Ethno-geographic distribution and histopathological classification of nasopharyngeal carcinoma in a single center in Nepal.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) shows geographic and ethnic variation with specific etiopathogenesis. This study characterized the distribution of NPC patients stratified by ethnicity, geography, and histology in a tertiary-level cancer center in Nepal. METHODS: A descriptive retrospective study was designed to analyze NPC cases from different regions among patients visiting the hospital from 2016 to 2021. Demographic and clinical information was obtained from medical records. Ethical approval was granted by the Nepal Health Research Council (NHRC). Data analyses and visualization were carried out with R software. RESULTS: During the six-year period, a total of 65 individuals were diagnosed with NPC, comprising 42 males and 23 females. Patient median age was 43 years (range 11-85 years). A bimodal age distribution of cases was observed with peaks in patients aged 30-39 years and 50-59 years. Of the NPC patients studied, 29 were from Koshi Province, with 7 cases from Ilam district and 6 cases from Morang district. There were 18 patients in Bagmati Province, and Kathmandu district had the highest number of cases within this region, with 8 patients. The highest proportion of cases were observed among patients of Janajati ethnicity (60%), including Rai, Limbu, and Sherpa people. Histologically, undifferentiated non-keratinizing NPC was the most commonly observed subtype, accounting for 43.1% of cases, followed by 20% differentiated non-keratinizing NPC and 4.6% keratinizing NPC across the entire sample population. The majority of patients (75.3%) were diagnosed at an advanced stage (stage III or IV) with none diagnosed at stage I. CONCLUSIONS: In our study, most cases of NPC occurred in patients from provinces in eastern Nepal (Koshi province), and of the Janajati ethnic community. The most common histological subtype was undifferentiated non-keratinizing carcinoma. Further epidemiological studies could address differences in prevalence and the challenge of late presentation of NPC patients in Nepal.

Effect of docosahexaenoic acid and olive oil supplementation on pup weight in alcohol-exposed pregnant rats.

Background: Low birth weight has been observed in offspring of alcoholic mothers due likely to unresolved inflammation and oxidative injury. Dietary lipids play a role in inflammation and its resolution. The primary objective was to investigate the effect of DHA and olive oil on the birth weight of pups born to alcohol-exposed dams. Methods: Pregnant rats were randomized to the control or three treatment (alcohol) groups. From gestational days (GD) 8-19, the control group received daily olive oil and malto/dextrose, whereas groups 2 and 3 received olive oil and low-dose alcohol or high-dose alcohol, respectively. Group 4 received daily DHA and high-dose alcohol. The dam's blood was collected on GD 15 and 20 for cytokine analysis. Dams were sacrificed on GD 20. The mean birth weight of pups was compared by one-way ANOVA with post hoc Duncan's test. Results: There was a significant increase in the pups' mean birth weight in the high-dose alcohol/DHA and high-dose alcohol/olive oil. Higher pro-inflammatory cytokines (IL-1ß and IL-12p70) were noted in the alcohol-exposed dams. Conclusions: DHA and olive oil supplementation in alcohol-exposed pregnant rats significantly increased their pups' birth weight despite having high pro-inflammatory cytokines. The mechanism of this effect remains to be determined.

Chitosan lecithin nanocomposite based electrochemical biosensor for glycine detection in biological matrices.

Increased glycine concentrations are associated with altered metabolism of cancer cells and is reflected in the bodily fluids of the brain cancer patients. Various studies have been conducted in past to detect glycine as an imaging biomarker via NMR Spectroscopy tools. However, the use is limited because of the low concentration and different in vivo detection due to overlapping of peaks with myo-inositol in same spectral position. Alongside, little is known about the electrochemical potential of Glycine as a biomarker for brain cancer. The prime impetus of this study was to check the feasibility of glycine as non-invasive biomarker for brain cancer. A divergent approach to detect glycine "non-enzymatically" via unique chitosan lecithin nanocomposite has been utilised during this study. The electrochemical inactivity at provided potential that prevented glycine to get oxidized or reduced without mediator was compensated utilising the chitosan-lecithin nanocomposite. Thus, a redox mediator (Prussian blue) was used for high sensitivity and indirect detection of glycine. The chitosan nanoparticles-lecithin nanocomposite is used as a matrix. The electrochemical analysis of the onco-metabolomic biomarker (glycine) utilizing cyclic voltammetry in glycine spiked multi-Purpose artificial urine was performed to check distribution of glycine over physiological range of glycine. A wide linear range of response varying over the physiological range from 7 to 240 µM with a LOD 8.5 µM was obtained, showing potential of detection in biological samples. We have further evaluated our results via simulating the interaction of mediator and matrix with Glycine by HOMO-LUMO band fluctuations.

Experience of patients on methadone maintenance treatment receiving take-home methadone doses during COVID-19 pandemic: A multi-site study from India.

BACKGROUND: Methadone take-home doses for opioid dependence treatment are strictly regulated due to diversion and overdose concerns, so patients must visit the clinic daily for dispensing. This was also done in India until the COVID-19 pandemic, when lockdown restriction compelled take- home dispensing of methadone. This study examined experience of patients who received take- home methadone during COVID-19 pandemic in India. METHODS: Observational, cross-sectional design. We contacted all consenting methadone centres in India during the lockdown and selected those that provided take-home doses for the study. Patients who received daily methadone before the lockdown and take-home doses after were interviewed using a study-specific questionnaire. RESULTS: The study had 210 participants. Take-home methadone was dispensed for 2.5 days on average in each dispensing. When taking methadone at home, 3.3% split their dose 25% took less than the prescribed dose to save it for a rainy days, and 3.3% reported an overdose episode. Adherence improved in 58.6% participants after take-home methadone. Participants perceived many benefits from take-home methadone such as reduced hospital visits and travel time to collect methadone, improvement in work, and financial savings. About 54.3% participants reported storing their take-home doses safely, and 1.9% reported that their family consumed methadone by mistake. CONCLUSIONS: Take-home methadone was found to be beneficial to most participants in terms of time saved and improved productivity. Preconceived concerns of providing take-home methadone in terms of its overdose, diversion, or accidental ingestion by others are not commonly seen when individuals are provided take-home doses of methadone.

Jejunovesical Fistula Diagnosis After Normal Vaginal Delivery: A Case Report.

Enterovesical fistula represents an abnormal communication between the intestine and bladder. The causes are diverticulitis (56.3%), malignant tumours, which are located mainly in the intestine (20.1%), and Crohn's disease (9.1%). Other causes include iatrogenic injury (3.2%); trauma; foreign bodies in the intestinal tract; radiotherapy; chronic appendicitis; tuberculosis; and syphilis. Normal vaginal delivery as a cause for enterovesical fistula has not been reported in many publications yet. We report a case of a 30-year-old female, who developed an jejunovesical fistula after normal vaginal delivery. It was diagnosed after diagnostic cystoscopy and computed tomography of the abdomen and pelvis. There was jejuno-vesical fistula. Resection of the segment of the jejunum with side-to-side anastomosis with bladder repair was done. A follow-up cystogram was done which showed no contrast extravasation into the peritoneum. The patient was followed up for 9 months after surgery. Keywords: case reports; fistula; jejunum; urinary bladder.

Primary retroperitoneal solitary fibrous tumor: A case report.

Primary retroperitoneal masses have numerous differential diagnoses, many of which are rare entities. These can be neoplastic or nonneoplastic. Among the rare conditions are solitary fibrous tumors, which can either be benign or malignant. It is a mesenchymal, spindle-cell tumor, reported first in 1931 as a pleural tumor by Klemperer et al. A 20-year-old lady, with abdominal pain for 6 months, was diagnosed with a retroperitoneal mass on the left lower abdomen on USG which was confirmed by an MRI scan of the abdomen. The patient underwent laparoscopy-assisted excision of the mass. The final histopathological reports and immunohistochemistry reports revealed a solitary fibrous tumor. Solitary fibrous tumors (SFTs) are rare tumors in the retroperitoneum. In our search, fewer than a hundred cases have been reported. It has a characteristic "patternless pattern" in a microscopic study. Adverse outcomes of SFTs are associated with atypical features in histology, such as nuclear pleomorphism, necrosis, increased cellularity, and mitoses >4/10 HPF and size more than 10 cm. The standard of care is surgical excision with clear margins. Open surgeries have been done traditionally; we present a case where we performed the excision laparoscopically.

A robust yet simple method to generate fluorescent amyloid nanofibers.

Covalent tagging of fluorophores is central to the mechanistic understanding of important biological processes including protein-protein interaction and protein aggregation. Hence, studies on fluorophore-tagged peptides help in elucidating the molecular mechanism of amyloidogenesis, its cellular internalization, and crosstalk potential. Despite the many advantages the covalently tagged proteins offer, difficulties such as expensive and tedious synthesis and purification protocols have become a matter of concern. Importantly, covalently tagged fluorophores could introduce structural constraints, which may influence the conformation of the monomeric and aggregated forms of proteins. Here, we describe a robust-yet-simple method to make fluorescent-amyloid nanofibers through a coassembly-reaction route that does not alter the aggregation kinetics and the characteristic ß-sheet-conformers of resultant nanofibers. Fluorescent amyloid nanofibers derived from insulin, lysozyme, Aß1-42, and metabolites were successfully fabricated in our study. Importantly, the incorporated fluorophores exhibited remarkable stability, remaining intact without leaching even after undergoing serial dilutions and prolonged storage periods. This method enables monitoring of cellular internalization of the fluorescent-amyloid-nanofibers and the detection of FRET-signals during interfibrillar interactions. This simple and affordable protocol may significantly help amyloid researchers working on both in vitro and animal models.

Nanotechnology based technological development in biofuel production: Current status and future prospects.

Depleting fossil fuels and net carbon emissions associated with their burning have driven the need to find alternative energy sources. Biofuels are near-perfect candidates for alternative energy sources as they are renewable and account for no net CO2 emissions. However, biofuel production must overcome various challenges to compete with conventional fuels. Conventional methods for bioconversion of biomass to biofuel include chemical, thermochemical, and biological processes. Substrate selection and processing, low yield, and total cost of production are some of the main issues associated with biofuel generation. Recently, the uses of nanotechnology and nanoparticles have been explored to improve the biofuel production processes because of their high adsorption, high reactivity, and catalytic properties. The role of these nanoscale particles and nanocatalysts in biomass conversion and their effect on biofuel production processes and yield are discussed in the present article. The applicability of nanotechnology in production processes of biobutanol, bioethanol, biodiesel, biohydrogen, and biogas under biorefinery approach are presented. Different types of nanoparticles, and their function in the bioprocess, such as electron transfer, pretreatment, hydrolysis, microalgae cultivation, lipid extraction, dark and photo fermentation, immobilization, and suppression of inhibitory compounds, are also highlighted. Finally, the current and potential applications of nanotechnology in biorefineries are also discussed.

Solution structure, dynamics and tetrahedral assembly of Anti-TRAP, a homo-trimeric triskelion-shaped regulator of tryptophan biosynthesis in Bacillus subtilis.

Cellular production of tryptophan is metabolically expensive and tightly regulated. The small Bacillus subtilis zinc binding Anti-TRAP protein (AT), which is the product of the yczA/rtpA gene, is upregulated in response to accumulating levels of uncharged tRNATrp through a T-box antitermination mechanism. AT binds to the undecameric ring-shaped protein TRAP (trp RNA Binding Attenuation Protein), thereby preventing it from binding to the trp leader RNA. This reverses the inhibitory effect of TRAP on transcription and translation of the trp operon. AT principally adopts two symmetric oligomeric states, a trimer (AT3) featuring a three-helix bundle, or a dodecamer (AT12) comprising a tetrahedral assembly of trimers, whereas only the trimeric form has been shown to bind and inhibit TRAP. We demonstrate the utility of native mass spectrometry (nMS) and small-angle x-ray scattering (SAXS), together with analytical ultracentrifugation (AUC) for monitoring the pH and concentration-dependent equilibrium between the trimeric and dodecameric structural forms of AT. In addition, we report the use of solution nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of AT3, while heteronuclear 15N relaxation measurements on both oligomeric forms of AT provide insights into the dynamic properties of binding-active AT3 and binding-inactive AT12, with implications for TRAP inhibition.

Freezability and Fertility Rates of Stallion Semen Supplemented With Trehalose in Lactose Extender.

Cryopreservation of stallion semen is often associated with poor post-thaw sperm quality. One of the reason for this diminished quality is osmotic stress that spermatozoa experiences during freezing and thawing process. The aim of the present study was to evaluate the cryoprotective effect of trehalose on stallion sperm quality and field fertility rates subjected to cooling and freeze-thawing process. Semen samples were collected from six Marwari breed stallions, divided into three different treatments in a final concentration of 150 × 106 sperm/mL by using Lactose based extender containing 0, 50, and 150 mM of trehalose then subjected to cryopreservation after equilibration. Sperm motility, acrosome integrity, plasma membrane integrity, mitochondrial membrane potential, DNA integrity and oxidative stress related parameters of the stallion spermatozoa were analyzed at fresh, prefreeze and post thaw stages. Thirty (30) reproductively healthy mares were inseminated with frozen-thawed semen either supplemented with (treatment) or without (control) trehalose to evaluate the field fertility. Results of the current study indicated that, the extender containing 50 mM trehalose has enhanced the functional plasma membrane, acrosomal, DNA integrities and augmented the mitochondrial membrane potential. Trehalose supplementation to the semen extender not only ameliorated the semen quality parameters, but also protected the stallion sperm from oxidative stress by reducing the levels of reactive oxygen species (ROS) and lipid peroxidation (LPO). The inclusion of 50 mM trehalose in semen extender resulted in significantly (P < .05) increased post-thaw progressive motility and viability compared to the control group. Mares inseminated with frozen-thawed semen supplemented with 50 mM trehalose tended to have better pregnancy rates than controls (non-significant [P < .05]) although a larger fertility trial is required to determine if this effect reaches the level of significance. In conclusion, addition of 50 mM trehalose yielded in better quality stallion semen after cooling and post-thawing in terms of reducing the oxidative stress and enhancing the motility, integrities of acrosome, plasma membrane, mitochondrial potential and DNA.

Organic-Inorganic Porphyrinoid Frameworks for Biomolecule Sensing.

Porphyrinoids and their analogous compounds play an important role in biosensing applications on account of their unique and versatile catalytic, coordination, photophysical, and electrochemical properties. Their remarkable arrays of properties can be finely tuned by synthetically modifying the porphyrinoid ring and varying the various structural parameters such as peripheral functionalization, metal coordination, and covalent or physical conjugation with other organic or inorganic scaffolds such as nanoparticles, metal-organic frameworks, and polymers. Porphyrinoids and their organic-inorganic conjugates are not only used as responsive materials but also utilized for the immobilization and embedding of biomolecules for applications in wearable devices, fast sensing devices, and other functional materials. The present review delineates the impact of different porphyrinoid conjugates on their physicochemical properties and their specificity as biosensors in a range of applications. The newest porphyrinoid types and their synthesis, modification, and functionalization are presented along with their advantages and performance improvements.

Cancer-targeted photoimmunotherapy induces antitumor immunity and can be augmented by anti-PD-1 therapy for durable anticancer responses in an immunologically active murine tumor model.

The complex immunosuppressive nature of solid tumor microenvironments poses a significant challenge to generating efficacious and durable anticancer responses. Photoimmunotherapy is a cancer treatment strategy by which an antibody is conjugated with a non-toxic light-activatable dye. Following administration of the conjugate and binding to the target tumor, subsequent local laser illumination activates the dye, resulting in highly specific target cell membrane disruption. Here we demonstrate that photoimmunotherapy treatment elicited tumor necrosis, thus inducing immunogenic cell death characterized by the release of damage-associated molecular patterns (DAMPs). Photoimmunotherapy-killed tumor cells activated dendritic cells (DC), leading to the production of proinflammatory cytokines, T cell stimulation, priming antigen-specific T cells, and durable memory T cell responses, which led complete responder mice to effectively reject new tumors upon rechallenge. PD-1 blockade in combination with photoimmunotherapy enhanced overall anticancer efficacy, including against anti-PD-1-resistant tumors. The combination treatment also elicited abscopal anticancer activity, as observed by reduction of distal, non-illuminated tumors, further demonstrating the ability of photoimmunotherapy to harness local and peripheral T cell responses. With this work we therefore delineate the immune mechanisms of action for photoimmunotherapy and demonstrate the potential for cancer-targeted photoimmunotherapy to be combined with other immunotherapy approaches for augmented, durable anticancer efficacy. Moreover, we demonstrate responses utilizing various immunocompetent mouse models, as well as in vitro data from human cells, suggesting broad translational potential.

Prevalence and clinical characteristics of headache among medical students of Nepal: A cross-sectional study.

BACKGROUND: Headache is a common neurological disorder, with a global prevalence of around 50%. It may affect people of any age, gender, education, socioeconomic status and occupation. Tension headache, migraine headache and cluster headache are commonly encountered headache types. The prevalence of headache problems is higher among medical students. This could potentially affect their academic performance and quality of life. The objective of this study is to find out the prevalence of headaches and their clinical characteristics among students of a medical college. MATERIALS AND METHODS: An online, single-centre, cross-sectional study was conducted among undergraduate medical students in Nepal. Stratified sampling followed by a simple random sampling technique was adopted depending upon the academic years of students. For data collection, pre-tested semi-structured questionnaire was used. The data entry and analysis were done by using Statistical Package for the Social Sciences (IBM-SPSS), version-23. The prevalence of headache and its subtypes were calculated. All the clinical characteristics associated with headaches were also studied. RESULTS: The prevalence of headache disorder was 65 (26.86%), with tension headache (69.23%) being the commonest one. It was highest among fourth-year students (37.84%) followed by first-year students (33.33%). Anxiety/stress (75.40%) was the most common precipitating factor. This problem stopped most of the students (63.09%) from doing daily activities. More than half of them (53.85%) practised self-medication in case of non-resolution of pain, and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently used. CONCLUSION: Headache was fairly prevalent among medical students. Anxiety/stress in medical life has led to headaches in the majority of students. The headache disturbed their daily activities and promoted self-medication practice. So, this problem should be properly looked into and addressed in time by the concerned authority.

Calmodulin promotes a Ca2+ -dependent conformational change in the C-terminal regulatory domain of CaV 1.2.

Calmodulin (CaM) binds to the membrane-proximal cytosolic C-terminal domain of CaV 1.2 (residues 1520-1669, CT(1520-1669)) and causes Ca2+ -induced conformational changes that promote Ca2+ -dependent channel inactivation (CDI). We report biophysical studies that probe the structural interaction between CT(1520-1669) and CaM. The recombinantly expressed CT(1520-1669) is insoluble, but can be solubilized in the presence of Ca2+ -saturated CaM (Ca4 /CaM), but not in the presence of Ca2+ -free CaM (apoCaM). We show that half-calcified CaM (Ca2 /CaM12 ) forms a complex with CT(1520-1669) that is less soluble than CT(1520-1669) bound to Ca4 /CaM. The NMR spectrum of CT(1520-1669) reveals spectral differences caused by the binding of Ca2 /CaM12 versus Ca4 /CaM, suggesting that the binding of Ca2+ to the CaM N-lobe may induce a conformational change in CT(1520-1669).

Morbidities, health problems, health care seeking and utilization behaviour among elderly residing on urban areas of eastern Nepal: A cross-sectional study.

BACKGROUND: Morbidity increases with age and enhances the burden of health problems that result in new challenges to meet additional demands. In the ageing population, health problems, and health care utilization should be assessed carefully and addressed. This study aimed to identify chronic morbidities, health problems, health care seeking behaviour and health care utilization among the elderly. METHODS: We conducted a community based, cross-sectional study in urban areas of the Sunsari district using face-to-face interviews. A total of 530 elderly participants were interviewed and selected by a simple proportionate random sampling technique. RESULTS: About half, 48.3%, elderly were suffering from pre-existing chronic morbidities, of which, 30.9% had single morbidity, and 17.4% had multi-morbidities. This study unfurled more than 50.0% prevalence of health ailments like circulatory, digestive, eye, musculoskeletal and psychological problems each representing the burden of 68.7%, 68.3%, 66.2%, 65.8% and 55.7% respectively. Our study also found that 58.7% preferred hospitals as their first contact facility. Despite the preferences, 46.0% reported visiting traditional healers for treatment of their ailments. About 68.1% reported having difficulty seeking health care and 51.1% reported visits to a health care facility within the last 6 months period. The participants with pre-existing morbidity, health insurance, and an economic status above the poverty line were more likely to visit health care facilities. CONCLUSION: Elderly people had a higher prevalence of health ailments, but unsatisfactory health care seeking and health care utilization behaviour. These need further investigation and attention by the public health system in order to provide appropriate curative and preventive health care to the elderly. There is an urgent need to promote geriatric health services and make them available at the primary health care level, the first level of contact with a national health system.

Zolpidem use and risk of suicide: A systematic review and meta-analysis.

INTRODUCTION: Zolpidem is one of the most commonly prescribed nonbenzodiazepine hypnotic drugs for insomnia. Published epidemiological studies linked zolpidem with the risk of suicide. However, to date, no meta-analysis investigated this association. Hence, we systematically reviewed and meta-analysed the current evidence from real-world studies reporting the risk of suicide with the use of zolpidem. METHODS: Medline (Ovid), Embase (Ovid), and PsycINFO databases were searched from inception till June 2021 for real-world evidence studies reporting the risk of suicide with the use of zolpidem. The quality assessment of included studies was assessed using the New-Castle Ottawa Scale (NOS). Random-effect meta-analysis was performed using a generic inverse variance method. RESULTS: This meta-analysis was based on four studies with 344,753 participants, of which 42,279 were zolpidem users. The methodological quality of all the included studies was of high quality. A significantly increased risk of suicide or suicide attempt was found in zolpidem users compared to non-users, with a pooled relative risk of 1.88 (95% CI: 1.54 - 2.30). Furthermore, an increased risk of suicidal death was observed in zolpidem users compared to non-users, with a pooled relative risk of 1.82 (95% CI: 1.43 - 2.30). Dose-response analysis also revealed a significantly increased risk of suicide in patients receiving ≥ 180cDDD (cumulative defined daily doses) of zolpidem (124 times), followed by 90-179cDDD (113 times) and <90cDDD (93 times) of zolpidem compared to non-users. CONCLUSION: In conclusion, zolpidem use was associated with an increased risk of suicide or suicide attempt and suicidal death. Therefore, careful prescribing practices must be followed by considering the risk-benefit profile.

Digital Capacity and Interest in mHealth Interventions Among Individuals on Opioid Agonist Maintenance Treatment: A Cross-Sectional Community-Based Study.

Background: Integrating mobile technologies in healthcare (mHealth) is helpful to manage various medical conditions. mHealth applications can bridge the gap in the management of patients with opioid use disorder (OUD). Research evaluating the feasibility of mHealth to address OUD is limited in developing countries. We aimed to assess the digital capacity and interest in mHealth interventions in patients maintained on opioid agonist treatment (OAT). Methods: 150 patients on OAT from a community drug treatment clinic in New Delhi, India, were included. We assessed the participants on their pattern of mobile and Internet use and their willingness to use mHealth technology to access health information and services related to OUD. Results: 88% of participants (n = 132) owned a mobile phone at assessment; 2.7% (n = 4) had never used a mobile phone in their lifetime. 70% (n = 105) participants had Internet access. 80% (n = 120) of participants showed interest in receiving text messages related to the management of OUD. 60% of participants showed a willingness to download and use applications for monitoring their substance use. Conclusions: In India, there is an interest among people on OAT to use mHealth interventions to manage their substance use. This population also has access to mobile phones and the necessary knowledge to install and run applications needed for various mHealth interventions.

Spectrofluorimetric-based approach to screen urine contamination in drinking water: A step toward the development of screening method for leptospirosis.

Hygiene hypothesis and sanitization are two important pivots of modern civilization. The drinking water should be free from urine and stool contamination. Coliform test is popular for understanding feces contamination. However, understanding urine contamination in drinking water is a difficult task. On the other hand, urine contamination can cause disease like leptospirosis. It occurs mainly in animals and infects humans through contaminated water, food, and soil and causes serious consequences. Rat urine is the most common source of such disease outbreaks. Further, sophisticated laboratories with high-end technologies may not be present at the site of disease outbreaks. In this context, we have proposed a spectrofluorimetric approach to screen urine contamination in water. The screening method can sense up to 156 nl/ml of rat urine.