Forest fire vulnerability in Nepal's chure region: Investigating the influencing factors using generalized linear model.

The Chure region, among the world's youngest mountains, stands out as highly susceptible to natural calamities, particularly forest fires. The region has consistently experienced forest fire incidents, resulting in the degradation of valuable natural and anthropogenic resources. Despite its vulnerability, there have been limited studies to understand the relationship of various causative factors for the recurring fire problem. Hence, to comprehend the influencing factors for the recurring forest fire problem and its extent, we utilized generalized linear modeling under binary logistic regression to combine the dependent variable of satellite detected fire points and various independent variables. We conducted a variance inflation factor (VIF) test and correlation matrix to identify the 14 suitable variables for the study. The analysis revealed that forest fires occurred mostly during the three pre-monsoon periods and had a significant positive relation with the area under forest, rangeland, bare-grounds, and Normalized Difference Vegetation Index (NDVI) (P < 0.05). Consequently, our model showed that the probability of fire incidents decreases with elevation, precipitation, and population density (P < 0.05). Among the significant variables, the forest areas emerges as the most influencing factor, followed by precipitation, elevation, area of rangeland, population density, NDVI, and the area of bare ground. The validation of the model was done through the area under the curve (AUC = 0.92) and accuracy (ACC = 0.89) assessments, which showed the model performed excellently in terms of predictive capabilities. The modeling result and the forest fire susceptible map provide valuable insights into the forest fire vulnerability in the region, offering baseline information about forest fires that will be helpful for line agencies to prepare management strategies to further prevent the deterioration of the region.

Prevalence and clinical characteristics of hyperuricemia among patients with chronic kidney disease under haemodialysis in a tertiary care center: a cross-sectional study.

Background: Hyperuricemia is common in chronic kidney disease patients. This study aimed to investigate the prevalence and clinical characteristics of hyperuricemia in patients with chronic kidney disease undergoing haemodialysis. Materials and methods: This cross-sectional study was conducted among 104 patients with chronic kidney disease who visited the haemodialysis unit of a tertiary centre hospital from 11 September 2022, to 11 November 2022. A convenience sampling technique was used. The data were collected using a proforma form, entered into, and analyzed using the Statistical Package for Social Sciences version 21. Results: The mean age group of the study participants was 54.02 ± 14.03 years, and around two-thirds were male (n=70, 67.3%). Almost half of the participants (50, 48.07%) had hyperuricemia with a mean uric acid level of 6.76 ± 2.62 mg/dl. The majority of the participants had associated hypertension (n=100, 96.2%). More than three-fourths of the respondents (83, 79.8%) had haemoglobin levels below the target range. Conclusion: Nearly half of the study participants had hyperuricemia.

Knowledge and practice regarding cancer screening in Nepal: a systematic review and meta-analysis.

Background: Cancer screening utilization can aid in the early diagnosis and treatment of cancer. However, the current scenario of the knowledge and practice regarding cancer screening remains unclear as the authors do not have sufficient studies. Hence, the authors conducted this systematic review and meta-analysis to assess the situation of cancer screening utilization and knowledge. Methods: A systematic literature review was conducted to identify all studies on knowledge and practice regarding cancer screening in the Nepalese population. Data extraction and analysis were done with SPSS and CMA-3. Results: The authors identified a total of 5238 studies after database searching, and 19 studies were included in a narrative synthesis. Lack of awareness and knowledge was the major barrier in cervical, breast, and testicular cancer screening. In cervical cancer screening, the most common reason for screening was the advice of health personnel in 85% of respondents, and the barrier was lack of awareness in 49.33% of participants. Conclusion: The knowledge and practice of cancer screening is lacking in Nepal, as shown by our review. More educational and awareness programs, easy access to screening services, and elimination of sociocultural barriers are necessary to increase the utilization of screening services.

Stroke epidemiology and outcomes of stroke patients in Nepal: a systematic review and meta-analysis.

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.

Disseminated tuberculosis in an immunocompetent woman from the Himalayan region of Nepal: A case report.

Disseminated tuberculosis (TB) resulting from lymphohematogenous dissemination of Mycobacterium tuberculosis during primary infection or reactivation of latent disease is rare among young immunocompetent patients. Central nervous system TB (CNS TB) is one of the most challenging clinical diagnoses with high fatality. Here, we describe a young immunocompetent female with no known comorbidities initially presented with military pulmonary TB and later developed CNS TB. This presentation of disseminated TB in immunocompetent patient warrant early diagnosis and treatment.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome: a case report from Nepal.

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.

Chronic myelomonocytic leukemia in a 72-year-old male from Nepal: A case report.

Chronic myelomonocytic leukemia (CMML) is a rare disease of clonal hematopoietic stem cells with an inherent risk of leukemic transformation, seen in an elderly male. Case Presentation: Herein, the authors report a case of CMML in a 72-year-old male who presented with fever and abdominal pain for 2 days with a history of easy fatigability. Examination revealed pallor and palpable supraclavicular nodes. Investigations showed leukocytosis with a monocyte count of 22% of white blood cell count, 17% blast cells in bone marrow aspiration, increased blast/promonocytes, and positive markers in immunophenotyping. The patient is planned for injection of azacitidine, 7 days cycle for a total of six cycles. Clinical Discussion: CMML is classified as overlapping myelodysplastic/myeloproliferative neoplasms. It can be diagnosed based on a peripheral blood smear, bone marrow aspiration and biopsy, chromosomal analysis, and genetic tests. The commonly used treatment options are hypomethylating agents like azacitidine and decitabine, allogeneic hematopoietic stem cell transplant, and cytoreductive agents like hydroxyurea. Conclusion: Despite various treatment options, the treatment is still unsatisfactory, demanding standard management strategies.

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.

Pulmonary barotrauma in COVID-19: A systematic review and meta-analysis.

BACKGROUND: An ever-increasing number of studies have reported an increased incidence of spontaneous pulmonary barotrauma such as pneumothorax, pneumomediastinum, and subcutaneous emphysema in patients with COVID-19. We conducted this systematic review and meta-analysis to assess the value and significance of the available data. METHODS: A thorough systematic search was conducted to identify studies of barotrauma in hospitalized patients with COVID-19. Data analysis of case reports was done using a statistical package for the social sciences (SPSS) version 22, and meta-analysis was performed using CMA-3. RESULTS: We identified a total of 4488 studies after thorough database searching.118 case reports and series, and 15 observational studies were included in the qualitative analysis. Fifteen studies were included in the quantitative analysis. The observational studies reported barotrauma in 4.2% (2.4-7.3%) among hospitalized patients; 15.6% (11-21.8%) among critically ill patients; and 18.4% (13-25.3%) in patients receiving invasive mechanical ventilation, showing a linear relationship of barotrauma with the severity of the disease. In addition, barotrauma was associated with a longer length of hospital stay, more extended ICU stay, and higher in-hospital mortality. Also, a slightly higher odds of barotrauma was seen in COVID-19 ARDS compared with non-COVID-19 ARDS. CONCLUSION: COVID-19 pneumonia is associated with a higher incidence of barotrauma. It presents unique challenges for invasive and non-invasive ventilation management. Further studies are required to unravel the underlying pathophysiology and develop safer management strategies.

Efficacy and Safety of Andexanet Alfa for Bleeding Caused by Factor Xa Inhibitors: A Systematic Review and Meta-Analysis.

Direct oral anticoagulants (DOAC) including factor Xa inhibitors are associated with bleeding events which can lead to severe morbidity and mortality. Reversal agents like andexanet alfa (AA) and 4F-PCC (Four-factor prothrombin concentrate complex) are available for treating bleeding that occurs with DOAC therapy but a comparison on their efficacy is lacking. In this study, we analyzed the efficacy and safety of patients treated with andexanet alfa for bleeding events from DOAC. Databases were searched for relevant studies where AA was used to determine efficacy and safety in bleeding patients who were on factor Xa inhibitors. Published papers were screened independently by two authors. RevMan 5.4 (The Cochrane Collaboration, 2020) was used for data synthesis. Odds ratio (OR) and mean difference (MD) was used to estimate the outcome with a 95% confidence interval (CI). Among 1245 studies were identified after a thorough database search and three studies were included for analysis. AA resulted in lower odds of mortality compared to 4F- PCC (OR, 0.37; 95% CI, 0.20-0.71) among patients with intracerebral hemorrhage. There was no difference in thrombotic events between patients receiving AA and 4F-PCC (OR, 2.40; 95% CI, 0.36-15.84). No differences in length of hospital stay and intensive care unit (ICU) stay were seen between patients receiving AA and 4F-PCC. In conclusion, andexanet alfa reduced in-hospital mortality in patients who had bleeding due to factor Xa inhibitors compared to 4F-PCC. However, there were no differences in thrombotic events, length of ICU, and hospital stay between patients treated with AA and 4F-PCC.

Radial Head Dislocation with Ipsilateral Proximal Shaft of Radius Fracture: A Case Report.

Radial head dislocations are uncommon in adults. They are commonly seen in children and are generally associated with proximal ulna fracture. Radial head dislocation with associated proximal radial shaft fracture is rarer than isolated radial head dislocation in adults. Due to the rarity of this complex injury, in the absence of keen observation and meticulous attention, the correct diagnosis might be missed leading to unsatisfactory management and related complications. Here, a similar case of radial head dislocation with associated proximal radial shaft fracture has been presented.

Anti-leucine-rich Glioma-inactivated-1 Encephalitis with Faciobrachial Dystonic Seizures and Behavioral Problems: A Case Report.

Anti-Leucine-rich glioma-inactivated-1 encephalitis is a subtype of autoimmune encephalitis characterized by cognitive impairment, faciobrachial dystonic seizures, and behavioural changes. There is no reported case from Nepal. We report a case of a 54-year old male who presented with abnormal body movement, behavioural changes, rapid eye movement sleep behavioural changes, and cognitive decline. Investigations revealed magnetic resonance imaging findings of fluidattenuated inversion recovery intensity signal in bilateral temporal lobes with anti-leucine-rich glioma-inactivated-1 antibody in serum leading to diagnosis of anti-leucine-rich glioma-inactivated-1 encephalitis. He was treated with steroids and intravenous immunoglobulin. Timely diagnosis is vital to prevent complications and improve outcomes.

Improved Free-Energy Landscape Quantification Illustrated with a Computationally Designed Protein-Ligand Interaction.

Quantifying the energy landscape underlying protein-ligand interactions leads to an enhanced understanding of molecular recognition. A powerful yet accessible single-molecule technique is atomic force microscopy (AFM)-based force spectroscopy, which generally yields the zero-force dissociation rate constant (koff ) and the distance to the transition state (Δx≠ ). Here, we introduce an enhanced AFM assay and apply it to probe the computationally designed protein DIG10.3 binding to its target ligand, digoxigenin. Enhanced data quality enabled an analysis that yielded the height of the transition state (ΔG≠ =6.3±0.2 kcal mol-1 ) and the shape of the energy barrier at the transition state (linear-cubic) in addition to the traditional parameters [koff (=4±0.1×10-4  s-1 ) and Δx≠ (=8.3±0.1 Å)]. We expect this automated and relatively rapid assay to provide a more complete energy landscape description of protein-ligand interactions and, more broadly, the diverse systems studied by AFM-based force spectroscopy.

Going Vertical To Improve the Accuracy of Atomic Force Microscopy Based Single-Molecule Force Spectroscopy.

Single-molecule force spectroscopy (SMFS) is a powerful technique to characterize the energy landscape of individual proteins, the mechanical properties of nucleic acids, and the strength of receptor-ligand interactions. Atomic force microscopy (AFM)-based SMFS benefits from ongoing progress in improving the precision and stability of cantilevers and the AFM itself. Underappreciated is that the accuracy of such AFM studies remains hindered by inadvertently stretching molecules at an angle while measuring only the vertical component of the force and extension, degrading both measurements. This inaccuracy is particularly problematic in AFM studies using double-stranded DNA and RNA due to their large persistence length (p ≈ 50 nm), often limiting such studies to other SMFS platforms (e.g., custom-built optical and magnetic tweezers). Here, we developed an automated algorithm that aligns the AFM tip above the DNA's attachment point to a coverslip. Importantly, this algorithm was performed at low force (10-20 pN) and relatively fast (15-25 s), preserving the connection between the tip and the target molecule. Our data revealed large uncorrected lateral offsets for 100 and 650 nm DNA molecules [24 ± 18 nm (mean ± standard deviation) and 180 ± 110 nm, respectively]. Correcting this offset yielded a 3-fold improvement in accuracy and precision when characterizing DNA's overstretching transition. We also demonstrated high throughput by acquiring 88 geometrically corrected force-extension curves of a single individual 100 nm DNA molecule in ∼40 min and versatility by aligning polyprotein- and PEG-based protein-ligand assays. Importantly, our software-based algorithm was implemented on a commercial AFM, so it can be broadly adopted. More generally, this work illustrates how to enhance AFM-based SMFS by developing more sophisticated data-acquisition protocols.

Rapid Characterization of a Mechanically Labile α-Helical Protein Enabled by Efficient Site-Specific Bioconjugation.

Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is a powerful yet accessible means to characterize mechanical properties of biomolecules. Historically, accessibility relies upon the nonspecific adhesion of biomolecules to a surface and a cantilever and, for proteins, the integration of the target protein into a polyprotein. However, this assay results in a low yield of high-quality data, defined as the complete unfolding of the polyprotein. Additionally, nonspecific surface adhesion hinders studies of α-helical proteins, which unfold at low forces and low extensions. Here, we overcame these limitations by merging two developments: (i) a polyprotein with versatile, genetically encoded short peptide tags functionalized via a mechanically robust Hydrazino-Pictet-Spengler ligation and (ii) the efficient site-specific conjugation of biomolecules to PEG-coated surfaces. Heterobifunctional anchoring of this polyprotein construct and DNA via copper-free click chemistry to PEG-coated substrates and a strong but reversible streptavidin-biotin linkage to PEG-coated AFM tips enhanced data quality and throughput. For example, we achieved a 75-fold increase in the yield of high-quality data and repeatedly probed the same individual polyprotein to deduce its dynamic force spectrum in just 2 h. The broader utility of this polyprotein was demonstrated by measuring three diverse target proteins: an α-helical protein (calmodulin), a protein with internal cysteines (rubredoxin), and a computationally designed three-helix bundle (α3D). Indeed, at low loading rates, α3D represents the most mechanically labile protein yet characterized by AFM. Such efficient SMFS studies on a commercial AFM enable the rapid characterization of macromolecular folding over a broader range of proteins and a wider array of experimental conditions (pH, temperature, denaturants). Further, by integrating these enhancements with optical traps, we demonstrate how efficient bioconjugation to otherwise nonstick surfaces can benefit diverse single-molecule studies.