Adverse drug reaction profile and prescription pattern of antihypertensive drug monotherapy at tertiary care hospital Nepalgunj, Nepal

Background: Hypertension is the leading cause of morbidity and mortality worldwide which requires long term therapy to prevent complication associated with it. As drugs are used for longer duration it is necessary to know potential undesirable effects for making the appropriate choice. Aim and objective of the study was to monitor the adverse drug reactions (ADRs) and to know prescribing pattern of antihypertensive monotherapy.Methods: The present work was an open, non-comparative, observational study conducted on seventy-three (73) hypertensive patients who were prescribed single antihypertensive drug at medical OPD of Nepalgunj Medical college by conducting patient interviews, recording the data on ADR monitoring form.Results: Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions (n=12), followed by diuretics (n= 6), Angiotensin converting enzyme inhibitors (n=3), β-blockers (n= 2) and Angiotensin receptor blocker (n=1). Among individual drugs, amlodipine was found to be the commonest drug associated with adverse drug reactions (n = 10). On analysis of prescription pattern again amlodipine was most commonly prescribed antihypertensive monotherapy followed by hydrochlorothiazide.Conclusions:Amlodipine was most commonly associated with ADRs and it was also most commonly prescribed antihypertensive drugs as monotherapy. The above findings would be useful for physicians in rational prescribing.

Learning Chemistry through Interactive Demonstration: A Pedagogical Perspective

This study was carried out to determine the achievement of school students in learning chemistry. Based on a quasi-experimental research strategy, this study looks at chemistry education at the secondary level. We chose three purposively selected public schools and six selected science teachers from those schools. A simple random sample was used to pick 120 students (57 females and 63 males). Generated data from CAT and CAS were examined manually and with IBM SPSS version -21. Pre-test results showed no significant differences in student performance by group or gender. Students in the experimental group performed well on the post-test, indicating that the interactive demonstration approach effectively taught chemistry. There was no need for students to act differently based on their gender, and they were all very supportive of each other's academic success. Most pupils struggle with understanding the concept of a chemical reaction. Overall, this study's findings imply that interactive demonstration substantially impacts student achievement and that gender does not play a role in student success. Thus, the interactive demonstration method (IDM) is advocated for use in the classroom to help students learn and understand the types of chemistry they will experience in their daily lives

Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change

Peer reviewe

Outcome analysis of Cohen’s cross trigonal ureteric reimplantation in paediatric age group

Introduction: Cohen’s cross trigonal ureteric reimplantation is the gold standard for surgical management of vesicoureteric reflux (VUR) in children with high success rate. The objective of this study was to evaluate and assess the outcome of open Cohen’s procedure in children with VUR.  Methods: A retrospective review of all patients with VUR who underwent Cohen’s procedure between March 2010 and February 2020 was done. The following were recorded for each patient: age, sex, grade of reflux, operative time, outcome and complications.  Results: The series consisted of 40 patients (25 girls and 15 boys) who underwent Cohen’s procedure with a mean age of 32 months (6 months to 8 years). Bilateral repairs were performed in 16 patients (40%) in the same setting and unilateral repair in 24 patients (60%). Twenty-two patients (55%) had grade IV VUR, 13 patients (32.5%) had grade V VUR and 05 patients (12.5%) had grade III VUR. Mean operative time for bilateral repairs was 249.4(200-290) minutes and 158.3(130-180) minutes for unilateral repair respectively. The mean length of hospital stay was 10.55 (7-15) days. Major complications included two persistent VURs, and one case of bladder hematoma. Postoperative ultrasound abdomen in all patients and micturating cystourethrogram in few patients was obtained, in which 38 patients (95%) had normal study. Conclusion: Cohen’s uretric reimplantation is a standard procedure in paediatric VUR. For better outcome, patient selection and refinement of operative technique should be pursued

Outcome analysis of Cohen’s cross trigonal ureteric reimplantation in paediatric age group

Introduction: Cohen’s cross trigonal ureteric reimplantation is the gold standard for surgical management of vesicoureteric reflux (VUR) in children with high success rate. The objective of this study was to evaluate and assess the outcome of open Cohen’s procedure in children with VUR.  Methods: A retrospective review of all patients with VUR who underwent Cohen’s procedure between March 2010 and February 2020 was done. The following were recorded for each patient: age, sex, grade of reflux, operative time, outcome and complications.  Results: The series consisted of 40 patients (25 girls and 15 boys) who underwent Cohen’s procedure with a mean age of 32 months (6 months to 8 years). Bilateral repairs were performed in 16 patients (40%) in the same setting and unilateral repair in 24 patients (60%). Twenty-two patients (55%) had grade IV VUR, 13 patients (32.5%) had grade V VUR and 05 patients (12.5%) had grade III VUR. Mean operative time for bilateral repairs was 249.4(200-290) minutes and 158.3(130-180) minutes for unilateral repair respectively. The mean length of hospital stay was 10.55 (7-15) days. Major complications included two persistent VURs, and one case of bladder hematoma. Postoperative ultrasound abdomen in all patients and micturating cystourethrogram in few patients was obtained, in which 38 patients (95%) had normal study. Conclusion: Cohen’s uretric reimplantation is a standard procedure in paediatric VUR. For better outcome, patient selection and refinement of operative technique should be pursued

The structure of Herpesvirus Fusion Glycoprotein B-Bilayer Complex reveals the protein-membrane and lateral protein-protein interaction

Glycoprotein B (gB) is a key component of the complex herpesvirus fusion machinery. We studied membrane interaction of two gB ectodomain forms and present an electron cryotomography structure of the gB-bilayer complex. The two forms differed in presence or absence of the membrane proximal region (MPR) but showed an overall similar trimeric shape. The presence of the MPR impeded interaction with liposomes. In contrast, the MPR-lacking form interacted efficiently with liposomes. Lateral interaction resulted in coat formation on the membranes. The structure revealed that interaction of gB with membranes was mediated by the fusion loops and limited to the outer membrane leaflet. The observed intrinsic propensity of gB to cluster on membranes indicates an additional role of gB in driving the fusion process forward beyond the transient fusion pore opening and subsequently leading to fusion pore expansion

Attitude Towards Online Education During Covid-19 Pandemic Among Bachelor Level Students of Jumla

Background: Health science students, since long time, have been using digital technology mainly for the research purposes only. Due to global spread of corona virus disease (COVID-19), education system has changed and adopted online education which was a solution for the continuity of teaching and learning process during COVID-19 pandemic. The main objective of this study was to assess the attitude towards online education among bachelor level health science students. Methods: A descriptive cross-sectional study was carried out at Karnali Academy of Health Sciences, Jumla. Complete enumeration was done. Total 68 bachelor level students were taken for the study. A pretested self administered questionnaire was used for data collection. Data were entered and analyzed by using SPSS version 16. Frequency and percentage were also computed for demographics variables. Chi-square test was applied to assess the association between socio-demographic variables and attitude level. Results: The study illustrated that, among the 68 bachelor level students, nearly two third (63.2%) students had negative attitude towards online education during COVID-19 pandemic. There was statistically significant association of attitude level with ethnicity, type of program and strength of internet connection (p≤0.05). Conclusion: Majority of students of Karnali Academy had negative attitude towards online education; and they had faced many difficulties like internet and electricity problem etc. Administration and faculty members should take necessary measures for improving online education

Osteopontin depletion in macrophages perturbs proteostasis via regulating UCHL1-UPS axis and mitochondria-mediated apoptosis

IntroductionOsteopontin (OPN; also known as SPP1), an immunomodulatory cytokine highly expressed in bone marrow-derived macrophages (BMMΦ), is known to regulate diverse cellular and molecular immune responses. We previously revealed that glatiramer acetate (GA) stimulation of BMMΦ upregulates OPN expression, promoting an anti-inflammatory, pro-healing phenotype, whereas OPN inhibition triggers a pro-inflammatory phenotype. However, the precise role of OPN in macrophage activation state is unknown.MethodsHere, we applied global proteome profiling via mass spectrometry (MS) analysis to gain a mechanistic understanding of OPN suppression versus induction in primary macrophage cultures. We analyzed protein networks and immune-related functional pathways in BMMΦ either with OPN knockout (OPNKO) or GA-mediated OPN induction compared with wild type (WT) macrophages. The most significant differentially expressed proteins (DEPs) were validated using immunocytochemistry, western blot, and immunoprecipitation assays.Results and discussionWe identified 631 DEPs in OPNKO or GA-stimulated macrophages as compared to WT macrophages. The two topmost downregulated DEPs in OPNKO macrophages were ubiquitin C-terminal hydrolase L1 (UCHL1), a crucial component of the ubiquitin-proteasome system (UPS), and the anti-inflammatory Heme oxygenase 1 (HMOX-1), whereas GA stimulation upregulated their expression. We found that UCHL1, previously described as a neuron-specific protein, is expressed by BMMΦ and its regulation in macrophages was OPN-dependent. Moreover, UCHL1 interacted with OPN in a protein complex. The effects of GA activation on inducing UCHL1 and anti-inflammatory macrophage profiles were mediated by OPN. Functional pathway analyses revealed two inversely regulated pathways in OPN-deficient macrophages: activated oxidative stress and lysosome-mitochondria-mediated apoptosis (e.g., ROS, Lamp1-2, ATP-synthase subunits, cathepsins, and cytochrome C and B subunits) and inhibited translation and proteolytic pathways (e.g., 60S and 40S ribosomal subunits and UPS proteins). In agreement with the proteome-bioinformatics data, western blot and immunocytochemical analyses revealed that OPN deficiency perturbs protein homeostasis in macrophages—inhibiting translation and protein turnover and inducing apoptosis—whereas OPN induction by GA restores cellular proteostasis. Taken together, OPN is essential for macrophage homeostatic balance via the regulation of protein synthesis, UCHL1-UPS axis, and mitochondria-mediated apoptotic processes, indicating its potential application in immune-based therapies