Previously, we reported the development of a human .sup.A gamma-globin gene lentivirus (LV), G.sup.b G, which expresses high levels of HbF to correct the sickle cell anemia (SCA) phenotype in the ...Berkeley SCA mouse model, and then modified the gamma-globin gene by substituting glycine at codon 16 with aspartic acid in the .sup.A gamma-globin gene to generate G.sup.b G.sup.M LV. In the present study, we evaluated the long-term safety of human .sup.A gamma-globin gene carrying G.sup.b G.sup.M LV in wild-type mice after primary and secondary transplants of G.sup.b G.sup.M -modified hematopoietic stem cells (HSC) over 18 months. The safety of the G.sup.b G.sup.M bone marrow transplant was assessed by monitoring the effects on body weight, hematology, histopathology, malignancy formation, and survival. Mice transplanted with Mock-transduced and spleen focus forming virus (SFFV) gamma-retroviral vector (RV)-transduced HSC served as negative and positive controls, respectively. The mean donor-cell engraftment was comparable across Mock, G.sup.b G.sup.M LV, and SFFV RV groups. There were no significant differences in body weight, clinical signs, immunophenotype, or histopathology in the G.sup.b G.sup.M -treated mice compared to controls. Four SFFV RV-treated mice, but none of the G.sup.b G.sup.M -treated mice, developed donor-derived, vector-positive lymphomas as demonstrated by flow cytometry analysis and in situ hybridization. These results highlight the safety of the administration of G.sup.b G.sup.M LV-modified HSC with long-term follow-up after primary and secondary transplants in mice. This data supported the initiation of phase 1/2 first-in-human SCA clinical trial in the United States.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Childhood overweight/obesity has become a major public health concern globally because of its adverse health consequences and escalating prevalence. The factors underlying the disease conditions ...manifested during adulthood commonly originate in childhood. Nepal is going through a transition where under-nutrition co-exists with obesity; however, there is a lack of well-documented information on childhood overweight or obesity in Nepal. This study was carried out to determine the prevalence and associated factors of childhood overweight/obesity among urban primary school children.
A cross-sectional survey was conducted from May to October of 2017. Behavioral data were collected using a structured self-administered questionnaire with parents of children aged 6-13 years old in grades 1-5 studying in private schools of Lalitpur district in Nepal. Study participants were selected using two-stage cluster random sampling from 10 private schools. Height and weight measurements of 575 children were taken and BMI-for-age-sex was calculated using WHO AnthroPlus. Data were analyzed using SPSS version 21. Associated factors were examined using Chi-square tests followed by multivariate logistic regression analyses.
The study found that out of 575 students, 107 (18.6%) were overweight and 41 (7.1%) were obese. Among 328 male children, 62 (19.0%) were overweight and 35 (10.6%) were obese. Likewise, among 247 female children, 45 (18.2%) were overweight and 6 (2.4%) were obese. Male children (aOR = 2.21, 95% CI: 1.38-3.53), children of mothers with a high school (aOR = 3.13, 95% CI: 1.39-7.12) or university level of education (aOR = 3.09, 95% CI: 1.23-7.70) and children of mothers in a professional field (aOR = 1.34, 95% CI: 1.02-4.05) had a greater likelihood of being overweight/obese. Likewise, students consuming energy-dense less nutrient food (aOR = 2.92, 95% CI: 1.66-5.12), lacking active travel to and from school (aOR = 2.38, 95% CI: 1.12-4.79) and those having sedentary behaviors (aOR = 3.01, 95% CI: 1.20-7.29) were likely to be overweight/obese.
More than one-quarter of the children in urban Lalitpur were found to be overweight/obese. High junk food consumption and sedentary activity were found to be significantly associated with childhood overweight/obesity. School health and awareness programs aiming to reduce the intake of energy-dense foods and promote an active lifestyle including active transportation to school among children are imperative. Future studies to objectively measure the type and amount of food intake and physical activity of students are recommended.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stakeholder engagement is important from the management point of view to capture knowledge, increase ownership, reduce conflict, encourage partnership, as well as to develop an ethical perspective ...that facilitates inclusive decision making and promotes equity. However, there is dearth of literature in the process of stakeholder engagement. The purpose of this paper is to describe the process of increasing stakeholder engagement and highlight the lessons learnt on stakeholder engagement while designing, implementing, and monitoring a study on diabetes and hypertension prevention in workplace settings in Nepal. We identified the stakeholders based on the 7P framework: Patients and public (clients), providers, payers, policy makers, product makers, principal investigators, and purchasers. The identified stakeholders were engaged in prioritization of the research questions, planning data collection, designing, implementing, and monitoring the intervention. Stakeholders were engaged through focus group discussions, in-depth interviews, participatory workshops, individual consultation, information sessions and representation in study team and implementation committees. The views of the stakeholders were synthesized in each step of the research process, from designing to interpreting the results. Stakeholder engagement helped to shape the methods and plan, and process for participant's recruitment and data collection. In addition, it enhanced adherence to intervention, mutual learning, and smooth intervention adoption. The major challenges were the time-consuming nature of the process, language barriers, and the differences in health and food beliefs between researchers and stakeholders. It was possible to engage and benefit from stakeholder's engagement on the design, implementation and monitoring of a workplace-based hypertension and diabetes management research program in Nepal.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Worksite-based health programs have shown positive impacts on employee health and have led to significant improvements in cardiovascular risk factor profiles. We aimed to determine the effect of ...cafeteria intervention on cardio-metabolic risk factors diet in a worksite setting (Dhulikhel Hospital) in Nepal.
In this one-arm pre-post intervention study, we recruited 277 non-pregnant hospital employees aged 18-60 with prediabetes or pre-hypertension. The study was registered in clinicaltrials.gov (NCT03447340; 2018/02/27). All four cafeterias in the hospital premises received cafeteria intervention encouraging healthy foods and discouraging unhealthy foods for six months. We measured blood pressure, fasting glucose level, glycated hemoglobin, cholesterol in the laboratory, and diet intake (in servings per week) using 24-hour recall before and six months after the intervention. The before and after measures were compared using paired-t tests.
After six months of cafeteria intervention, the median consumption of whole grains, mono/polyunsaturated fat, fruits, vegetable and nuts servings per week increased by 2.24(p<0.001), 2.88(p<0.001), 0.84(p<0.001) 2.25(p<0.001) and nuts 0.55 (p<0.001) servings per week respectively. The median consumption of refined grains decreased by 5.07 servings per week (p<0.001). Mean systolic and diastolic blood pressure decreased by 2 mmHg (SE = 0.6; p = 0.003) and 0.1 mmHg (SE = 0.6; p = 0.008), respectively. The low-density lipoprotein (LDL) was significantly reduced by 6 mg/dL (SE = 1.4; p<0.001).
Overall, we found a decrease in consumption of refined grains and an increase in consumption of whole grains, unsaturated fats, fruits, and nuts observed a modest reduction in blood pressure and LDL cholesterol following a 6-month cafeteria-based worksite intervention incorporating access to healthy foods.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Postnatal care services helps in detecting and subsequently managing life threatening complications. With the ubiquitous use of the mobile phone in Nepal, social media based postpartum education has ...the potential to increase PNC knowledge among pregnant women. This study aimed to assess the effect of social media-based health education program on PNC knowledge among pregnant women attending Dhulikhel hospital, Nepal.
We conducted a two-arm open-label randomized controlled trial among literate pregnant women visiting Dhulikhel hospital for ANC check-up from May to August, 2021. A computer-based program allocated 229 pregnant women owning smartphones with internet connectivity in a 1:1 ratio to either intervention (n = 109) or usual care (n = 120). We assessed PNC knowledge in the participants by interviewing in-person or via phone. The intervention group received a 16 minutes video on PNC and the participants were reminded to view the video every week via telephone for a month. Control group received usual care. The primary outcome of the study was change in PNC knowledge score. We utilized intent-to-treat analysis and measured the effect of the intervention on PNC knowledge score using simple linear regression analysis.
The mean PNC knowledge score increased by additional 8.07 points among pregnant women in the intervention group compared to the control group (95% CI: 2.35: 13.80; p-value = 0.006). The maternal care attribute knowledge increased by 4.31 points (95% CI: 1.51-7.10, p-value = 0.03) and newborn care attribute knowledge increased by 3.39 points (95% CI: 0.41-6.37, p-value = 0.02) among pregnant women in the intervention compared to the control group.
A social media-based health education is effective in improving PNC knowledge score among pregnant women. Further research is needed to evaluate if this increased knowledge is translated into the increased utilization of PNC care.
ClinicalTrials.gov ID: NCT05132608.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of several C. perfringens food- and nonfood-borne human gastrointestinal diseases. The enterotoxin ...gene (cpe) is located on either the chromosome (for most C. perfringens type A food poisoning strains) or large conjugative plasmids (for the remaining type A food poisoning and most, if not all, other CPE-producing strains). In all CPE-positive strains, the cpe gene is strongly associated with insertion sequences that may help to assist its mobilization and spread. During disease, CPE is produced when C. perfringens sporulates in the intestines, a process involving several sporulation-specific alternative sigma factors. The action of CPE starts with its binding to claudin receptors to form a small complex; those small complexes then oligomerize to create a hexameric prepore on the membrane surface. Beta hairpin loops from the CPE molecules in the prepore assemble into a beta barrel that inserts into the membrane to form an active pore that enhances calcium influx, causing cell death. This cell death results in intestinal damage that causes fluid and electrolyte loss. CPE is now being explored for translational applications including cancer therapy/diagnosis, drug delivery, and vaccination.
Clostridium perfringens is an extremely versatile pathogen of humans and livestock, causing wound infections like gas gangrene (clostridial myonecrosis), enteritis/enterocolitis (including one of the ...most common human food-borne illnesses), and enterotoxemia (where toxins produced in the intestine are absorbed and damage distant organs such as the brain). The virulence of this Gram-positive, spore-forming, anaerobe is largely attributable to its copious toxin production; the diverse actions and roles in infection of these toxins are now becoming established. Most C. perfringens toxin genes are encoded on conjugative plasmids, including the pCW3-like and the recently discovered pCP13-like plasmid families. Production of C. perfringens toxins is highly regulated via processes involving two-component regulatory systems, quorum sensing and/or sporulation-related alternative sigma factors. Non-toxin factors, such as degradative enzymes like sialidases, are also now being implicated in the pathogenicity of this bacterium. These factors can promote toxin action in vitro and, perhaps in vivo, and also enhance C. perfringens intestinal colonization, e.g. NanI sialidase increases C. perfringens adherence to intestinal tissue and generates nutrients for its growth, at least in vitro. The possible virulence contributions of many other factors, such as adhesins, the capsule and biofilms, largely await future study.
Background Stakeholder engagement is important from the management point of view to capture knowledge, increase ownership, reduce conflict, encourage partnership, as well as to develop an ethical ...perspective that facilitates inclusive decision making and promotes equity. However, there is dearth of literature in the process of stakeholder engagement. The purpose of this paper is to describe the process of increasing stakeholder engagement and highlight the lessons learnt on stakeholder engagement while designing, implementing, and monitoring a study on diabetes and hypertension prevention in workplace settings in Nepal. Methodology We identified the stakeholders based on the 7P framework: Patients and public (clients), providers, payers, policy makers, product makers, principal investigators, and purchasers. The identified stakeholders were engaged in prioritization of the research questions, planning data collection, designing, implementing, and monitoring the intervention. Stakeholders were engaged through focus group discussions, in-depth interviews, participatory workshops, individual consultation, information sessions and representation in study team and implementation committees. Results The views of the stakeholders were synthesized in each step of the research process, from designing to interpreting the results. Stakeholder engagement helped to shape the methods and plan, and process for participant’s recruitment and data collection. In addition, it enhanced adherence to intervention, mutual learning, and smooth intervention adoption. The major challenges were the time-consuming nature of the process, language barriers, and the differences in health and food beliefs between researchers and stakeholders. Conclusion It was possible to engage and benefit from stakeholder’s engagement on the design, implementation and monitoring of a workplace-based hypertension and diabetes management research program in Nepal.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The co-existence of undernutrition and overnutrition is a global public health threat. We aim to report the burden of both nutritional deficiency (Protein-Energy Malnutrition) and overweight (high ...Body Mass Index) in Nepal over a decade (2010-2019) and observe the changes through trend charts. We did a secondary data analysis using the Institute for Health Metrics and Evaluation (IHME)'s Global Burden of Disease (GBD) database to download age-standardized data on Protein Energy Malnutrition (PEM) and high Body Mass Index (BMI). We presented the trend of death, Disability Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years Lost due to Disability (YLD) of PEM and high BMI in Nepal from 2010 to 2019 and also compared data for 2019 among South Asian countries. Between 2010 and 2019, in Nepal, the Disability Adjusted Life Years (DALYs) due to PEM were declining while high BMI was in increasing trend. Sex-specific trends revealed that females had higher DALYs for PEM than males. In contrast, males had higher DALYs for high BMI than females. In 2019, Nepal had the highest death rate for PEM (5.22 per 100,000 populations) than any other South Asian country. The burden of PEM in terms of DALY was higher in under-five children (912 per 100,000 populations) and elderly above 80 years old (808.9 per 100,000 populations), while the population aged 65-69 years had the highest burden of high BMI (5893 per 100,000 populations). In the last decade, the DALYs for risk factors contributing to PEM such as child growth failure (stunting and wasting), unsafe water, sanitation and handwashing, and sub-optimal breastfeeding have declined in Nepal. On the contrary, the DALYs for risk factors contributing to high BMI, such as a diet high in sugar-sweetened beverages, a diet high in trans fatty acid, and low physical activity, have increased. This could be a possible explanation for the increasing trend of high BMI and decreasing trend of PEM. Rapidly growing prevalence of high BMI and the persistent existence of undernutrition indicate the double burden of malnutrition in Nepal. Public health initiatives should be planned to address this problem.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cervical cancer ranks as the most common cancer among Nepalese women with a high incidence and mortality. Despite evidence that effective screening programs reduce disease burden, screening services ...are under-utilized. Cancer stigma can be a major barrier to cervical cancer screening uptake among Nepalese women.
This study assessed the association between cancer stigma and cervical cancer screening uptake among women residing in semi-urban areas of Kavrepalanchok district (Dhulikhel and Banepa), Nepal.
We conducted a cross-sectional study among 426 women aged 30-60 years using telephone interview method from 15th June to 15th October 2021. A validated Cancer Stigma Scale (CASS) was used to measure cancer stigma and categorized women as presence of cancer stigma if the mean total score was greater than three. We obtained information on cervical cancer screening uptake through self-reported responses. Univariable and multivariable logistic regression were performed to assess the association between cancer stigma and cervical cancer screening uptake. We adjusted socio-demographic: age, ethnicity, occupation, religion and education, and reproductive health variables: parity, family planning user, age of menarche and age at first sexual intercourse during multivariable logistic regression.
Twenty-three percent of women had cancer stigma and 27 percent reported that they had ever been screened for cervical cancer. The odds of being screened was 0.23 times lower among women who had stigma compared to those who had no stigma (95% CI: 0.11-0.49) after adjusting for confounders: age, ethnicity, occupation, religion, education, parity, contraceptive use, age of menarche and age at first sexual intercourse.
Women residing in semi-urban areas of Nepal and had cancer stigma were less likely to have been screened for cervical cancer. De-stigmatizing interventions may alleviate cancer stigma and contribute to higher uptake of cervical cancer screening.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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