41 results on '"Tshering, Sherpa"'
Search Results
2. Effect of Shoot Pruning on Growth, Flowering and Fruiting Characteristics of Different Guava (Psidium Guajava L.) Cultivars
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Santhoshkumar G M, Nilesh Bhowmick, Aditi Chakraborty, Amarendra Nath Dey, Arunava Ghosh, Puspendu Dutta, Prahlad Deb, Novin Chamling, Nim Tshering Sherpa, and Bidyarani Devi Senjam
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Heading back ,vegetative buds ,guava ,rejuvenation ,fruit quality ,Plant culture ,SB1-1110 - Abstract
A field trial was conducted to study the effect of shoot pruning on growth, flowering and fruiting characteristics of different guava cultivars. The experiment was carried out during Jan. 2018 to June 2019. The experiment was laid out in Randomized Block Design (RBD) with seven cultivars as treatments including L-49 (T1), Allahabad Safeda (T2), Baruipur (T3), Doodh Khaja (T4), Kafri (T5), Bhagalpur (T6) and Harichal (T7). Shoot pruning in guava is an alternative practice used to control the excessive growth and vigor of the plant. The plants were pruned from 120 cm above the ground level as heading back to facilitate the production of new shoots from below the cut point and allow the primary shoots. These results revealed that, guava cultivar baruipur was best in terms of number of primary shoots (58.17), length of primary shoots (135.82 cm) at 12 months after pruning, flowering percentage (66.11%) and better fruit characteristics.
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- 2022
- Full Text
- View/download PDF
3. Use of the Western blot technique to identify the immunogenic proteins of Borrelia burgdorferi for developing a Lyme disease vaccine
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Katherine Loomba, Danilo Shi, Tshering Sherpa, Justin Chen, Thomas J. Daniels, Charles S. Pavia, and Dong Zhang
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Lyme disease ,Borrelia burgdorferi ,Vaccine ,Flagellin ,Western blot ,Antibodies ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Lyme disease is a serious infectious disease having a restricted worldwide distribution for which there is no vaccine available for human use. Objective: This study was designed to determine common reactive antigens involved in Borrelia burgdorferi (Bb) infection that are recognized in mammalian sera that may be useful for vaccine development. Methods: Blood samples were collected from patients with documented Lyme disease, and from rabbits and mice experimentally infected with either tick-transmitted or culture-grown Borrelia burgdorferi. All samples were then processed for sera. For performing the Western blots, sonicated Bb organisms (whole cell lysates) and protein ladders were separated by protein gel electrophoresis. Immune reactivities of the electrophoresed proteins with the serum samples were then probed with anti-HRP IgG reagent. Results: Rabbit, mouse and human sera consistently reacted with the 41 kDa band of Bb which corresponded to the flagellin protein – the major protein component of this organism’s periplasmic flagella, also known as axial filaments or fibrils. Various other Bb antigens of wide molecular weight ranges were also recognized by rabbit and human sera, and less frequently with mouse sera. Conclusion: The strong immune response to the 41 kDa flagellin protein by the different mammalian species suggests the utility of a possible vaccine targeting this protein, although other proteins may also be appropriate, for preventing Lyme disease following a bite from an infected tick.
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- 2023
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4. Prevalence and characteristics of abnormal Papanicolaou smear: A retrospective study from Sikkim, India
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Tseten Wangyal Bhutia, Lhakit Lepcha, Ashok Tshering Sherpa, and Priya Darshini Pradhan
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high-grade squamous intraepithelial lesion ,low grade squamous intraepithelial lesion ,papanicolaou ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BACKGROUND: Cervical intraepithelial neoplasia and cervical cancer remain chief health complications for women globally. Cervical cytology by Papanicolaou (Pap)-stained smears is an effective means of screening for cervical premalignant and malignant situations. This study was designed to determine and assess the prevalence and characteristics of abnormal Pap smears in this region of Sikkim, India. MATERIALS AND METHODS: This retrospective study was conducted in the Departments of Pathology at Multi-Specialty Hospital in Gangtok, Sikkim. All Pap smears screened during 2018 and 2020 were included in this study. Approximately 1256 Pap smears were reported based on Bethesda III System (2001). All abnormal smears patients' data were collected and evaluated accordingly. RESULTS: Most of the patients screened during the 2 years belonged to the ethnic group of Bhutias (15.45%), followed by Rai (12.90%), and the majority were aged 31–40 years (43.78%). Epithelial abnormalities categorized as atypical squamous cells of undetermined significance, atypical squamous cells-high-grade lesions, low grade squamous intraepithelial lesion, and high grade squamous intraepithelial lesion were found in 18.07%, 15.04%, 7.25%, and 4.77% of the women, respectively. The majority of the women with abnormal Pap smear were associated with inflammatory response, with moderate inflammation (33.07%), followed by severe (30.75%) and mild (24.36%) inflammation. The most common pattern was inflammatory which includes neutrophilic infiltration and reactive cellular changes with 66.6% of the case having irregular uterine bleeding (P = 0.002) followed by abnormal vaginal discharge (P = 0.3) and lower abdominal pain (P = 0.005). CONCLUSION: Prevalence of abnormal Pap smears in Sikkim, India is relatively low compared with other states of India. In contrast, the prevalence of progressive glandular anomalies with inflammation was observed to be high.
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- 2021
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5. Menstrual Hygiene: Practice and Challenges Among Adolescent girls of a Private School of Urban Nepal
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Neeti Singh, Ang Tshering Sherpa, Srijana Pandey, and Amita Pradhan
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mhm ,private school ,urban sector ,Medicine - Abstract
Background: Menstrual health hygiene management (MHM) is the basic right of every female. In developing countries like Nepal, this right is less understood or utilized. Parental and family influences and hence the societal influences plays vital role in behavioral change. In urban sector, the girls studying in the private schools are mostly from privileged background. So there is a need to observe the pattern of practices among private school girls which reflects the scenarios in privileged urban sector. Aims and Objectives: This study is to explore the practices and challenges for menstrual health hygiene management among adolescent girls of a Private school in Urban Nepal. Material and Methods: A cross sectional study was conducted in a private school selected purposely in the month of April and May 2019. Girls from grade seven and above were included in the study. Results: All the girls were aware about the process of menstruation. The practices and believes were influenced by their family and facilities provided to them rather knowledge gained at school. All the participants prefer to use disposal pads and 6.3% of participants reported that they use both pads and reusable cloths. Most girls did not change the pads at school (56.2%). All the participants reported that they were hesitant to take help from teachers due to awkwardness. Conclusions: Practices of the individuals is influenced by family beliefs. Again, adolescents spend many hours daily in schools. So strict measures to implement facility in schools for MHM should be taken.
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- 2019
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- View/download PDF
6. Nutritional Status Assessment of Adolescent School Going Children in Solukhumbu, Nepal
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Ang Tshering Sherpa, Neeti Singh, Puspa Babu Basnet, and Mingmar Chhiring Sherpa
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BMI ,Children ,Nutrition ,Solukhumbu ,Stunting ,Medicine - Abstract
Introduction: Around 25% of the total population in Nepal is adolescents (10 to 19 years old). Nutritional programs in Nepal are targeted to young children and pregnant women but neglected among adolescent. Such approach may result poor nutritional status among them. This will lead to poor health outcome and poor academic performance among school children. Thus we aimed to study the nutritional status assessment of adolescent school children in Solukhumbu. Material and Methods: It was a cross sectional study conducted over a period of two and half months (May-July 2018) in a government school at Salleri, Solukhumbu, Nepal. Study participants are 192 students, both male and female, from the age group 10 to 17 years old. Body Mass Index and Height for age was determined by anthropometry. The interview was done by using structured questionnaires to elicit socio-demographic variables. Results: Among 192 students age 10-17 years old, 122(63.5%) were female and 70(36.5%) were male. The majority was Janajati 160(83.3%), Major religion was Hindu 99(51.6%) and Buddhist 93(43.2%), Agriculture was the major occupation of both parents. The literacy rate of the father is 63.2% and mother is 39.9 percent. The majority are underweight 53(27.6%), overweight 11 (5.7%) and obese 3(1.6%). Median Height for Age was 94 (±6.5) with a minimum of 76 and a maximum of 112 and 99(51.6%) are stunted. Conclusions: Stunting, underweight and overweight were prevalent among adolescent children in the school. The causes of these problems should be identified by doing further research and intervention should be done accordingly.
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- 2019
- Full Text
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7. Mutagenic effect on seed germination, seedling growth and seedling survival of Bael (Aegle marmelos Correa.)
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Chakraborty, Aditi, primary, Tshering Sherpa, Nim, additional, Subba, Susan, additional, and Kumar, Vivek, additional
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- 2023
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8. Comparison of incidence of post spinal hypotension between pre-loading and co-loading of fluid in parturient undergoing elective caesarean section with perfusion index greater than 3.5
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Dr. Tshering Sherpa, Dr. Pradeep Rajbhandari, Dr. Devendra Maharjan, Dr. Abhisesh Kumar Pradhan, Dr. Peru Pradhan, and Dr. Gyabina Maharjan
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General Medicine - Published
- 2022
9. Regulation of cardiac myocyte cyclic AMP production by intracellular α1-adrenergic receptors
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Fiore, Chase M., primary, Rudokus, Michael, additional, Tshering Sherpa, Rinzhin, additional, Moshal, Karni S., additional, Agarwal, Shailesh R., additional, and Harvey, Robert D., additional
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- 2023
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10. Role of mitochondrial pka in compartmentation of cAMP signaling in cardiac ventricular myocytes
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Tshering Sherpa, Rinzhin, primary, Moshal, Karni S., additional, Agarwal, Shailesh R., additional, and Harvey, Robert D., additional
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- 2023
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11. Looking into the Laboratory Staffing Issues that Affected Ambulatory Care Clinical Laboratory Operations during the COVID-19 Pandemic
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Faisal M, Huq Ronny, Tshering, Sherpa, Tenzin, Choesang, and Shana, Ahmad
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Biochemistry (medical) ,Clinical Biochemistry - Abstract
Objective Our New York City Municipal Public Health System-based multisite ambulatory and school-based Gotham Health clinics offer waived point-of-care tests and provider-performed microscopy to the local communities. Our Gotham Health laboratory service conducts system-wide centralized implementation, monitoring, and oversight of the POCT operations. Laboratory staffing has always been an issue for us as there is a decades-long shortage of laboratory staff, primarily licensed medical technologists and technicians, in New York, like many other states. Our clinical laboratory operations team struggled to hire qualified people even before the COVID-19 pandemic onset. It has faced more significant challenges with the emergence of SARS-CoV-2 pandemic cases in New York City and across the country since mid-March 2020. Methods As staffing continues to be a struggle, it directly affected the POCT performances and a system-wide reduction in the test numbers during the pandemic. We investigated to identify the factors that made staffing more challenging. Results The impact on our POCT started after laboratory staff relocated to the acute care hospital laboratories to provide testing support during the pandemic’s peak. That caused significant delays or complete cessation of POCT operations in the clinics due to a lack of oversight support. We also experienced the risk of more vacated positions where staff already feel overworked, overwhelmed, and emotionally drained, causing professional burnout. The significant challenges identified are noncompliance with vaccine mandates resulting in job dismissal and voluntary resignations in exchange for higher-paying laboratories. Finally, the other challenges identified were frequent sick calls due to mental fatigue, retirement of seasoned staff, and inability to attract qualified technologists to meet the demands of increasing test-ordering patterns. Conclusions Determining the factors that culminated in the staffing issues becoming more challenging during the COVID-19 pandemic in our ambulatory care clinic laboratory operations will help us in future crisis planning and mitigation.
- Published
- 2022
12. Mitochondrial bound PKA contributes to cyclic-AMP compartmentation in human airway smooth muscle cells
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Rinzhin Tshering Sherpa, Karni S. Moshal, Shailesh R. Agarwal, Rennolds S. Ostrom, and Robert D. Harvey
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Biophysics - Published
- 2023
13. ASSOCIATION OF RANDOM BLOOD SUGAR WITH BODY MASS INDEX IN HABITANTS OF SUBURBAN KATHMANDU DISTRICT
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Srijana Pandey, Ang Tshering Sherpa, Amita Pradhan, and Neeti Singh
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business.industry ,Cross-sectional study ,Blood sugar ,Overweight ,medicine.disease ,Obesity ,Waist–hip ratio ,Diabetes mellitus ,medicine ,Population study ,medicine.symptom ,business ,Body mass index ,Demography - Abstract
Background: Diabetes mellitus is increasing in alarming number worldwide. The main predisposing factor being daily lifestyle which leads to obesity and other complications. Early diagnosis and life style modification among high risk group can decrease the burden of disease. This study was done to find out the random blood sugar level and assess the relationships between body mass index (BMI), waist hip ratio (WHR) and random blood sugar among the study population. Methods: A cross sectional study was done using retrospective data collected at the health camp conducted during month of October 2018. The study area was Nagarjun and Chandragiri municipalities of Kathmandu district. The data was analyzed using SPSS version 21. The chi square test was used to assess relation between BMI,WHR and Random blood sugar. Results: The number of participants in this study was 274. Majority of the participants, (92.7%) had random blood sugar level 200mg/dl or less. Those having RBS of more than 200mg/dl were 7.3%. Among all participants, 16.06% were obese. Further the obese participants showed high waist hip ratio in 81.8% and 9.1% of them had moderate or low waist hip ratio. Further, 46 participants showed diabetic blood sugar level and were either overweight (39.13%) or obese (28.26%). Conclusions: This study concluded that those who had diabetic blood sugar level or high waist hip ratio had increases BMI. So such screening and preventive programme should be further expanded and even at clinical level. Additionally, patients must be counseled the reason for measuring BMI and RBS and its application for their health promotion.
- Published
- 2021
14. Female autonomy and fertility pattern among women working in formal sector in Kathmandu valley
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Neeti Singh, Srijana Pandey, Nijina Tamrakar, Ang Tshering Sherpa, and Sunil Chitrakar
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Pregnancy ,business.industry ,media_common.quotation_subject ,Total fertility rate ,Fertility ,Affect (psychology) ,medicine.disease ,Family planning ,Respondent ,Medicine ,Observational study ,business ,Autonomy ,Demography ,media_common - Abstract
Background: Fertility rate is declining more among women with higher education around the world. This may be due to number of years spent for achieving higher degree, choice of work and age at marriage. With growing autonomy of urban women and late age at marriage increases high risk pregnancy and declines number of children leading to decrease in young population. So, this study was done to explore the fertility pattern and associated factors among working women at formal sectors. Methods: An observational study was done among women working at formal sectors within Kathmandu valley. A respondent driven sampling was used to achieve total 101 sample size. The study period was October and November 2019. Results: Median age of the participants was 40 and median age at marriage was 26.62 years. The association between level of education and age at marriage was statistically significant. The median age of pregnancy of the participants were 27 years and 58.4% of women had only one live child. Average number of desired children was 1.69 whereas actual number of children was 1.32. The gap between desired and number of children is statistically significant. Only 35.6% reported to have used some form of contraceptive devices as the measure of family planning. Conclusions: Fertility behavior of working women is not completely influenced by their working status except for higher age at marriage, pregnancy and desired number of children which in long term may affect in the growth of country.
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- 2020
15. IoT Based Automated Irrigation Management Technique for Climate Smart Agriculture
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G. T. Patle and Tshering Sherpa
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- 2022
16. Regulation of cardiac myocyte cyclic AMP production by intracellular α1-adrenergic receptors
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Chase M. Fiore, Michael Rudokus, Rinzhin Tshering Sherpa, Karni S. Moshal, Shailesh R. Agarwal, and Robert D. Harvey
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Biophysics - Published
- 2023
17. Role of mitochondrial pka in compartmentation of cAMP signaling in cardiac ventricular myocytes
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Rinzhin Tshering Sherpa, Karni S. Moshal, Shailesh R. Agarwal, and Robert D. Harvey
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Biophysics - Published
- 2023
18. Efficient Intracellular Delivery of Cell-Impermeable Cargo Molecules by Peptides Containing Tryptophan and Histidine
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Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, and Keykavous Parang
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histidine ,Peptide-based Drug Delivery Systems ,phosphopeptides ,tryptophan ,Organic chemistry ,QD241-441 - Abstract
We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high-performance liquid chromatography (HPLC), respectively. These peptides did not show significant toxicity up to 100 µM in ovarian cancer (SK-OV-3) and leukemia cancer (CCRF-CEM) cells. Furthermore, the cellular uptake of a fluorescence (F’)-labeled cell-impermeable phosphopeptide (F’-GpYEEI) was enhanced in the presence of linear (WH)5 and cyclic [WH]5 by 2- and 8-fold, respectively, compared to the uptake of the phosphopeptide alone. The cellular uptake was not significantly changed in the presence of endocytosis inhibitors. Furthermore, the intracellular uptake of the fluorescently-labeled anti-HIV drug, emtricitabine (F’-FTC), by linear (WH)5 and cyclic [WH]5 in SK-OV-3 cancer cell lines was found to be enhanced by 3.5- and 9-fold, respectively, compared to that of the drug alone. Fluorescent uptake experiments confirmed the localization of F’-GpYEEI-loaded cyclic [WH]5 intracellularly in the SK-OV-3 cancer cell line after 3 h of incubation. Thus, these data demonstrated that [WH]5 containing tryptophan and histidine enhanced the cellular uptake of F’-GpYEEI and emtricitabine.
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- 2018
- Full Text
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19. Menstrual Hygiene: Practice and Challenges Among Adolescent girls of a Private School of Urban Nepal
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Amita Pradhan, Srijana Pandey, Neeti Singh, and Ang Tshering Sherpa
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medicine.medical_specialty ,business.industry ,Private school ,education ,lcsh:R ,lcsh:Medicine ,private school ,mhm ,Menstrual hygiene ,Family medicine ,urban sector ,Medicine ,General Agricultural and Biological Sciences ,business - Abstract
Background: Menstrual health hygiene management (MHM) is the basic right of every female. In developing countries like Nepal, this right is less understood or utilized. Parental and family influences and hence the societal influences plays vital role in behavioral change. In urban sector, the girls studying in the private schools are mostly from privileged background. So there is a need to observe the pattern of practices among private school girls which reflects the scenarios in privileged urban sector. Aims and Objectives: This study is to explore the practices and challenges for menstrual health hygiene management among adolescent girls of a Private school in Urban Nepal. Material and Methods: A cross sectional study was conducted in a private school selected purposely in the month of April and May 2019. Girls from grade seven and above were included in the study. Results: All the girls were aware about the process of menstruation. The practices and believes were influenced by their family and facilities provided to them rather knowledge gained at school. All the participants prefer to use disposal pads and 6.3% of participants reported that they use both pads and reusable cloths. Most girls did not change the pads at school (56.2%). All the participants reported that they were hesitant to take help from teachers due to awkwardness. Conclusions: Practices of the individuals is influenced by family beliefs. Again, adolescents spend many hours daily in schools. So strict measures to implement facility in schools for MHM should be taken.
- Published
- 2019
20. Reproductive Health Status of Married Women Participating In Cervical Cancer Screening In Kathmandu
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Peru Pradhan, Ang Tshering Sherpa, Neeti Singh, Amita Pradhan, and Manisha Bajracharya
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Pregnancy ,medicine.medical_specialty ,Cervical polyp ,business.industry ,Cross-sectional study ,Cervicitis ,medicine.disease ,medicine.anatomical_structure ,Family medicine ,Reproductive rights ,medicine ,Risk factor ,business ,Cervix ,Reproductive health - Abstract
Background: Reproductive health of women has been the central agenda of Cairo conference since its inception in 1999. As a signatory country for Cairo Conference, Nepal government is also committed for reproductive rights for Nepalese women. Despite this, reproductive health challenges do exist in Nepal. This prompted us to determine the reproductive health status of married women attending in cervical cancer screening in Kathmandu. Methods: Cross sectional study was designed to include retrospective data of married women, obtained during cervical cancer screening camp conducted by KIST Medical College at Laga Khala Clinic, Lagan, Kathmandu on 12-02- 2017. Among married women (131) attended cervical 100 women’s records with complete set of data for reproductive health variables required for the study were included in this study. Statistical analysis was done descriptively. Results: Participant’s age is between 21 years to 61 years, 83% are literate and 46% are employed. Adolescence marriage and pregnancy were two main problems noted. Cervical examination in relation showed 3% (3) VIA positive, 33% (33) Cervicitis, 10% (10) cervical polyp, 7% (7) atrophic vaginitis, 4% (4) cervical erosion and 43% (43) healthy cervix. Regarding Knowledge about risk factor majority 92% (92) had either no knowledge or only some extent of knowledge. Conclusions: Married women who lives in Kathmandu has significant reproductive health problem. Urban health program should address these issues.
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- 2019
21. Nutritional Status Assessment of Adolescent School Going Children in Solukhumbu, Nepal
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Mingmar Chhiring Sherpa, Ang Tshering Sherpa, Puspa Babu Basnet, and Neeti Singh
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Solukhumbu ,Stunting ,Cross-sectional study ,business.industry ,Literacy rate ,lcsh:R ,lcsh:Medicine ,Nutritional status ,Total population ,Anthropometry ,Overweight ,Health outcomes ,BMI ,medicine ,medicine.symptom ,Underweight ,business ,Children ,Demography ,Nutrition - Abstract
Introduction: Around 25% of the total population in Nepal is adolescents (10 to 19 years old). Nutritional programs in Nepal are targeted to young children and pregnant women but neglected among adolescent. Such approach may result poor nutritional status among them. This will lead to poor health outcome and poor academic performance among school children. Thus we aimed to study the nutritional status assessment of adolescent school children in Solukhumbu.Material and Methods: It was a cross sectional study conducted over a period of two and half months (May-July 2018) in a government school at Salleri, Solukhumbu, Nepal. Study participants are 192 students, both male and female, from the age group 10 to 17 years old. Body Mass Index and Height for age was determined by anthropometry. The interview was done by using structured questionnaires to elicit socio-demographic variables.Results: Among 192 students age 10-17 years old, 122(63.5%) were female and 70(36.5%) were male. The majority was Janajati 160(83.3%), Major religion was Hindu 99(51.6%) and Buddhist 93(43.2%), Agriculture was the major occupation of both parents. The literacy rate of the father is 63.2% and mother is 39.9 percent. The majority are underweight 53(27.6%), overweight 11 (5.7%) and obese 3(1.6%). Median Height for Age was 94 (±6.5) with a minimum of 76 and a maximum of 112 and 99(51.6%) are stunted.Conclusions: Stunting, underweight and overweight were prevalent among adolescent children in the school. The causes of these problems should be identified by doing further research and intervention should be done accordingly.
- Published
- 2019
22. Perinatal Mortality Review in a Tertiary Care Hospital: Way Forward to Address SDG Health Goal 3
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Ajay Dhakal, Manisha Bajracharya, Heera Tuladhar, Sunita Bhandari, Meenu Maharjan, and Ang Tshering Sherpa
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Pregnancy ,medicine.medical_specialty ,business.industry ,Antepartum haemorrhage ,Obstetrics ,Incidence (epidemiology) ,Intrauterine growth restriction ,Gestational age ,medicine.disease ,Gestational diabetes ,Health care ,medicine ,business ,Prospective cohort study - Abstract
Introduction: Sustainable development goal 3 targets at ensuring healthy lives and promoting well-being for all at all ages. One of the component for achievement of this goal is improvement of maternal and child health; the indicators of which is perinatal mortality rate. The aim of this study was to evaluate the cause of perinatal death in a tertiary care medical centre, which may help to reduce the incidence of perinatal death and improve the quality of care. Methods: A prospective study was done over a period of one year from April 2016 to March 2017. Causes of perinatal deaths based on PSANZ classification were recorded along with patients demographics and also avoidable factors were evaluated. Results: Out of total 1275 deliveries, there were 21 perinatal deaths including three intrauterine foetal deaths, one still birth and seven early neonatal deaths. The perinatal mortality rate was 16.27 per 1000 birth. Majority of perinatal deaths (19%) occurred due to congenital anomalies followed by (14%) hypertensive disorder in pregnancy, intrapartum hypoxia (14%), unexplained causes (14%), 9.5% cord prolapse, antepartum haemorrhage (9.5%), 5% due to intrauterine growth restriction, gestational diabetes mellitus or preterm labour. Most of the mothers whose baby had perinatal deaths had ANC outside. Most of the deaths occurred in between gestational age of 37 to 41 weeks. Perinatal mortality was more in multigravida. Delay to seek health care and inadequate antenatal checkups were the most common avoidable factors. Conclusions: Congenital anomalies and hypertensive disorders during pregnancy were the most common causes of perinatal death. Delay in health seeking behaviour was the most common avoidable factors for perinatal death. We recommend early identification of high risk pregnancy through proper antenatal screening, educating pregnant women to identify danger signs of pregnancy, creating public awareness about importance of antenatal checkups, vigilant labour monitoring for foetal distress, to reduce some categories of deaths.
- Published
- 2019
23. SCALE INVARIANCE OF TOPOGRAPHIC DEPRESSIONS ON HIMALAYAN DEBRIS-COVERED GLACIERS
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Joshua M. Blackstock, Ryan Strickland, Matthew D. Covington, Jason Gulley, Dawa Tshering Sherpa, and Rijan Bhakta Kayastha
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geography ,geography.geographical_feature_category ,Glacier ,Scale invariance ,Debris ,Geomorphology ,Geology - Published
- 2021
24. Using the '3Es' Method to Evaluate REDD+ Project in Nepal
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Doma Tshering Sherpa
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Community level ,Renewable Energy, Sustainability and the Environment ,Natural resource economics ,media_common.quotation_subject ,Equity (finance) ,Payment ,Education ,Forest resource ,Sustainability ,User group ,Economics ,Reducing emissions from deforestation and forest degradation ,Environmental planning ,Carbon stock ,General Environmental Science ,media_common - Abstract
This case demonstrates the utility of the 3Es (effectiveness, efficiency, and equity) in examining Reducing Emissions from Deforestation and Forest Degradation (REDD+) project in Nepal. REDD+ offers results-based payments for conserving and managing forests sustainably and enhancing forest carbon stocks. This will benefit communities’ efforts to conserve forest resources and prevent deforestation; conserving integrity of forests in turn benefits the global carbon budget. This case uses the 3Es to examine one case in Nepal of distributing the REDD+ funds among local participants. Of the 3Es, equity is getting attention worldwide but there is still debate on which principle of 3Es should be given priority to achieve overall effectiveness of REDD+. This case finds that equity is a fundamental requirement to achieve the other Es (efficiency and effectiveness) in REDD+ implementation. Further, I find that distributive equity is the most important and understood in three different ways in Nepal: rights, needs, and performance. There is an argument between communities and experts on which equity should be given priority. I recommend that the issue of needs based equity vs. performance-based equity should be solved by formation of guidelines of sharing benefits at two levels. First, the benefit distribution from international sources/markets to community forest user groups should be based on the ownership of carbon and performance of communities participating in REDD+. Second, at community level, communities should decide on the form of benefit distribution according to their needs. The primacy of equity in this case will likely find international echoes in other environmental policies and in other countries.
- Published
- 2017
25. Design and Development of Semi-Automatic Electrical Incinerator Using Arduino
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Ashya Chettri, Shristhi Shrestha, Kiran Tamang, Jus Bahadur Kami, Phur Tshering Sherpa, Bandana Sharma, Deepak Rasaily, and Nitesh Kumar
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Computer science ,business.industry ,Controller (computing) ,Dispose pattern ,GeneralLiterature_MISCELLANEOUS ,Automotive engineering ,law.invention ,Incineration ,Filter (video) ,Relay ,law ,Arduino ,Chimney ,Electricity ,business - Abstract
Incineration is the key form of treatment for waste-to-energy. The existing incinerator developed is simple in design; it did not consist of a dustbin to store the waste. The waste disposed directly went through the heating chamber with no control technology i.e., the switch of chamber is controlled manually. This disadvantage is covered by our system as the switch is automatically controlled with the use of a controller. Arduino is used to control the sweeping of the valve. Programming is done with various condition to meet the requirement of the proposed work. The system is environmental friendly as it has a chimney with a filter installed in it. With the use of this system it is easier to dispose waste. It is portable as it is a wheel based incinerator. This portable wherein furnace and valve is automatically operated based on Arduino program. System is reliable and efficient as it is wheel based. The most attractive is it has inbuilt smart dustbin in it. About 65-80% of the energy content in the organic substances can be utilize to produce electricity.
- Published
- 2019
26. Equity in Sharing the Potential Benefits of REDD+ in
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Doma Tshering Sherpa and Ann Brower
- Subjects
040101 forestry ,010504 meteorology & atmospheric sciences ,Equity (finance) ,04 agricultural and veterinary sciences ,Environmental economics ,Livelihood ,01 natural sciences ,Incentive ,Community forestry ,Climate change mitigation ,Sustainable management ,Reducing emissions from deforestation and forest degradation ,Economics ,0401 agriculture, forestry, and fisheries ,Revenue ,0105 earth and related environmental sciences - Abstract
Reducing Emissions from Deforestation and Forest Degradation (REDD+) is an incentive based climate change mitigation measure that focuses on reducing carbon emissions by rewarding communities’ efforts in the conservation, sustainable management of forests and enhancement of carbon stocks. Assuming REDD+ revenues are generated, there is a question about how the benefits should be distributed. This paper uses the 3Es (Effectiveness, Efficiency and Equity) criteria in sharing the benefits of REDD+ to examine a case study in one of Nepal’s REDD+ pilot projects implemented in community forests. While concerns about equity in REDD+ are getting attention worldwide, the literature is not clear on which principle of 3Es should be given priority to achieve overall effectiveness in reducing the carbon emissions. Our research finds that equity should be prioritised to achieve efficiency and effectiveness of REDD+. Further, we find distributive equity to be the most important. Distributive equity is understood in three different ways in Nepal: rights, needs, and performance. But there is a debate on which equity should be given priority. The issues of needs vs. performance in determining what is equitable should be solved by the formulation of guidelines for how benefits should be shared at two levels in Nepal. First, the vertical distribution of benefits should be based on the ownership of carbon benefits and performance criteria. Second, at the community level, the community itself should determine the form of horizontal benefit-distribution, based on its definition of needs.Journal of Forest and Livelihood 13(1) May, 2015, Page : 20-29
- Published
- 2016
27. Hedgehog signaling induced metabolic reprogramming is essential for M2 polarization of macrophages in breast cancer
- Author
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Dominique C Hinshaw, Ann Hanna, Tshering Sherpa, Rajeev Samant, and Lalita Shevde
- Subjects
Immunology ,Immunology and Allergy - Abstract
Current treatments for breast cancer offer little relief to patients with metastatic disease. The aberrant activation of Hedgehog (Hh) signaling enables cancer cells to survive, proliferate, and metastasize. Effective metastasis depends upon the surrounding immune microenvironment. Macrophages (MΦ) can be polarized to M1 (inflammatory) or M2 (suppressive), and increased populations of M2 tumor infiltrating MΦs are correlated with worse prognosis. We have discovered that Hh signaling contributes to M2 polarization. M1 and M2 MΦs have inherently different metabolic profiles, so we hypothesize that Hh signaling alters M2 MΦ metabolism to reflect M1 MΦ metabolism, leading to diminished M2 phenotype and function within the tumor microenvironment (TME). Methodology includes a mouse model of mammary carcinoma, RNA-seq, mass spectrometry-based metabolomics, confocal imaging, and flow cytometry. We elucidated the impact of Hh signaling blockade on the metabolism of MΦs diminishing their M2 polarization. Inhibition of Hh signaling reduces MΦ O-GlcNAcylation which directly correlates with the diminished suppressive attributes of M2 MΦs through the reduced activity of STAT6. Since STAT6 plays a dual role in governing the M2 phenotype and fatty acid oxidation, this ultimately enacts a metabolic cascade, including lipid utilization, cellular bioenergetics and mitochondrial morphology and function, that metabolically alters M2 MΦs to resemble M1 MΦs. We have discovered that blockade of Hh signaling initiates a metabolic cascade diminishing the M2 phenotype and function. This knowledge will help us to better understand how to target and diminish the pro-tumorigenic phenotypes of MΦs in the TME and at the metastatic site.
- Published
- 2020
28. Population Based Study of Cervical Cancer Screening in Bharatpur, Nepal
- Author
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Mari Nygård, Gary M. Clifford, Johanne Sundby, Silvia Franceschii, Ang Tshering Sherpa, and Balman Singh Karki
- Subjects
Gynecology ,Cervical cancer ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Cross-sectional study ,Incidence (epidemiology) ,Developing country ,Cancer ,medicine.disease ,Cervical cancer screening ,Family medicine ,medicine ,Cluster randomised controlled trial ,Pap test ,business - Abstract
Cervical cancer is the most common form of cancer among women in developing countries. Hospital based data in Nepal also showed cervical cancer is most commonly occurring cancer among women in Nepal. Pap smear is the very significant screening test for reduction of incidence and mortality from cervical cancer but many developing countries failed to obtain high coverage of target population. Hence failed to achieve major impact of cervical cancer screening. National guidelines for cervical cancer and prevention in Nepal is formulated in 2010 and set target population age range of 30-60 with 50% coverage of target population with in a five years span. This study was aimed to elicit baseline survey of cervical cancer screening in a locale where resource for cervical cancer screening is easily available. Population based cross sectional study was done from October 2006 to March 2007. 1547 ever married women aged 16–59 were selected with cluster randomization procedure from Bharatpur municipalities, where BPKMCH (BP Koirala Memorial Cancer Hospital) is located. Free cervical cancer screening was conducted in collaboration with International Agency for Research on Cancer (IARC) France and BPKMCH. Ethical clearance was obtained from Nepal Health Research council. Interviews were performed using a standard questionnaire to elicit required information. Out of 1033 participants 394 were 16-29 years old. Among them 117 (30%) had at least one Pap test prior coming to the clinic. 16(4%) were age 16-19, 42(11%) were age 20-24 and 59 (15%) were age 25-29. This concludes Present opportunistic cervical cancer screening in Bharatpur is directed towards screening significant proportion of women with less risk.DOI: http://dx.doi.org/10.3126/jmmihs.v1i4.11994Journal of Manmohan Memorial Institute of Health SciencesVol. 1, Issue 4, 2015page : 3-8
- Published
- 2015
29. Alternative Splicing Governs Cone Cyclic Nucleotide-gated (CNG) Channel Sensitivity to Regulation by Phosphoinositides
- Author
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Tshering Sherpa, Michael D. Varnum, and Gucan Dai
- Subjects
Male ,Phosphatidylinositol 4,5-Diphosphate ,Gene isoform ,genetic structures ,Allosteric regulation ,Cyclic Nucleotide-Gated Cation Channels ,Biology ,Biochemistry ,Evolution, Molecular ,Exon ,Dogs ,Phosphatidylinositol Phosphates ,Membrane Biology ,Animals ,Humans ,Protein Isoforms ,Cyclic nucleotide-gated ion channel ,Eye Proteins ,Molecular Biology ,Ion channel ,urogenital system ,fungi ,Alternative splicing ,Exons ,Cell Biology ,Cell biology ,Alternative Splicing ,nervous system ,Retinal Cone Photoreceptor Cells ,Female ,sense organs ,Heterologous expression ,Precursor mRNA - Abstract
Precursor mRNA encoding CNGA3 subunits of cone photoreceptor cyclic nucleotide-gated (CNG) channels undergoes alternative splicing, generating isoforms differing in the N-terminal cytoplasmic region of the protein. In humans, four variants arise from alternative splicing, but the functional significance of these changes has been a persistent mystery. Heterologous expression of the four possible CNGA3 isoforms alone or with CNGB3 subunits did not reveal significant differences in basic channel properties. However, inclusion of optional exon 3, with or without optional exon 5, produced heteromeric CNGA3 + CNGB3 channels exhibiting an ∼2-fold greater shift in K1/2,cGMP after phosphatidylinositol 4,5-biphosphate or phosphatidylinositol 3,4,5-trisphosphate application compared with channels lacking the sequence encoded by exon 3. We have previously identified two structural features within CNGA3 that support phosphoinositides (PIPn) regulation of cone CNG channels: N- and C-terminal regulatory modules. Specific mutations within these regions eliminated PIPn sensitivity of CNGA3 + CNGB3 channels. The exon 3 variant enhanced the component of PIPn regulation that depends on the C-terminal region rather than the nearby N-terminal region, consistent with an allosteric effect on PIPn sensitivity because of altered N-C coupling. Alternative splicing of CNGA3 occurs in multiple species, although the exact variants are not conserved across CNGA3 orthologs. Optional exon 3 appears to be unique to humans, even compared with other primates. In parallel, we found that a specific splice variant of canine CNGA3 removes a region of the protein that is necessary for high sensitivity to PIPn. CNGA3 alternative splicing may have evolved, in part, to tune the interactions between cone CNG channels and membrane-bound phosphoinositides.
- Published
- 2014
30. Retinal regeneration is facilitated by the presence of surviving neurons
- Author
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Tshering Sherpa, Mariel Ryan, Samuel S. Hunter, Tim McGinn, Deborah L. Stenkamp, Tyler Lankford, Barrie D. Robison, Ruth A. Frey, and Chi Sun
- Subjects
Retina ,genetic structures ,Retinal ,Biology ,eye diseases ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,medicine.anatomical_structure ,nervous system ,Developmental Neuroscience ,Retinal ganglion cell ,chemistry ,medicine ,Optic nerve ,biology.protein ,Axon guidance ,sense organs ,Sonic hedgehog ,Muller glia ,Neuroscience ,Retinal regeneration - Abstract
Teleost fish regenerate their retinas after damage, in contrast to mammals. In zebrafish subjected to an extensive ouabain-induced lesion that destroys all neurons and spares Muller glia, functional recovery and restoration of normal optic nerve head (ONH) diameter take place at 100 days postinjury. Subsequently, regenerated retinas overproduce cells in the retinal ganglion cell (RGC) layer, and the ONH becomes enlarged. Here, we test the hypothesis that a selective injury, which spares photoreceptors and Muller glia, results in faster functional recovery and fewer long-term histological abnormalities. Following this selective retinal damage, recovery of visual function required 60 days, consistent with this hypothesis. In contrast to extensively damaged retinas, selectively damaged retinas showed fewer histological errors and did not overproduce neurons. Extensively damaged retinas had RGC axons that were delayed in pathfinding to the ONH, and showed misrouted axons within the ONH, suggesting that delayed functional recovery following an extensive lesion is related to defects in RGC axons exiting the eye and/or reaching their central targets. The atoh7, fgf8a, Sonic hedgehog (shha), and netrin-1 genes were differentially expressed, and the distribution of hedgehog protein was disrupted after extensive damage as compared with selective damage. Confirming a role for Shh signaling in supporting rapid regeneration, shha(t4) +/- zebrafish showed delayed functional recovery after selective damage. We suggest that surviving retinal neurons provide structural/molecular information to regenerating neurons, and that this patterning mechanism regulates factors such as Shh. These factors in turn control neuronal number, retinal lamination, and RGC axon pathfinding during retinal regeneration.
- Published
- 2014
31. Novel CNG Channelopathy Model Generated using CRISPR/Cas9-Mediated Genome Editing in Zebrafish
- Author
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Peter C. Meighan, Samuel S. Hunter, Michael D. Varnum, Lindsey M. Morey, and Tshering Sherpa
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Channelopathy ,biology ,Genome editing ,Biophysics ,medicine ,CRISPR ,Computational biology ,medicine.disease ,biology.organism_classification ,Zebrafish - Published
- 2018
32. Human papillomavirus infection in women with and without cervical cancer in Nepal
- Author
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Gary M. Clifford, Sadhina Shrestha, Mari Nygård, Balman Singh Karki, Ang Tshering Sherpa, Silvia Franceschi, Peter J.F. Snijders, Chris J.L.M. Meijer, Salvatore Vaccarella, Pathology, and CCA - Oncogenesis
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Prevalence ,Uterine Cervical Neoplasms ,Comorbidity ,Cervical intraepithelial neoplasia ,Malignancy ,Risk Assessment ,Young Adult ,Nepal ,Risk Factors ,Epidemiology ,Medicine ,Humans ,Mass Screening ,Neoplasm Invasiveness ,Young adult ,Cervix ,Mass screening ,Neoplasm Staging ,Cervical cancer ,Gynecology ,Vaginal Smears ,business.industry ,Obstetrics ,Papillomavirus Infections ,virus diseases ,Middle Aged ,medicine.disease ,Uterine Cervical Dysplasia ,Tumor Virus Infections ,medicine.anatomical_structure ,Oncology ,Female ,business ,Papanicolaou Test - Abstract
Cervical cancer is the most common malignancy among Nepalese women. Rational prevention measures are informed by epidemiological data on human papillomavirus (HPV) prevalence.Cervical specimens were obtained from 932 married women aged 15-59 years from the general population of Bharatpur, Nepal, as well as from 61 locally diagnosed invasive cervical cancers (ICC). HPV was detected using a GP5+/6+ PCR-based assay.Among the general population, the overall prevalence of HPV was 8.6% (6.1% for high-risk types). Prevalence of abnormal Pap smears was 3.6%, including five high-grade squamous intraepithelial lesions. Residence in slum housing, lower education level,or =3 sexual partners in a woman's lifetime, and husband's extramarital affairs were significantly associated with HPV positivity. HPV prevalence was relatively constant across all age groups. HPV16 was the most common type, both among the general population (1.9%) and among 54 women with HPV-positive ICC (68.5%). HPV18 (22.2%) and 45 (5.6%) were also common in ICC.Nepal has an intermediate burden of HPV infection, lower than many areas in India and China. Approximately 80% of cervical cancer in Nepal is theoretically preventable by HPV16/18 vaccines. In the meantime, screen-and-treat approaches should be encouraged to overcome difficulties that were encountered to recall women with screening-positive findings.
- Published
- 2010
33. Ganglion cell regeneration following whole-retina destruction in zebrafish
- Author
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Jordan A. Sand, Dianne E. Mallory, Lei Li, Tshering Sherpa, Shane M. Fimbel, Deborah L. Stenkamp, Hans Maaswinkel, David R. Hyde, and Scott D. Spritzer
- Subjects
Retinal Ganglion Cells ,Time Factors ,genetic structures ,Growth Cones ,Neurotoxins ,Optic Disk ,Optic disk ,Article ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Proliferating Cell Nuclear Antigen ,medicine ,Animals ,Ouabain ,Zebrafish ,Vision, Ocular ,Cell Proliferation ,Retinal regeneration ,Retina ,Behavior, Animal ,Cell Death ,biology ,Regeneration (biology) ,Gene Expression Regulation, Developmental ,Recovery of Function ,biology.organism_classification ,Denervation ,eye diseases ,Nerve Regeneration ,Ganglion ,medicine.anatomical_structure ,Bromodeoxyuridine ,Retinal ganglion cell ,Optic nerve ,Biological Assay ,sense organs ,Neuroscience ,Biomarkers - Abstract
The retinas of adult teleost fish can regenerate neurons following injury. The current study provides the first documentation of functional whole retina regeneration in the zebrafish, Danio rerio, following intraocular injection of the cytotoxin, ouabain. Loss and replacement of laminated retinal tissue was monitored by analysis of cell death and cell proliferation, and by analysis of retina-specific gene expression patterns. The spatiotemporal process of retinal ganglion cell (RGC) regeneration was followed through the use of selective markers, and was found to largely recapitulate the spatiotemporal process of embryonic ganglion cell neurogenesis, over a more protracted time frame. However, the re-expression of some ganglion cell markers was not observed. The growth and pathfinding of ganglion cell axons was evaluated by measurement of the optic nerve head (ONH), and the restoration of normal ONH size was found to correspond to the time of recovery of two visually-mediated behaviors. However, some abnormalities were noted, including overproduction of RGCs, and progressive and excessive growth of the ONH at longer recovery times. This model system for whole-retina regeneration has provided an informative view of the regenerative process.
- Published
- 2008
34. Molecular genetic diversity and characterization of conjugation genes in the fish parasite Ichthyophthirius multifiliis
- Author
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Elisabeth MacColl, M. Mozammal Hossain, WeiShu Chang, Theodore G. Clark, Matthew D. Therkelsen, Tshering Sherpa, Michael C. Schatz, Hannah Ellerbrock, Ravi H. Jariwala, Lily A. Johnston, James Gurtowski, Wei-Jen Chang, and Donna Cassidy-Hanley
- Subjects
Hypotrich ,Genome ,DNA, Mitochondrial ,Polymorphism, Single Nucleotide ,Phylogenetics ,Genetics ,Animals ,Molecular Biology ,Gene ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,Hymenostomatida ,Ciliate ,Likelihood Functions ,biology ,Ichthyophthirius multifiliis ,Models, Genetic ,Reproduction ,Tetrahymena ,Fishes ,Bayes Theorem ,Sequence Analysis, DNA ,biology.organism_classification ,United States ,Sexual reproduction - Abstract
Ichthyophthirius multifiliis is the etiologic agent of "white spot", a commercially important disease of freshwater fish. As a parasitic ciliate, I. multifiliis infects numerous host species across a broad geographic range. Although Ichthyophthirius outbreaks are difficult to control, recent sequencing of the I. multifiliis genome has revealed a number of potential metabolic pathways for therapeutic intervention, along with likely vaccine targets for disease prevention. Nonetheless, major gaps exist in our understanding of both the life cycle and population structure of I. multifiliis in the wild. For example, conjugation has never been described in this species, and it is unclear whether I. multifiliis undergoes sexual reproduction, despite the presence of a germline micronucleus. In addition, no good methods exist to distinguish strains, leaving phylogenetic relationships between geographic isolates completely unresolved. Here, we compared nucleotide sequences of SSUrDNA, mitochondrial NADH dehydrogenase subunit I and cox-1 genes, and 14 somatic SNP sites from nine I. multifiliis isolates obtained from four different states in the US since 1995. The mitochondrial sequences effectively distinguished the isolates from one another and divided them into at least two genetically distinct groups. Furthermore, none of the nine isolates shared the same composition of the 14 somatic SNP sites, suggesting that I. multifiliis undergoes sexual reproduction at some point in its life cycle. Finally, compared to the well-studied free-living ciliates Tetrahymena thermophila and Paramecium tetraurelia, I. multifiliis has lost 38% and 29%, respectively, of 16 experimentally confirmed conjugation-related genes, indicating that mechanistic differences in sexual reproduction are likely to exist between I. multifiliis and other ciliate species.
- Published
- 2014
35. Retinal regeneration is facilitated by the presence of surviving neurons
- Author
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Tshering, Sherpa, Tyler, Lankford, Tim E, McGinn, Samuel S, Hunter, Ruth A, Frey, Chi, Sun, Mariel, Ryan, Barrie D, Robison, and Deborah L, Stenkamp
- Subjects
Retinal Ganglion Cells ,Time Factors ,genetic structures ,Ependymoglial Cells ,Gene Expression ,Retinal Horizontal Cells ,Zebrafish Proteins ,eye diseases ,Axons ,Retina ,Article ,Nerve Regeneration ,Animals, Genetically Modified ,nervous system ,Animals ,Hedgehog Proteins ,sense organs ,Vision, Ocular ,Zebrafish ,Photoreceptor Cells, Vertebrate ,Retinal Neurons - Abstract
Teleost fish regenerate their retinas after damage, in contrast to mammals. In zebrafish subjected to an extensive ouabain-induced lesion that destroys all neurons and spares Müller glia, functional recovery and restoration of normal optic nerve head (ONH) diameter take place at 100 days postinjury. Subsequently, regenerated retinas overproduce cells in the retinal ganglion cell (RGC) layer, and the ONH becomes enlarged. Here, we test the hypothesis that a selective injury, which spares photoreceptors and Müller glia, results in faster functional recovery and fewer long-term histological abnormalities. Following this selective retinal damage, recovery of visual function required 60 days, consistent with this hypothesis. In contrast to extensively damaged retinas, selectively damaged retinas showed fewer histological errors and did not overproduce neurons. Extensively damaged retinas had RGC axons that were delayed in pathfinding to the ONH, and showed misrouted axons within the ONH, suggesting that delayed functional recovery following an extensive lesion is related to defects in RGC axons exiting the eye and/or reaching their central targets. The atoh7, fgf8a, Sonic hedgehog (shha), and netrin-1 genes were differentially expressed, and the distribution of hedgehog protein was disrupted after extensive damage as compared with selective damage. Confirming a role for Shh signaling in supporting rapid regeneration, shha(t4) +/- zebrafish showed delayed functional recovery after selective damage. We suggest that surviving retinal neurons provide structural/molecular information to regenerating neurons, and that this patterning mechanism regulates factors such as Shh. These factors in turn control neuronal number, retinal lamination, and RGC axon pathfinding during retinal regeneration.
- Published
- 2013
36. Retinal proliferation response in the buphthalmic zebrafish, bugeye
- Author
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Tshering Sherpa, Deborah L. Stenkamp, Ruth A. Frey, Barrie D. Robison, and Samuel S. Hunter
- Subjects
Retinal Ganglion Cells ,animal structures ,genetic structures ,Optic Disk ,Optic disk ,HSP27 Heat-Shock Proteins ,Vision Disorders ,Cell Count ,Biology ,Article ,Animals, Genetically Modified ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,medicine ,In Situ Nick-End Labeling ,Animals ,Regeneration ,Eye Abnormalities ,Fluorescent Antibody Technique, Indirect ,Ganglion cell layer ,Zebrafish ,Intraocular Pressure ,Retinal regeneration ,Cell Proliferation ,Retina ,Hydrophthalmos ,Retinal ,medicine.disease ,biology.organism_classification ,Sensory Systems ,eye diseases ,Cell biology ,Ophthalmology ,Buphthalmos ,Disease Models, Animal ,Low Density Lipoprotein Receptor-Related Protein-2 ,medicine.anatomical_structure ,Retinal ganglion cell ,chemistry ,Gene Expression Regulation ,sense organs ,Stress, Mechanical ,Neuroscience ,Neuroglia - Abstract
The zebrafish retina regenerates in response to acute retinal lesions, replacing damaged neurons with new neurons. In this study we test the hypothesis that chronic stress to inner retinal neurons also triggers a retinal regeneration response in the bugeye zebrafish. Mutations in the lrp2 gene in zebrafish are associated with a progressive eye phenotype (bugeye) that models several risk factors for human glaucoma including buphthalmos (enlarged eyes), elevated intraocular pressure (IOP), and upregulation of genes related to retinal ganglion cell pathology. The retinas of adult bugeye zebrafish showed high rates of ongoing proliferation which resulted in the production of a small number of new retinal neurons, particularly photoreceptors. A marker of mechanical cell stress, Hsp27, was strongly expressed in inner retinal neurons and glia of bugeye retinas. The more enlarged eyes of individual bugeye zebrafish showed disrupted retinal lamination, and a persistent reduced density of neurons in the ganglion cell layer (GCL), although total numbers of GCL neurons were higher than in control eyes. Despite the presence of a proliferative response to damage, the adult bugeye zebrafish remained behaviorally blind. These findings suggest the existence of an unsuccessful regenerative response to a persistent pathological condition in the bugeye zebrafish.
- Published
- 2010
37. Hepatitis C virus seroprevalence in the general female population of 9 countries in Europe, Asia and Africa.
- Author
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Clifford, Gary M., Waterboer, Tim, Dondog, Bolormaa, You Lin Qiao, Kordzaia, Dimitri, Hammouda, Doudja, Keita, Namory, Khodakarami, Nahid, Raza, Syed Ahsan, Ang Tshering Sherpa, Zatonski, Witold, Pawlita, Michael, Plummer, Martyn, and Franceschi, Silvia
- Subjects
AGE distribution ,CONFIDENCE intervals ,HEPATITIS C ,HEPATITIS viruses ,LIVER tumors ,PAPILLOMAVIRUSES ,POPULATION ,POPULATION geography ,SEROLOGY ,VIRAL antibodies ,DISEASE prevalence ,PARITY (Obstetrics) ,DESCRIPTIVE statistics - Abstract
Background: New oral treatments with very high cure rates have the potential to revolutionize global management of hepatitis C virus (HCV), but population-based data on HCV infection are missing in many low and middle-income countries (LMIC). Methods: Between 2004 and 2009, dried blood spots were collected from age-stratified female population samples of 9 countries: China, Mongolia, Poland, Guinea, Nepal, Pakistan, Algeria, Georgia and Iran. HCV antibodies were detected by a multiplex serology assay using bead-based technology. Results: Crude HCV prevalence ranged from 17.4% in Mongolia to 0.0% in Iran. In a pooled model adjusted by age and country, in which associations with risk factors were not statistically heterogeneous across countries, the only significant determinants of HCV positivity were age (prevalence ratio for ≥45 versus <35 years = 2.84, 95%CI 2.18-3.71) and parity (parous versus nulliparous= 1.73, 95%CI 1.02-2.93). Statistically significant increases in HCV positivity by age, but not parity, were seen in each of the three countries with the highest number of HCV infections: Mongolia, Pakistan, China. There were no associations with sexual partners nor HPV infection. HCV prevalence in women aged ≥45 years correlated well with recent estimates of female HCV-related liver cancer incidence, with the slight exception of Pakistan, which showed a higher HCV prevalence (5.2%) than expected. Conclusions: HCV prevalence varies enormously in women worldwide. Medical interventions/hospitalizations linked to childbirth may have represented a route of HCV transmission, but not sexual intercourse. Combining dried blood spot collection with high-throughput HCV assays can facilitate seroepidemiological studies in LMIC where data is otherwise scarce. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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38. Extracting Modulation Transfer Function of the Visual System from Contrast Sensitivity Function in External Noise
- Author
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Tshering Sherpa, Michael D. Varnum, and Chunming Liu
- Subjects
Protein subunit ,Guanosine ,chemistry.chemical_element ,Biology ,Calcium ,Sensory Systems ,Cell biology ,Ophthalmology ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Extracellular ,Channel blocker ,sense organs ,Viability assay ,Cyclic nucleotide-gated ion channel ,Cytotoxicity - Abstract
Purpose: To determine if achromatopsia associated F525N and T383fsX mutations in the CNGB3 subunit of cone photoreceptor cyclic nucleotide-gated (CNG) channels increases susceptibility to cell death in photoreceptor-derived cells. Methods: Photoreceptor-derived 661W cells were transfected with cDNA encoding wild-type (WT) CNGA3 subunits plus WT or mutant CNGB3 subunits, and incubated with the membrane-permeable CNG channel activators 8-(4-chlorophenylthio) guanosine 3′,5′-cyclic monophosphate (CPT-cGMP) or CPT-adenosine 3′,5′-cyclic monophosphate (CPTcAMP). Cell viability under these conditions was determined by measuring lactate dehydrogenase release. Channel ligand sensitivity was calibrated by patch-clamp recording after expression of WT or mutant channels in Xenopus oocytes. Results: Coexpression of CNGA3 with CNGB3 subunits containing F525N or T383fsX mutations produced channels exhibiting increased apparent affinity for CPT-cGMP compared to WT channels. Consistent with these effects, cytotoxic ity in the presence of 0.1 μM CPT-cGMP was enhanced relative to WT channels, and the increase in cell death was more pronounced for the mutation with the largest gain-of-function effect on channel gating, F525N. Increased susceptibility to cell death was prevented by application of the CNG channel blocker L-cis-diltiazem. Increased cytotoxicity was also found to be dependent on the presence of extracellular calcium. Conclusions: These results indicate a connection between disease-associated mutations in cone CNG channel subunits, altered CNG channel-activation properties, and photoreceptor cytotoxicity. The rescue of cell viability via CNG channel block or removal of extracellular calcium suggests that cytotoxicity in this model depends on calcium entry through hyperactive CNG channels.
- Published
- 2013
39. Age-Related Cone Abnormalities in Zebrafish with Genetic Lesions in Sonic Hedgehog
- Author
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Kalyani Muhunthan, Rosanna Satterfield, Tshering Sherpa, David A. Cameron, Deborah L. Stenkamp, and Thomas S. Vihtelic
- Subjects
Aging ,animal structures ,Light ,genetic structures ,Mutant ,Gene Expression ,Retina ,Article ,chemistry.chemical_compound ,In Situ Nick-End Labeling ,medicine ,Animals ,Hedgehog Proteins ,RNA, Messenger ,Sonic hedgehog ,Fluorescent Antibody Technique, Indirect ,Zebrafish ,Alleles ,In Situ Hybridization ,Cell Proliferation ,Cell Death ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Regeneration (biology) ,Retinal Degeneration ,Rod Opsins ,Retinal ,Anatomy ,Zebrafish Proteins ,biology.organism_classification ,Embryonic stem cell ,Phenotype ,Cell biology ,Radiation Injuries, Experimental ,medicine.anatomical_structure ,Microscopy, Fluorescence ,chemistry ,Mutation ,embryonic structures ,Retinal Cone Photoreceptor Cells ,biology.protein ,sense organs - Abstract
PURPOSE. Sonic hedgehog (Shh) signaling is essential for photoreceptor differentiation and retinal cell survival in embryonic zebrafish. The study was conducted to determine whether adult heterozygous carriers of mutant alleles for the sbh gene display retinal abnormalities. METHODS. Retinal cryosections from young, middle-aged, and senescent wild-type and sonic-you +/- (syu +/- ) zebrafish were probed with retinal cell type-specific markers. Contralateral retinal flatmounts from these fish, and from adult albino zebrafish subjected to light-induced photoreceptor damage followed by regeneration, were hybridized with blue cone opsin cRNA for quantitative analysis of the blue cone pattern. Retinal expression of shh mRNA was measured by quantitative RT-PCR. RESULTS. Regions of cone loss and abnormal cone morphology were observed in the oldest syu +/- zebrafish, although no other retinal cell type was affected. This phenotype was age-related and genotype-specific. Cone distribution in the oldest syu +/- zebrafish was predominantly random, as assessed by measuring the short-range pattern, whereas that of wild-type fish and the younger syu +/- zebrafish was statistically regular. A measure of long-range pattern revealed atypical cone aggregation in the oldest syu +/- zebrafish. The light-treated albino zebrafish displayed random cone patterns immediately after light toxicity, but showed cone aggregation on regeneration. Retinas from the syu +/- fish showed reduced expression of shh mRNA compared with those of wild-type siblings. CONCLUSIONS. The syu +/- zebrafish presents a model for the study of hereditary age-related cone abnormalities. The syu +/- retinas most likely experience progressive cone photoreceptor loss, accompanied by cone regeneration. Shh signaling may be required to maintain cone viability throughout life.
- Published
- 2008
40. Hepatitis C virus seroprevalence in the general female population of 9 countries in Europe, Asia and Africa
- Author
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Ang Tshering Sherpa, Syed Ahsan Raza, You-Lin Qiao, D Kordzaia, Gary M. Clifford, Michael Pawlita, Doudja Hammouda, Bolormaa Dondog, Martyn Plummer, Namory Keita, Witold Zatonski, Silvia Franceschi, Tim Waterboer, and Nahid Khodakarami
- Subjects
Cancer Research ,medicine.medical_specialty ,Epidemiology ,Hepatitis C virus ,Population ,medicine.disease_cause ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Seroprevalence ,education ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,HPV infection ,virus diseases ,medicine.disease ,Sexual intercourse ,Infectious Diseases ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,030211 gastroenterology & hepatology ,business ,Liver cancer ,Research Article ,Demography - Abstract
Background New oral treatments with very high cure rates have the potential to revolutionize global management of hepatitis C virus (HCV), but population-based data on HCV infection are missing in many low and middle-income countries (LMIC). Methods Between 2004 and 2009, dried blood spots were collected from age-stratified female population samples of 9 countries: China, Mongolia, Poland, Guinea, Nepal, Pakistan, Algeria, Georgia and Iran. HCV antibodies were detected by a multiplex serology assay using bead-based technology. Results Crude HCV prevalence ranged from 17.4% in Mongolia to 0.0% in Iran. In a pooled model adjusted by age and country, in which associations with risk factors were not statistically heterogeneous across countries, the only significant determinants of HCV positivity were age (prevalence ratio for ≥45 versus
- Full Text
- View/download PDF
41. Alternative Splicing for CNGA3 Controls Channel Sensitivity to Regulation by Phosphoinositides
- Author
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Gucan Dai, Michael D. Varnum, Elizabeth D. Rich, Tshering Sherpa, Changhong Peng, and Daylene Mills
- Subjects
Genetics ,Channel sensitivity ,Exon ,Alternative splicing ,Pi ,Biophysics ,Functional significance ,Heterologous expression ,Biology ,Cyclic nucleotide-gated ion channel ,Precursor mRNA - Abstract
Precursor mRNA encoding CNGA3 subunits of cone photoreceptor CNG channels undergoes alternative splicing, generating variants differing in the N-terminal cytoplasmic region of the protein. In humans, four CNGA3 protein variants arise from alternative splicing, but the functional significance of these changes has been a persistent mystery. Because CNGA3 subunits mediate cone CNG channel regulation by phosphoinositides (PIs), we hypothesized that alternative splicing may tune channel sensitivity to PIs. Heterologous expression of the four CNGA3 variants alone or with CNGB3 subunits did not reveal significant differences in basic channel properties. However, inclusion of optional exon e3, with or without optional exon e5, produced heteromeric CNGA3+CNGB3 channels exhibiting an approximately three-fold greater shift in K1/2,cGMP after PIP2 or PIP3 compared to channels lacking the sequence encoded by exon e3. The relative abundance of exon e3-containing retinal transcripts was ∼20% by qPCR. We have previously identified two structural features within CNGA3 that support PI regulation of cone CNG channels: an N-terminal and a C-terminal component; specific mutations within these regions eliminated PI sensitivity of CNGA3+CNGB3 channels. The e3 variant enhanced the component of PI modulation that depends on the C-terminal region, rather than the nearby N-terminal region, consistent with an allosteric effect on PI sensitivity. Alternative splicing of CNGA3 occurs in multiple species, although the exact variants are not conserved across CNGA3 orthologs. Optional exon e3 is unique to humans, even compared to other primates. In parallel, we found that a specific splice variant of canine CNGA3 removes a region that is necessary for high sensitivity to PIs. Presumably, alternative splicing in CNGA3 has evolved to regulate the interactions between the channel and membrane-bound phospholipids. Together, these results reveal an important mechanism of channel control that may have broad implications.
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