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We report the discovery of a novel dual inhibitor targeting fungal sterol 14α-demethylase (CYP51 or Erg11) and human 5-lipoxygenase (5-LOX) with improved potency against 5-LOX due to its reduction of the iron center by its phenylenediamine core. A series of potent 5-LOX inhibitors containing a phenylenediamine core, were synthesized that exhibit nanomolar potency and >30-fold selectivity against the LOX paralogs, platelet-type 12-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity against ovine cyclooxygenase-1 and human cyclooxygnease-2. The phenylenediamine core was then translated into the structure of ketoconazole, a highly effective anti-fungal medication for seborrheic dermatitis, to generate a novel compound, ketaminazole. Ketaminazole was found to be a potent dual inhibitor against human 5-LOX (IC50 = 700 nM) and CYP51 (IC50 = 43 nM) in vitro. It was tested in whole blood and found to down-regulate LTB4 synthesis, displaying 45% inhibition at 10 µM. In addition, ketaminazole selectively inhibited yeast CYP51 relative to human CYP51 by 17-fold, which is greater selectivity than that of ketoconazole and could confer a therapeutic advantage. This novel dual anti-fungal/anti-inflammatory inhibitor could potentially have therapeutic uses against fungal infections that have an anti-inflammatory component.

BackgroundFriedreich ataxia, an autosomal recessive neurodegenerative and cardiac disease, is caused by abnormally low levels of frataxin, an essential mitochondrial protein. All Friedreich ataxia patients carry a GAATTC repeat expansion in the first intron of the frataxin gene, either in the homozygous state or in compound heterozygosity with other loss-of-function mutations. The GAA expansion inhibits frataxin expression through a heterochromatin-mediated repression mechanism. Histone modifications that are characteristic of silenced genes in heterochromatic regions occur at expanded alleles in cells from Friedreich ataxia patients, including increased trimethylation of histone H3 at lysine 9 and hypoacetylation of histones H3 and H4.Methodology/principal findingsBy chromatin immunoprecipitation, we detected the same heterochromatin marks in homozygous mice carrying a (GAA)(230) repeat in the first intron of the mouse frataxin gene (KIKI mice). These animals have decreased frataxin levels and, by microarray analysis, show significant gene expression changes in several tissues. We treated KIKI mice with a novel histone deacetylase inhibitor, compound 106, which substantially increases frataxin mRNA levels in cells from Friedreich ataxia individuals. Treatment increased histone H3 and H4 acetylation in chromatin near the GAA repeat and restored wild-type frataxin levels in the nervous system and heart, as determined by quantitative RT-PCR and semiquantitative western blot analysis. No toxicity was observed. Furthermore, most of the differentially expressed genes in KIKI mice reverted towards wild-type levels.Conclusions/significanceLack of acute toxicity, normalization of frataxin levels and of the transcription profile changes resulting from frataxin deficiency provide strong support to a possible efficacy of this or related compounds in reverting the pathological process in Friedreich ataxia, a so far incurable neurodegenerative disease.

BackgroundMultidrug-resistant tuberculosis (MDR-TB), characterized by isoniazid and rifampicin resistance, is caused by chromosomal mutations that restrict treatment options and complicate tuberculosis management. This study sought to investigate the prevalence of pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) tuberculosis, as well as mutation pattern, in Nepalese patients with MDR/rifampicin-resistant (RR)-TB strains.MethodsA cross-sectional study was conducted on MDR/RR-TB patients at the German Nepal Tuberculosis Project from June 2017 to June 2018. The MTBDRsl line probe assay identified pre-XDR-TB and XDR-TB. Pre-XDR-TB included MDR/RR-TB with resistance to any fluoroquinolone (FLQ), while XDR-TB included MDR/RR-TB with resistance to any FLQ and at least one additional group A drug. Mutation status was determined by comparing bands on reaction zones [gyrA and gyrB for FLQ resistance, rrs for SILD resistance, and eis for low-level kanamycin resistance, according to the GenoType MTBDRsl VER 2.0, Hain Lifescience GmbH, Nehren, Germany definition of pre-XDR and XDR] to the evaluation sheet. SPSS version 17.0 was used for data analysis.ResultsOut of a total of 171 patients with MDR/RR-TB, 160 had (93.57%) had MTBC, of whom 57 (35.63%) had pre-XDR-TB and 10 (6.25%) had XDR-TB. Among the pre-XDR-TB strains, 56 (98.25%) were FLQ resistant, while 1 (1.75%) was SLID resistant. The most frequent mutations were found at codons MUT3C (57.14%, 32/56) and MUT1 (23.21%, 13/56) of the gyrA gene. One patient had SLID resistant genotype at the MUT1 codon of the rrs gene (100%, 1/1). XDR-TB mutation bands were mostly detected on MUT1 (30%, 3/10) of the gyrA and rrs, MUT3C (30%, 3/10) of the gyrA, and MUT1 (30%, 3/10) of the rrs.ConclusionsPre-XDR-TB had a significantly higher likelihood than XDR-TB, with different specific mutation bands present in gyrA and rrs genes.

BackgroundHepatitis B is a global health problem with high morbidity and mortality. The risk of transmission is more common among health care personnels and medical students during their professional health trainings. Vaccination is the most effective means of prevention. The main objective of this study was to determine the level of knowledge, attitude, and practice regarding Hepatitis B and vaccination among pre-clinical students in a medical college.Materials and methodsA web-based, single-center, descriptive cross-sectional study was conducted among pre-clinical medical students in Bangladesh from April 28, 2024, to May 4, 2024. The whole sampling technique method was used taking the entire population for our study. Data were collected using a self-administered questionnaire and analyzed using JMP Pro V17 Statistical Software.ResultsSixty-one (34%) students were vaccinated against Hepatitis B, of whom 18% received all three doses with a booster dose. The most common reason for non-vaccination was lack of awareness of one's vaccination status (43%). The median knowledge, attitude, and practice (KAP) scores were 54 (50-60), 19 (17-21) and 20 (19-23) respectively, and they were moderately positively correlated. Forty-six (25.98%) students had a good overall KAP score (≥ 102).ConclusionOnly one-third of the students had been vaccinated, and the commonest reason for non-vaccination was lack of awareness of one's vaccination status. Nearly one-fourth of the participants had good knowledge, attitude, and practice related to Hepatitis B. Therefore, education regarding Hepatitis B infection, risk factors, and importance of vaccination is a must among pre-clinical medical students in Bangladesh.

Prostate cancer screening using prostate-specific antigen (PSA) testing is controversial but remains prevalent in many countries. There is little information in Sweden or elsewhere on the spatial variation in PSA testing. This study aims to describe the spatio-temporal variation in PSA testing prior to a prostate cancer diagnosis in the Stockholm region at the municipality and small area levels. A population-based register study comprised men aged 40 years and over living in the Stockholm region during 2007-2016. For Stockholm in 2016, we reported the proportion of men who had a PSA test for the preceding one, two, five and ten years by ten-year age groups. The age-standardised proportion of men having a PSA test was reported for municipalities by calendar years. We used spatial smoothing for calculating the age-standardised proportion of men having a PSA test in a small area for each calendar year. In 2016, 74.0% and 77.8% of men aged 60-69 and 70-79 years respectively had taken a PSA test in the previous ten years. The municipalities of Danderyd and Ekerö showed high proportions of PSA testing. A marked heterogeneity in such proportions within each municipality was observed. The odds ratio for having a PSA test for those born in Sweden was 2.22 (95% CI 2.00-2.52). Opportunistic PSA testing is widespread with three quarters of men in their sixties and seventies having had a test in the preceding decade. We found evidence for marked geographical heterogeneity, where more affluent and metropolitan areas had higher levels of testing. Variations in PSA testing was associated with socio-economic position and demographic factors including education, income and country of birth.

[This corrects the article DOI: 10.1371/journal.pone.0264673.].

Unremitting decline in crop productivity and nutrient recovery are resulted due to dearth of need based fertilizer recommendation over blanket application apart from nitrogen pollution in several means. An advance nutrient management tactic, GreenSeeker (GS) has developed and used in many field crops following the principle of four "R" (right source, right amount at right time, and place) nutrients stewardship technologies. But no studies have been conducted for evaluation of GS in mustard for improving productivity, profitability and nutrient use efficiency (NUE) while minimizing environmental risks. With this objective, a study was planned to conduct an experiment in rabi season of 2021-22 and 2022-23 to assess optical sensor based nitrogen management in mustard over blanket recommendation. The experiment was comprised of ten N treatments including control in randomized block design in triplicates. Research findings indicated that application of GreenSeeker based N significantly improved all growth traits and yield parameters in Brassica juncea L. Per cent enhancement in seed yield, net monetary returns and benefit-cost ratio was higher as 19.3 and 64.5%, 125.1 & 36.2% and 58.8 & 24.4%, respectively under GS based multi split N application over RDF and control. Further, real time N management with GS acquired higher crop production efficiency (CPE) (19.9 kg/day) with lesser cost/kg production (Rs 15.7/kg). Split application of N using GS increased oil yield by 79.9 and 26% over control and recommended dose of fertilizer (RDF) with maximum oil content (42.3%), and increases soil organic carbon (SOC) content by 16.1% from its initial value. Moreover, GS crop sensor could be the probable solution to minimize the crop nitrogen requirement by 15-20% with a yield enhancement of about 18.7% over RDF.

BackgroundLow back pain stands as a prevalent contributor to pain-related disability on a global scale. In addressing chronic low back pain (CLBP), there is a growing emphasis on incorporating psychological strategies into the management process. Among these, pain education interventions strive to reshape pain beliefs and mitigate the perceived threat of pain. This randomized controlled trial sought to assess the effects of pain education on various aspects, including pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals grappling with CLBP.MethodsThe clinical trial, retrospectively registered with the Clinical Trials Registry of India (CTRI/2021/08/035963), employed a two-arm parallel randomized design. Ninety-two participants with CLBP were randomly assigned to either the standard physiotherapy care with a pain education program or the control group. Both groups underwent a 6-week intervention. Assessment of pain intensity (using NPRS), disability (using RMDQ), self-efficacy (using the general self-efficacy scale), and well-being (using WHO 5I) occurred both before and after the 6-week study intervention.FindingsPost-intervention score comparisons between the groups revealed that the pain education intervention led to a significant reduction in disability compared to the usual standard care at 6 weeks (mean difference 8.2, p < 0.001, effect size Cohen d = 0.75), a decrease in pain intensity (mean difference 3.5, p < 0.001, effect size Cohen d = 0.82), and an improvement in the well-being index (mean difference 13.7, p < 0.001, effect size Cohen d = 0.58).ConclusionThe findings suggest that integrating a pain education program enhances the therapeutic benefits of standard physiotherapy care for individuals dealing with chronic LBP. In conclusion, the clinical benefits of pain education become apparent when delivered in conjunction with standard care physiotherapy during the management of chronic low back pain.

In Nepal, visceral leishmaniasis (VL) has been targeted for elimination as a public health problem by 2026. Recently, increasing numbers of VL cases have been reported from districts of doubtful endemicity including hills and mountains, threatening the ongoing VL elimination program in Nepal. We conducted a multi-disciplinary, descriptive cross-sectional survey to assess the local transmission of Leishmania donovani in seven such districts situated at altitudes of up to 1,764 meters in western Nepal from March to December 2019. House-to-house surveys were performed for socio-demographic data and data on past and current VL cases. Venous blood was collected from all consenting individuals aged ≥2 years and tested with the rK39 RDT. Blood samples were also tested with direct agglutination test, and a titer of ≥1:1600 was taken as a marker of infection. A Leishmania donovani species-specific PCR (SSU-rDNA) was performed for parasite species confirmation. We also captured sand flies using CDC light traps and mouth aspirators. The house-to-house surveys documented 28 past and six new VL cases of which 82% (28/34) were without travel exposure. Overall, 4.1% (54/1320) of healthy participants tested positive for L. donovani on at least one serological or molecular test. Among asymptomatic individuals, 17% (9/54) were household contacts of past VL cases, compared to 0.5% (6/1266) among non-infected individuals. Phlebotomus argentipes, the vector of L. donovani, was found in all districts except in Bajura. L. donovani was confirmed in two asymptomatic individuals and one pool of sand flies of Phlebotomus (Adlerius) sp. We found epidemiological and entomological evidence for local transmission of L. donovani in areas previously considered as non-endemic for VL. The national VL elimination program should revise the endemicity status of these districts and extend surveillance and control activities to curb further transmission of the disease.

BackgroundInformal caregivers played a significant role in caring for COVID-19 patients during hospitalization in Nepal. This study aimed to understand the experiences of family caregivers attending to their relatives in a COVID-19 hospital in Nepal.MethodsA descriptive phenomenological approach was adopted to understand the caregiver's experience in supporting their relatives admitted to the COVID-19 hospital of the BP Koirala Institute of Health Sciences (BPKIHS). Thirteen caregivers of COVID-19 positive patients were purposively selected from April to June, 2022. Face-to-face interviews were conducted at a caregiver residential facility using the interview schedule developed by the department for the purpose of data collection after obtaining ethical clearance from the Institutional review committee of BPKIHS. Data were audio recorded and manually analyzed.ResultsAmong the 13 caregivers, six were male and seven were female. The findings were categorized into five domains: challenges encountered, changes in physical and mental health, changes in roles and responsibilities, positive experiences, and strategies to ease caregiving tasks. Major challenges included financial burdens, communication problems, stigmatization, Insecurity, substandard accommodation, and visitor restrictions. Caregivers reported negative emotions, unmet physical health needs, and shifts in family and occupational roles. Despite these challenges, caregivers attempted to cope positively and acknowledged the efforts of healthcare personnel and other family members. Suggestions for improving caregiving included providing essential medical and basic services within the hospital, enhancing accommodation facilities, establishing proper communication channels, and allowing visitations.ConclusionsCaregivers of COVID-19 patients face significant challenges during the caregiving process. Enhancing hospital services, promoting effective communication, fostering positive attitudes, and ensuring a safe environment can facilitate caregiving tasks.

IntroductionThe lack of standardized methods for detecting biofilms continues to pose a challenge to microbiological diagnostics since biofilm-mediated infections induce persistent and recurrent infections in humans that often defy treatment with common antibiotics. This study aimed to evaluate diagnostic parameters of four in vitro phenotypic biofilm detection assays in relation to antimicrobial resistance in aerobic clinical bacterial isolates.MethodsIn this cross-sectional study, bacterial strains from clinical samples were isolated and identified following the standard microbiological guidelines. The antibiotic resistance profile was assessed through the Kirby-Bauer disc diffusion method. Biofilm formation was detected by gold standard tissue culture plate method (TCPM), tube method (TM), Congo red agar (CRA), and modified Congo red agar (MCRA). Statistical analyses were performed using SPSS version 17.0, with a significant association considered at pResultAmong the total isolates (n = 226), TCPM detected 140 (61.95%) biofilm producers, with CoNS (9/9) (pConclusionIt is suggested that TM be used for biofilm detection, after TCPM. Unlike MCRA, black pigmentation in colonies formed on CRA declined with time. MDR- and XDR-biofilm formers were frequent among the clinical isolates.

ObjectivesTo determine the availability and readiness of health facilities to provide family planning, antenatal care and basic emergency obstetric and newborn care in Nepal in 2021. Secondary objectives were to identify progress since 2015 and factors associated with readiness.MethodThis is a secondary analysis of cross-sectional Nepal Health Facility Survey (NHFS) data collected in 2015 and 2021. The main outcome measures were availability and readiness of family planning, antenatal care, and basic emergency obstetric and newborn care services. Readiness indices were calculated using WHO-recommended service availability and readiness assessment (SARA) methods (score range 0 to 100%, with 100% indicating facilities are fully prepared to provide a specific service). We used independent t-tests to compare readiness indices in 2015 and 2021. Factors potentially associated with readiness (rurality setting, ecological region, managing authority, management meeting, quality assurance activities, and external supervision) were explored using multivariable linear regression.ResultsThere were 940 and 1565 eligible health facilities in the 2015 and 2021 surveys, respectively. Nearly all health facilities provided family planning (2015: n = 919 (97.8%); 2021: n = 1530 (97.8%)) and antenatal care services (2015: n = 920 (97.8%); 2021: n = 1538 (98.3%)) in both years, but only half provided delivery services (2015: n = 457 (48.6%); 2021: n = 804 (51.4%)). There were suboptimal improvements in readiness indices over time: (2015-21: family planning 68.0% to 70.9%, pConclusionsReadiness to deliver family planning, antenatal care and basic emergency obstetric and newborn care services in Nepal remains inadequate, with little improvement observed over six years.

Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.

BackgroundTransmissibility within closed settings, such as households, can provide a strategic way to characterize the virus transmission patterns because the denominator can be well defined. We aimed to characterize the household transmission of Severe Acute Respiratory Syndrome Coronavirus (SARS CoV-2) and its associated risk factors.MethodsThis prospective case-ascertained study was conducted among the household contacts of laboratory-confirmed SARS CoV-2 cases residing in Ballabgarh, Haryana. We enrolled 148 index cases and their 645 household contacts between December 16, 2020 and June 24, 2021. We defined household contact as any person who had resided in the same household as a confirmed COVID-19 case. Baseline data collection and sample collection for real time- reverse transcriptase polymerase chain reaction (RT-PCR) and IgM/IgG against SARS CoV-2 were done on day 1 visit, and followed for a period of 28 days. RT-PCR was repeated on day 14 or whenever the contact is symptomatic and blood sample for serology was repeated on day 28. We estimated household secondary infection rate (SIR) and other epidemiological indicators-median incubation period and serial interval. We employed binomial logistic regression to quantify risk factors associated with infection.ResultsThe household SIR was 30.5% (95% CI: 27.1-34.1%). The secondary clinical attack rate was 9.3% (95% CI: 7.2-11.8). The risk factors that showed higher susceptibility to infection were household contacts who were the primary care giver of the case, whose index cases were symptomatic, those with underlying medical conditions, those living in overcrowded households, who were sharing toilet with the index cases and also who were not wearing a mask when coming in contact with the case. The median (IQR) incubation period was 4 days (4, 5), mean (SD) serial interval 6.4 (±2.2) days, and median (IQR) serial interval 5 days (5, 7).ConclusionHouseholds favour secondary transmission of SARS CoV- 2, hence, index cases are recommended to self-isolate and wear masks; and household contacts to follow strict COVID infection control measures within households when a family member is infected.

IntroductionThe aim of this study was to examine the risk of adverse perinatal outcomes in women diagnosed with GDM by the World Health Organization (WHO) 1999 criteria, and in those retrospectively identified by the Norwegian-2017 and WHO-2013 criteria but not by WHO-1999 criteria. We also examine the effect of maternal overweight/obesity and ethnicity.Material and methodsWe used pooled data from four Norwegian cohorts (2002-2013), encompassing 2970 mother-child pairs. Results from universally offered 75-g oral glucose tolerance tests measuring fasting plasma glucose (FPG) and 2-hour glucose (2HG) were used to assign women into three diagnostic groups: Diagnosed and treated by WHO-1999 (FPG≥7.0 or (2HG ≥7.8 mmol/L), identified by WHO-2013 (FPG ≥5.1 or 2HG ≥8.5 mmol/L), and identified by Norwegian-2017 criteria (FPG ≥5.3 or 2HG ≥9.0 mmol/L). Perinatal outcomes included large-for-gestational-age (LGA) infants, cesarean section, operative vaginal delivery, preterm birth and preeclampsia.ResultsCompared to the non-GDM group, women diagnosed with GDM by either of the three criteria had an increased risk of large-for-gestational-age infants (adjusted odds ratios (OR) 1.7-2.2). Those identified by the WHO-2013 and Norwegian-2017 criteria but not diagnosed and treated by WHO-1999 criteria had an additional increased risk of cesarean section (OR 1.36, 95% CI 1.02,1.83 and 1.44, 95% CI 1.03,2.02, respectively) and operative vaginal delivery (OR 1.35, 95% CI 1.1,1.7 and 1.5, 95% CI 1.1,2.0, respectively). The proportions of LGA neonates and cesarean section were higher for women with GDM in both normal-weight and overweight/obese women. Asians had a lower risk of delivering large-for-gestational-age infants than Europeans applying national birthweight references, but maternal glucose values were similarly positively associated with birthweight in all ethnic groups.ConclusionsWomen who met the WHO-2013 and Norwegian-2017 criteria, but were not diagnosed by the WHO-1999 criteria and therefore not treated, had an increased risk of LGA, cesarean section and operative vaginal delivery compared to women without GDM.

Rural and urban America have becoming increasingly divided, both politically and economically. Entrepreneurship can help rural communities catch back up by jumpstarting economic growth, creating jobs, and building resilience to economic shocks. However, less is known about firm creation in rural areas compared to urban areas. To that end, in this paper we ask: What factors predict firm creation in rural America? Our analysis, based on a comparative framework involving multiple machine learning modeling techniques, helps addresses three gaps in academic literature on rural firm creation. First, entrepreneurship research stretches across disciplines, often using econometric methods to identify the effect of a specific variable, rather than comparing the predictive importance of multiple variables. Second, research on firm creation centers on high-tech, urban firms. Third, modern machine learning techniques have not yet been applied in an integrated way to address rural entrepreneurship, a complex economic and policy problem that defies simple, monocausal claims. In this paper, we apply four machine learning methods (subset selection, lasso, random forest, and extreme gradient boosting) to a novel dataset to examine what social and economic factors are predictive of firm growth in rural Texas counties from 2008-2018. Our results suggest that some factors commonly discussed as promoting entrepreneurship (e.g., access to broadband and patents) may not be as predictive as socioeconomic ones (age distribution, ethnic diversity, social capital, and immigration). We also find that the strength of specific industries (oil, wind, healthcare, and elder/childcare) predicts firm growth, as does the number of local banks. Most factors predictive of firm growth in rural counties are distinct from those in urban counties, supporting the argument that rural entrepreneurship is a distinct phenomenon worthy of distinct focus. More broadly, this multi-model approach can offer initial, focusing guidance to policymakers seeking to address similarly complex policy problems.

PurposeRetinal function beyond foveal vision is not routinely examined in the clinical screening and management of diabetic retinopathy although growing evidence suggests it may precede structural changes. In this study we compare optical coherence tomography (OCT) based macular structure with function measured objectively with the ObjectiveFIELD Analyzer (OFA), and with Matrix perimetry. We did that longitudinally in Type 2 diabetes (T2D) patients with mild Diabetic Macular Oedema (DMO) with good vision and a similar number of T2D patients without DMO, to evaluate changes in retinal function more peripherally over the natural course of retinopathy.MethodsBoth eyes of 16 T2D patients (65.0 ± 10.1, 10 females), 10 with baseline DMO, were followed for up longitudinally for 27 months providing 94 data sets. Vasculopathy was assessed by fundus photography. Retinopathy was graded using to Early Treatment of Diabetic Retinopathy Study (ETDRS) guidelines. Posterior-pole OCT quantified a 64-region/eye thickness grid. Retinal function was measured with 10-2 Matrix perimetry, and the FDA-cleared OFA. Two multifocal pupillographic objective perimetry (mfPOP) variants presented 44 stimuli/eye within either the central 30° or 60° of the visual field, providing sensitivities and delays for each test-region. OCT, Matrix and 30° OFA data were mapped to a common 44 region/eye grid allowing change over time to be compared at the same retinal regions.ResultsIn eyes that presented with DMO at baseline, mean retinal thickness reduced from 237 ± 25 μm to 234.2 ± 26.7 μm, while the initially non-DMO eyes significantly increased their mean thickness from 250.7 ± 24.4 μm to 255.7 ± 20.6 μm (both pConclusionsChanges in retinal function measured by OFA possibly offer greater power to monitor DMO over time than Matrix perimetry data.

This work helps to identify the source of pollution in water and characterize the water quality which is essential to water management for sustainable development. Therefore, the main objective of this work is to evaluate the spatial distribution of the water quality of Ratuwa river and its tributaries. The water samples were collected from six discrete sampling locations and fifteen parameters were tested using respective well-calibrated equipment and standard APHA methods. The physicochemical analysis, water quality index, and correlation matrix method were employed to evaluate the spatial variation of the water quality of Ratuwa river. Turbidity was the most polluting factor in river water. The results showed the spatial variation of the water quality index (WQI) from 39.3 to 70.5, which fell in the range of "good" to "poor" water quality status. None of the water samples was either "excellent" or "unsuitable for drinking." The water quality was "Poor" upstream and downstream of Ratuwa river due to the high value of turbidity. Chaju river was found to have unpolluted whereas Dipeni river was slightly polluted due to domestic and municipal wastes. Hence, the deterioration of water quality can be attributed to natural and anthropogenic sources.

Immune defense is a complex trait that affects and is affected by many other host factors, including sex, mating, and dietary environment. We used the agriculturally relevant fungal emtomopathogen, Beauveria bassiana, and the model host organism Drosophila melanogaster to examine how the impacts of sex, mating, and dietary environment on immunity are interrelated. We showed that the direction of sexual dimorphism in immune defense depends on mating status and mating frequency. We also showed that post-infection dimorphism in immune defense changes over time and is affected by dietary condition both before and after infection. Supplementing the diet with protein-rich yeast improved post-infection survival but more so when supplementation was done after infection instead of before. The multi-directional impacts among immune defense, sex, mating, and diet are clearly complex, and while our study shines light on some of these relationships, further study is warranted. Such studies have potential downstream applications in agriculture and medicine.

Eight workers involved in packing cross-linked water-soluble acrylic acid polymer, an organic substance, developed pulmonary fibrosis, and the upper lobe was the most affected. The dust concentration in the polymer packing workstation was measured. Chest computed tomography (CT) was obtained for 82 individuals, including the 8 workers mentioned above. Three workers were histopathologically examined. In six of these eight workers, central pulmonary fibrosis and secondary bulla formation caused pneumothorax. Histopathologically, multiple centrilobular fibrotic foci were observed. Chest CT revealed centrilobular nodular opacity and interlobular septal thickening, suggesting early lesions in the workers because the dust concentration was remarkably high. Although the pathogenesis of the disease is unclear, we reported the occurrence of pulmonary fibrosis caused by the exposure to cross-linked water-soluble acrylic acid polymers in humans as it has not been reported earlier.

Introduction This study was conducted with the objective to analyze the out-of-pocket (OOP) healthcare expenditure and catastrophic healthcare expenditure (CHE) on chronic non-communicable diseases (CNCD) among the elderly population, and the association of CHE on CNCD with associated factors among the same population. Materials and methods We collected data from the elderly population of Dharan Sub-metropolitan city of the Eastern Nepal via door-to-door survey and face-to-face interview. The ten wards out of twenty were chosen by lottery method, and the equal proportion out of 280 samples was purposively chosen from each of ten wards (28 participants from each selected ward). The data were entered in Microsoft Excel 2019 v16.0 and statistical analysis was performed by using statistical package for social sciences, IBM SPSS® v21. The chi-square test was used to test the group differences. Multivariable logistic regression was used to determine independent factors associated with CHE (all variables with P < 0.20), and adjusted odds ratios (AOR) were calculated at 95% confidence interval (CI). Results The median household, food and health expenditures were 95325 (72112.50–126262.50), 45000 (33000–60000) and 2100 (885.00–6107.50) NPR respectively. The proportion of the participants with CHE was 14.6%. The single living participants had 3.4 times higher odds of catastrophic health expenditure (AOR = 3.4, 95% CI = 1.2–9.6, P-value = 0.022) than those who are married. Similarly, those who had cancer had 0.1 times lower odds of CHE (AOR = 0.1, 95% CI = 0.0–0.2, P-value = Conclusion The elder population had significant financial health shocks due to chronic health ailments. There should be the provision of mandatory health insurance programmes for elderly to cut down the catastrophic healthcare expenditure. Similarly, there should be the provision of exemption scheme for vulnerable elderly who are more likely to face catastrophic expenditure from all available health facilities.

The COVID-19 pandemic posed a major global health challenge. Preventive measures against the spread of COVID-19 require the involvement of all sections of society. Knowledge and attitude towards COVID-19 preventive measures influence human practices. We describe the knowledge, attitude and practice (KAP) of COVID-19 preventive measure in Bhutan. This was a cross-sectional survey using multistage-cluster sampling involving participants from all 20 districts of the country. The knowledge was assessed using 12 items, attitude using 6 Likert items and practice using 10 items. There was total of 1708 respondents. The mean knowledge was 10.7, (SD = 1.5; range 0-12); 86.38% had good knowledge, 10.95% had average knowledge, 2.69% had poor knowledge. The common sources of knowledge were television (84.9%) and family and friends (74.7%). Those younger than 30 years were associated with good knowledge. The fear of contracting COVID-19 was reported by 96% and 86.4% agreed that appropriate preventive measures can help control the spread of COVID-19. Nearly all the respondents (97%) wore mask while going out and majority practiced good hand hygiene (87.9%) and proper cough etiquette (84.1%). The knowledge on COVID-19 preventive measures was good and the majority held positive attitudes and practices.

Early detection of lung cancer is a crucial factor for increasing its survival rates among the detected patients. The presence of carbonyl volatile organic compounds (VOCs) in exhaled breath can play a vital role in early detection of lung cancer. Identifying these VOC markers in breath samples through innovative statistical and machine learning techniques is an important task in lung cancer research. Therefore, we proposed an experimental approach for generation of VOC molecular concentration data using unique silicon microreactor technology and further identification and characterization of key relevant VOCs important for lung cancer detection through statistical and machine learning algorithms. We reported several informative VOCs and tested their effectiveness in multi-group classification of patients. Our analytical results indicated that seven key VOCs, including C4H8O2, C13H22O, C11H22O, C2H4O2, C7H14O, C6H12O, and C5H8O, are sufficient to detect the lung cancer patients with higher mean classification accuracy (92%) and lower standard error (0.03) compared to other combinations. In other words, the molecular concentrations of these VOCs in exhaled breath samples were able to discriminate the patients with lung cancer (n = 156) from the healthy smoker and nonsmoker controls (n = 193) and patients with benign pulmonary nodules (n = 65). The quantification of carbonyl VOC profiles from breath samples and identification of crucial VOCs through our experimental approach paves the way forward for non-invasive lung cancer detection. Further, our experimental and analytical approach of VOC quantitative analysis in breath samples may be extended to other diseases, including COVID-19 detection.

Background The Joint United Nations Programme on AIDS (UNAIDS) has emphasized on the incidence-prevalence ratio (IPR) and incidence-mortality ratio (IMR) to measure the progress in HIV epidemic control. In this paper, we describe the status of epidemic control in India and in various states in terms of UNAIDS’s recommended metrices. Method The National AIDS Control Programme (NACP) of India spearheads work on mathematical modelling to estimate HIV burden based on periodically conducted sentinel surveillance for providing guidance to program implementation and policymaking. Using the results of the latest round of HIV Estimations in 2019, IPR and IMR were calculated. Results National level IPR was 0.029 [0.022–0.037] in 2019 and ranged from 0.01 to 0.15 in various States and Union Territories (UTs). Corresponding Incidence-Mortality Ratio was at 0.881 [0.754–1.014] nationally and ranged between 0.20 and 12.90 across the States/UTs. Conclusions Based on UNAIDS recommended indicators for HIV epidemic control, namely IPR and IMR; national AIDS response in India appears on track. However, the program success is not uniform and significant heterogeneity as well as expanding epidemic was observed at the level of States or UTs. Reinforcing States/UTs specific and focused HIV prevention, testing and treatment initiatives may help in the attainment of 2030 Sustainable Development Goals of ending AIDS as a public health threat by 2030.

Alternative pet foods may offer benefits concerning environmental sustainability and the welfare of animals processed into pet foods. However, some worry these may compromise the welfare of pets. We asked 2,639 dog guardians about one dog living with them, for at least one year. Among 2,596 involved in pet diet decision-making, pet health was a key factor when choosing diets. 2,536 provided information relating to a single dog, fed a conventional meat (1,370 = 54%), raw meat (830 = 33%) or vegan (336 = 13%) diet for at least one year. We examined seven general indicators of ill health: unusual numbers of veterinary visits, medication use, progression onto a therapeutic diet after initial maintenance on a vegan or meat-based diet, guardian opinion and predicted veterinary opinion of health status, percentage of unwell dogs and number of health disorders per unwell dog. Dogs fed conventional diets appeared to fare worse than those fed either of the other two diets. Dogs fed raw meat appeared to fare marginally better than those fed vegan diets. However, there were statistically significant differences in average ages. Dogs fed raw meat were younger, which has been demonstrated to be associated with improved health outcomes. Additionally, non-health related factors may have improved apparent outcomes for dogs fed raw meat, for three of seven general health indicators. We also considered the prevalence of 22 specific health disorders, based on predicted veterinary assessments. Percentages of dogs in each dietary group considered to have suffered from health disorders were 49% (conventional meat), 43% (raw meat) and 36% (vegan). Significant evidence indicates that raw meat diets are often associated with dietary hazards, including nutritional deficiencies and imbalances, and pathogens. Accordingly, the pooled evidence to date indicates that the healthiest and least hazardous dietary choices for dogs, are nutritionally sound vegan diets.

Resting-state blood-oxygen-level-dependent (BOLD) signal acquired through functional magnetic resonance imaging is a proxy of neural activity and a key mechanism for assessing neurological conditions. Therefore, practical tools to filter out artefacts that can compromise the assessment are required. On the one hand, a variety of tailored methods to preprocess the data to deal with identified sources of noise (e.g., head motion, heart beating, and breathing, just to mention a few) are in place. But, on the other hand, there might be unknown sources of unstructured noise present in the data. Therefore, to mitigate the effects of such unstructured noises, we propose a model-based filter that explores the statistical properties of the underlying signal (i.e., long-term memory). Specifically, we consider autoregressive fractional integrative process filters. Remarkably, we provide evidence that such processes can model the signals at different regions of interest to attain stationarity. Furthermore, we use a principled analysis where a ground-truth signal with statistical properties similar to the BOLD signal under the injection of noise is retrieved using the proposed filters. Next, we considered preprocessed (i.e., the identified sources of noise removed) resting-state BOLD data of 98 subjects from the Human Connectome Project. Our results demonstrate that the proposed filters decrease the power in the higher frequencies. However, unlike the low-pass filters, the proposed filters do not remove all high-frequency information, instead they preserve process-related higher frequency information. Additionally, we considered four different metrics (power spectrum, functional connectivity using the Pearson’s correlation, coherence, and eigenbrains) to infer the impact of such filter. We provided evidence that whereas the first three keep most of the features of interest from a neuroscience perspective unchanged, the latter exhibits some variations that could be due to the sporadic activity filtered out.

In the aftermath of shock events, policy responses tend to be crafted under significant time constraints and high levels of uncertainty. The extent to which individuals comply with different policy designs can further influence how effective the policy responses are and how equitably their impacts are distributed in the population. Tools which allow policymakers to model different crisis trajectories, policy responses, and behavioral scenarios ex ante can provide crucial timely support in the decision-making process. Set in the context of COVID-19 shelter in place policies, in this paper we present the COVID-19 Policy Evaluation (CoPE) tool, which is an agent-based modeling framework that enables researchers and policymakers to anticipate the relative impacts of policy decisions. Specifically, this framework illuminates the extent to which policy design features and behavioral responsiveness influence the efficacy and equity of policy responses to shock events. We show that while an early policy response can be highly effective, the impact of the timing is moderated by other aspects of policy design such as duration and targeting of the policy, as well as societal aspects such as trust and compliance among the population. More importantly, we show that even policies that are more effective overall can have disproportionate impacts on vulnerable populations. By disaggregating the impact of different policy design elements on different population groups, we provide an additional tool for policymakers to use in the design of targeted strategies for disproportionately affected populations.

BackgroundElevated blood pressure or hypertension is responsible for around 10 million annual deaths globally, and people residing in low and middle-income countries are disproportionately affected by it. India is no exception, where low rate of treatment seeking for hypertension coupled with widespread out-of-pocket payments (OOPs) have been a challenge. This study assessed the pattern of health care seeking behaviour and financial protection along with the associated factors among hypertensive individuals in rural West Bengal, India.Method and findingsA cross-sectional study was conducted in Birbhum district of the state of West Bengal, India, during 2017-2018, where 300 individuals were recruited randomly from a list of hypertensives in a population cohort. Healthcare seeking for hypertension and related financial protection in terms of-OOPs and expenses relative to monthly per-capita family expenditure, were analysed. Findings indicated that 47% of hypertensives were not on treatment. Among those under treatment, 80% preferred non-public facilities, and 91% of them had wide-spread OOPs. Cost of medication was a major share of expenses followed by transportation cost to access public health care facility. Multivariable logistic regression analysis indicated longer duration of disease (adjusted odds ratio (aOR): 5.68, 95% Confidence Interval (CI) 1.24-25.99) and health care seeking from non-public establishment (aOR: 34.33, CI: 4.82-244.68) were associated with more incident of OOPs. Linear regression with generalized linear model revealed presence of co-morbidities (adjusted coefficient (aCoeff)10.28, CI: 4.96,15.61) and poorer economic groups (aCoeffpoorest 11.27, CI 3.82,18.71; aCoefflower-middle 7.83, CI 0.65,15.00 and aCoeffupper-middle 7.25, CI: 0.80,13.70) had higher relative expenditure.ConclusionThis study suggests that individuals with hypertension had poor health care seeking behaviour, preferred non-public health facilities and had suboptimal financial protection. Economically poorer individuals had higher burden of health expenditure for treatment of hypertension, which indicated gaps in equitable health care delivery for the control of hypertension.

Oroxylum indicum (L.) Kurz, a medicinal plant, shows numerous pharmacological properties which may be attributed to the bioactive compounds produced by O. indicum or due to associated endophytes. In the present study, leaf of O. indicum was evaluated for the presence of associated fungal endophytes, and antioxidant and cytotoxic activities of bioactive compounds produced from them. Using culture-dependent approach, eight fungal endophytes belonging to five different genera were identified. Two endophytes Daldinia eschscholtzii and Ectophoma multirostrata have been reported for the first time from the leaf of O. indicum plant. High-performance thin-layer chromatography (HPTLC) of ethyl acetate (EA) extract of isolated fungal endophytes showed a distinct fingerprinting profile in EA extract of Colletotrichum gloeosporioides. Among identified endophytes, EA extract of C. gloeosporioides showed significant antioxidant activity against DPPH free radical, superoxide anion radical, nitric oxide radical and hydroxyl radical with EC50 values of 22.24±1.302 μg/mL, 67.46±0.576 μg/mL, 80.10±0.706 μg/mL and 61.55±1.360 μg/mL, respectively. EA extract of C. gloeosporioides exhibited potential cytotoxicity against HCT116, HeLa and HepG2 cancer cell lines with IC50 values of 76.59 μg/mL, 176.20 μg/mL and 1750.70 μg/mL, respectively. A comparative HPTLC fingerprinting and the antioxidant activity of C. gloeosporioides associated with two different hosts (leaf of O. indicum and dead twigs of other plant) showed that C. gloeosporioides produces bioactive compounds in a host-dependent manner.

BackgroundThe economic and social costs of autism are significant. This study evaluates the cost-effectiveness of early intensive Applied Behaviour Analysis (ABA)-based interventions for autistic pre-school children in the UK.MethodsA de novo economic analysis was developed in Microsoft Excel comparing early intensive ABA-based interventions compared with treatment as usual (TAU). The analysis used 15.5-year time horizon, with costs and benefits discounted a 3.5%. The model structure was based on cohort structure to capture changes in adaptive behaviour and cognitive ability over time. The analysis was informed by an individual patient data (IPD) meta-analysis of available evidence.ResultsAdopting a public sector perspective, early intensive ABA-based therapies were associated with greater incremental costs and greater benefits. When pessimistic assumptions were made regarding the long-term effects of treatment incremental costs were £46,103 and incremental quality-adjusted life years (QALYs) were 0.24, resulting in an incremental cost-effectiveness ratio (ICER) of £189,122 per quality-adjusted life year (QALY). When optimistic assumptions were made about long-term effects, incremental costs were £39,233 with incremental benefits of 0.84 QALYs. The resulting ICER was £46,768 per QALY. Scenario analyses emphasised the importance of assumptions made regarding adult outcomes and type of school attended, both of which significantly affect the results of the analysis.ConclusionsThe results of this economic analysis suggest that early intensive ABA-based interventions are unlikely to represent value for money, based on a £20,000 to £30,000 per QALY threshold typically adopted to inform UK healthcare funding decisions. However, important gaps in the available evidence, limit the strength of the conclusions that can be drawn from the presented analysis. Further research, focusing on the trajectory of autistic children following intervention is likely to be highly beneficial to resolving some of these uncertainties.

The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. Conversely, residues predicted essential for Lep-Lepr interaction displayed divergence between teleosts and tetrapods. Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. Leptin system of Anabantiformes was phylogenetically closer to that of Pleuronectiformes, Scombriformes and Perciformes. Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts.

Purpose The COVID-19 pandemic has undoubtedly altered the routine of life and caused unanticipated changes resulting in severe psychological responses and mental health crisis. The study aimed to identify psycho-social factors that predicted distress among Indian population during the spread of novel Coronavirus. Method An online survey was conducted to assess the predictors of distress. A global logistic regression model was built, by identifying significant factors from individual logistic regression models built on various groups of independent variables. The prediction capability of the model was compared with the random forest classifier. Results The respondents (N = 1060) who are more likely to be distressed, are in the age group of 21-35 years, are females (OR = 1.425), those working on site (OR = 1.592), have pre-existing medical conditions (OR = 1.682), do not have health insurance policy covering COVID-19 (OR = 1.884), have perceived seriousness of COVID-19 (OR = 1.239), have lack of trust in government (OR = 1.246) and whose basic needs’ fulfillment are unsatisfactory (OR = 1.592). The ones who are less likely to be distressed, have higher social support and psychological capital. Random forest classifier correctly classified 2.3% and 17.1% of people under lower and higher distress respectively, with respect to logistic regression. Conclusions This study confirms the prevalence of high distress experienced by Indians at the time of COVID-19 and provides pragmatic implications for psychological health at macro and micro levels during an epidemiological crisis.

ImportanceIntensity and duration of the COVID-19 pandemic, and planning required to balance concerns of saving lives and avoiding economic collapse, could depend significantly on whether SARS-CoV-2 transmission is sensitive to seasonal changes.ObjectiveHypothesis is that increasing temperature results in reduced SARS CoV-2 transmission and may help slow the increase of cases over time.SettingFifty representative Northern Hemisphere countries meeting specific criteria had sufficient COVID-19 case and meteorological data for analysis.MethodsRegression was used to find the relationship between the log of number of COVID-19 cases and temperature over time in 50 representative countries. To summarize the day-day variability, and reduce dimensionality, we selected a robust measure, Coefficient of Time (CT), for each location. The resulting regression coefficients were then used in a multivariable regression against meteorological, country-level and demographic covariates.ResultsMedian minimum daily temperature showed the strongest correlation with the reciprocal of CT (which can be considered as a rate associated with doubling time) for confirmed cases (adjusted R2 = 0.610, p = 1.45E-06). A similar correlation was found using median daily dewpoint, which was highly colinear with temperature, and therefore was not used in the analysis. The correlation between minimum median temperature and the rate of increase of the log of confirmed cases was 47% and 45% greater than for cases of death and recovered cases of COVID-19, respectively. This suggests the primary influence of temperature is on SARS-CoV-2 transmission more than COVID-19 morbidity. Based on the correlation between temperature and the rate of increase in COVID-19, it can be estimated that, between the range of 30 to 100 degrees Fahrenheit, a one degree increase is associated with a 1% decrease-and a one degree decrease could be associated with a 3.7% increase-in the rate of increase of the log of daily confirmed cases. This model of the effect of decreasing temperatures can only be verified over time as the pandemic proceeds through colder months.ConclusionsThe results suggest that boreal summer months are associated with slower rates of COVID-19 transmission, consistent with the behavior of a seasonal respiratory virus. Knowledge of COVID-19 seasonality could prove useful in local planning for phased reductions social interventions and help to prepare for the timing of possible pandemic resurgence during cooler months.

PurposeThis study aimed to determine the survival outcome and prognostic factors of patients with nasopharyngeal cancer accessing treatment in Yogyakarta, Indonesia.MethodsData on 759 patients with NPC diagnosed from 2007 to 2016 at Dr Sardjito General Hospital were included. Potential prognostic variables included sociodemographic, clinicopathology and treatment parameters. Multivariable analyses were implemented using semi-parametric Cox proportional hazards modelling and fully parametric survival analysis.ResultsThe median time of observation was 14.39 months. In the whole cohort the median observed survival was 31.08 months. In the univariable analysis, age, education status, insurance type, BMI, ECOG index, stage and treatment strategy had an impact on overall survival (OS) (p values ConclusionsMedian OS for the cohort was low compared to those reported in both endemic and non-endemic regions. By combining the findings of multivariable analyses, we showed that age, education status, ECOG index, stage and first treatment modality were independent predictors for the OS.

Background Respiratory Tract Infections (RTIs) and Gastro-Intestinal (GI) infections are the leading causes of child mortality and morbidity. This study investigates the associations between the individual, household and slum-level determinants of children’s health and vulnerability to RTIs and GI infections in peri-urban slums in India; an area of research interest at the Childhood Infections and Pollution Consortium. Methods The 2015–16 Indian National Family Health Survey was used for data analysis on children aged 0–5 years. NFHS-4 includes data on slums in eight Indian cities, including Delhi, Meerut, Kolkata, Indore, Mumbai, Nagpur, Hyderabad, Chennai. The outcome variables, having fever and cough (FeCo) and diarrhoea in the last two weeks, were used to define the phenotype of infections; for this analysis fever and cough were measures of RTIs and diarrhoea was used to measure GI infections. Exposures considered in this study include variables at the individual, household and slum level and were all informed by existing literature. Multilevel models were used to estimate the association between exposures and outcomes variables; a prior of Cauchy distribution with a scale of 2.5 was selected when building the multilevel logistic models. Results The total sample size of the number of children included in the analysis was n = 1,424. Data was imputed to account for missingness, and the original and imputed sample showing similar distributions. Results showed that diarrhoea and FeCo were both found to be more present in younger children than older children by a few months. In fixed effects, the odds of developing FeCo were higher if the mother perceives the child was born smaller than average (AOR 4.41, 1.13–17.17, PConclusion The determinants of health, both social and related to health care, at all levels demonstrated linkages to child morbidity in RTIs and GI infections. The empirical evidence highlights the need for contextualised ideas at each level, including one health approach when designing interventions to improve child health.

Background Physicians have long noted a substantial discrepancy between the reasons for hospital admission and ultimate causes of death, particularly among older adults or patients with complex underlying diseases. However, objective data on this phenomenon are lacking. We aimed to examine the risk of in-hospital death caused by a reason other than the original reason for hospitalization and its association with underlying kidney disease in a nationwide inpatient database. Methods In this retrospective cohort study, we studied 639,556 Japanese adults who died in the hospital from 2012 to 2015, using data from Japan’s Diagnosis Procedure Combination database. We analyzed the discrepancy rate between reasons for hospital admission and death and associated factors using the International Classification of Diseases, 10th Revision (ICD-10) diagnostic codes and seven related categories. Results Among non-chronic kidney disease (CKD) (590,551), CKD (24,708), and end-stage kidney disease (ESKD) (24,297) patients, the median age was 77 years (interquartile range [IQR]: 67–84 years), 83 years (IQR: 75–88), and 75 years (IQR: 67–81), and 25.7%, 30.3%, and 41.6% died from a reason other than the original reason for hospitalization, respectively. Multivariate logistic regression analyses determined CKD/ESKD as the predominant risk factor for this discrepancy, rather than older age, male sex, obesity, and other comorbidities. Sankey diagrams that presented diagnostic changes from hospital admission to death revealed multiple wider segments connecting to different disease classifications, particularly to congestive and septic death in CKD and ESKD patients, respectively. Death owing to another disease classification led to an increase in the median length of hospital stay by 5–7 days and to a 1.3-–1.4-fold increase in medical costs across the populations. Conclusions A substantial proportion of patients with CKD and ESKD died during hospitalization for a reason other than their original reason for admission, leading to increased length of hospital stay and cost.

Nitrate transport in cyanobacteria is mediated by ABC-transporter, which consists of a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). Under salt stress, recombinant glycinebetaine (GB) not only protected the rate of nitrate transport in transgenic Anabaena PCC 7120, rather stimulated the rate by interacting with the ABC-transporter proteins. In silico analyses revealed that nrtA protein consisted of 427 amino acids, the majority of which were hydrophobic and contained a Tat (twin-arginine translocation) signal profile of 34 amino acids (1–34). The nrtC subunit of 657 amino acids contained two hydrophobic distinct domains; the N-terminal (5–228 amino acids), which was 59% identical to nrtD (the ATP-binding subunit) and the C-terminal (268–591), 28.2% identical to nrtA, suggesting C-terminal as a solute binding domain and N-terminal as ATP binding domain. Subunit nrtD consisted of 277 amino acids and its N-terminal (21–254) was an ATP binding motif. Phylogenetic analysis revealed that nitrate-ABC-transporter proteins are highly conserved among the cyanobacterial species, though variation existed in sequences resulting in several subclades. Nostoc PCC 7120 was very close to Anabaena variabilis ATCC 29413, Anabaena sp. 4–3 and Anabaena sp. CA = ATCC 33047. On the other, Nostoc spp. NIES-3756 and PCC 7524 were often found in the same subclade suggesting more work before referring it to Anabaena PCC 7120 or Nostoc PCC 7120. The molecular interaction of nitrate with nrtA was hydrophilic, while hydrophobic with nrtC and nrtD. GB interaction with nrtACD was hydrophobic and showed higher affinity compared to nitrate.

Primary healthcare systems worldwide suffer from major gaps in infrastructure and human resources. One key infrastructure gap is access to reliable electricity, absence of which can significantly affect the quantity and quality of healthcare services being delivered at rural primary health facilities. However, absence of granular empirical evidence is a barrier for quantitatively understanding the significance of electricity access as one of the determinants of access to reliable primary healthcare. Using data from India's District Level Household and Facility Survey, we develop zero-inflated negative binomial models with co-variates and state-level fixed effects to estimate the relationship between levels of electricity access and the quantity of basic health services delivered at Primary Health Centers (PHCs). We find that lack of electricity access is associated with a significant and large decrease in the number of deliveries (64 percent), number of in-patients (39 percent), and number of out-patients (38 percent). We further find that lower level of electricity access at primary health centers is disproportionately associated with adverse effects on women's access to safe and quality healthcare.

BackgroundPeople who inject drugs (PWIDs) have sub-optimal HIV and HCV testing as the available testing services are inadequate in low and middle-income countries. We examined a model of Community-Led Testing (CLT) in Nepal, exploring the feasibility of HIV and HCV testing by trained lay service providers who had similar backgrounds to those of PWIDs. We also assessed the prevalence of HIV and HCV within this study population and the associated risk factors among PWIDs.MethodsA mix-methods cross-sectional study was conducted among 1029 PWIDs in five major districts of Nepal from July 2019 to February 2020. Trained PWID peers performed the screening for HIV and HCV using Rapid Diagnostic Test (RDT) kits. Acceptability and feasibility of the testing was assessed. The participants' sociodemographic characteristics and injecting and non-injecting risk characteristics were determined. The association of risk and prevention characteristics with testing results were assessed using multiple logistic regression.ResultsPWIDs shared that the test providers were friendly and competent in counseling and testing. Of total PWIDs (n = 1,029), 20.6% were HCV-positive and 0.2% were HIV-positive. HCV positivity was associated with needle sharing (AOR: 1.83, 95% CI: 1.27,2.64; p = 0.001) and reuse of syringe/needle (AOR: 2.26; 95% CI: 1.34, 3.79; p = 0.002). In addition, PWIDs were more likely to be HCV-positive who started opioid substitution therapy (OST) (AOR: 1.88, 95% CI: 1.26, 2.80, p = 0.002) and attended the rehabilitation center (AOR: 1.66, 95% CI: 1.10, 2.53, p = 0.017).ConclusionsThis CLT model was found to be a novel approach of testing of HIV and HCV which was acceptable to PWIDs in Nepal and showed the high prevalence of HCV and its association with injecting-related risk behaviors and being users of OST and rehabilitation. The findings highlight the need of community-led testing in hotspots, OST settings, and rehabilitation centers to screen new HIV and HCV infections.

Mungbean (Vigna radiata L.) is an important food grain legume, but its production capacity is threatened by global warming, which can intensify plant stress and limit future production. Identifying new variation of key root traits in mungbean will provide the basis for breeding lines with effective root characteristics for improved water uptake to mitigate heat and drought stress. The AVRDC mungbean mini core collection consisting of 296 genotypes was screened under modified semi-hydroponic screening conditions to determine the variation for fourteen root-related traits. The AVRDC mungbean mini core collection displayed wide variations for the primary root length, total surface area, and total root length, and based on agglomerative hierarchical clustering eight homogeneous groups displaying different root traits could be identified. Germplasm with potentially favorable root traits has been identified for further studies to identify the donor genotypes for breeding cultivars with enhanced adaptation to water-deficit stress and other stress conditions.

Runoff from heavy precipitation events can lead to microbiological contamination of source waters for public drinking water supplies. Philadelphia is a city of interest for a study of waterborne acute gastrointestinal illness (AGI) because of frequent heavy precipitation, extensive impervious landcover, and combined sewer systems that lead to overflows. We conducted a time-series analysis of the association between heavy precipitation and AGI incidence in Philadelphia, served by drinking water from Delaware River and Schuylkill River source waters. AGI cases on each day during the study period (2015-2017) were captured through syndromic surveillance of patients' chief complaint upon presentation at local emergency departments. Daily precipitation was represented by measurements at the Philadelphia International Airport and by modeled precipitation within the watershed boundaries, and we also evaluated stream flowrate as a proxy of precipitation. We estimated the association using distributed lag nonlinear models, assuming a quasi-Poisson distribution of the outcome variable and with adjustment for potential confounding by seasonal and long-term time trends, ambient temperature, day-of-week, and major holidays. We observed an association between heavy precipitation and AGI incidence in Philadelphia that was primarily limited to the spring season, with significant increases in AGI that peaked from 8 to 16 days following a heavy precipitation event. For example, the increase in AGI incidence related to airport precipitation above the 95th percentile (vs no precipitation) during spring reached statistical significance on lag day 7, peaked on day 16 (102% increase, 95% confidence interval: 16%, 252%), and declined while remaining significantly elevated through day 28. Similar associations were observed in analyses of watershed-specific precipitation in relation to AGI cases within the populations served by drinking water from each river. Our results suggest that heavy precipitation events in Philadelphia result in detectable local increases in waterborne AGI.

BACKGROUND:Sinapis alba is a wild member of the Brassicaceae family reported to possess genetic resistance against major biotic and abiotic stresses of oilseed brassicas. However, the resistance nature of S. alba was not exploited generously due to the unavailability of usable genome sequences in public databases. Therefore, the present study was conducted to assemble the first draft genome from raw whole genome shotgun sequences with annotation and develop simple sequence repeat markers for molecular genetics and marker-assisted breeding. RESULTS:The raw genome sequences had 96x coverage on the Illumina platform with 170 Gbp data. The developed assembly by SOAPdenovo2 has ~459 Mbp genome size covered in 403,423 contigs with an average size of 1138.04 bp. The assembly was BLASTX with Arabidopsis thaliana which showed 32.9% positive hits between both plants. The top hit species distribution analysis showed the highest similarity with A. thaliana. A total of 809,597 GO level annotations were recorded after BLASTX results, and 34,012 sequences were annotated with different enzyme codes grouped under seven classes. The gene prediction tool AUGUSTUS identified 113,107 probable genes with an average size of 684 bp. The biochemical pathway annotation assigned 16,119 potential genes to 152 KEGG maps and 1751 enzyme codes. The development of potential SSRs from the de-novo assembly yielded 70731 unique primer pairs. Out of 159 randomly selected SSR markers for validation, 149 successfully amplified in S. alba. However, 10 SSR markers did not amplify during the validation experiment. CONCLUSION:The annotated genome assembly with a large number of SSRs was developed in the present study. To the best of our knowledge, this is the first report of S. alba genome assembly development, annotation, and SSRs mining to date. The data presented here will be a very important resource for future crop improvement programs, especially for resistant breeding.

Roots enable the plant to survive in the natural environment by providing anchorage and acquisition of water and nutrients. In this study, root architectural traits of 153 mungbean genotypes were compared under optimum and low phosphorus (P) conditions. Significant variations and medium to high heritability were observed for the root traits. Total root length was positively and significantly correlated with total root surface area, total root volume, total root tips and root forks under both optimum P (r = 0.95, r = 0.85, r = 0.68 and r = 0.82 respectively) and low P (r = 0.95, r = 0.82, r = 0.71 and r = 0.81 respectively). The magnitudes of the coefficient of variations were relatively higher for root forks, total root tips and total root volume. Total root length, total root surface area and total root volume were major contributors of variation and can be utilized for screening of P efficiency at the seedling stage. Released Indian mungbean varieties were found to be superior for root traits than other genotypic groups. Based on comprehensive P efficiency measurement, IPM-288, TM 96-25, TM 96-2, M 1477, PUSA 1342 were found to be the best highly efficient genotypes, whereas M 1131, PS-16, Pusa Vishal, M 831, IC 325828 were highly inefficient. Highly efficient genotypes identified would be valuable genetic resources for P efficiency for utilizing in the mungbean breeding programme.

The leading cause of death in Pulmonary Arterial Hypertension (PAH) is right ventricular (RV) failure. The tumor suppressor p53 has been associated with left ventricular hypertrophy (LVH) and remodeling but its role in RV hypertrophy (RVH) is unclear. The purpose of this study was to determine whether pharmacological activation of p53 by Quinacrine affects RV remodeling and function in the pulmonary artery banding (PAB) model of compensated RVH in mice. The effects of p53 activation on cellular functions were studied in isolated cardiomyocytes, cardiac fibroblasts and endothelial cells (ECs). The expression of p53 was examined both on human RV tissues from patients with compensated and decompensated RVH and in mouse RV tissues early and late after the PAB. As compared to control human RVs, there was no change in p53 expression in compensated RVH, while a marked upregulation was found in decompensated RVH. Similarly, in comparison to SHAM-operated mice, unaltered RV p53 expression 7 days after PAB, was markedly induced 21 days after the PAB. Quinacrine induced p53 accumulation did not further deteriorate RV function at day 7 after PAB. Quinacrine administration did not increase EC death, neither diminished EC number and capillary density in RV tissues. No major impact on the expression of markers of sarcomere organization, fatty acid and mitochondrial metabolism and respiration was noted in Quinacrine-treated PAB mice. p53 accumulation modulated the expression of Heme Oxygenase 1 (HO-1) and Glucose Transporter (Glut1) in mouse RVs and in adult cardiomyocytes. We conclude that early p53 activation in PAB-induced RVH does not cause substantial detrimental effects on right ventricular remodeling and function.

The sodium (Na+)-chloride cotransporter (NCC) expressed in the distal convoluted tubule (DCT) is a key molecule regulating urinary Na+ and potassium (K+) excretion. We previously reported that high-K+ load rapidly dephosphorylated NCC and promoted urinary K+ excretion in mouse kidneys. This effect was inhibited by calcineurin (CaN) and calmodulin inhibitors. However, the detailed mechanism through which high-K+ signal results in CaN activation remains unknown. We used Flp-In NCC HEK293 cells and mice to evaluate NCC phosphorylation. We analyzed intracellular Ca2+ concentration ([Ca2+]in) using live cell Ca2+ imaging in HEK293 cells. We confirmed that high-K+-induced NCC dephosphorylation was not observed without CaN using Flp-In NCC HEK29 cells. Extracellular Ca2+ reduction with a Ca2+ chelator inhibited high-K+-induced increase in [Ca2+]in and NCC dephosphorylation. We focused on Na+/Ca2+ exchanger (NCX) 1, a bidirectional regulator of cytosolic Ca2+ expressed in DCT. We identified that NCX1 suppression with a specific inhibitor (SEA0400) or siRNA knockdown inhibited K+-induced increase in [Ca2+]in and NCC dephosphorylation. In a mouse study, SEA0400 treatment inhibited K+-induced NCC dephosphorylation. SEA0400 reduced urinary K+ excretion and induced hyperkalemia. Here, we identified NCX1 as a key molecule in urinary K+ excretion promoted by CaN activation and NCC dephosphorylation in response to K+ load.

Financing municipal solid waste (MSW) services is one of the key challenges faced by cities in developing countries. This study used plastic waste, a constituent of MSW, to explore the possibility of generating revenue for financing MSW management in the municipalities of Nepal. The results of this study suggest that plastic material recovery could generate revenue, which is equivalent to 1.38 times of the plastic-waste-related management cost when collection efficiency reaches 66.7%. An increase in 1% of recovery rate and collection efficiency could cover an additional 4.64% and 2.06% of the costs of managing plastic waste, respectively. In addition, an increase in tax on imported plastic materials could also motivate recovery of plastic waste for recycle and reuse. An additional 1% tax on plastic imports would be sufficient to cover plastic-related waste management when plastic waste recovery and collection efficiency rates are low. This plastic recovery- revenue exercise could be expanded to other materials such as paper and metal to fully understand the possibility of sustainable financing of MSW management and reducing environmental harm in developing countries like Nepal.