SubFoveal Choroidal Imaging in High Myopic Nepalese Cohort

Current image captioning models produce fluent captions, but they rely on a one-size-fits-all approach that does not take into account the preferences of individual end-users. We present a method to generate descriptions with an adjustable amount of content that can be set at inference-time, thus providing a step toward a more user centered approach to image captioning

Prevalence of Refractive Errors in Nepalese Children and Adults: A Systematic Review With Meta-Analysis

Clinical relevance: Country-specific estimates of the prevalence of refractive errors are important to formulate national eye health policies for refractive care services. Background: The purpose of this study was to systematically synthesise available literature and estimate the prevalence of refractive errors in the Nepalese population. Methods: PubMed, Scopus, and Web of Science databases were systematically searched for articles on refractive errors and presbyopia published in English language until 27 September 2022. Population and school-based quantitative, cross-sectional prevalence studies and Rapid Assessment of Avoidable Blindness survey repository data were included. The quality of the included studies was assessed using the Newcastle Ottawa scale adapted for cross-sectional studies. Data extraction was performed with consensus among the reviewers. Meta-analysis of the prevalence was performed using the Random effects model to estimate the pooled proportions. Results: A total of 38 studies with 101 701 participants were included: 18 studies in children (n = 31 596) and 20 in adults (n = 70 105). In children, the estimated pooled prevalence of overall refractive errors was 8.4% (95% CI: 4.8 to 12.9) with myopia, hypermetropia and astigmatism prevalent in 7.1% (95% CI: 3.7 to 11.4), 1.0% (95% CI: 0.7 to 1.3) and 2.2% (95% CI: 0.9 to 3.9), respectively. In adults, the prevalence of refractive errors, uncorrected refractive errors, and uncorrected presbyopia were 11.2% (95% CI: 8.0 to 14.9), 7.3% (95% CI: 5.4 to 9.5) and 78.9% (95% CI: 69.1 to 87.3), respectively. Conclusions: The pooled prevalence of refractive errors is relatively low while uncorrected refractive errors and presbyopia are high in Nepalese population suggesting a need for better access to refractive care services in the country. The paucity of quality evidence on prevalence of refractive errors, particularly in children, indicates a need for a well-designed population-based study to accurately estimate the current prevalence of refractive errors

Molecular Basis of Membrane Pore Formation by Amyloid Beta Peptide

Alzheimer\u27s Disease (AD) is a neurodegenerative disorder that affects around 50 million people worldwide and causes cognitive decline, brain atrophy and death. Despite extensive basic and clinical studies and drug development efforts, currently no effective treatments are available for AD. The amyloid β (Aβ) peptide is neurotoxic and is tightly associated with AD pathology, but the molecular mechanism of its action remains unclear. There are various forms of Aβ in the brain, ranging from the full length Aβ1-42 to shorter peptides, such as a strongly toxic Aβ25-35 fragment. The Amyloid Cascade Hypothesis (ACH) postulated that extracellular Aβ deposits cause the disease. More recently, the soluble Aβ oligomers came into the focus of research as they proved to be the major neurotoxic entities. One of the mechanisms by which Aβ peptides, including Aβ25-35, kill neurons is membrane perforation and disruption of cellular homeostasis. Although direct membrane interaction and pore formation by Aβ has been documented, the detailed structural aspects of membrane pores remain elusive. Here, we quantitatively describe the structure of Aβ25-35 in aqueous buffer and in lipid environment, its binding to membranes, pore formation, and the details of membrane pores. We have shown that membrane binding of Aβ25-35 is electrostatically driven. Aβ25-35 forms β-barrel like structures ranging from hexamers to octamers and then assemble into supra-molecular structures forming calcium-conducting pores in the membrane with radius of 6 Å to 7 Å. The structural features of Aβ25-35 pores depend on the content of cholesterol in the membranes. Moreover, the aggregation and structural changes of a series of Aβ fragments have been analyzed to identify the segment(s) of highest propensity for fibrillogenesis that might serve as initiators of Aβ aggregation and conversion into toxic species. Finally, the structures of the full-length Aβ1-42 and a hypertoxic version pEAβ 3-42, in lipid environment have been analyzed by solid state nuclear magnetic resonance. Collectively, these studies will elucidate the structural details of membrane pores formed by Aβ peptides as targets for new anti-AD therapies

Earthquake Impacts on the Livelihoods of Community Forest Users in Sindhupalchok District, Nepal, and Their Perceptions towards Forest Conservation

Community forests are a crucial component of farming systems and people’s livelihoods in the rural middle hills of Nepal, where the population depends upon the forest for fuelwood, fodder, and leaf litter for their daily needs. This study aims to assess the perception of community forest user groups towards their postearthquake situations by using the five forms of capital from the sustainable livelihood framework. It further analyzes whether forest user’s attitudes towards forest conservation have changed or not. In addition to household interviews with 68 earthquake-affected households and extensive visits to the study area, key informant interviews and focus group discussions were conducted. This study confirms that the community forest user groups perceived negative effects on the natural, physical, human, and financial capitals, whereas they perceived a positive effect on social capital after the earthquake. Controlled access to forest products, such as timber collection during the recovery phase, restricted their resilience, although nontimber forest products supported it. Low agricultural production because of the scarcity of water for irrigation, as well as the soil infertility because of the landslides, caused local people to shift towards nonagricultural activities for income generation. Further, out-migration for job opportunities resulted in an inflow of remittances and, thus, manpower shortages were observed. Our results show that, despite facing the postdisaster impact on their livelihoods, 92% of the respondents were found to be positive towards forest conservation. This was because of their emotional attachment to the forest and the benefits received from the forest in the past. Local institutional policies and mechanisms must be strengthened to provide communities with the knowledge, skills, and practices for effective postdisaster recovery or for upcoming disasters, as well as the benefits of promoting sustainable forest conservation

Earthquake Impacts on the Livelihoods of Community Forest Users in Sindhupalchok District, Nepal, and Their Perceptions towards Forest Conservation

Community forests are a crucial component of farming systems and people’s livelihoods in the rural middle hills of Nepal, where the population depends upon the forest for fuelwood, fodder, and leaf litter for their daily needs. This study aims to assess the perception of community forest user groups towards their postearthquake situations by using the five forms of capital from the sustainable livelihood framework. It further analyzes whether forest user’s attitudes towards forest conservation have changed or not. In addition to household interviews with 68 earthquake-affected households and extensive visits to the study area, key informant interviews and focus group discussions were conducted. This study confirms that the community forest user groups perceived negative effects on the natural, physical, human, and financial capitals, whereas they perceived a positive effect on social capital after the earthquake. Controlled access to forest products, such as timber collection during the recovery phase, restricted their resilience, although nontimber forest products supported it. Low agricultural production because of the scarcity of water for irrigation, as well as the soil infertility because of the landslides, caused local people to shift towards nonagricultural activities for income generation. Further, out-migration for job opportunities resulted in an inflow of remittances and, thus, manpower shortages were observed. Our results show that, despite facing the postdisaster impact on their livelihoods, 92% of the respondents were found to be positive towards forest conservation. This was because of their emotional attachment to the forest and the benefits received from the forest in the past. Local institutional policies and mechanisms must be strengthened to provide communities with the knowledge, skills, and practices for effective postdisaster recovery or for upcoming disasters, as well as the benefits of promoting sustainable forest conservation

Membrane Binding And Pore Formation By A Cytotoxic Fragment Of Amyloid Β Peptide

Amyloid β (Aβ) peptide contributes to Alzheimer\u27s disease by a yet unidentified mechanism. In the brain tissue, Aβ occurs in various forms, including an undecapeptide Aβ25-35, which exerts a neurotoxic effect through the mitochondrial dysfunction and/or Ca2+-permeable pore formation in cell membranes. This work was aimed at the biophysical characterization of membrane binding and pore formation by Aβ25-35. Interaction of Aβ25-35 with anionic and zwitterionic membranes was analyzed by microelectrophoresis. In pore formation experiments, Aβ25-35 was incubated in aqueous buffer to form oligomers and added to Quin-2-loaded vesicles. Gradual increase in Quin-2 fluorescence was interpreted in terms of membrane pore formation by the peptide, Ca2+ influx, and binding to intravesicular Quin-2. The kinetics and magnitude of this process were used to evaluate the rate constant of pore formation, peptide-peptide association constants, and the oligomeric state of the pores. Decrease in membrane anionic charge and high ionic strength conditions significantly suppressed membrane binding and pore formation, indicating the importance of electrostatic interactions in these events. Circular dichroism spectroscopy showed that Aβ25-35 forms the most efficient pores in β-sheet conformation. The data are consistent with an oligo-oligomeric pore model composed of up to eight peptide units, each containing 6-8 monomers

Membrane Binding and Pore Formation by a Cytotoxic Fragment of Amyloid β Peptide

Amyloid β (Aβ) peptide contributes to Alzheimer\u27s disease by a yet unidentified mechanism. In the brain tissue, Aβ occurs in various forms, including an undecapeptide Aβ25-35, which exerts a neurotoxic effect through the mitochondrial dysfunction and/or Ca2+-permeable pore formation in cell membranes. This work was aimed at the biophysical characterization of membrane binding and pore formation by Aβ25-35. Interaction of Aβ25-35 with anionic and zwitterionic membranes was analyzed by microelectrophoresis. In pore formation experiments, Aβ25-35 was incubated in aqueous buffer to form oligomers and added to Quin-2-loaded vesicles. Gradual increase in Quin-2 fluorescence was interpreted in terms of membrane pore formation by the peptide, Ca2+ influx, and binding to intravesicular Quin-2. The kinetics and magnitude of this process were used to evaluate the rate constant of pore formation, peptide-peptide association constants, and the oligomeric state of the pores. Decrease in membrane anionic charge and high ionic strength conditions significantly suppressed membrane binding and pore formation, indicating the importance of electrostatic interactions in these events. Circular dichroism spectroscopy showed that Aβ25-35 forms the most efficient pores in β-sheet conformation. The data are consistent with an oligo-oligomeric pore model composed of up to eight peptide units, each containing 6-8 monomers

Distribution of Microplastic Contamination in Sapta-Gandaki River System, Nepal

Microplastic (MP) contamination has been reported in many Rivers worldwide. However, there is an increasing concern regarding data quality, particularly in the studies that do not account for positive and negative controls. Additionally, spatiotemporal distribution of MP in transboundary Himalayan River is underexplored. Here, we report spatiotemporal distribution of MP in the second largest river of Nepal; Sapta-Gandaki River system which is 810 km long starting from Himalayan headstream to the Ganges with a catchment area of 46,300 km^2. A total of 120 integrated water samples were collected in pre and post monsoons from 30 sites (2850-140 masl) along three tributaries of Saptagandaki River. The MP data were corrected for procedural blanks (n=23) and positive controls (n=18). We found that the MPs count (cut off size ≥30μm) in pre (dry) monsoon time was significantly higher (61.2±27.8 MP/L, p<0.01) than in post monsoon (winter) time (24.7±10.8 MP/L). High count was observed in the sites near major cities and highways. A gradual increase in MPs count was observed as the River stretches up to downstream (r=-0.6). The shape, size, and color dominance were fragments>pellets>fibers, 30-100>100-250>250-500>500-5000µm, blue>black>transparent; respectively. Most MP particles consisted of polyethylene terephthalate, cellophane, polyethylene, polyvinyl chloride type material. Annual flux discharge calculation showed that Saptagandaki River discharges 0.7×10^8 MP/s. The findings of this study provide baseline data for MPs contamination in one of the major Himalayan River water systems of Nepal and the data could be useful to identify potential control measures