Feasibility study of total marrow lymphoid irradiation with volumetric modulated arc therapy: clinical implementation in a tertiary care center.

PURPOSE: Total marrow lymphoid irradiation (TMLI) with volumetric modulated arc therapy (VMAT) is challenging due to large treatment fields with multiple isocenters, field matching at junctions, and targets being surrounded by many organs at risk. This study aimed to describe our methodology for safe dose escalation and accurate dose delivery of TMLI treatment with the VMAT technique based on early experience at our center. MATERIALS AND METHODS: Computed tomography (CT) scans were acquired in head-first supine and feet-first supine orientations for each patient with an overlap at mid-thigh. VMAT plans were generated for 20 patients on the head-first CT images with either three or four isocenters in the Eclipse treatment planning system (Varian Medical Systems Inc., Palo Alto, CA) and the treatment was delivered in a Clinac 2100 C/D linear accelerator (Varian Medical Systems Inc., Palo Alto, CA). RESULTS: Five patients were treated with a prescription dose of 13.5 Gy in 9 fractions and 15 patients were treated with an escalated dose of 15 Gy in 10 fractions. The mean doses to 95% of the clinical target volume (CTV) and planning target volume (PTV) were 14.3 ± 0.3 Gy and 13.6 ± 0.7 Gy for the prescription doses of 15 Gy, and 13 ± 0.2 Gy and 12.3 ± 0.3 Gy for the prescription doses of 13.5 Gy, respectively. Mean dose to the lung in both schedules was 8.7 ± 0.6 Gy. The overall time taken to execute the treatment plans was approximately 2 h for the first fraction and 1.5 h for subsequent fractions. The average in-room time of 15.5 h per patient over 5 days leads to potential changes in the regular treatment schedules for other patients. CONCLUSION: This feasibility study highlights the methodology adopted for safe implementation of TMLI with the VMAT technique at our institution. Escalation of dose to the target with adequate coverage and sparing of critical structures was achieved with the adopted treatment technique. Clinical implementation of this methodology at our center could serve as a practical guide to start the VMAT-based TMLI program safely by others who are keen to start this service.

Epidemiological, Serological, and Entomological Investigation of New Visceral Leishmaniasis Foci in Nepal.

The aim of this study was to explore epidemiological, serological, entomological, and social aspects of visceral leishmaniasis (VL) in new foci in Nepal. The study was conducted in 11 villages of five districts that had been previously free of VL but that reported new cases between 2019 and 2021. We screened 1,288 inhabitants using rK39 tests and investigated the epidemiological and clinical characteristics of 12 recent VL cases. A total of 182 community members were interviewed about knowledge, attitude, and practices regarding VL. They then underwent an awareness training; 40 of them had a second interview at 6 months to assess the training impact. Vector surveys were conducted in six houses per village to assess sandfly density and infection rates. The prevalence of VL infection was 0.5% and 3.2% among screened populations in Dolpa and Kavre districts, respectively, while the other districts had no rK39-positive cases. No association between travel history and VL infection was found. Phlebotomus argentipes sandflies were collected in three districts at high altitudes (from 1,084 to 4,450 m). None of the sandflies captured had Leishmania donovani DNA. People in new foci were not aware of VL symptoms, vectors, or preventive measures. The training significantly improved their knowledge and practice in seeking medical care in case of illness. The epidemiological, serological, and entomological investigations suggest indigenous focal transmission of VL. An integrated package of strategic interventions should be implemented by the national VL elimination program in districts with new VL foci.

Performance of oyster mushroom (Pleurotus ostreatus) on paddy straw, water hyacinth and their combinations.

This study aimed to investigate the performance of oyster mushrooms on different substrate combinations, including rice straw alone, rice straw and water hyacinth (1:1), rice straw and water hyacinth (1:2), and rice straw and water hyacinth (2:1), in Pokhara, Kaski from April to June in 2022. A Completely Randomized Design with four replications was used to analyze the growth and yield parameters of the four different substrate combinations. The data were analyzed using R-Studio. Highly significant results (P > 0.001) were found in all growth and yield parameters. The best response in terms of days to colonization, pinhead formation, and total crop duration was observed with rice straw alone (11.5, 13.25, and 54.00 days, respectively). The stipe length, pileus diameter, and fruiting body per bunch had their highest values (3.44 cm, 5.21 cm, and 34.50 cm, respectively) with rice straw alone, followed by rice straw and water hyacinth in a 2:1 ratio (3.05 cm, 4.63 cm, and 34.25 cm, respectively). The maximum total fresh yield of mushrooms (1.53 kg with 153.16% BE) was observed for rice straw alone, followed by rice straw and water hyacinth in a 2:1 ratio (1.17 kg with 116.5% BE), while the poorest yield (0.76 kg with 76.38% BE) was observed in the case of rice straw and water hyacinth in a 1:2 ratio. The highest profitability was observed for mushroom production using rice straw alone with a B:C ratio of 1.24, followed by using rice straw and water hyacinth in a 2:1 ratio (1.03), while the lowest B:C ratio was observed for rice straw and water hyacinth in a 1:2 ratio (0.74). Overall, the best treatment was found to be rice straw alone, followed by rice straw and water hyacinth in a 2:1 ratio. These results suggest that using rice straw alone or in combination with water hyacinth in a 2:1 ratio can be an effective strategy for oyster mushroom cultivation.

Prevalence of Left Ventricular Diastolic Dysfunction in Patients with Essential Hypertension.

BACKGROUND: Left Ventricular Diastolic Dysfunction is considered a critical link between hypertension and heart failure, particularly in individuals with heart failure and preserved ejection fraction. The aim of this study is to assess the prevalence and factors associated with clinical parameters of left ventricular diastolic dysfunction in patients with essential hypertension. METHODS: A hospital-based cross-sectional study was done among 68 newly diagnosed and known hypertensive patients visiting out patientdepartmentat Bir hospital. Patients who meet the inclusion criteria were chosen alternatively by referring OPD register. Patients with hypertension had undergone echocardiography to see whether left ventricular diastolic dysfunction was present and was compared to other clinical parameters like age, sex, body mass index, and dyslipidemia using the student t-test/chi-square test. RESULTS: The prevalence of left ventricular diastolic dysfunction in essential hypertensive patients was 33.8%. About 25% patients had grade 1; 7.4% and 1.5% of patients had grade 2 and grade 3 diastolic dysfunction respectively. Patients who had a duration of hypertension of more than five years were more than nine times (OR 9.14; 2.89-28.87) more likely to have Left ventricular diastolic dysfunction. Age and Body Mass Index were found statistically significant with diastolic dysfunction (P<0.05). CONCLUSIONS: Left ventricular diastolic dysfunction was found prevalent in hypertensive patients.  Age, Body mass index, Dyslipidemia and Duration of hypertension were found to be statistically significant with diastolic dysfunction  Keywords: Diastolic dysfunction; hypertension; Nepal; prevalence.

Prevalence of post kala-azar dermal leishmaniasis (PKDL) and treatment seeking behavior of PKDL patients in Nepal.

BACKGROUND: In Nepal, the burden of post kala-azar dermal leishmaniasis (PKDL) is not known since there is no active case detection of PKDL by the national programme. PKDL patients could pose a challenge to sustain visceral leishmaniasis (VL) elimination. The objective of this study was to determine the prevalence of PKDL and assess PKDL patients' knowledge on VL and PKDL, and stigma associated with PKDL. METHODOLOGY/PRINCIPAL FINDINGS: Household surveys were conducted in 98 VL endemic villages of five districts that reported the highest number of VL cases within 2018-2021. A total of 6,821 households with 40373 individuals were screened for PKDL. Cases with skin lesions were referred to hospitals and examined by dermatologists. Suspected PKDL cases were tested with rK39 and smear microscopy from skin lesions. An integrated diagnostic approach was implemented in two hospitals with a focus on management of leprosy cases where cases with non-leprosy skin lesions were tested for PKDL with rK39. Confirmed PKDL patients were interviewed to assess knowledge and stigma associated with PKDL, using explanatory model interview catalogue (EMIC) with maximum score of 36. Among 147 cases with skin lesions in the survey, 9 (6.12%) were confirmed as PKDL by dermatologists at the hospital. The prevalence of PKDL was 2.23 per 10,000 population. Among these 9 PKDL cases, 5 had a past history of VL and 4 did not. PKDL cases without a past history of VL were detected among the "new foci", Surkhet but none in Palpa. None of the cases negative for leprosy were positive for PKDL. There was very limited knowledge of PKDL and VL among PKDL cases. PKDL patients suffered to some degree from social and psychological stigma (mean ± s.d. score = 17.89 ± 12.84). CONCLUSIONS/SIGNIFICANCE: Strengthening the programme in PKDL case detection and management would probably contribute to sustenance of VL elimination. Awareness raising activities to promote knowledge and reduce social stigma should be conducted in VL endemic areas.

Follow-up assessment of visceral leishmaniasis treated patients and the impact of COVID-19 on control services in Nepal.

BACKGROUND: Follow-up assessment of visceral leishmaniasis (VL) treated cases is important to monitor the long term effectiveness of treatment regimens. The main objective of this study was to identify the gaps and challenges in the follow-up of treated VL cases, to monitor treatment outcome and to assess the impact of COVID-19 on VL elimination services and activities. METHODS: Clinicians treating VL patients, district focal persons for VL, and patients treated for VL in seven high endemic districts in Nepal during 2019-2022 were interviewed to collect data on challenges in the follow-up of VL treated patients as per national strategy. RESULTS: Follow up status was poor in two districts with the largest number of reported cases. The majority of cases were children under 10 years of age (44.2%). Among 104 VL treated cases interviewed, 60.6% mentioned that clinicians had called them for follow-up but only 37.5% had complied. Among 112 VL treated cases followed up, 8 (7.14%) had relapse and 2 (1.8%) had PKDL. Among 66 cases who had VL during the COVID-19 lock down period, 32 (48.5%) were diagnosed within 1 week; however, 10 (15.1%) were diagnosed only after 4 weeks or more. During the COVID-19 pandemic, there was no active search for VL because of budget constraints and lack of diagnostic tests, and no insecticide spraying was done. CONCLUSION: Relapses and PKDL are challenges for VL elimination and a matter of concern. Successful implementation of the national strategy for follow up of treated VL cases requires addressing elements related to patients (awareness, transport, communication) clinicians (compliance) and organization of service delivery (local health worker training and deployment). COVID-19 did not have much impact on VL diagnosis and treatment; however, public health programmes including active case detection and insecticide spraying for vector control were severely reduced.

Functional Outcome of Proximal Femoral Nailing in Intertrochanteric Fracture.

BACKGROUND: Intertrochanteric fracture of femur is one of the commonest fracture seen in elderly, osteoporotic female. The main stay of treatment is fixation with dynamic hip screw or intramedullary device like Proximal Femoral Nail. Intramedullary devices are found to be more biomechanically advantageous. The functional outcome of these fractures depends on the type of fixation, age and stability of fracture. The objective of this study is to assess the functional outcome of Proximal Femoral Nail in intertrochanteric fracture. METHODS: An observational study was conducted in Kathmandu Medical College, Sinamangal from January 2018 to May 2019. 32 patients with intertrochanteric fracture were treated with proximal femoral nail during this period. The functional outcome was measured at 6 weeks, 12 weeks and 6 months using Harris hip score. RESULTS: There were 46.9% males and 53.1% females with mean age of 71.09 ±12.35 years. Most of the patients sustained injury after falling from standing height (53.1%). The functional outcome measured at final follow up (6 months) with Harris hip score was good in 62.5% and excellent in 28.1% patients likewise follow up in 12 weeks was good in 15.6%. CONCLUSIONS: Proximal Femoral Nail in trochanteric fractures seem to provide a good functional outcome at 6 months follow up. This technique, therefore appears to be a viable option in the management of intertrochanteric fracture of femur.

Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle.

Arterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are important contributors to age-induced arterial dysfunction. This study investigated the hypothesis that aging alters integrin function in a matrix stiffness-dependent manner, which contributes to decreased VSM contractility in aged soleus muscle feed arteries (SFA). The effect of RGD-binding integrins on contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses to norepinephrine, phenylephrine, and angiotensin II. Results indicated that constrictor responses in presence of RGD were impaired in old compared to young SFA. VSM cells isolated from young and old SFA were used for functional experiments using atomic force microscopy and high-resolution imaging. Aging was associated with a modulation of integrin ß1 recruitment at cell-matrix adhesions that was matrix and substrate stiffness dependent. Our data showed that substrate stiffening drives altered integrin ß1 expression in aging, while soft substrates abolish age-induced differences in overall integrin ß1 expression. In addition, substrate stiffness and matrix composition contribute to the modulation of SMα-actin cytoskeleton architecture with soft substrates reducing age effects. Our results provide new insights into age-induced structural changes at VSM cell level that translates to decreased functionality of aged resistance soleus feed arteries.

What affects farmers in choosing better agroforestry practice as a strategy of climate change adaptation? An experience from the mid-hills of Nepal.

Determinants for choosing climate change adaptation strategies and selecting improved agroforestry practices have rarely been explored, while numerous studies have been conducted on climate change and agroforestry. This paper discusses; local understanding of climate change, climatic impacts, and factors that affect farmers' choices of adaptation strategies, and agroforestry practices. We focused on three districts located in the mid-hills of Nepal, where farmers were adopting agroforestry practices in two forms; traditional and improved practices. We followed three techniques of social survey; household survey (n = 420), focus group discussions (n = 6), and key informant interviews (n = 24). Almost all farmers of the study areas were experiencing climatic challenges, but only 59.29% of them accepted that the challenges are induced by climate change and, likewise, 55.24% have adopted climate change adaptation measures. Diversifying crop production, shifting farming practices, changing occupation, and emigration were local adaptation strategies. Livelihood improvement, income generation, and food production were the primary motives for adopting agroforestry practices in the study area. Agroforestry as an adaptation measure to climate change was considered secondary by most farmers. Statistical analysis using a logit model revealed that age, education, and habit of growing commercial species significantly influenced farmers adopting climate change adaptation strategies. Likewise, age, education, gender, habit of growing commercial species, and income from tree products significantly influenced the choice of improved agroforestry practices as a better option. Though agroforestry was widely considered a strategy to combat climate change, only some farmers accepted it due to their awareness level. Therefore, education programs such as training, farmer field schools, door-to-door visits, etc., should be intensified to sensitize farmers about climate change and encourage them to adopt improved agroforestry practices. The findings of the study could reinforce local, national, and international allied agencies to design operative actions in the days to come.

Non-Steroidal Anti-Inflammatory Drugs in Orthopedic Outpatient Cases in a Tertiary Care Teaching Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Non-steroidal anti-inflammatory drugs are major drugs in treatment of pain and inflammation of different orthopedic conditions. There are different classes of non-steroidal anti-Inflammatory Drugs based on their selectivity to cyclooxygenase enzyme which has significant differences in safety profile. This study aims to determine the prevalence of non-steroidal anti-inflammatory drugs prescription in the orthopaedic outpatient department of a tertiary care hospital. METHODS: This was a descriptive cross-sectional study conducted among the patients in the orthopedic outpatient department of tertiary care hospital from December 2020 to March 2021. Ethical approval was taken from the Institutional Review Committee of the college (Ref: 0311202007). Convenient sampling was done. A structured proforma was used with consent. The data were analyzed with Social Statistical Package for the Social Sciences version 20. Point estimate at 95% Confidence Interval was done and frequency and percentage were calculated. RESULTS: Out of 140 orthopaedic out patient department prescriptions screened, 118 (84.28%) (78.25-90.30 at 95% Confidence Interval) prescriptions included non-steroidal anti-inflammatory drugs. Aceclofenac 76 (64.4%) was the most prescribed non-steroidal anti-inflammatory drug. CONCLUSIONS: Aceclofenac was the most preferred agent for the treatment in the department of orthopedics. The most common proton pump inhibitor used alone with non-steroidal anti-inflammatory drugs was rabeprazole.

Disseminated cryptococcosis and hepatitis C virus infection: A fatal co-infection.

BACKGROUND AND PURPOSE: We report a case of disseminated cryptococcosis in a treatment-naïve patient, incidentally diagnosed with hepatitis C virus (HCV) infection and renal parenchymal disease. The patient succumbed to death given the very late diagnosis of the disease. CASE REPORT: A 54-year-old male presented with the chief complaints of abdominal pain, chest pain, and phlegmy cough for a month. There was a past history of decreased urine output, lower limb swelling, and fever lasting for 15-20 days. After a general physical examination, the differential diagnosis of hepatitis C-related liver disease with hepatic encephalopathy, disseminated tuberculosis, and septic shock was made. Radiological examination revealed renal parenchymal disease on ultrasound abdomen and opacity with reticulonodular opacity in the bilateral lung zones. In laboratory investigations, serum reactive sample was tested for anti-HCV antibodies. In addition, Cryptococcus var grubii was identified in blood culture using the matrix-assisted laser desorption ionization-time of flight mass spectrometry (Bruker Daltonics, Germany). The patient succumbed to death before the initiation of any specific antifungal therapy. CONCLUSION: Cryptococcosis-HCV co-infection is a fatal condition with a fulminant course that might be difficult to treat.

Rising trends of neurocysticercosis: A serological report from tertiary-care hospital in South India.

INTRODUCTION: Taenia solium is a common two-host parasitic cestode, residing in both humans (definitive) and pigs (intermediate). Invasion of this parasitic cyst into central nervous system leads to a condition known as neurocysticercosis (NCC). The World Health Organization (WHO) considers NCC as one of the "most neglected" tropical zoonotic diseases. The disease is presented with pleomorphic clinical manifestations, of which epilepsy is the most common. Diagnosis of NCC is carried out by serological tests and imaging methods. Only a few studies from Andhra Pradesh, Kerala, Tamil Nadu, and Pondicherry are available regarding the seropositive levels of NCC in South India. MATERIALS AND METHODS: A descriptive analysis was carried out on NCC suspected patients attending outpatient or inpatient department of different clinics majorly from neurology, medicine, pediatrics, ophthalmology, and skin at Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, a tertiary care hospital in South India. A total of 391 patient samples (either serum or cerebrospinal fluid or urine) for 5 years from January 2011 to December 2015 were taken into the study. Serological investigations such as enzyme-linked immunosorbent assay and enzyme-linked immunoelectro transfer blot were performed for assessing the seropositivity levels of NCC. RESULTS: The overall seropositive cases of NCC in the study population were found to be 32.5% of which positive male cases (59.1%) exceeding females (40.9%). The frequency of adult positive cases (77.2%) was more than that of pediatrics cases (22.8%) with an average of 30.9 years of age. CONCLUSIONS: NCC seropositive levels show an increasing trend with the study period. This necessitates a proper attention to the unnoticed spread of the parasitic disease, which affects the quality of life in the community. Quality screening and diagnostic strategy should be implied along with proper awareness for preventive measure practices have to be set up to reduce the impact of morbidity caused by NCC.