBV) infection constitutes a global health issue with limited current therapeutic efficacy owing to the persistence of viral episomal DNA (cccDNA). The CRISPR/Cas9 system, a newly developed, powerful tool for genome editing and potential gene therapy, requires efficient delivery of CRISPR components for successful therapeutic application. Here, we investigated the effects of lentiviral- or adeno-associated virus 2 (AAV2) vector-mediated delivery of 3 guide (g)RNAs/Cas9 selected from 16 gRNAs. These significantly suppressed HBV replication in cells, with WJ11/Cas9 exhibiting highest efficacy and chosen for in vivo study. AAV2/WJ11-Cas9 also significantly inhibited HBV replication and significantly reduced cccDNA in the tested cells. Moreover, AAV2/WJ11-Cas9 enhanced entecavir effects when used in combination, indicative of different modes of action. Notably, in humanized chimeric mice, AAV2/WJ11-Cas9 significantly suppressed HBcAg, HBsAg, and HBV DNA along with cccDNA in the liver tissues without significant cytotoxicity; accordingly, next generation sequencing data showed no significant genomic mutations. To our knowledge, this represents the first evaluation of the CRISPR/Cas9 system using an HBV natural infection mode. Therefore, WJ11/Cas9 delivered by comparatively safer AAV2 vectors may provide a new therapeutic strategy for eliminating HBV infection and serve as an effective platform for curing chronic HBV infection.

Objective:To estimate the economic burden of overweight in Bangladesh.Design:We used data from Household Income and Expenditure Survey, 2010. A prevalence-based approach was used to calculate the population attributable fraction (PAF) for diseases attributable to overweight. Cost of illness methodology was used to calculate annual out of pocket (OOP) expenditure for each disease using nationally representative survey data. The cost attributable to overweight for each disease was estimated by multiplying the PAF by annual OOP expenditure. The total cost of overweight was estimated by adding PAF-weighted costs of treating the diseases.Setting:Nationwide, covering the whole of Bangladesh.Participants:Individuals whose BMI ≥ 25 kg/m2.Results:The total cost attributable to overweight in Bangladesh in 2010 was estimated at US$147·38 million. This represented about 0·13 % of Bangladesh’s Gross Domestic Product and 3·69 % of total health care expenditure in 2010. The sensitivity analysis revealed that the total cost could be as high as US$334 million or as low as US$71 million.Conclusions:A substantial amount of health care resource is devoted to the treatment of overweight-related diseases in Bangladesh. Effective national strategies for overweight prevention programme should be established and implemented.

Avian-origin influenza viruses like H5N1 and H7N9 often cause severe symptoms with high mortality in humans. Animal models are useful for clarification of the mechanisms of pathogenicity of these infections. In this study, to expand the potential utility of the Northern tree shrew (Tupaia belangeri) for influenza virus infection, we assessed the pathogenicity of H5N1 and H7N9 avian influenza viruses in tupaia. Infectious virus was detected continuously from nasal, oral, tracheal, and conjunctival swab samples in the animals infected with these viruses. H5N1 influenza virus infection of tupaia caused severe diffuse pneumonia with fever and weight loss. In contrast, H7N9 influenza virus infection caused focal pneumonia. The severity of pneumonia was correlated with proinflammatory cytokine transcript levels. These results indicated that tupaia can be another suitable animal model for avian influenza virus research.

Cervical cancer is the fourth most common cancer among women worldwide, with approximately 70% of cases involving infection with human papillomavirus (HPV) genotypes 16 and 18. According to International Agency for Research on Cancer, more than 50 million Bangladeshi women are at risk of developing cervical cancer, and 17 686 new cases and 10 362 deaths occur annually. If diagnosed at the precursor stage, however, cervical cancer is a condition that can be successfully treated. As a result, screening programs are necessary to identify the disease before it progresses to invasive cancer. In the present review, we discuss the overall situation of cervical cancer in Bangladesh, summarizing the sociodemographic status of affected women, associated risk factors, screening approaches, and treatment options. We emphasize the potential of visual inspection with acetic acid (VIA) as a cost-effective screening approach for detecting cervical lesions among poor women in the community. In a resource-limited country such as Bangladesh, VIA may represent an ideal model to build an effective awareness campaign through urban and rural hospitals, community-based clinics, and other health facilities available in industry.

Mammary gland cancer is the most common cancer occurring in women globally. Incidences of this cancer in Japan are on the increase. Annually, more than 70,000 new cases are recorded in Japan and about 1.7 million in the world. Many cases are still difficult to cure completely, and animal models are required for the characterization of the biology, therapeutic strategy, and preventive measures for spontaneous mammary tumor. The mouse model used currently has some limitations owing to structural differences between mouse and human mammary glands. Tupaia belangeri (tree shrew), which belongs to the Tupaiidae family, shows relatively high genetic homology and structural similarity to human mammary glands. Here, we characterized the spontaneous mammary tumors in 61 female tree shrews of different ages. The incidence rate was 24.6% (15/61), and the rate of simultaneous or metachronous multiplex tumors was 60% (9/15). From the incidence pattern, some cases seemed to be of familial mammary gland tumor, as the offspring of female tree shrews No. 3 and 9 and male tree shrew No. 11 showed a high incidence rate, of 73.3% (11/15). Average incidence age for tumor development was 2 years and 3 months, and the earliest was 10 months. Histochemical analysis indicated that spontaneous mammary gland tumors in the tree shrew show the features of intraductal papillary adenomas (22 cases), except 2 tubulopapillary carcinoma cases (No. 75 and 131). All the cases were positive for the progesterone receptor, whereas 91.3% were positive for the estrogen receptor, and 4.3% were HER-2 positive. We have also confirmed the expression of nectin-4 in some mammary tumor cells. Additionally, we subjected tree shrews to cytodiagnosis or X-ray CT. Thus, the findings of this study highlight the potential of the tree shrew as a valuable new animal model for mammary gland tumor study.

Background: Tumour registry data on intracranial and intraspinal tumours from a newly set up tertiary hospital of Bangladesh is presented here to provide substantial information about the current trends. Materials & methods: Hospital records of patients admitted under the neurosurgery service between January 2016 upto December 2017 were evaluated. Causes with a principal diagnosis of brain and spinal cord tumours were identified. Diagnosis with WHO grading and the histological subtypes are recorded. Results: 86 cases of various tumours were retrieved out of total 98 neurosurgical cases. 70 of these tumours were of intracranial origin and 16 of intraspinal origin. Male to female ratio was approximately 1.28:1. The mean age of the patients was 45.9 years (range 3-75 years). Paediatric and adult patients accounted for 12.6% and 87.4% respectively. Most of the tumours were found in the 6th decade. Paediatric intracranial tumours were predominately by medulloblastoma while adult population showed highest incidence of astrocytic tumours. Some rare entities were also encountered such as intracranial germinoma, Diffuse large B cell lymphoma (DLBCL) and squamous cell carcinoma in a pre-existing intracranial epidermoid cyst. Conclusions: Distribution of CNS tumour among this population gives a glimpse of the prevalence rate of such tumours in our community. This data can be linked to other national and international tumour registry for improved therapeutics and research. J MEDICINE JUL 2019; 20 (1) : 34-37

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer mortality worldwide. Infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is the most predominant cause of HCC. Concerns arise for the presence of additional risk factors, as there is still a large proportion of patients without HBV or HCV infection. Previous studies have reported that higher intake of fruits and vegetables and reduced consumption of red/processed meat might play a protective role in HCC etiology, though the nationwide proof is limited. Hence, we studied multiple risk factors including food habit, lifestyle, and clinical implications of HCC patients in Bangladeshi. Demographic, clinical, and biochemical data, as well as data on food habits, were collected in this study. Our results indicated that a high intake of rice (AOR 4.28, 95% CI 1.48 to 14.07, p = 0.011), low intake of fruits (AOR = 4.41 95% CI 1.48-15.46; p = 0.012), leafy vegetables (AOR = 2.80, 95% CI 1.32-6.08; p = 0.008), and fish (AOR = 4.64 95% CI 2.18-10.23; p

Many epigenetically inactivated genes involved in ovarian cancer (OC) development and progression remain to be identified. In this study we undertook an integrated approach that consisted of identification of genome-wide expression patterns of primary OC samples and normal ovarian surface epithelium along with a pharmacologic unmasking strategy using 3 OC and 3 immortalized normal ovarian epithelial cell lines. Our filtering scheme identified 43 OC specific methylated genes and among the 5 top candidates (GULP1, CLIP4, BAMBI, NT5E, TGFβ2), we performed extended studies of GULP1. In a training set, we identified GULP1 methylation in 21/61 (34%) of cases with 100% specificity. In an independent cohort, the observed methylation was 40% (146/365) in OC, 12.5% (2/16) in borderline tumors, 11% (2/18) in cystadenoma and 0% (0/13) in normal ovarian epithelium samples. GULP1 methylation was associated with clinicopathological parameters such as stage III/IV (p = 0.001), poorly differentiated grade (p = 0.033), residual disease (p

This study was conducted to investigate the antioxidant, antibacterial, anthelmintic, and cytotoxic activities of the crude methanol extract of Bonamia semidigyna (Roxb.) leaves and its derived fractions in different experimental models. Leaves of B. semidigyna were extracted with methanol (MBS) and the resultant successively fractionated into n-hexane (NBS), petroleum ether (PBS), chloroform (CBS), and ethyl acetate (EBS) soluble fractions. Later, the plant extractives were investigated for antioxidant, antibacterial, anthelmintic and cytotoxic properties. Phytochemical study was carried out using standard methods and polyphenols content were determined by spectrophotometric techniques. Antioxidant activity was evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity, hydrogen peroxide (H2O2) scavenging activity, ferric reducing power, and total antioxidant capacity assays. Disc diffusion technique used to evaluate the antibacterial efficacy and anthelmintic activity was determined using aquarium worm (Tubifex tubifex) whereas cytotoxicity was evaluated using brine shrimp lethality bioassay. The phytochemical study revealed the presence of alkaloids, flavonoids, terpenoids, tannins, saponins, phenolic, steroids, sterols, quinones, oxalate, coumarins, and emodins in the plant extractives. In addition, the quantitative phytochemical analysis showed the significant amount of polyphenol contents. In antioxidant assays, the crude methanol extract and EBS fraction exhibited the most potent antioxidant activity among all the extractives. The crude methanol extract and EBS fraction also possessed significant antibacterial and anthelmintic potentials while moderate cytotoxic activities were found for all the plant extractives. The present study confirmed that the crude methanol extract of B. semidigyna and its EBS fraction, possibly due to its high polyphenol contents possess significant antioxidant, antibacterial, and anthelmintic properties.

Acute respiratory illness, primarily pneumonia, is the main cause of mortality in children under five years in most developing countries - result in 1.9 million deaths each year. To reduce mortality from these diseases, WHO introduced case management guidelines based on simple clinical signs for diagnosing pneumonia followed by empirical treatment with antibiotics. For management purposes, pneumonia is subclassified according to its severity by using general danger sign, chest indrawing or fast breathing. But these factors are influenced by malaria, meningitis, hyperactive airway disorder, bronchiolitis and fever. So clinical profile and their chest radiographs were analyzed in children aged 2-59 months who presented to a health facility with severe pneumonia using WHO guidelines. The purpose was to observe the clinical profile, evaluate radiological features of severe pneumonia and also to correlate the efficacy of clinical criteria with that of radiological findings. The study was conducted under the department of Pediatrics, Mymensingh Medical College Hospital and the samples were collected from the Inpatient department of Pediatrics in this hospital. It was a cross sectional observational study. 100 consecutive samples were collected from mothers with their children aged 2-59 months who met the inclusion criteria. Out of 100 children 56 were male and 44 were female children and male female ratio was 1.3:1. Majority (66%) of the children were partially immunized, 37% children were fully immunized and only 7% children were unimmunized as per EPI schedule. 42% of the children were malnourished and 13% were severely malnourished. Regarding clinical presentation all the patients presented with fever with cough (100%), 88% with difficult breathing, 11% had wheeze and 25% presented with general danger signs. Among the physical signs' temperature raised in 92%, Chest indrawing in 88%, flaring of alaenasi 78%, central cyanosis in 15%, pallor in 28%, stridor in 3%, bulged fontanel in 2% cases and BCG scar present in 65% of the cases. Clinical diagnosis of the studied cases revealed bronchiolitis in 31%, lobar pneumonia in 23%, bronchopneumonia in 27%, asthma in 12% and pulmonary tuberculosis in 7% cases. Routine examination of blood revealed 70% children were mild to moderately pale, 63% leukocytosis, 52% neutrophilic leukocytosis, 15% lymphocytic leukocytosis, ESR was raised in 52% of cases. Chest X-ray showed normal skiagram in 36%, consolidation in 23%, bronchopneumonia in 16%, nonspecific infection in 17% and hilar lymphadenopathy in 7% cases. 12% patients responded with ampicillin alone, 30% required gentamicin in addition, 39% required cloxacillin in addition to ampicillin and gentamicin, only ceftriaxone in 12% and 7% cases required anti tubercular treatment. Steroid used in 30% cases and bronchodilator in 42% cases. Immediate hospital outcome of these patients showed 78% cases improved, 12% patients left hospital against medical advice and 8% patients died in the hospital. CBMJ 2018 July: Vol. 07 No. 02 P: 24-33

Most cancers are genetically heterogeneous diseases, and many genes or gene products have altered their expressions or activities in cancer cells due to a variety of genetic and epigenetic mechanisms in DNA. Copy number aberrations (CNAs), common genomic events during carcinogenesis, are known to affect a large fraction of genome and extensively studied for last several decades.

YAP1 is one of the most important effectors of the Hippo pathway and has crosstalk with other cancer promoting pathways. YAP1 contributes to cancer development in various ways that include promoting malignant phenotypes, expansion of cancer stem cells and drug resistance of cancer cells. Because pharmacologic or genetic inhibition of YAP1 suppresses tumor progression and increases the drug sensitivity, targeting YAP1 may open a fertile avenue for a novel therapeutic approach in relevant cancers. Recent enormous studies have established the efficacy of immunotherapy, and several immune checkpoint blockades are in clinical use or in the phase of development to treat various cancer types. Immunosuppression in the tumor microenvironment (TME) induced by cancer cells, immune cells and associated stromal cells promotes tumor progression and causes drug resistance. Accumulated evidences of scientific efforts from the last few years suggest that YAP1 influences macrophages, myeloid-derived suppressor cells and regulatory T-cells to facilitate immunosuppressive TME. Although the underlying mechanisms is not clearly discerned, it is evident that YAP1 activating pathways in different cellular components induce immunosuppressive TME. In this review, we summarize the evidences involved in the dual roles of YAP1 in cancer development and immunosuppression in the TME. We also discuss the possibility of YAP1 as a novel therapeutic target.

It remains unclear whether PAX6 acts as a crucial transcription factor for lung cancer stem cell (CSC) traits. We demonstrate that PAX6 acts as an oncogene responsible for induction of cancer stemness properties in lung adenocarcinoma (LUAD). Mechanistically, PAX6 promotes GLI transcription, resulting in SOX2 upregulation directly by the binding of GLI to the proximal promoter region of the SOX2 gene. The overexpressed SOX2 enhances the expression of key pluripotent factors (OCT4 and NANOG) and suppresses differentiation lineage factors (HOPX and NKX2-1), driving cancer cells toward a stem-like state. In contrast, in the differentiated non-CSCs, PAX6 is transcriptionally silenced by its promoter methylation. In human lung cancer tissues, the positive linear correlations of PAX6 expression with GLI and SOX2 expression and its negative correlations with HOPX and NKX2-1 expression were observed. Therapeutically, the blockade of the PAX6-GLI-SOX2 signaling axis elicits a long-lasting therapeutic efficacy by limiting CSC expansion following chemotherapy. Furthermore, a methylation panel including the PAX6 gene yielded a sensitivity of 79.1% and specificity of 83.3% for cancer detection using serum DNA from stage IA LUAD. Our findings provide a rationale for targeting the PAX6-GLI-SOX2 signaling axis with chemotherapy as an effective therapeutic strategy and support the clinical utility of PAX6 gene promoter methylation as a biomarker for early lung cancer detection.

Aims: Coronary artery disease is a devastating disease precisely because an otherwise healthy person in the prime of life may die or become disabled without warning. The objectives were to study the clinical profile, risk factors prevalence, angiographic distribution and severity of coronary artery stenosis in acute coronary syndrome (ACS) patients admitted in Cardiology Department of Dhaka Medical College Hospital, Dhaka.Materials and Methods: A total of 800 patients of ACS were analyzed for various risk factors, angiographic patterns and severity of coronary artery disease at DMCH, Dhaka, Bangladesh.Results: Mean age of presentation was 51.27±8.80 years. Majority were male 628 (78.5%) and rest were females (21.5%). Most patients had ST elevated myocardial infarction (STEMI) 509 (63.6%) followed by non-STEMI (NSTEMI) 207 (25.9%) and Unstable Angina (UA) 84 (10.5%). Risk factors: smoking was present in 388 (48.5%), hypertension in 289 (36.13%), diabetes in 235 (29.38%), dyslipidaemia in 169 (21.13%) and obesity in 356 (44.5%) patients. Singlevessel disease was present in 30.32% patients, Doublevessel disease was present in 23.23% patients and Triple vessel disease was present in 27.15% patients.Conclusion: STEMI was the most common presentation. ACS occurred earlier in comparison to Western population. Smoking was most prevalent risk factor. Diabetic patients had more multivessel disease.Bangladesh Heart Journal 2018; 33(1) : 10-15