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Aims: Access to hemodialysis (HD) is limited in Nepal due to geographical terrain and hemodialysis centers being mostly limited to capital city of the country. Therefore, CAPD is likely to be a better option of dialysis in Nepal. In 1998, continuous ambulatory peritoneal dialysis (CAPD) was initiated in Nepal without success. High rate of peritonitis was cited for failure. Hot tropical climate of Nepal along with poor sense of hygiene among patients is thought to be responsible for the high rate of peritonitis. A new CPD program was started in 2002 in our institute. As only center for dialysis in eastern Nepal, the institute serves to around 25% of the population of Nepal. We reviewed the incidence of peritonitis and factors predisposing to peritonitis. Materials and Methods: A total of 30 patients who were initiated on chronic peritoneal dialysis since 2002 to 2005 were included in the study. Two CAPD nursed follow-up this patients and were responsible for the data recording along with resident doctor in dialysis unit. Peritonitis was diagnosed if patient reported cloudy effluent and/or pain abdomen and had dialysate white cell count > 100/mL of which 50% or more were polymorphonuclear leukocytes. All patients were on prophylactic mupirocine ointment. Patients complicated with peritonitis (N = 8) and patients without peritonitis (N=22) were compared. Results: Most patients were male (N=26). Mean duration of dialysis was 12 month per patients (Total patients month= 362). Nine episodes of peritonitis in eight patients were recorded during this period. Six episode of peritonitis were culture positive (staphylocoocus aureous-2, Psedornonous aurigonosae-1, other gram negative organism-2, fungal-1). Culture sterile peritonitis was recorded in 3 episodes (patients). Two patients in each group were shifted to hemodialysis therapy. End stage related due to diabetes mellitus and low serum albumin were predisposing factors for development of peritonitis. Conclusion: Peritonitis is not a limiting factor for growth of CAPD in Nepal. Low serum albumin and diabetes patients are prone for CAPD related peritonitis. [ABSTRACT FROM AUTHOR]

A young Nepali woman having characteristics angiographic findings of moyamoya disease and manifesting hemiballismus and parkinsonism is reported. To the best of our knowledge, this is the fi rst case report of moyamoya disease from Nepal. [ABSTRACT FROM AUTHOR]

Background and Objectives: Gallstone disease (GD) is a prevalent health issue globally, particularly in developed nations, and has notable associations with cardiovascular disease (CVD). This prospective observational cross-sectional study aimed to investigate the association between gallstone disease and carotid intima-media thickness (CIMT), a marker of carotid atherosclerosis, in a tertiary care setting., Method: Conducted at a tertiary care center, the study included 96 participants (48 with gallstone disease and 48 age and sex-matched controls). Data collection involved demographic information, BMI calculation, abdominal ultrasonography for gallstone detection, and carotid ultrasonography for CIMT measurement. Statistical analysis was performed using SPSS version 26., Results: The study revealed higher CIMT values in GD patients compared to controls ( P <0.001). Additionally, a positive correlation was observed between CIMT and age (r=0.450, P <0.001) and BMI (r=0.550, P <0.001). The Cohen's d-test indicated a clinically significant difference in CIMT between GD patients and controls (d=1.47)., Conclusion: This study revealed a significant association between gallstone disease and elevated CIMT, correlating with higher BMI indicating a potential link between gallstone disease and increased risk of carotid atherosclerosis. These findings highlight the importance of assessing cardiovascular risk in patients with gallstone disease, highlighting the potential utility of carotid ultrasonography as a non-invasive screening tool. Early intervention strategies may be warranted to mitigate cardiovascular risks associated with gallstone disease., Competing Interests: All the authors declare no competing interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Tenecteplase, a new thrombolytic drug, is now widely recommended and used for treating acute ischemic stroke, and timely thrombolysis within 4.5 hours is crucial for better outcomes. However, due to limited stroke awareness, transportation difficulties, and inadequate access to experts and comprehensive stroke care centers, fewer than 15% of stroke patients in Nepal receive thrombolytic therapy. The "drip and ship" model, which involves starting thrombolysis at a noncomprehensive stroke care center and transferring the patient to another center for further care, can effectively overcome these obstacles, provided trained personnel are available at non-comprehensive stroke care centers. We report a case of acute ischemic stroke treated with thrombolysis within 4.5 hours of symptom onset at a non-comprehensive stroke care center, followed by transfer to another center for ongoing care, demonstrating the feasibility and potential benefits of the drip and ship model in resource-limited settings.

Background: Rosacea is a chronic inflammatory skin condition that predominantly manifests as facial flushing, irritation, and acne. Rosacea and cancer are thought to be linked by the commonality of inflammatory and immune response dysfunction. Studies that have looked into this possible association have reported mixed results., Objective: Given the conflicting literature on this topic, our study sought to evaluate the overall association between rosacea and several cancers commonly investigated in the literature., Methods: A systematic review was conducted using the Cochrane, PubMed, Embase, and Ovid databases. Studies were screened independently for inclusion of rosacea and glioma and breast, thyroid, hepatic, or skin cancers. Using information from the articles, rosacea and each cancer were categorized as having a positive, negative, or unclear association., Results: Our systematic review included 39 full-text studies that investigated the association between rosacea and various malignancies. Among the malignancies of concern, 41% (16/39) of the studies reported an association with basal cell carcinoma, with 2 cohorts revealing an adjusted risk ratio (RR) of 1.50 (95% CI 1.35-1.67) and 0.72 (95% CI 0.56-0.93). In total, 33% (13/39) of the studies reported an association with squamous cell carcinoma, with 2 cohorts revealing an adjusted RR of 1.4 (95% CI 1.02-1.93) and 1.30 (95% CI 0.90-1.88). A total of 8% (3/39) of the studies reported an association between breast cancer and melanoma, with breast cancer cohorts revealing an adjusted RR of 8.453 (95% CI 1.638-43.606), 1.03 (95% CI 0.89-1.20), and 1.36 (95% CI 1.18-1.58) and melanoma cohorts revealing an adjusted RR of 1.10 (95% CI 0.95-1.27), 0.63 (95% CI 0.47-0.85), and 0.96 (95% CI 0.57-1.62). A total of 5% (2/39) of the studies reported an association among nonmelanoma skin cancers, hepatic cancer, and thyroid carcinomas, with nonmelanoma skin cancer cohorts revealing an adjusted RR of 1.36 (95% CI 1.26-1.47) and 2.66 (95% CI 1.53-4.61), hepatic cancer cohorts revealing an adjusted RR of 1.42 (95% CI 1.06-1.90) and 1.32 (95% CI 0.89-1.95), and thyroid carcinoma cohorts revealing an adjusted RR of 1.06 (95% CI 0.68-1.65) and 1.59 (95% CI 1.07-2.36). Only 1 cohort reported an association with glioma, revealing an adjusted RR of 1.36 (95% CI 1.18-1.58). According to our review, patients with rosacea were statistically more likely to have nonmelanoma skin cancers, breast cancer, and glioma. Rosacea was not found to be substantially associated with melanoma. The associations between rosacea and hepatic and thyroid cancers were unclear because of conflicting results., Conclusions: The current literature shows that rosacea is significantly associated with increased odds of nonmelanoma skin cancers, glioma, and breast cancer. Rosacea does not appear to be associated with melanoma. Further studies should be conducted to clarify the association between thyroid and hepatic cancers and rosacea., (©Luna Thapa, Joyce Xia, William Guo, Hunya Usmani, Devin Miller, Daniel Lozeau. Originally published in JMIR Dermatology (http://derma.jmir.org), 08.11.2023.)

A man in his early 80s presented with acute onset aphasia and right-sided weakness with an NIH Stroke Scale (NIHSS) of 17. He was last seen normal 9 hours before the presentation. MRI of the brain showed acute infarcts in the left caudate, lentiform nucleus and corona radiata. MRI angiogram (MRA) revealed an occluded left main middle cerebral artery (MCA) and an associated ipsilateral patent duplicated middle cerebral artery (DMCA). Mechanical thrombectomy (MT) was performed, and he was discharged with an NIHSS of 8. In this report, we review and discuss the challenges during the intervention of MCA occlusion in the presence of duplicated MCA, a rare anomaly., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Globally, the majority of strokes affect people residing in lower- and lower-middle-income countries (LMICs), but translating evidence-based knowledge into clinical practice in regions with limited healthcare resources remains challenging. As an LMIC in South Asia, stroke care has remained a healthcare problem previously unaddressed at a national scale in Nepal. The Nepal Stroke Project (NSP) aims to improve acute stroke care in the tertiary healthcare sector of Nepal. We hereby describe the methods applied and analyze the barriers and facilitators of the NSP after 18 months., Methods: The NSP follows a four-tier strategy: (1) quality improvement by training healthcare professionals in tertiary care centers; (2) implementation of in-hospital stroke surveillance and quality monitoring system; (3) raising public awareness of strokes; and (4) collaborating with political stakeholders to facilitate public funding for stroke care. We performed a qualitative, iterative analysis of observational data to analyze the output indicators and identify best practices., Results: Both offline and online initiatives were undertaken to address quality improvement and public awareness. More than 1,000 healthcare professionals across nine tertiary care hospitals attended 26 stroke-related workshops conducted by Nepalese and international stroke experts. Monthly webinars were organized, and chat groups were made for better networking and cross-institutional case sharing. Social media-based public awareness campaigns reached more than 3 million individuals. Moreover, live events and other mass media campaigns were instituted. For quality monitoring, the Registry of Stroke Care Quality (RES-Q) was introduced. Collaboration with stakeholders (both national and international) has been initiated., Discussion: We identified six actions that may support the development of tertiary care centers into essential stroke centers in a resource-limited setting. We believe that our experiences will contribute to the body of knowledge on translating evidence into practice in LMICs, although the impact of our results must be verified with process indicators of stroke care., Competing Interests: TF and JM were employed by Boehringer Ingelheim International GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Tunkl, Paudel, Bajaj, Thapa, Tunkl, Chandra, Shah, Karmacharya, Subedi, Jalan, Ghimire, Ghimire, Dorje, Begli, Golenia, Gajurel, Shreyan, Sharma, Krauss, Pandian, Fischer, van der Merwe, Wick, Hacke and Gumbinger.)

The electrochemical activation of dinitrogen at ambient temperature and pressure for the synthesis of ammonia has drawn increasing attention. The faradaic efficiency (FE) as well as ammonia yield in the electrochemical synthesis is far from reaching the requirement of industrial-scale production. In aqueous electrolytes, the competing electron-consuming hydrogen evolution reaction (HER) and poor solubility of nitrogen are the two major bottlenecks. As the electrochemical reduction of nitrogen involves proton-coupled electron transfer reaction, rationally engineered electrolytes are required to boost FE and ammonia yield. In this Review, we comprehensively summarize various electrolyte engineering strategies to boost the FE in aqueous and non-aqueous medium and suggest possible approaches to further improve the performance. In aqueous medium, the performance can be improved by altering the electrolyte pH, transport velocity of protons, and water activity. Other strategies involve the use of hybrid and water-in-salt electrolytes, ionic liquids, and non-aqueous electrolytes. Existing aqueous electrolytes are not ideal for industrial-scale production. Suppression of HER and enhanced nitrogen solubility have been observed with hybrid and non-aqueous electrolytes. The engineered electrolytes are very promising though the electrochemical activation has several challenges. The outcome of lithium-mediated nitrogen reduction reaction with engineered non-aqueous electrolyte is highly encouraging., (© 2023 Wiley-VCH GmbH.)

Background: With an increasing burden of stroke, it is essential to minimize the incidence of stroke and improve stroke care by emphasizing areas that bring out the maximum impact. The care situation remains unclear in the absence of a national stroke care registry and a lack of structured hospital-based data monitoring. We conducted this systematic review and meta-analysis to assess the status of stroke care in Nepal and identify areas that need dedicated improvement in stroke care., Methods: A systematic literature review was conducted to identify all studies on stroke epidemiology or stroke care published between 2000 and 2020 in Nepal. Data analysis was done with Statistical Package for Social Sciences (SPSS) and Comprehensive Meta-analysis (CMA-3)., Results: We identified 2533 studies after database searching, and 55 were included in quantitative and narrative synthesis. All analyses were done in tertiary care settings in densely populated central parts of Nepal. Ischemic stroke was more frequent (70.87%) than hemorrhagic (26.79%), and the mean age of stroke patients was 62,9 years. Mortality occurred in 16.9% (13-21.7%), thrombolysis was performed in 2.39% of patients, and no studies described thrombectomy or stroke unit care., Conclusion: The provision of stroke care in Nepal needs to catch up to international standards, and our systematic review demonstrated the need to improve access to quality stroke care. Dedicated studies on establishing stroke care units, prevention, rehabilitation, and studies on lower levels of care or remote regions are required., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Stroke is a major global health problem and was the second leading cause of death worldwide in 2020. However, the lack of public stroke awareness especially in low- and middle-income countries (LMICs) such as Nepal severely hinders the effective provision of stroke care. Efficient and cost-effective strategies to raise stroke awareness in LMICs are still lacking. This study aims to (a) explore the feasibility of a social media-based stroke awareness campaign in Nepal using a cost-benefit analysis and (b) identify best practices for social media health education campaigns., Methods: We performed a stroke awareness campaign over a period of 6 months as part of a Stroke Project in Nepal on four social media platforms (Facebook, Instagram, Twitter, TikTok) with organic traffic and paid advertisements. Adapted material based on the World Stroke Day Campaign and specifically created videos for TikTok were used. Performance of the campaign was analyzed with established quantitative social media metrics (impressions, reach, engagement, costs)., Results: Campaign posts were displayed 7.5 million times to users in Nepal. 2.5 million individual social media users in Nepal were exposed to the campaign on average three times, which equals 8.6% of Nepal's total population. Of those, 250,000 users actively engaged with the posts. Paid advertisement on Facebook and Instagram proved to be more effective in terms of reach and cost than organic traffic. The total campaign cost was low with a "Cost to reach 1,000 users" of 0.24 EUR and a "Cost Per Click" of 0.01 EUR., Discussion: Social media-based campaigns using paid advertisement provide a feasible and, compared to classical mass medias, a very cost-effective approach to inform large parts of the population about stroke awareness in LMICs. Future research needs to further analyze the impact of social media campaigns on stroke knowledge., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tunkl et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Out of many atherosclerotic complications, peripheral arterial disease (PAD) is also important one. To prevent morbidity and mortality related with PAD, early detection is must, and is possible by duplex screening. This study aims at screening for PAD in patients with type 2 Diabetes mellitus., Methods: This study is single centered cross- sectional, observational study conducted in department of internal medicine of DMCRI- a tertiary care hospital. A total of 140, type 2 diabetes patients were screened for peripheral arterial disease by duplex ultrasound after taking informed consent and fulfilling inclusion and exclusion criteria., Results: In our study among 140 Participants, 50% are male and 50% are female with mean age of 57.6 ± 10.4 years standard deviation (SD) and mean duration of diabetes was 8.31± 5.9 SD years with 13.6% were alcohol consumer; 1.4% were smokers; 59.3% of them had high blood pressure; (28.6%) had dyslipidaemia and 11.4% had hypothyroidism. The prevalence of PAD in type 2 diabetes was 27.1% in our study. The mean of glycated hemoglobin (HBA1c) was 7.23 ± 1.75% and while performing analytical test {chi-square (χ)}, we found there was no association between HBA1c level and presence of peripheral arterial disease., Conclusions: The prevalence of peripheral arterial disease is high almost more than one quarter (27.1%). Screening of diabetic patients is must especially those aged and high glycated hemoglobin for early detection and effective management of PAD.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS) is a rare neurodegenerative inherited disorder that is characterized by stroke-like episodes, seizures, endocrine, and multiple system involvement. It is important to consider it as a differential diagnosis in a young patient with stroke-like episodes as it is progressive and has multiple complications., Case Presentation: A 28-year-old male presented with slurring of speech and drowsiness for 7 h. He was a diagnosed case of type 2 diabetes mellitus, Wolf-Parkinson-White syndrome, and bilateral hearing loss., Clinical Findings and Investigations: The patient had expressive aphasia with impaired fluency, repetition, and naming. After being discharged, he represented with loss of consciousness and involuntary movements of the whole body. MRI and MRS showed extension of hyperintense lesions to parieto-occipital regions from temporal regions not limited by vascular territories. MELAS was considered, which was confirmed by molecular genetic analysis. Coenzyme Q10 was used for MELAS. Insulin, Linagliptin, and levetiracetam were used for diabetes and seizures. Regular follow-up was advised to the patient.MELAS is an important syndrome to consider in any young patient presenting with unexplained stroke disorders. A high index of suspicion is needed in an appropriate clinical setting to avoid misdiagnosis., Competing Interests: No conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background Headache disorders are among the most prevalent and disabling conditions worldwide. People, however, do not seek early advice in developing countries. Objective To study clinical profile of patients with headache and their existing knowledge, attitude, and practice regarding primary headaches. Method Descriptive cross-sectional study conducted among 196 patients. Patients were selected using purposive sampling technique fulfilling inclusion criteria. Patients were interviewed based on semi-structural headache questionnaire and data was collected from 4th October to 21st December 2021. Descriptive statistics was used for analysis and interpretation. Result Among 196 participants, 74% were females, 29.6% of patients were between (31 to 40) years of age. The majority were Hindu and belongs to province 3; 36.7% were homemakers, and 32.2% were literate. Migraine headache was the most common type with 14.3% reporting aura. Most reported headache within 1 to 5 years. The commonest triggers were sunlight 64.8%, crowd 54.7%, stress 39.8%, fasting state 31.7%, cold 26.3%. Almost 39% believed that headache could be a chronic neurologic disorder. Majority had knowledge of the causes, triggers, and the relieving factors. Fifty-five percent seek help of a doctor for first time, and the rest seek help of a pharmacist or self-medication. Only 19% tried to manage the headache triggers; 66.8% felt that lifestyle modification is the best treatment for headache comparing drugs. Conclusion Migraine headache was the commonest headache occurring at middle age group with sunlight being the most common trigger factor. Lifestyle modification was perceived to be the best for headache management.

Objective  Endovascular therapy has become the mainstay of treatment of acute ischemic stroke (AIS) due to large vessel occlusion. A direct aspiration first-pass technique (ADAPT) using large bore aspiration catheters has been introduced as a rapid, simple method for achieving good revascularization and good clinical outcomes. The aim of this study was to assess the safety and efficacy of ADAPT in the treatment of AIS due to large-vessel occlusion in the Nepali patient population. Materials and Methods  Retrospective data were collected for all consecutive patients treated for AIS with ADAPT from March 2019 through January 2021 at two hospitals. Outcomes were successful revascularization (modified thrombolysis in cerebral infarction score of 2b-3), time to revascularization, procedural complications, and good clinical outcome (modified Rankin Scale score of 0 to 2) and mortality at 90 days. Statistical Analysis  Retrospective data were collected and descriptive statistics were calculated. Results  Sixty-eight patients treated for AIS with ADAPT were included. The median National Institutes of Health Stroke Scale score at presentation was 13 (IQR 10-13.25). The median time from arterial puncture to revascularization was 40 minutes (IQR 30-45). Successful revascularization was achieved in 54 patients (79.4%). No cases of symptomatic intracranial hemorrhage occurred. At 90-day follow-up, good clinical outcome was achieved in 57 patients (83.8%), and 4 patients died (5.9%). Conclusion  A direct aspiration first pass technique appears to be a fast, simple, safe, and effective method for the management of AIS in the Nepali patient population., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Myasthenia gravis is a neuromuscular junction disorder characterised by fluctuating muscle weakness, improved by using anti-cholinesterase drugs. In addition to the autoimmune aetiology, various factors such as infections, surgery, and drugs are known to precipitate the condition. We report a case of a 15-year-old boy with D-penicillamine-induced myasthenia gravis who presented with facial diplegia, dysphagia, and drooling of saliva, 6 years after the initiation of treatment for Wilson's disease. Therefore, clinicians should be more vigilant while prescribing patients with chelating drugs like D-penicillamine with regular monitoring of the new symptoms and keeping a very low threshold for the suspicion of myasthenia gravis., Keywords: d-penicillamine; myasthenia gravis; pyridostigmine; Wilson's disease.

Background: The COVID-19 pandemic has challenged the entire globe and the need for a vaccine is supreme. Since many vaccines along with Covishield have been granted emergency use authorization, the evaluation and monitoring of safety are crucial. Covishield was rolled out in Nepal on January 27, 2021. So through this study, we aim to identify the prevalence of Adverse Events Following Immunization in general with the first dose of Covishield vaccine, compare Adverse Events Following Immunization in prior COVID-19 positive cases and Adverse Events Following Immunization in co-morbid individuals., Methods: This was a descriptive cross-sectional study conducted in 440 sample from May 2021 till July 2021 in a provincial government hospital of western Nepal. Ethical approval was received from Ethical Review Board, Nepal Health Research Council (Registration no: 279/2021 P). Simple random sampling was used. Point estimate was done at 95% confidence interval and descriptive analysis was done to identify the prevalence of Adverse Events Following Immunization within one week after Covishield vaccination in the studied population., Results: 79.77% of the study population complaint at least one or more Adverse Events Following Immunization. Fever, myalgia, headache, pain at the injection site, arthralgia, chills, and fever are the most common Adverse Events Following Immunization. 42.73% of the study population self-medicated to manage Adverse Events Following Immunization, 7.89% took leave from work while 0.28% needed medical attention. No major Adverse Events Following Immunization relevance with prior-COVID history or co-morbidity was seen., Conclusions: Majority of the vaccinated participants had minor adverse effects on the first-day post-vaccination while most of the Adverse Events Following Immunization subsided within seven days.

Background: Stroke related studies in Nepal are primarily hospital-based and mainly from the capital city., Objectives: We aimed to estimate the prevalence of stroke and stroke risk factors in the South-Western community of Nepal., Methods: A cross-sectional study was conducted from May to August 2018 among 549 randomly selected Nepalese participants from diverse ethnicity, aged ≥15 years, in a region with the availability of neurological support facilities. Data were collected using a stroke questionnaire designed for the purpose. Stroke was identified by enumerators using the Balance-Eyes-Face-Arms-Speech-Time (BEFAST) scale, and a senior neurologist confirmed it. We assessed the presence of major risk factors associated with stroke., Results: The crude and age-standardised prevalence of stroke were 2368 and 2967 per 100,000 respectively. Of all the surveyed participants, 61% (n=335) reported consumption of full-fat dairy products >3 days per week, 87.6% (n=481) reported a high intake of salt (>5 g/day), 83.6% (n=459) with a low intake of fruits and vegetables (<400 g/day), 45.2% (n=248) with perceived stress related to work or home, 51.6% (n=283) with financial stress (283, 51.6%), 86.7% (n=457) with low high-density lipoprotein, 96.2% (n=507) with high blood urea nitrogen, 47.1% (n=356) were either overweight or obese 20.4% (n=112) with hypertension and 6.2% (n=34) with diabetes., Conclusions: The prevalence of stroke in the community of the South-Western part of Nepal is relatively higher than that estimated in South-Asia and global context. Our findings suggest an urgent community intervention, particularly with healthy lifestyles changes for future stroke prevention in the high-risk group., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest concerning the research, authorship, and/or publication of this article, (Copyright © 2021 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has significantly affected health care delivery globally. COVID-19 is associated with varied neurological manifestations including acute ischemic stroke. In densely populated South Asian nations like Nepal that have suboptimal baseline health care systems, we foresee unique challenges during this pandemic to ensure effective stroke management as well as the safety of health care workers involved in the management of stroke patients. Keywords: COVID-19; health care workers; safety; stroke management.

Responses to the death of a spouse vary; although some are at increased risk of poorer physical and mental health outcomes, others have more resilient responses. In light of the limited scope of research on widows' experiences in Nepal, a setting where widows are often marginalized, we explore themes of resilience in Nepali widows' lives. Drawing from a larger qualitative study of grief and widowhood, a thematic narrative analysis was performed on narratives from four widows that reflected resilient outcomes. Individual assets and social resources contributed to these widows' resilient outcomes. Forgetting, acceptance, and moving forward were complemented by confidence and strength. Social support and social participation were key to widows' resilient outcomes. These four narratives reflect the sociocultural context that shape widows' resilient outcomes in Nepal. Future studies on the emergent themes from this exploratory study will help identify how best to encourage resilient outcomes among widows.

Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR) was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic) was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2 . Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67) and 27 had ischemic stroke (mean age 56.12 ± 13.08). The mean e-GFR (mL/minute per 1.732m 2 ) at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005). Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.27). The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical intervention (p=0.4) did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion : Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy., Competing Interests: Competing interests: No competing interests were disclosed.

Objective: Persistent complex bereavement disorder (PCBD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), has not been well studied in socioculturally diverse populations. Thus, this qualitative study examined (a) how widows in Nepal understand grief, (b) whether a local construct of PCBD exists, and (c) its comparability with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), terminology., Methods: Using an adapted Explanatory Model Interview Catalogue (EMIC) framework, semistructured interviews with 25 widows and 12 key informants, as well as three focus-group discussions (n = 20), were conducted between October 2014 and April 2015. Through an inductive grounded theory-based approach, we used the constant comparative method, iteratively coding transcripts to identify themes and patterns in the data. Also, we created two lists of grief responses, one of early reactions and another all reactions to grief, based on the frequency of mention., Results: No single term for grief was reported. Widows reported a local construct of PCBD, which was broadly compatible with DSM-5 terminology but with important variation reflecting societal influence. Surviving torture during conflict, economic and family stressors, and discrimination were mentioned as important determinants that prolong and complicate grief. Suicidal ideation was common, with about 31% and 62% of widows reporting past-year and lifetime suicidality, respectively. Findings may not be generalizable to all Nepali widows; participants were recruited from a non-governmental organization, from Kathmandu and its neighboring districts, and were primarily of reproductive age., Conclusions: While PCBD symptoms proposed in DSM-5 were mentioned as relevant by study participants, some components may need adaptation for use in non-Western settings, such as Nepal.

Introduction . Epilepsy continues to increase worldwide but, unfortunately, many high school students have inadequate knowledge of and negative beliefs towards the disease. We aimed to assess the knowledge, beliefs, and practices of epilepsy among high school students of Central Nepal. Materials and Methods . A cross-sectional study was performed involving 1360 high school students from 33 private schools across Bharatpur, from June 2013 to July 2013, to assess their knowledge, beliefs, and practices (KBP) on epilepsy using a standardized questionnaire. The differences in mean KBP scores between different sexes, religions, and those personally knowing versus not knowing someone with epilepsy were assessed using independent t -tests; a Pearson correlation was calculated to assess the relationship between KBP scores and age. Results . Of 1360 participants, 79 (5.8%) students had never heard or read about epilepsy and were consequently excluded from statistical analysis. Only 261 out of 1360 (19.2%) had personally known someone with epilepsy. The mean KBP scores were 5.0/8, 7.4/12, and 1.7/3, respectively. Statistically significant differences were only observed in the knowledge component of the KBP score; female scored higher than males ( p < 0.001) and, interestingly, students who had personally known a person with epilepsy actually knew less than those who had not known one ( p = 0.018). We also found a significant negative correlation between knowledge and age ( p = 0.003). Conclusions . The overall knowledge, beliefs, and practices appear to be inadequate, emphasizing the need for further educational intervention., Competing Interests: The authors declare that there are no competing interests.

Little research exists on social isolation and health among widows despite their marginalization in South Asia. Using a conceptual framework that delineates distinct forms of social support, our results provide a preliminary analysis of the role social support plays in the well-being of Nepali widows. Between 2011 and 2012, we conducted 42 in-depth interviews in the Kathmandu valley and Surkhet district. Low social support was a common theme, principally lacking in the domains of emotional and instrumental support and was described as increasing women's vulnerability to mistreatment and economic insecurity. Policies and programs that foster these types of support may have positive effects on widows' well-being.

Background: Baseline stroke knowledge in a targeted population is indispensable to promote the effective stroke education. We report the baseline knowledge, attitude, and practice (KAP) of high school students with respect to stroke from Nepal., Materials and Methods: A self-structured questionnaire survey regarding KAP about stroke was conducted in high school students of 33 schools of Bharatpur, Nepal. Descriptive statistics including Chi-square test was used, and the significant variables were subjected to binary logistic regression., Results: Among 1360 participants, 71.1% had heard or read about stroke; 30.2% knew someone with stroke. 39.3% identified brain as the organ affected. Sudden onset limb/s weakness/numbness (72%) and hypertension (74%) were common warning symptom and risk factor identified. 88.9% would take stroke patients to a hospital. Almost half participants (55.5%) felt ayurvedic treatment be effective. 44.8% felt stroke as a hindrance to a happy life and 86.3% believed that family care was helpful for early recovery. Students who identified at least one risk factor were 3.924 times ( P < 0.001, confidence interval [CI] = 1.867-8.247) or those who identified at least one warning symptom were 2.833 times ( P ≤ 0.023, CI = 1.156-6.944) more likely to take stroke patients to a hospital., Conclusion: KAP of high school Nepalese students regarding stroke was satisfactory, and the students having knowledge about the risk factors and warning symptoms were more likely to take stroke patients to a hospital. However, a few misconceptions persisted.

Widows are a vulnerable population in Nepal. This study examined Nepalese widows' experiences of violence, their coping strategies, and barriers faced in seeking help. Study participants were recruited from Women for Human Rights, an NGO in Nepal. A stratified purposive sampling approach was used to select 51 widows and 5 staff members for in-depth interviews. Twenty-seven women who experienced violence were included in this analysis. Data were analyzed and synthesized using a thematic analysis procedure. Widows reported a range of violent experiences perpetrated by family and community members that spanned psychological, physical, and sexual abuse. Women dealt with abusive experiences using both adaptive (e.g., attempting to move ahead, seeking social support, using verbal confrontation) and maladaptive coping strategies (e.g., suicidal thoughts or self-medication). However, they faced barriers to seeking help such as insensitivity of the police, perceived discrimination, and general lack of awareness of widows' problems and needs. Findings highlight the need for interventions across the individual, family, community, and policy levels. Avenues for intervention include creating awareness about widows' issues and addressing cultural beliefs affecting widows' lives. Furthermore, efforts should focus on empowering widows, promoting healthy coping, and addressing their individual needs., (© The Author(s) 2015.)

Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "<2" or "≥2." Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003-1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals.

Background: Stroke is the major cause of morbidity and mortality worldwide. The number of stroke patients receiving recombinant tissue plasminogen activator (rt-PA), also known as Alteplase, in the developing world is extremely low. We aim to study the feasibility and efficacy of thrombolysis for the 1(st) time in our country., Materials and Methods: In this retrospective study (July 2012-August 2015), acute ischemic stroke patients who were thrombolyzed within 3 h of stroke onset were included. Their demographic profiles, clinical profiles, risk factors, type of thrombolytic used, and outcomes were systematically recorded and analyzed., Results: A total of 9 patients were thrombolyzed. The mean time from the onset of stroke symptoms to first dose of rt-PA (onset to treatment) was 1.2 h. Six patients had good neurological outcome as measured by modified Rankin Scale (mRS). The median mRS at discharge was 3. Thrombolysis-related post treatment complication was noted in 44.4%, of which nonfatal intracranial bleed occurred only in 2 patients (22.2%). None of the patients receiving intravenous tenecteplase had thrombolysis-related complications, and none of the patients had fatal intracranial bleed., Conclusion: This study clearly demonstrates the beginning of a feasible and effective thrombolysis in the treatment of acute ischemic stroke in Nepal.

Non-disclosure of significant or emotionally charged information can have psychological and physical health consequences. Widowhood in Nepal is highly stigmatised and therefore is a sensitive topic. This study sought to understand why and to whom women do not disclose their status as widows. Thematic content analysis of 31 in-depth interviews and 6 focus groups was conducted with primarily high-caste widows of reproductive age from the Kathmandu Valley, Surkhet, Chitwan and Kavre districts of Nepal. A codebook was developed based upon recurring concepts and applied to all transcripts using Atlas.ti. Due to discomfort or stigmatisation, many women concealed their status as widows in the community through behaviours impacting their daily lives. Non-disclosure to children was frequently described, often as a way to protect them from psychological sequelae. Concealment of widowhood is a coping strategy Nepali women use to shield themselves against societal stigma and to manage bereavement in their children. Efforts are needed to support widows in dealing with mental health issues related to disclosure and the psychosocial impact on their children.

Introduction: Anti-thrombotic, statins and antihypertensive drugs are commonly used for the management of acute ischemic stroke in Nepal but there is no evidence regarding their efficacy in our context. This study aims to explore the efficacy of these combined medications (anti-thrombotic, statins and antihypertensive drugs) in acute ischemic stroke patients for the first time and to assess the risk factors present in those patients., Methods: The study was conducted on 37 acute ischemic stroke patients admitted and treated at the Neurology Department of College of Medical Sciences-Teaching Hospital, Chitwan, Nepal and they were followed at three months (90±10 days). The initial stroke severity and functional disability were evaluated at admission and at 3 months using National Institute of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) respectively. The outcome parameters were functional independence (mRS≤2) and mortality at three months (mRS=6). Frequency distribution, Mann-Whitney U-test and χ2 test were performed for statistical analysis., Results: Out of 37 patients, 27 (73%) were Smoker, 22 (59.5%) had hypertension and 19 (51.4%) were alcohol consumer. The stroke severity on admission was statistically significant with functional independence (P=0.003) and mortality (P=0.015) at three month. Similarly, Rankin grade on admission was statistically significant with functional independence (P=0.001) and mortality (P=0.048) at three month. At three months, 20 (69%) survived patients were independent while mortality was seen in eight (21.6%) patients., Conclusions: The management of acute ischemic stroke with combined anti-thrombotic, statins and antihypertensive drugs seems promising and efficacious in mild to moderately severe ischemic stroke.

Acute kidney injury (AKI) is a common and major complication of sepsis. Sepsis-induced AKI is associated with higher morbidity and mortality. A prospective study was designed to include all the patients with a provisional diagnosis of sepsis with AKI admitted in our intensive care unit from August 2009 to September 2010. Detailed demographic data including various clinical parameters, co-morbidities, investigations, complications and outcome were entered in a designated proforman and were analyzed. A total of 53 subjects with the provisional diagnosis of sepsis with AKI were included in the study. The majority of patients (60.37%) were female. The mean age of the study population was 45.84 ± 20.5 years. Forty-nine percent of the subjects were <45 years old and 26.4% patients were >65 years. Among the co-morbid conditions, 9.4% subjects had diabetes mellitus type 2. Among the primary causes of AKI, 72% of the cases were due to medical causes, in which pneumonia was the major cause, and 28% were due to surgical causes, in which cholecystitis was the major cause. 47.1% cases expired, 11.3% subjects left against medical advice and 41.5% cases had favorable outcome. Among the expired cases, 20.7% subjects expired within 24 h; for others, the median hospital stay was four days. This prospective study showed that the major causes of AKI were medical illness and pneumonia. Mortality in sepsis-induced AKI is significantly high. This highlights the importance of prevention of AKI in sepsis by early and renal-friendly aggressive treatment of sepsis and the need for improvement in the management of such AKI cases.

Introduction: Vitamin D deficiency has been associated with many neurological illnesses. The status of Vitamin D in Nepalese ischemic stroke patients is still unknown. This study aims to assess the status of vitamin D and its association with stroke risk factors in patients with acute ischemic stroke from Central Nepal., Methods: A total of 60 patients with ischemic stroke were included in the study. Their clinical profile and Vitamin D status were assessed. Frequency distribution, Pearson χ2test and Kruskal-Wallis test were performed for statistical analysis using SPSS-IBM 20., Results: The median (IQR) age of the patient was 65 (53.25, 70.75) years, ranging from 18-87 years. Thirty-four (56.7%) were males. Fourty-eight (80%) patients had hypertension and 34 (56.7%) were smoker. Previous stroke was present in six (10%) cases. Thirty-seven (61.6%) patients had low levels of Vitamin D out of which 26 (43.3%) had vitamin D insufficiency and 11 (18.3%) had vitamin D deficiency. Vitamin D level was significantly associated with previous history of stroke (P=0.043)., Conclusions: Vitamin D deficiency occurs in patients with ischemic stroke. Previous episodes of stroke with low vitamin D levels could be a cause of recurrent strokes. Further studies are necessary to establish the role of vitamin D in acute ischemic stroke in Nepalese population.

Objective: To investigate how the social status of high-caste Nepali widows of reproductive age impacts their sexual and reproductive health care., Methods: Twenty-one in-depth interviews and 1 focus group (n=6) were conducted between September and November 2012 in the Kathmandu, Kavre, and Chitwan districts of Nepal. Participants were members of Women for Human Rights, Single Women Group. Interviews and the focus group with widows followed a semi-structured interview guide designed to elicit information on sexual and reproductive health problems, knowledge about them, and barriers to care. Two researchers used inductive and deductive coding to analyze transcripts for themes using ATLAS.ti., Results: Widows reported facing substantial obstacles to accessing sexual and reproductive health care. Widows suspected of having sexual and reproductive health problems, or who discussed or tried to access these services, could be ostracized by their families and experience severe economic and psychological consequences. Additionally, widows feared discrimination, lack of confidentiality, and sexual harassment by male providers if their status was known. These barriers appeared to stem from the perception that sexual relationships are necessary for widows to require care for gynecologic problems., Conclusion: Widows expressed a need for sexual and reproductive health care and described cultural and systematic barriers to accessing this care; these barriers need to be addressed., (Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Introduction: Nepal cannot afford renal replacement therapy for End Stage Renal Disease due to lack of resources. Early diagnosis of Chronic Kidney Disease and its risk factors may reduce the need of renal replacement therapy., Methods: A community-based screening on, 3218 people ≥20 years were assessed by door-to-door survey in Dharan, Nepal. Health status, lifestyle habit, physical examination and blood pressure were evaluated. Spot urine was examined for proteins and glucose by dipstick. Fasting blood glucose and serum creatinine were measured in a subset of 1000 people and the prevalence of Chronic Kidney Disease was evaluated., Results: Overweight, obesity, hypertension, diabetes and proteinuria were found in 20%, 5.0%, 38.6%, 7.5%, and 5.1% respectively. In the subset group, Chronic Kidney Disease was detected in 10.6%. Multivariate analysis indicated age (P <0.0001) and diabetes (P = 0.027) as statistically significant predictors for Chronic Kidney Disease. Total of 848 patients entered the management program of lifestyle modification and pharmacologic intervention. Glycemic and blood pressure control was achieved in 60% and 72%, respectively. Regression or stabilization of proteinuria was reported in 52% of patients., Conclusions: Burden of Chronic Kidney Disease and cardiovascular risk factors are high in Dharan. Reasonable control of blood sugar, hypertension and proteinuria was achieved in this program. Findings indicate that activation a large prevention and intervention program to tackle Chronic Kidney Disease and Cardiovascular Disease in Nepal is needed.

A 27-year-old man presented with diplopia without features of raised intracranial pressure. He had left sixth cranial nerve (CN) palsy. Initial investigations in the form of blood tests, cerebrospinal fluid (CSF) opening pressure including CSF analysis and CT head were normal. He represented with paraparesis after 3 weeks. Examination revealed sixth CN palsy (eye twist) and new left-sided twelfth CN palsy (tongue twist), and hence Godtfredsen syndrome was diagnosed. MRI showed vertebral and clivus metastases. He showed partial response to high dose steroid. The statement 'sixth CN palsy may be a false localising sign' in neurology, should be followed by '....it can also be a true initial sign of clivus mass.'

Background. This study was carried out to establish the prevalence of cardiovascular risks such as hypertension, obesity, and diabetes in Eastern Nepal. This study also establishes the prevalence of metabolic syndrome (MS) and its relationships to these cardiovascular risk factors and lifestyle. Methods. 14,425 subjects aged 20-100 (mean 41.4 ± 15.1) were screened with a physical examination and blood tests. Both the International Diabetic Federation (IDF) and National Cholesterol Education Programme's (NCEP) definitions for MS were used and compared. Results. 34% of the participants had hypertension, and 6.3% were diabetic. 28% were overweight, and 32% were obese. 22.5% of the participants had metabolic syndrome based on IDF criteria and 20.7% according to the NCEP definition. Prevalence was higher in the less educated, people working at home, and females. There was no significant correlation between the participants' lifestyle factors and the prevalence of MS. Conclusion. The high incidence of dyslipidemia and abdominal obesity could be the major contributors to MS in Nepal. Education also appears to be related to the prevalence of MS. This study confirms the need to initiate appropriate treatment options for a condition which is highly prevalent in Eastern Nepal.

Introduction: Access to hemodialysis is limited in Nepal due to geographical terrain and hemodialysis centers being mostly limited to major city. Therefore, continuous ambulatory peritoneal dialysis is likely to be a better option in Nepal. In 1998, CAPD was initiated in Nepal without success. High rate of peritonitis was cited for failure. Hot tropical climate and poor sense of hygiene among patients was thought to be responsible for the high rate of peritonitis. A new CPD program was started in 2002 in our institute. We reviewed the incidence of peritonitis and factors predisposing., Methods: All chronic renal failure patients on CAPD since 2002 to 2007 were included in the study. They were followed up for complications and treatment outcome. Patients complicated with peritonitis (N=19) and patients without peritonitis (N=31) were compared., Results: A total of 50 patients were enrolled and mean duration of dialysis was 12 month per patients (Total patients month=600). Twenty six episodes of peritonitis in 19 patients were recorded during this period. Fourteen episode of peritonitis were culture positive. Culture sterile peritonitis was recorded in 12 episodes. Low serum albumin was predisposing factors for peritonitis and peritonitis rate was higher in end stage disease related due to diabetes mellitus., Conclusion: Peritonitis rate was comparable in our new program. Thus peritonitis is not a limiting factor for growth of CAPD in Nepal. Hypoalbuminemic and diabetic patients are prone for CAPD related peritonitis.

Introduction: This study was conducted to explore cardiovascular autonomic neuropathy and its pattern in chronic kidney disease patients., Methods: Autonomic function using five standard tests was examined in 20 diabetic patients with CKD, 20 age and sex matched diabetic patients without CKD and 20 age and sex matched controls. Analysis of difference between the autonomic function was done in the three groups using Chi-square test or Fischer's test., Results: Total 20 (100%) diabetic CKD patients were found to have autonomic neuropathy. Of these, 2 (10%) patients had early parasympathetic damage, 8 (40%) patients had definite parasympathetic damage, and 10 (50%) patients had combined damage. Heart rate response to standing was statistically significant (p = 0.014) among diabetic CKD patients when compared with diabetic patients without CKD. Combined form of autonomic dysfunction was more frequent in advanced stages of diabetic CKD. Three (42.85%) patients in stage 3 CKD, 4 (66.66%) patients in stage 4 CKD and 5 (71.42%) patients in stage 5 CKD, had combined autonomic failure., Conclusions: Autonomic neuropathy is common in native Nepalese diabetic CKD patients. Heart rate response to standing is significantly abnormal in diabetic CKD patients in comparison with diabetes mellitus patient without CKD. Severity of autonomic dysfunction increases with severity of CKD..

Somatostatin receptor subtypes, especially subtype 2 (SSTR2), exert their antitumor (cytostatic and/or cytotoxic) and anti-angiogenic effects. Here we aimed to investigate the anti-angiogenic effect of SSTR2 gene transfer into pancreatic cancer cell line PC-3, and the mechanisms involved in this effect. The full-length human SSTR2 complementary DNA was introduced into pancreatic cancer cell line PC-3 by lipofectamine-mediated transfection, and stable expression of SSTR2 was detected by immunohistochemistry and RT-PCR. Athymic mice were separately xenografted with SSTR2-expressing cells (experimental group), vector control and mock control cells. Intratumoral microvessel density (MVD) was assessed by immunohistochemistry. Immunohistochemistry and RT-PCR were used to determine the expression of angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase (MMP)-2 in xenograft tumors. MVD was significantly lower in the experimental group (5.16 +/- 1.34) than that in the vector control (16.52 +/- 2.25) and mock control (15.32 +/- 2.53) (P < 0.05). The immunohistochemical assay showed a significant decrease in the expression of VEGF, bFGF and MMP-2 protein in the experimental group compared with the vector control and mock control, considering both the integral optical density and area of staining (P < 0.05). RT-PCR showed a significant reduction of VEGF, bFGF and MMP-2 mRNA expression in the experimental group compared with the vector control and mock control (P < 0.05). Thus, introduction of the SSTR2 gene, the expression of which is frequently lost in human pancreatic adenocarcinoma, exerts its anti-angiogenic effects by down-regulating the expression of the factors, which are involved in tumor angiogenesis and metastasis, suggesting SSTR2 gene transfer as a promising strategy of gene therapy for pancreatic cancer.

Objectives: Several studies reported that somatostatin receptor subtypes, especially subtype 2 (SSTR2), exerted their cytostatic and/or cytotoxic effects on various types of tumors. The aim of this study was to investigate the antitumor effect of SSTR2 gene transfer to the pancreatic cancer cell line PC-3 and the mechanisms involved in this effect., Methods: The full-length human SSTR2 cDNA was introduced into pancreatic cancer cell line PC-3 by lipofectamine-mediated transfection; positive clones were screened by G418, and stable expression of SSTR2 was detected by the immunohistochemical SABC method and RT-PCR. Athymic mice were separately xenografted with SSTR2-expressing cells (experimental group), vector control, and mock control cells. TUNEL assay was used to determine the apoptotic index (AI) in the tumors of these groups. The immunohistochemical SP method was used to determine expression of apoptosis-regulating genes Bcl-2 and Bax and re-expression of SSTR2 and to assess intratumoral microvessel density (MVD). Moreover, tumor volume and weight were compared among these 3 groups., Results: Restoration of SSTR2 was observed in the experimental group both in vitro and in vivo. The AI was significantly higher in the experimental group (3.39 +/- 0.84%) compared with that in the vector control (0.69 +/- 0.08%) and mock control (0.68 +/- 0.09%) (P < 0.05). MVD was significantly lower in the experimental group (6.30 +/- 1.71) than that in the vector control (12.64 +/- 1.69) and mock control (13.50 +/- 1.86) (P < 0.05). Furthermore, a significant decrease in Bcl-2 and increase in Bax protein expression were detected in the experimental group compared with the vector control and mock control (P < 0.05). A significant negative correlation of protein expression between Bcl-2/Bax ratio and SSTR2 was observed in these tumors (P < 0.05). Tumor volume and weight were significantly decreased in the experimental group compared with the vector control and mock control (P < 0.05) groups. However, no significant differences were observed between the vector control and mock control (P > 0.05)., Conclusion: Re-expression of the SSTR2 gene, the expression of which is frequently lost in human pancreatic adenocarcinoma, induces apoptosis, which may be mediated via down-regulation of Bcl-2 and up-regulation of Bax (alteration of Bcl-2/Bax ratio) and inhibits tumor angiogenesis in pancreatic carcinoma, resulting in inhibition of tumor growth.

Aim: To investigate the anti-angiogenic effect of somatostatin receptor subtype 2 (SSTR2) gene transfer into pancreatic cancer cell line PC-3, and the mechanisms involved in this effect., Methods: The full length human SSTR2 cDNA was introduced into pancreatic cancer cell line PC-3 by lipofectamine-mediated transfection. Positive clones were screened by G418 and stable expression of SSTR2 was detected by immunohistochemistry SABC methods and RT-PCR. Enzyme-linked immunosorbent assay (ELISA) was used to detect vascular endothelial growth factor (VEGF) levels in the cell culture supernatants of SSTR2-expressing cells, vector control and mock control cells. Furthermore, the expressions of VEGF and matrix metalloproteinase-2 (MMP-2) were detected by immunohistochemistry SABC methods and RT-PCR in these cells., Results: VEGF levels in the cell culture supernatants were significantly reduced in the SSTR2-expressing cells (first week, 172.63+/-21.2 ng/L and after two months, 198.85+/-26.44 ng/L) compared with the vector control (first week, 790.39+/-86.52 ng/L and after two months, 795.69+/-72.35 ng/L) and mock control (first week, 786.42+/-90.62 ng/L and after two months, 805.32+/-84.36 ng/L) (P<0.05). The immunohistochemical assay showed a significant reduction of the integral optical density of VEGF and MMP-2 in the SSTR2-expressing cells (42.25+/-8.6 and 70.5+/-6.25, respectively) compared with the vector control (85.75+/-12.9 and 110.52+/-13.5, respectively) and mock control (82.6+/-9.28 and 113.56+/-9.62, respectively) (P<0.05). Conversely, the average gray value of VEGF and MMP-2 was significantly increased in the SSTR2-expressing cells (121.56+/-8.43 and 134.46+/-19.95, respectively) compared with the vector control (55.72+/-5.6 and 62.26+/-12.68, respectively) and mock control cells (58.48+/-6.2 and 65.49+/-9.16, respectively) (P<0.05). Moreover, the expressions of VEGF mRNA and MMP-2 mRNA were significantly reduced in the SSTR2-expressing cells (0.1384+/-0.017 and 0.2343+/-0.070, respectively) compared with the vector control (1.024+/-0.117 and 0.806+/-0.119, respectively) and mock control (1.085+/-0.105 and 0.714+/-0.079, respectively) (P<0.05)., Conclusion: The expression of reintroduced human SSTR2 gene exerts its antiangiogenic effects by down-regulating the expressions of the factors involved in tumor angiogenesis and metastasis, suggesting SSTR2 gene transfer as a new strategy of gene therapy for pancreatic cancer.