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Prognostic markers are the biomarkers used to measure the disease progression and patient outcome regardless of treatment in coronavirus disease 2019 (COVID-19). This study aimed to analyze laboratory parameters as prognostic markers for the early identification of disease severity. In this study, 165 patients attending Sukraraj Tropical and Infectious Disease Hospital with COVID-19 were enrolled and divided into severe and non-severe groups. The demographic data, underlying co-morbidities, and laboratory findings were analyzed and compared between severe and non-severe cases. The correlation between the disease criticality and laboratory parameters was analyzed. Cut-off values of parameters for severe patients were speculated through the receiver operating characteristics (ROC) curve, and regression analysis was performed to determine the risk factors. Patients with severe COVID-19 infection had significantly higher absolute neutrophil count, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), ferritin, positive carbohydrate reactive protein (CRP), glucose, urea, creatinine, and aspartate aminotransferase, while lower absolute lymphocyte count, absolute eosinophil count (AEC), and red blood cell count in comparison to non-severe infection. ROC analysis gave a cut-off value (sensitivity, specificity) of age, AEC, NLR, PLR, and ferritin as 47.5 years (70.2, 64.7%), 335 cells/mm3 (74, 67%) 3.3 (68.4, 63.7%), 129 (77.2, 51%), and 241 ng/mL (74.0%, 65.0%) respectively. Risk factor analysis showed higher age, low AEC, high ferritin, and positive CRP as independent risk factors associated with severe COVID-19 infection. Hematological and inflammatory markers, including novel NLR and PLR, should be assessed to aid clinicians in the early identification of severe cases, prioritization of cases, and effective management to decrease the mortality of COVID-19 patients.

Keshav Lamichhane,1,* Nabaraj Adhikari,1,* Anup Bastola,2 Lina Devkota,2 Parmananda Bhandari,2 Binod Dhungel,1 Upendra Thapa Shrestha,1 Bipin Adhikari,3 Megha Raj Banjara,1 Komal Raj Rijal,1 Prakash Ghimire1 1Central Department of Microbiology, Tribhuvan University, Kathmandu, Nepal; 2Sukraraj Tropical and Infectious Disease Hospital, Teku, Kathmandu, Nepal; 3Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK*These authors contributed equally to this workCorrespondence: Komal Raj RijalCentral Department of Microbiology, Tribhuvan University, Kirtipur, Kathmandu, NepalEmail rijalkomal@gmail.comIntroduction: Oropharyngeal candidiasis are the commonest fungal infections among HIV-positive patients. The main objective of this study was to explore biofilm-producing Candida species causing oropharyngeal infections among HIV patients attending Sukraraj Tropical and Infectious Diseases Hospital (STIDH) in Kathmandu, Nepal.Methods: Oropharyngeal swabs were collected from the HIV-positive patients between July and December 2019. A total of 174 oropharyngeal swabs were cultured on Sabouraud Dextrose Agar (SDA). All samples were inoculated on SDA slants supplemented with chloramphenicol and underwent incubation at 37°C for 24– 48 hours. Any visible growth reported was processed for the identification of the species. Candida species were differentiated based on the growth and colour of the isolates on CHROM agar candida. Biofilm production in Candida species was determined by the microtiter plate method (MPM). Antifungal susceptibility testing was performed using the disc diffusion method.Results: Among 174 oropharyngeal samples, 23.6% (n=41/174) of them had oropharyngeal infections and 36.6% of the oropharyngeal infections (15/41) had CD4 T-lymphocytes count below 200 cells/mm3 who were also active tobacco users (p< 0.05). Among Candidial growth, 61% (25/41) were Candida albicans and 39% (16/41) were non-albicans. Of 41 Candida spp., 65% (27/41) were biofilm producers. An equal proportion of Candida albicans (4 isolates) and non-albicans (4 isolates) were strong biofilm producers. C. albicans isolates were sensitive towards clotrimazole (96%; 24/25) and fluconazole (92%; 23/25), whereas sensitivity towards ketoconazole was only 48% (12/25). Non-albicans Candida was highly sensitive to amphotericin-B (62.5%; 10/16) followed by clotrimazole (56.2%; 9/16). The biofilm-producing Candida isolates showed the highest resistivity (51.9%; 14/27) to ketoconazole and lowest (22.2%; 6/27) to clotrimazole.Conclusion: Oropharyngeal candidiasis is a common opportunistic infection among HIV-infected individuals. The majority of cases of oropharyngeal candidiasis are caused by biofilm producers Candida albicans and non-albicans Candida. Biofilm producers Candida were more resistant towards commonly used antifungal drugs.Keywords: oral candidiasis, HIV, Candida albicans, biofilm, antifungal susceptibility test

Rooku KC,1,* Sadiksha Adhikari,1,* Anup Bastola,2 Lina Devkota,2 Parmananda Bhandari,2 Prabina Ghimire,3 Bipin Adhikari,4 Komal Raj Rijal,1 Megha Raj Banjara,1 Prakash Ghimire1 1Central Department of Microbiology, Tribhuvan University, Kathmandu, Nepal; 2Sukraraj Tropical and Infectious Diseases Hospital, Kathmandu, Nepal; 3Nepal Medical College, Jorpati, Kathmandu, Nepal; 4Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK*These authors contributed equally to this workCorrespondence: Komal Raj RijalCentral Department of Microbiology, Tribhuvan University, Kirtipur, Kathmandu, NepalEmail rijalkomal@gmail.comIntroduction: Opportunistic bacterial and fungal infections are the major cause of morbidity and mortality among immune suppressed HIV-positive patients. The main objective of this study was to determine bacterial and fungal organisms causing respiratory infections and their susceptibility to commonly prescribed antimicrobials among HIV patients attending a tertiary infectious disease hospital in Kathmandu.Methods: Sputum samples were collected from the HIV-positive patients attending Sukraraj Tropical and Infectious Disease Hospital (STIDH) from August 2017 to March 2018. A total of 100 sputum samples were cultured on conventional bacterial and fungal culture media. Bacterial and fungal isolates were identified based on their colony characteristics, microscopic morphology and various biochemical tests. Antibiotic susceptibility test (AST) of bacterial isolates was performed by modified Kirby Bauer disc diffusion method.Results: Out of 100 sputum samples cultured, 24% (n=24) showed bacterial growth, 42% (n=42) showed fungal growth and 10% (n=10) had both bacterial and fungal growth. Among bacteria, 91.6% (n=22) were monomicrobial and 8.4% (n=2) were polymicrobial in growth, of which, Klebsiella pneumoniae (37.5%) were predominant isolates, followed by Pseudomonas aeruginosa (29.2%), and Escherichia coli (16.7%). The antibiotic susceptibility test (AST) showed 68% (17/25) of bacterial isolates were multi-drug resistant (MDR) and among them 41.2% (7/17) were found to be extended spectrum β lactamase (ESBL) producers. Fungal growth was observed in 42% of samples (42/100). A total of six different species of Candida and four different genera of molds were identified. On species differentiation, Candida albicans (20%) were followed by Candida parapsilosis (4%), and Candida dubliniensis (3%); and various molds were Aspergillus fumigatus (4%), Aspergillus flavus (2%), and Penicillium species (5%). CD4 count was inversely associated with bacterial and fungal infections. Fifty percent of the patients with the fungal infections had a CD4 count below 200. No fungal organisms were isolated from HIV-positive patients under antifungal drug treatment.Conclusion: HIV-positive patients with a CD4 count less than 200 cells/μL are more vulnerable to opportunistic infections of bacterial and fungal origin. Early isolation, identification and appropriate treatment can reduce mortality due to co-infections. Routine screening of opportunistic pathogens is critical to contain the disease progression.Keywords: HIV, CD4, bacterial and fungal infection, opportunistic infections

Glaucoma is a group of ocular diseases that cause irreversible blindness. It is characterized by multifactorial degeneration of the optic nerve axons and retinal ganglion cells (RGCs), resulting in the loss of vision. Major components of glaucoma pathogenesis include glia-driven neuroinflammation and impairment of mitochondrial dynamics and bioenergetics, leading to retinal neurodegeneration. In this review article, we summarize current evidence for the emerging role of apolipoprotein A-I binding protein (AIBP) as an important anti-inflammatory and neuroprotective factor in the retina. Due to its association with toll-like receptor 4 (TLR4), extracellular AIBP selectively removes excess cholesterol from the plasma membrane of inflammatory and activated cells. This results in the reduced expression of TLR4-associated, cholesterol-rich lipid rafts and the inhibition of downstream inflammatory signaling. Intracellular AIBP is localized to mitochondria and modulates mitophagy through the ubiquitination of mitofusins 1 and 2. Importantly, elevated intraocular pressure induces AIBP deficiency in mouse models and in human glaucomatous retina. AIBP deficiency leads to the activation of TLR4 in Müller glia, triggering mitochondrial dysfunction in both RGCs and Müller glia, and compromising visual function in a mouse model. Conversely, restoring AIBP expression in the retina reduces neuroinflammation, prevents RGCs death, and protects visual function. These results provide new insight into the mechanism of AIBP function in the retina and suggest a therapeutic potential for restoring retinal AIBP expression in the treatment of glaucoma.

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp-/- mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.

Spinal tuberculosis usually involves intervertebral disc, pardiscal vertebra and has associated perivertebral collection. Involvement of vertebral body including the posterior element, noncontagious vertebral involvement and sparing of intervertebral discs is typical of metastasis. Index case, a 19 years old Nepali patient presented to our hospital with complaints of severe backache. Blood and urine investigations were normal except elevated erythrocyte sedimentation rate and C- reactive protein. A contrast enhanced computed tomography (CT) showed lytic lesions in clivus, C7, T10, and L3 vertebral bodies with involvement of right sided posterior elements of C7 and T10. Mild surrounding soft tissue was seen. Contrast enhanced MRI showed similar findings and also lesions in S1 and right sacral ala. Possibility of metastatic lesion was considered over tuberculosis. A CT guided biopsy from right pedicle of T10 vertebra confirmed tubercular etiology.

The mechanical properties of solid tumors influence tumor cell phenotype and the ability to invade surrounding tissues. Using bioengineered scaffolds to provide a matrix microenvironment for patient-derived glioblastoma (GBM) spheroids, this study demonstrates that a soft, brain-like matrix induces GBM cells to shift to a glycolysis-weighted metabolic state, which supports invasive behavior. We first show that orthotopic murine GBM tumors are stiffer than peritumoral brain tissues, but tumor stiffness is heterogeneous where tumor edges are softer than the tumor core. We then developed 3D scaffolds with μ-compressive moduli resembling either stiffer tumor core or softer peritumoral brain tissue. We demonstrate that the softer matrix microenvironment induces a shift in GBM cell metabolism toward glycolysis, which manifests in lower proliferation rate and increased migration activities. Finally, we show that these mechanical cues are transduced from the matrix via CD44 and integrin receptors to induce metabolic and phenotypic changes in cancer cells.

Background: Improved technologies for chromatin accessibility sequencing such as ATAC-seq have increased our understanding of gene regulation mechanisms, particularly in disease conditions such as cancer. Methods: This study introduces a computational tool that quantifies and establishes connections between chromatin accessibility, transcription factor binding, transcription factor mutations, and gene expression using publicly available colorectal cancer data. The tool has been packaged using a workflow management system to allow biologists and researchers to reproduce the results of this study. Results: We present compelling evidence linking chromatin accessibility to gene expression, with particular emphasis on SNP mutations and the accessibility of transcription factor genes. Furthermore, we have identified significant upregulation of key transcription factor interactions in colon cancer patients, including the apoptotic regulation facilitated by E2F1, MYC, and MYCN, as well as activation of the BCL-2 protein family facilitated by TP73. Conclusion: This study demonstrates the effectiveness of the computational tool in linking chromatin accessibility to gene expression and highlights significant transcription factor interactions in colorectal cancer. The code for this project is openly available on GitHub.

Escherichia coli in untreated milk leads to economic losses from subclinical mastitis and reduced milk production, while also posing a public health risk due to the emergence of antimicrobial resistant strains, particularly associated with consuming unpasteurized milk and dairy products. This study aimed to determine the prevalence and antimicrobial resistance (AMR) of E. coli isolated from buffalo milk in Siddarthanagar Municipality of Rupandehi district, Nepal. A total of 102 milk samples were collected from lactating buffaloes. The isolation and identification of E. coli were carried out using enrichment media, selective media, and biochemical tests. Antimicrobial susceptibility testing was carried out using the Kirby–Bauer disk diffusion method on Mueller–Hinton agar (Merck), according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. Resistance was tested against gentamicin, amikacin, ciprofloxacin, enrofloxacin, ceftriaxone, ceftazidime, cotrimoxazole, and chloramphenicol. In addition to this, farmers were administered a questionnaire consisting of both open- and close-ended questions to identify various animal-related and management-related risk factors associated with the prevalence of E. coli. The prevalence of E. coli in our study was 29.4% (n = 30/102). Ceftriaxone and ceftazidime showed 100% resistance, while cotrimoxazole and amikacin showed 86.7% and 80% resistance, respectively. Furthermore, 86.7% of E. coli isolates were multidrug resistant (MDR). Despite suggestive trends, associations between E. coli prevalence and risk factors lacked statistical significance, necessitating further research. While some antibiotics exhibited effectiveness, many faced resistance, highlighting the need for prudent antimicrobial usage and increased awareness among farmers. Raising awareness about milk pasteurization and implementing food safety practices is essential for ensuring farmers and public health.

Background Nepal implemented a pilot of the Supervision, Performance Assessment, and Recognition Strategy (SPARS) program aimed to increase health workers’ ability to manage medicines through on- the-job training and support from a new cadre of Medicines Management Supervisors (MMS). This study aims to assess the implementation costs.Methods Data from the SPARS central database and facilities was analysed to assess the total cost of the SPARS pilot including 293 public health facilities from 12 districts of 3 provinces, from May 2022 until July 2023. We estimated the number of health facilities to achieve a successful performance status, defined as a SPARS score ≥ 18.75 out of 25 (75%) and estimated the cost per facility to reach a successful score.Results In total, 293 facilities received 838 visits, performed by 48 MMS for an estimated total cost of $226,531. 124 facilities (44.3%) reached a score of 18.75 points after two or more visits. On average, it costs $1827 USD per facility to reach a successful SPARS score.Conclusion This study assesses the costs of implementing SPARS in 12 districts in Nepal. These findings can provide insights into further scaling up SPARS in Nepal or in other countries.

IntroductionHealth information systems (HISs) should provide accessible and high-quality information to patients. However, the challenge lies in understanding patients’ trust preferences for health information. This study explores how different information sources (e.g., online platforms, interpersonal sources) are trusted under varying health conditions, focusing on symptom intensity and disease type.MethodsUsing a 2 × 2 × 4 between-subject design, 243 participants from a US college were presented with vignettes of acute or chronic diseases with varying symptom intensities and information sources. Participants rated their trust levels, including both cognitive and behavioral trust, in the health information and recommendations provided by one of the information sources, which was randomly assigned. Logistic regression and ANOVA were employed for the statistical analysis.ResultsThe analysis results revealed that trust is generally higher for interpersonal sources like doctors and family/friends compared to online sources like WebMD and Wikipedia when patients are making health decisions. Doctors are the most trusted source during health-related decision making. However, there are no significant differences in cognitive trust among interpersonal sources or among online sources. Furthermore, symptom intensity and disease type did not significantly alter trust levels across various information sources. These findings suggest that people prefer professional medical advice regardless of their health conditions.DiscussionThe study highlights the need for HIS to incorporate features that provide “doctor-verified” information and promote interactive engagement to enhance patients’ trust in information source. Additionally, it distinguishes between cognitive and behavioral trust, revealing distinct trust patterns that can inform the strategic development of HIS for varied health conditions. Understanding these trust dynamics can inform the design of effective, patient-centered HIS that better support health education, information seeking, and decision-making.

A-Kinase anchoring protein 1 (AKAP1) is a multifunctional mitochondrial scaffold protein that regulates mitochondrial dynamics, bioenergetics, and calcium homeostasis by anchoring several proteins, including protein kinase A, to the outer mitochondrial membrane. Glaucoma is a complex, multifactorial disease characterized by a slow and progressive degeneration of the optic nerve and retinal ganglion cells (RGCs), ultimately resulting in vision loss. Impairment of the mitochondrial network and function is linked to glaucomatous neurodegeneration. Loss of AKAP1 induces dynamin-related protein 1 dephosphorylation-mediated mitochondrial fragmentation and loss of RGCs. Elevated intraocular pressure triggers a significant reduction in AKAP1 protein expression in the glaucomatous retina. Amplification of AKAP1 expression protects RGCs from oxidative stress. Hence, modulation of AKAP1 could be considered a potential therapeutic target for neuroprotective intervention in glaucoma and other mitochondria-associated optic neuropathies. This review covers the current research on the role of AKAP1 in the maintenance of mitochondrial dynamics, bioenergetics, and mitophagy in RGCs and provides a scientific basis to identify and develop new therapeutic strategies that could protect RGCs and their axons in glaucoma.

Increased secretion of hyaluronic acid (HA), a glycosaminoglycan abundant in the brain extracellular matrix (ECM), correlates with worse clinical outcomes for glioblastoma (GBM) patients. GBM cells aggressively invade the brain parenchyma while encountering spatiotemporal changes in their local ECM, including HA concentration. To investigate how varying HA concentrations affect GBM invasion, patient-derived GBM cells are cultured within a soft, 3D matrix in which HA concentration is precisely varied and cell migration observed. Data demonstrate that HA concentration can determine the invasive activity of patient-derived GBM cells in a biphasic and highly sensitive manner, where the absolute concentration of HA at which cell migration peaked is specific to each patient-derived line. Furthermore, evidence that this response relies on phosphorylated ezrin, which interacts with the intracellular domain of HA-engaged CD44 to effectively link the actin cytoskeleton to the local ECM is provided. Overall, this study highlights CD44-HA binding as a major mediator of GBM cell migration that acts independently of integrins and focal adhesion complexes and suggests that targeting HA-CD44-ezrin interactions represents a promising therapeutic strategy to prevent tumor cell invasion in the brain.

The COVID-19 pandemic has affected higher education institutions (HEIs) worldwide and reshaped the existing educational system. Due to travel constraints and physical separation, there has been a global shift toward distance learning, and Nepal is no exception. This research intends to assess the practicality of online education by evaluating learners' experiences amidst COVID-19. A cross-sectional study was directed among HEIs students in Nepal using self-structured questionnaires. Our study revealed that 64.6% of the respondents were unsatisfied with online classes. More than half of the respondents (53.4%) use cell phones for online studies. Online education was reported to be unappealing to 28.8% of respondents. Variables such as age group (p = 0.05), enjoying class (p < 0.001), hours spent for an online class in a day (p = 0.05), and period for educational work using an electronic device (p = 0.1) were found significant with satisfaction level using both bivariate test and inferential test of univariate binary logistics regression. The challenges and opportunities encountered among students and faculties are highlighted along with the recommendations for fortifying communication in online-based teaching/learning.

Alzheimer's disease (AD) is a worldwide problem. Currently, there are no effective drugs for AD treatment. Scrophularia buergeriana Miquel (SB) is a traditional herbal medicine used in Korea to treat various diseases. Our previous studies have shown that ethanol extract of SB roots (SBE, Brainon®) exhibits potent anti-amnesic effects in Aβ1-42- or scopolamine-treated memory impairment mice model and neuroprotective effects in a glutamate-induced SH-SY5Y cell model. In this study, we evaluated the therapeutic effects of Brainon® and its mechanism of action in senescence-accelerated mouse prone 8 (SAMP8) mice. Brainon® (30 or 100 mg/kg/day) was orally treated to six-month-old SAMP8 mice for 12 weeks. Results revealed that Brainon® administration effectually ameliorated cognitive deficits in Y-maze and passive avoidance tests. Following the completion of behavioral testing, western blotting was performed using the cerebral cortex. Results revealed that Brainon® suppressed Aβ1-42 accumulation, Tau hyperphosphorylation, oxidative stress, and inflammation and alleviated apoptosis in SAMP8 mice. Brainon® also promoted synaptic function by downregulating the expression of AChE and upregulating the expression of p-CREB/CREB and BDNF. Furthermore, Brainon® restored SAMP8-reduced expression of ChAT and -dephosphorylated of ERK and also decreased AChE expression in the hippocampus. Furthermore, Brainon® alleviated AD progression by promoting mitophagy/autophagy to maintain normal cellular function as a novel finding of this study. Our data suggest that Brainon® can remarkably improve cognitive deficiency with the potential to be utilized in functional food for improving brain health.

Background: Reperfusion injury, characterized by oxidative stress and inflammation, poses a significant challenge in cardiac surgery with cardiopulmonary bypass (CPB). Deferoxamine, an iron-chelating compound, has shown promise in mitigating reperfusion injury by inhibiting iron-dependent lipid peroxidation and reactive oxygen species (ROS) production. Objectives: The objective of our study was to analyze and evaluate both the efficacy and safety of a new and promising intervention, that is, deferoxamine for ischemia-reperfusion injury (I/R). Design: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines are used to perform the study. Data sources and methods: We conducted a systematic review following PRISMA guidelines to assess the efficacy and safety of deferoxamine in reducing I/R injury following CPB. A comprehensive search of electronic databases, namely, PubMed, Scopus, and Embase, yielded relevant studies published until August 18, 2023. Included studies evaluated ROS production, lipid peroxidation, cardiac performance, and morbidity outcomes. Results: (a) ROS production : Multiple studies demonstrated a statistically significant decrease in ROS production in patients treated with deferoxamine, highlighting its potential to reduce oxidative stress. (b) Lipid peroxidation : Deferoxamine was associated with decreased lipid peroxidation levels, indicating its ability to protect cardiac tissue from oxidative damage during CPB. (c) Cardiac performance : Some studies reported improvements in left ventricular ejection fraction and wall motion score index with deferoxamine. Conclusion: Our review shows that deferoxamine is an efficacious and safe drug that can be used to prevent myocardial I/R injury following CPB. It also highlights the need for trials on a larger scale to develop potential strategies and guidelines on the use of deferoxamine for I/R injury.

The interplay between the gut microbiome and fermented foods has significant implications for human health and nutrition. Fermented foods, rich in beneficial microorganisms such as Lactic Acid Bacteria (LAB) including Lactobacillus spp., have attracted considerable research interest due to their potential probiotic effects. The six Nepalese fermented foods selected for this research—homemade yogurt, commercial yogurt, gundruk, tama, chhurpi, and achaar—are recognized for their diverse microbial profiles and purported health benefits, commonly consumed across various regions of Nepal. This study aims to elucidate their probiotic potential through tests such as acid and salt tolerance and their antimicrobial effects against five pathogens (Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Salmonella spp.). A total of 120 samples of these six different fermented foods were collected from households and local markets in Chitwan District. Among 120 fermented food samples, 103 samples (85.83%) were found to be LAB positive. Out of the total sample, 64 samples (53.30%) were found to be Lactobacillus spp. positive. These positive isolates were further tested for their pH tolerance, NaCl tolerance, and antibacterial potential. Upon research, 18 isolates were found to be tolerant at pH 2, and 21 isolates were found to be tolerant at 8% NaCl concentration. The highest antibacterial effect of Lactobacillus spp. was found against Staphylococcus aureus with ZOI 18 mm and lowest against Escherichia coli. The study here contributes to the importance of utilizing the microbial diversity present in fermented foods, along with providing valuable insights for developing novel probiotic interventions for enhancing gut and overall health. Moreover, the research highlights the potential of traditional fermented foods as a valuable source of probiotic strains, paving the way for innovative approaches to improve health through diet.

Glioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alternative RNA splicing. The acidic pH in the core switches before messenger RNA splicing of the ribosomal gene RPL22L1 towards the RPL22L1b isoform. This allows cells to survive acidosis, increases stemness and correlates with worse patient outcome. Mechanistically, RPL22L1b promotes RNA splicing by interacting with lncMALAT1 in the nucleus and inducing its degradation. Contrarily, in the tumour edge region, RPL22L1a interacts with ribosomes in the cytoplasm and upregulates the translation of multiple messenger RNAs including TP53. We found that the RPL22L1 isoform switch is regulated by SRSF4 and identified a compound that inhibits this process and decreases tumour growth. These findings demonstrate how distinct GBM cell populations arise during tumour growth. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy.

Glioblastoma (GBM) is characterized by extensive microvascular hyperproliferation. In addition to supplying blood to the tumor, GBM vessels also provide trophic support to glioma cells and serve as conduits for migration into the surrounding brain, promoting recurrence. Here, we enrich CD31-expressing glioma vascular cells (GVCs) and A2B5-expressing glioma tumor cells (GTCs) from primary GBM and use RNA sequencing to create a comprehensive molecular interaction map of the secreted and extracellular factors elaborated by GVCs that can interact with receptors and membrane molecules on GTCs. To validate our findings, we utilize functional assays, including a hydrogel-based migration assay and in vivo mouse models to demonstrate that one identified factor, the little-studied integrin binding sialoprotein (IBSP), enhances tumor growth and promotes the migration of GTCs along the vasculature. This perivascular niche interactome will serve as a resource to the research community in defining the potential functions of the GBM vasculature.

Introduction Children below the age of 15 years account for the majority of acquired immunodeficiency syndrome (AIDS)-related deaths in Nepal. Antiretroviral therapy (ART) improves health and prolongs lives of people with human immunodeficiency virus (HIV). Poor adherence to ART provides clue to a sub-therapeutic level of antiretroviral drug, which can facilitate multi-drug resistance of similar regimen, leading to treatment failure and death. The objective of this study was to determine the level of adherence to ART and its associated factors among HIV-infected children aged 0-14 years in Pokhara Academy of Health Sciences (PoAHS), Pokhara, Nepal. Material and methods This cross-sectional study was conducted between September 15th, 2020 and February 15th, 2021, and included 57 HIV-infected children. Caregivers of the children were questioned with a pre-tested, semi-structured questionnaire, which was later translated verbally to Nepali. Trained doctors took the interviews. Acquired data was entered using SPSS version 17 software for analysis. Level of significance was set at p

The escalating frequency of climate change-induced droughts poses a severe threat to rainfed maize cultivation in Thailand's upper Nan River Basin (NRB). Utilizing the standardized precipitation evapotranspiration index, this study comprehensively examines spatial and temporal drought patterns and their potential agricultural impact. Findings indicate a significant shift in precipitation patterns with wetter wet seasons, drier dry seasons and rising temperatures. The upper NRB experiences prolonged and severe droughts, while the lower region faces higher drought intensity, signalling an increased likelihood of extended and severe drought episodes in the upper region. Assessing maize cultivation suitability, factoring in environmental variables and drought impact under observed and climate change scenarios, reveals the current moderate suitability at 42.2%, projected to expand, and unsuitable regions expected to double. Different shared socioeconomic pathways (SSPs) show varied outcomes, with SSP5-8.5 indicating increased suitability in highly suitable areas and SSP2-4.5 demonstrating improvements in moderately suitable areas. The study underscores the need for tailored adaptation strategies in water management during droughts to enhance crop production, especially in dry seasons, in the upper NRB amid a changing climate. HIGHLIGHTS The upper Nan River Basin (NRB) tends to experience a wetter wet season and drier dry season with rising temperatures.; The upper region of the basin will likely experience extended periods of drought with higher severity.; The research findings highlight the impact of drought severity and other environmental variables on maize cultivation in the upper NRB.;

Abstract Background Health system-delivered evidence-based interventions (EBIs) are important to reducing amenable under-5 mortality (U5M). Implementation research (IR) can reduce knowledge gaps and decrease lags between new knowledge and its implementation in real world settings. IR can also help understand contextual factors and strategies useful to adapting EBIs and their implementation to local settings. Nepal has been a leader in dropping U5M including through adopting EBIs such as integrated management of childhood illness (IMCI). We use IR to identify strategies used in Nepal’s adaptation and implementation of IMCI. Methods We conducted a mixed methods case study using an implementation research framework developed to understand how Nepal outperformed its peers between 2000–2015 in implementing health system-delivered EBIs known to reduce amenable U5M. We combined review of existing literature and data supplemented by 21 key informant interviews with policymakers and implementers, to understand implementation strategies and contextual factors that affected implementation outcomes. We extracted relevant results from the case study and used explanatory mixed methods to understand how and why Nepal had successes and challenges in adapting and implementing one EBI, IMCI. Results Strategies chosen and adapted to meet Nepal’s specific context included leveraging local research to inform national decision-makers, pilot testing, partner engagement, and building on and integrating with the existing community health system. These cross-cutting strategies benefited from facilitating factors included community health system and structure, culture of data use, and local research capacity. Geography was a critical barrier and while substantial drops in U5M were seen in both the highest and lowest wealth quintiles, with the wealth equity gap decreasing from 73 to 39 per 1,000 live births from 2001 to 2016, substantial geographic inequities remained. Conclusions Nepal’s story shows that implementation strategies that are available across contexts were key to adopting and adapting IMCI and achieving outcomes including acceptability, effectiveness, and reach. The value of choosing strategies that leverage facilitating factors such as investments in community-based and facility-based approaches as well as addressing barriers such as geography are useful lessons for countries working to accelerate adaptation and implementation of strategies to implement EBIs to continue achieving child health targets.

Background: There is continued research to find new faster, highly accurate, easily accessible, and portable methods of confirming endotracheal tube position during intubation. A newer modality for visualizing endotracheal tube location is transtracheal or transcricothyroid ultrasonography. The aim of this study was to see if ultrasound machine can also be routinely used for the confirmation of endotracheal tube position in operating theaters along with capnograph. Methods: The study was observational and prospective, conducted from January 2017 to July 2017. Study locations were at the Tribhuvan University Teaching Hospital and Manmohan Cardiothoracic Vascular and Transplant Center operating rooms. Sample size taken was 95. Results: In the study, 11 patients had esophageal intubation out of the 95. The accuracy of both ultrasonography and capnography was found to be 96.84%. For ultrasonography, the sensitivity, specificity, along with positive predictive value and negative predictive value were 97.62%, 90.91%, 98.80%, and 83.33%, respectively, while that for capnography were found to be 96.43%, 100%, 100%, and 78.57%, respectively. The kappa value was calculated to be 0.749, which suggested the degree of agreement of result between the methods to be good. Compared to capnography, ultrasonography was found to be significantly faster for the confirmation of endotracheal tube location by 16.36 s (15.70–17.02) (P = 0.011). Conclusion: Both waveform capnography and ultrasonography were found to be accurate and reliable in confirming endotracheal tube location. The use of ultrasound during intubation can help confirm endotracheal tube location faster and also aid in precision when used along with capnography. Manual bag ventilations are not necessary when confirming endotracheal tube position by ultrasonography and thus may help in preventing aspiration of gastric contents into the lungs of the patient.

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp−/− mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.