Physical activity and its correlates among school teachers in a semi-urban district of Nepal.

Regular physical activity (PA) is one of the effective strategies for mitigating non-communicable diseases, promoting healthy ageing, and preventing premature mortality. In South Asia, up to 34.0% of adults are insufficiently active, and up to 44.1% of adults in Nepal. We sought to assess self-reported PA status and its correlates among teachers in the semi-urban district of Nepal. A cross-sectional descriptive study was conducted among teachers at randomly selected public secondary schools in Bhaktapur, Nepal, from November 2018-April 2019. PA status was assessed in Metabolic Equivalent to task minutes per week using the International Physical Activity Questionnaire (IPAQ)-Long Form. Point estimates and odds ratios were calculated at a 95% confidence interval, and a p-value <0.05 was considered statistically significant. Among the 360 participants, the mean (SD) age was 40.3 (10.2) years, with 52.5% female participation. A low level of PA was seen among 11.9% (95% CI: 8.4-15.2) of teachers, and more than half (56.0%) of the activity was only moderate intensity. Domestic and garden work was the main contributor (43.0%) of total PA, while leisure time was the least (14.0%). Among the socio-demographic factors, only sex was significantly associated (p = 0.005) with PA. Participants living in locations with walkable areas were 3.4 times (95% CI: 1.6-7.3) more likely to be engaged in moderate-to-high level PA than those without. In our study, the point prevalence of insufficient PA among teachers working at public secondary schools was higher than the national point prevalence. PA promotion programs targeting sedentary populations like school teachers should be developed to reduce the point prevalence of insufficient PA.

Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid.

Transglutaminase 2 (TG2) is a multifunctional protein that promotes or suppresses tumorigenesis, depending on intracellular location and conformational structure. Acyclic retinoid (ACR) is an orally administered vitamin A derivative that prevents hepatocellular carcinoma (HCC) recurrence by targeting liver cancer stem cells (CSCs). In this study, we examined the subcellular location-dependent effects of ACR on TG2 activity at a structural level and characterized the functional role of TG2 and its downstream molecular mechanism in the selective depletion of liver CSCs. A binding assay with high-performance magnetic nanobeads and structural dynamic analysis with native gel electrophoresis and size-exclusion chromatography-coupled multi-angle light scattering or small-angle X-ray scattering showed that ACR binds directly to TG2, induces oligomer formation of TG2, and inhibits the transamidase activity of cytoplasmic TG2 in HCC cells. The loss-of-function of TG2 suppressed the expression of stemness-related genes, spheroid proliferation and selectively induced cell death in an EpCAM+ liver CSC subpopulation in HCC cells. Proteome analysis revealed that TG2 inhibition suppressed the gene and protein expression of exostosin glycosyltransferase 1 (EXT1) and heparan sulfate biosynthesis in HCC cells. In contrast, high levels of ACR increased intracellular Ca2+ concentrations along with an increase in apoptotic cells, which probably contributed to the enhanced transamidase activity of nuclear TG2. This study demonstrates that ACR could act as a novel TG2 inhibitor; TG2-mediated EXT1 signaling is a promising therapeutic target in the prevention of HCC by disrupting liver CSCs.

Hepatic stellate cell stearoyl co-A desaturase activates leukotriene B4 receptor 2 - ß-catenin cascade to promote liver tumorigenesis.

Hepatocellular carcinoma (HCC) is the 3rd most deadly malignancy. Activated hepatic stellate cells (aHSC) give rise to cancer-associated fibroblasts in HCC and are considered a potential therapeutic target. Here we report that selective ablation of stearoyl CoA desaturase-2 (Scd2) in aHSC globally suppresses nuclear CTNNB1 and YAP1 in tumors and tumor microenvironment and prevents liver tumorigenesis in male mice. Tumor suppression is associated with reduced leukotriene B4 receptor 2 (LTB4R2) and its high affinity oxylipin ligand, 12-hydroxyheptadecatrienoic acid (12-HHTrE). Genetic or pharmacological inhibition of LTB4R2 recapitulates CTNNB1 and YAP1 inactivation and tumor suppression in culture and in vivo. Single cell RNA sequencing identifies a subset of tumor-associated aHSC expressing Cyp1b1 but no other 12-HHTrE biosynthetic genes. aHSC release 12-HHTrE in a manner dependent on SCD and CYP1B1 and their conditioned medium reproduces the LTB4R2-mediated tumor-promoting effects of 12-HHTrE in HCC cells. CYP1B1-expressing aHSC are detected in proximity of LTB4R2-positive HCC cells and the growth of patient HCC organoids is blunted by LTB4R2 antagonism or knockdown. Collectively, our findings suggest aHSC-initiated 12-HHTrE-LTB4R2-CTNNB1-YAP1 pathway as a potential HCC therapeutic target.

Bulbar Onset Amyotrophic Lateral Sclerosis: A Case Report.

Amyotrophic lateral sclerosis is a rare, progressive, incurable neurodegenerative disorder that affects motor neurons leading to progressive muscle weakness, disability, and eventually death. A 45-year-old male, initially presented with hoarseness, flickering of tongue, and intermittent aspirations. In course of three years, patient developed motor aphasia, frequent aspirations and an inability to hold his neck. Patient was diagnosed with a bulbar onset type of amyotrophic lateral sclerosis on the basis of neurodegenerative features with normal radiographic imaging. For the prevention of recurrent aspiration pneumonia, he was managed with a percutaneous endoscopic gastrostomy tube. As he started developing respiratory failure tracheostomy was performed and kept on a continuous bi-level positive airway pressure ventilator, in the meantime, two courses of injection Edaravone were given. Early evaluation, diagnosis and management of the condition is a cornerstone for better prognosis of disease and survival. Keywords: amyotrophic lateral sclerosis; aspiration pneumonia; case reports; edaravone.

A case of giant primary splenic hydatid cyst: Case report.

Introduction: Primary splenic hydatidosis is a rare zoonotic disease, common in grazing regions of the world. Primary splenic hydatid cyst is rare and accounts for <2% of patients. Splenectomy is advocated in case of giant hydatid cyst locating in central and hilum area; however, spleen salvaging operations are done in superficial cyst, cysts localized to one pole of the spleen or cysts that are unresectable due to extensive adhesions and in children. Presentation of case: We present a case of 29-year male patient from rural areas presented with the complain of left hypochondriac pain and tenderness along with the history of farming and cattle raising. There was no other significant history. Clinical findings and investigations: Physical examination showed mildly distended abdomen, mild tenderness over left hypochondrium. Routine laboratory investigations were sent. Ultrasound and CT scan of the abdomen showed giant splenic cyst measuring approx. 15 × 14 × 11 cm along with daughter cysts. Postoperatively, cyst was sent for histopathological examination. Intervention and outcome: Preoperatively, vaccinations against Pneumococcus, Hemophilus influenzae and Meningococcus along with Albendazole (15 mg/kg/day) was given 2 weeks before the planned operation. Total splenectomy was performed and diagnosis was confirmed by histopathological examination. Albendazole was continued for 2 more weeks. Patient remains asymptomatic thereafter and regularly followed up in OPD basis. Relevance and impact: Presence of isolated splenic cyst should raise suspicion for primary splenic hydatid cyst in endemic areas. Splenectomy versus spleen salvaging options should be analyzed and performed as per the indications. Splenic hydatid cyst is one of the rare clinical findings and there is very much high chance that it goes undiagnosed during the clinical practice. So, the main motive behind writing this article is to shed knowledge on basic approach to this splenic finding.

Effect of Educational Intervention Based on Theory of Planned Behaviour on Physical Activity Intention among Secondary School Teachers of Nepal.

Any bodily movement produced by skeletal muscle which requires energy expenditure is known as physical activity (PA). WHO has recommended that at least 150 minutes of moderate or 75 minutes of vigorous-intensity PA or a combination of both per week is required for health benefits. Physical inactivity is one of the strongest risk factors for noncommunicable diseases (NCDs) and other conditions and is attributable to 6% of global premature death. However, data on the PA of teachers are unavailable in Nepal. They are considered one of the risk groups for NCDs because of the less active nature of their job. So, we aimed to evaluate the effect of the educational intervention based on the theory of planned behaviour on PA intention among secondary school teachers in Bhaktapur district, Nepal. For this study, we recruited 126 teachers from 6 schools. Each intervention and control group contained three randomly selected secondary schools. All the teachers from the selected schools were enrolled in the respective groups. A quasiexperimental (pretest-posttest control group) study design was used to test the effectiveness of the intervention on attitude, behaviour control, subjective norms, and intention for engaging in regular PA. Both groups underwent baseline and follow-up assessments at four weeks using the self-administered questionnaire developed for this study. The intervention group delivered a one-hour lecture session supported by audio-video materials for PA promotion. The effect was analysed by comparing the changes in the theory of planned behaviour (TPB) constructs within and between intervention and control groups. The difference in scores between and within the groups was tested using Student's t-test. Adjusted difference-in-difference scores were calculated through linear regression. Data analysis was done using Statistical Package for Social Science version 26.0. The adjusted mean score increase in TPB constructs due to the interaction of time and intervention increased from 0.641 to 1.381. The highest gain (beta = 1.381) was seen in the intention score, while a minor improvement was seen in perceived behavioural control (beta = 0.641). After the intervention, the net increase in PA intention score was 9.35% compared to the control group. Thus, the promotion package was effective in increasing PA intention. The findings of this study and educational package could be helpful in encouraging teachers to engage in PA in other schools.

Screen time and its correlates among children aged 3-10 years during COVID-19 pandemic in Nepal: a community-based cross-sectional study.

OBJECTIVE: This study aims to determine the prevalence of high screen time among schoolchildren aged 3-10 years in Bhaktapur, its correlates and the parents' strategies to reduce screen time during the COVID-19 pandemic in Nepal. METHODS AND ANALYSIS: This cross-sectional descriptive study was conducted during March 2021. A total of 630 households were selected for the study from 21 randomly selected clusters in Bhaktapur, Nepal. Correlates of high screen time were determined using a logistic model. P<0.002 was taken as significant. RESULTS: Among all the participants, the mean (SD) age was 7.0 (2.2) years, with 50.3% male participation. Few participants had online classes (n=24, 3.8%). The prevalence of high screen time among the participants was very high (55.2%, 95% CI=51.3% to 59.1%), which is even higher in boys (61.8%, 95% CI=58.0% to 65.6%). The median screen time before the COVID-19 pandemic was 1.0 hours (mean rank=275.8) which increased to 2.2 hours (mean rank=116.6) during the pandemic (p<0.001). Participants having smartphones were about seven times (adjusted OR=6.9, 95% CI=1.5 to 31.3, p=0.013) more likely to have high screen time than those who did not have the device. Most parents used to reprimand and urge their children to play outside to limit their screen usage. CONCLUSION: During the COVID-19 pandemic, about one in two schoolchildren of 3-10 years had higher screen time than before the COVID-19 pandemic. Parents' strategies to reduce screen time were not effective. An intervention study is recommended to design and test effective strategies to reduce screen time and its negative effects on children's health.

Burden and Risk Factors of Diabetic Retinopathy Among Diabetic Patients Attending a Multispecialty Tertiary Eye Hospital in Nepal.

INTRODUCTION: As the number of people with diabetes mellitus is increasing because of urbanization and change in dietary habits and sedentary lifestyle, the number of diabetic retinopathy is also expected to increase in future. [1] [sa2] We aimed to find out the prevalence of diabetic retinopathy and associated risk factors among diabetic patients in the tertiary eye hospital. MATERIALS AND METHODS: This is the observational cross-sectional study enrolling 420 diabetic patients visiting the multispecialty tertiary eye hospital between March 2020 and February 2021. Anthropometry measurement, laboratory risk profiles and blood pressure were recorded Results: The prevalence of any diabetic retinopathy, proliferative diabetic retinopathy, and diabetic macular edema were 30.96 %, 6.19 %, and 5.95 % respectively. The duration of DM (p=0.001), hypertension (p=0.04), high SBP (p=0.023), abdominal obesity (p=0.015), high LDL(p=0.011) cholesterol, low HDL cholesterol(p=0.012), and creatinine (p=0.001) were associated with DR in our study. CONCLUSION: A holistic approach should target to control the modifiable risk factors like blood sugar, blood pressure, lipid profile, kidney function, and obesity to prevent DR. Anthropometric assessment of waist to height and waist circumference should be included in the holistic health promotion strategy in Nepal as BMI may not be risk factors for DR in Nepalese people.

Abdominal Obesity among Outpatients in a Tertiary Level Eye ENT Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Abdominal obesity, as abnormal fat accumulation that presents a risk to health, is a global epidemic. There is evidence to support a trait of abdominal adipose deposition despite normal body mass index in south asian populations with greater cardiometabolic risks. Thus, this study aimed to find out the prevalence of abdominal obesity using the waist to height ratio among outpatients in a tertiary level hospital. METHODS: This descriptive cross-sectional study was conducted among outpatients at a tertiary level hospital in Nepal from January 2016 to December 2018. Ethical approval was taken from the Ethical Review Board of Nepal Health Research Council (Reference no. 207/2019). Convenience sampling was done. The data were entered into excel and analyzed using Statistical Package for Social Sciences version 24. Point estimate at 99% confidence interval was calculated along with frequency and proportion for binary data. RESULTS: Among 25,511 participants, 21,834 (85.6%) (85.0- 86.2 at 99% Confidence Interval) participants had abdominal obesity using Waist-to-Height Ratio, higher in women 12,397 (86.4%) than men 9,437 (84.5%). The mean age of the participants was 53.37±13.15 years and more than half 17,075 (55.7%) of all participants were female. CONCLUSIONS: The prevalence of abdominal obesity among hospital outpatients is higher than in other community-based studies. As hospitals attract large crowds and provide excellent opportunities for screening patients, their attendants, as well as providing opportunities for health promotion, we recommend the introduction of opportunistic obesity screening in all health facilities using weight to height ratio in a phased manner.

Diabetes Mellitus among Adult Outpatients Visiting a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Diabetes mellitus is a chronic metabolic disease characterised by elevated blood sugar levels and is a pandemic of public health importance. Screening programs can help reduce morbidity and mortality by preventing or delaying complications. This study aimed to find out the prevalence of diabetes mellitus among adult outpatients visiting a tertiary care centre. Methods: This descriptive cross-sectional study was conducted among outpatients visiting a tertiary care centre between 1 January 2019 to 31 December 2019. Ethical approval was obtained from the Ethical Review Board (Registration number: 408/2020 P). Patients with unknown history of diabetes participating in free random blood sugar examinations were included in the study. Systematic random sampling was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 385 adult outpatients, 17 (4.42%) (2.37-6.47, 95% Confidence Interval) had diabetes. The mean random blood sugar level of the diabetic patients was 281.41±57.49 mg/dl. Conclusions: The prevalence of diabetes mellitus among adult outpatients was similar to previous studies conducted in similar settings. Random blood sugar test in hospital outpatient settings is feasible to identify people with diabetes mellitus. Keywords: diabetes mellitus; hospital; Nepal; outpatient.

BMI, waist to height ratio and waist circumference as a screening tool for hypertension in hospital outpatients: a cross-sectional, non-inferiority study.

OBJECTIVE: This non-inferiority study aimed to determine the burden of obesity in a hospital outpatient setting of a developing country, using three commonly employed metrics as predictors of hypertension (HTN). DESIGN: A cross-sectional study design was adopted. SETTING: This study was conducted in Health Promotion and Risk Factor Screening Services of a tertiary hospital for eye and ear, nose, throat in a semiurban area of Nepal. PARTICIPANTS: 2256 randomly selected outpatients between 40 and 69 years old. OUTCOME MEASURES: The three obesity metrics and HTN were analysed for association using correlation, the area under the receiver operating characteristic (ROC) curve and ORs. RESULTS: The prevalence of obesity or overweight by body mass index (BMI) was 58.29%; by waist-to-height ratio (WHtR) was 85.95%, high waist circumference (WC) was observed among 66.76% of participants. Female participants had a greater prevalence of high WC (77.46%) than males (53.73%) (p<0.001). Prevalence of HTN and pre-HTN were 40.67% and 36.77%, respectively. The areas under the ROC curve were significantly higher than 0.5 for BMI (0.593), WHtR (0.602) and WC (0.610). CONCLUSION: This study showed that WHtR and WC measured were not inferior to BMI as a metric for obesity detection and HTN prediction. Because of its low cost, simplicity of measurement and better ability to predict HTN, it may become a more usable metric in health facilities of low-income and middle-income countries.

Treatment Strategies in Acute Post-operative Endophthalmitis after Cataract Surgery at a Tertiary Eye Hospital in Nepal: A 5-year Retrospective Review.

INTRODUCTION: Despite best possible preventive measures, acute postoperative endophthalmitis (POE) is still the most devastating, sight-threatening complication after intraocular surgery and the most feared complication by treating surgeons. MATERIALS AND METHODS: It is a retrospective study of 22 eyes diagnosed as acute POE following cataract surgery in the last 5 years (2015-2019), aimed to evaluate the treatment strategies used in its management. Main outcome measures evaluated were rates of repeat intravitreal injection, adjunctive therapeutic regimens, pars plana vitrectomy (PPV) and visual outcome. RESULTS: Twenty one eyes (95.45%) received repeated intravitreal injection. Adjuvant intravitreal steroid was used in 12 eyes (54.54%), oral steroid in 16 eyes (72.72%) and oral antibiotic in 8 eyes (36.36%). PPV was done in 8 eyes (34.78%) and all 8 eyes that underwent PPV had a vision of Hand Movement (HM) close to face. 7 eyes (87.5%) had early PPV within 1 week of diagnosis. The median best corrected visual acuity (BCVA) improved from 1.00 logMar to 0.8 logMar following treatment at 3 months follow up (p= 0.117). CONCLUSION: Repeat intravitreal injections were commonly employed. Early PPV was performed more commonly regardless of the visual acuity at the time of diagnosis of acute POE.

Use of Intravitreal Bevacizumab Injection among Patients Undergoing Surgical Retinal Interventions at Tertiary Eye Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Intravitreal Bevacizumab injection has now become a routine procedure for retina specialists throughout the world. Easy availability of this monoclonal antibody molecule even in Nepal has brought a revolution in the management of various retinal diseases. This study aims to find out the prevalence of the use of intravitreal Bevacizumab for retinal diseases at the tertiary eye hospital. METHODS: This descriptive cross-sectional study was carried out in the retina department at a tertiary care hospital from January 2017 to December 2019 after obtaining ethical clearance from Nepal Health Research Council (Ref: 125/2020P). The sample size was calculated and the study enrolled all patients who received intravitreal Bevacizumab for retinal diseases using convenience sampling technique. Data were analyzed using Statistical Package for Social Science Version 21. Point estimate at 95% Confidence Interval was calculated, along with frequency and percentage for binary data. RESULTS: Out of 959 total surgical retinal interventions done 296 (30.86%) at 95% Confidence Interval (27.93-33.78) patients received intravitreal Bevacizumab. Out of total intravitreal Bevacizumab injections, 143 (36.7%) injections were given to retinal vein occlusions patients, 127 (32.6%) injections were given to diabetic retinopathy patients and 66 (17%) injections was given to age-related macular degeneration patients. Males 176 (59.5%) outnumbered the females 120 (40.5%) in receiving intravitreal Bevacizumab. Mean baseline Logarithm of the Minimal Angle of Resolution visual acuity, 1.1, improved to, 0.75, after 3 months of intravitreal Bevacizumab. CONCLUSIONS: Intravitreal Bevacizumab was one of the commonest retinal interventions used. Retinal vein occlusion, diabetic retinopathy, and age-related macular degeneration were the commonest retinal diseases needing intravitreal Bevacizumab.

Self-reported psychological distress during the COVID-19 outbreak in Nepal: findings from an online survey.

BACKGROUND: A lower respiratory tract infection caused by novel coronavirus termed as Corona Virus Disease (COVID-19) was first identified in China and subsequently took the form of pandemic. Studies on disease outbreak in the past and recent COVID-19 outbreak have demonstrated increased psychological distress and adverse impacts on mental health and psychological wellbeing of people. However, the impact of COVID-19 on psychological wellbeing of people in Nepal hasn't been studied adequately. So, this paper aims to report the findings from a social media survey on psychological impacts of COVID-19 in Nepal. METHODS: Data were collected through social media from 2082 Nepalese respondents between 23rd April, 2020 and 3rd May, 2020. A total of 2014 respondents who were currently residing in Nepal were included in the analysis. RESULTS: The study suggested that half of the respondents suffered from at least one symptom of psychological distress whereas 32% suffered from two or more symptoms of psychological distress such as restlessness, fearfulness, anxiety and worry and sadness in the past 2 weeks preceding the survey date. The findings further suggested that respondents having lower family income, residing in rented room, and participants from province 2 were more likely to suffer from both single and multiple symptoms of psychological distress. CONCLUSION: The study has shown high prevalence of psychological distress amongst the Nepalese respondents following COVID-19 outbreak. Appropriate mental health and psychosocial support response needs to be instituted to adequately respond to psychological impacts of the epidemic.

Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase.

We previously reported the importance of induced nuclear transglutaminase (TG) 2 activity, which results in hepatic cell death, in ethanol-induced liver injury. Here, we show that co-incubation of either human hepatic cells or mouse primary hepatocytes derived from wild-type but not TG2-/- mice with pathogenic fungi Candida albicans and C. glabrata, but not baker's yeast Saccharomyces cerevisiae, induced cell death in host cells by enhancing cellular, particularly nuclear, TG activity. Further pharmacological and genetic approaches demonstrated that this phenomenon was mediated partly by the production of reactive oxygen species (ROS) such as hydroxyl radicals, as detected by a fluorescent probe and electron spin resonance. A ROS scavenger, N-acetyl cysteine, blocked enhanced TG activity primarily in the nuclei and inhibited cell death. In contrast, deletion of C. glabrata nox-1, which encodes a ROS-generating enzyme, resulted in a strain that failed to induce the same phenomena. A similar induction of hepatic ROS and TG activities was observed in C. albicans-infected mice. An antioxidant corn peptide fraction inhibited these phenomena in hepatic cells. These results address the impact of ROS-generating pathogens in inducing nuclear TG2-related liver injuries, which provides novel therapeutic targets for preventing and curing alcoholic liver disease.

Phenosafranin inhibits nuclear localization of transglutaminase 2 without affecting its transamidase activity.

Transglutaminase 2 (TG2) localizes to the nucleus and induces apoptosis through a crosslinking inactivation of Sp1 in JHH-7 cells treated with acyclic retinoid. We screened an inhibitor suppressing transamidase activity in the nucleus without affecting transamidase activity itself. Phenosafranin was found to inhibit nuclear localization of EGFP-tagged TG2 and dose-dependently reduce nuclear transamidase activity without affecting the activity in a tube. We concluded that phenosafranin was a novel TG2 inhibitor capable of suppressing its nuclear localization.