Search

In 2008, Bangladesh initiated Preventive Chemotherapy (PCT) for school-age children (SAC) through bi-annual school-based mass drug administration (MDA) to control Soil-Transmitted Helminth (STH) infections. In 2016, the Ministry of Health and Family Welfare's Program on Lymphatic Filariasis Elimination and STH (ELFSTH) initiated district-level community impact assessments with Children Without Worms (CWW) using standardized, population-based sampling to measure the post-intervention STH burden across all ages (≥ 1 yr) for the three STH species. The Integrated Community-based Survey for Program Monitoring (ICSPM) was developed by CWW and was used to survey 12 districts in Bangladesh from 2017-2020. We excluded the first two district data as piloting caused some sampling errors and combined the individual demographic and parasite-specific characteristics from the subsequent 10 districts, linking them with the laboratory data for collective analysis. Our analysis identified district-specific epidemiologic findings, important for program decisions. Of the 17,874 enrolled individuals, our results are based on 10,824 (61.0%) stool samples. Overall, the prevalence of any STH species was substantially reduced to 14% from 79.8% in 2005. The impact was similar across all ages. STH prevalence was 14% in 10 districts collectively, but remained high in four districts, despite their high reported PCT coverage in previous years. Among all, Bhola district was unique because it was the only district with high T.trichuris prevalence. Bangladesh successfully lowered STH prevalence across all ages despite targeting SAC only. Data from the survey indicate a significant number of adults and pre-school age children (PSAC) were self-deworming with purchased pills. This may account for the flat impact curve across all ages. Overall prevalence varied across surveyed districts, with persistent high transmission in the northeastern districts and a district in the central flood zone, indicating possible service and ecological factors. Discrepancies in the impact between districts highlight the need for district-level data to evaluate program implementation after consistent high PCT coverage.

Background. Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) are a growing problem globally and recur even after liver transplant (LT). We aim to characterize the gut dysbiosis in patients who developed recurrent NAFLD compared with patients without recurrence following LT. Methods. Twenty-one patients who received LT for NASH and had a protocol liver biopsy performed beyond 1-y post-LT were included prospectively (January 2018–December 2018). Genomic DNA extraction, next-generation sequencing, and quantitative PCR analysis were performed on stool samples collected within 1.1 ± 1.6 y from time of liver biopsy. Results. Recurrent NAFLD was noted in 15 of the 21 included patients. Stool microbiome analysis at the genus level showed significant loss of Akkermansia and increasing Fusobacterium associated with NAFLD recurrence. Quantitative PCR analysis revealed significantly decreased relative abundance of Firmicutes in patients with NAFLD activity scores (NASs) ≥5 as compared with patients with lower NAS scores, whereas Bacteroidetes were significantly increased with higher NAS (P < 0.05). Firmicutes (P = 0.007) and Bifidobacterium group (P = 0.037) were inversely correlated, whereas Bacteroidetes (P = 0.001) showed a positive correlation with higher hepatic steatosis content. The Firmicutes/Bacteroidetes ratios were higher in patients without NAFLD or NASH as compared with patients diagnosed with NAFLD or NASH at the time of sample collection. Conclusions. Akkermansia, Firmicutes, and Bifidobacterium may play protective roles in the development of recurrent NAFLD in LT recipients, whereas Fusobacteria and Bacteroidetes may play pathogenic roles. These findings highlight the potential role of the “gut-liver” axis in the pathogenesis of NAFLD recurrence after LT.

Background While head circumference (HC) has been related to intracranial volume and brain size, its association with cognitive function remains unclear. We sought to understand the relationship among various biological and socioeconomic risk factors, HC and cognitive development.Methods We analysed data across resource-poor settings in Bangladesh, India, Nepal, Peru, South Africa and Tanzania from the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development longitudinal birth cohort study. Participating children were enrolled and followed up between 2009 and 2014. A final sample of 1210 children aged 0–24 months were included in the analyses. The main outcomes were HC for age Z-score and cognitive, gross motor and language scores from Bayley Scales of Infant Development-III tests. Length, weight and HC were measured monthly, and cognitive tests were administered at 6, 15 and 24 months of age. To disentangle the associations between risk factors and HC from linear growth and to distinguish the direct and indirect effects of these risk factors on cognitive function, we conducted mediation analysis using longitudinal models to account for all data measured during follow-up.Results Average HC-for-age Z-score (HCAZ) was −0.54 (95% CI −0.47 to −0.62) near birth and −1.01 (95% CI −0.94 to −1.08) at 24 months. Children with higher enrolment weight (p

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (

Barley spot blotch (SB) caused by Cochliobolus sativus is one of the major constrains to barley production in warmer regions worldwide. The study was undertaken to identify and estimate effects of loci underlying quantitative resistance to SB at the seedling and adult plant stages. A panel of 261 high input (HI-AM) barley genotypes consisting of released cultivars, advanced breeding lines, and landraces, was screened for resistance to SB. The seedling resistance screening was conducted using two virulent isolates from Morocco (ICSB3 and SB54) while the adult plant stage resistance was evaluated at two hot spot locations, Faizabad and Varanasi, in India under artificial inoculation using a mixture of prevalent virulent isolates. The HI-AM panel was genotyped using DArT-Seq high-throughput genotyping platform. Genome wide association mapping (GWAM) was conducted using 13,182 PAV and 6,311 SNP markers, for seedling and adult plant resistance. Both GLM and MLM model were employed in TASSEL (v 5.0) using principal component analysis and Kinship Matrix as covariates. Final disease rating and Area Under Disease Progress Curve (AUDPC) were used for the evaluation of adult stage plant resistance. The GWAM analysis indicated 23 QTL at the seedling stage (14 for isolate ICSB3 and 9 for isolate SB54), while 15 QTL were detected at the adult plant stage resistance (6 at Faizabad and 9 at Varanasi) and 5 for AUDPC based resistance at Varanasi. Common QTL at seedling and adult plant stages were found across all barley chromosomes. Seedling stage QTL explained together 73.24% of the variance for seedling resistance to isolate ICSB3 and 49.26% for isolate SB54, whereas, QTL for adult plant stage resistance explained together 38.32%, 44.09% and 26.42% of the variance at Faizabad and Varanasi and AUDPC at Varanasi, respectively. Several QTL identified in this study were also reported in previous studies using bi-parental and association mapping populations, corroborating our results. The promising QTL detected at both stages, once validated, can be used for marker assisted selection (MAS) in SB resistance barley breeding program.

Mucosal immunity is dominated by secretory IgA and IgM, although these are less favorable compared to IgG molecules for therapeutic development. Polymeric IgA and IgM are actively transported across the epithelial barrier via engagement of the polymeric Ig receptor (pIgR), but IgG molecules lack a lumen-targeted active transport mechanism, resulting in poor biodistribution of IgG therapeutics in mucosal tissues. In this work, we describe the discovery and characterization of single-domain antibodies (VHH) that engage pIgR and undergo transepithelial transport across the mucosal epithelium. The anti-pIgR VHH panel displayed a broad range of biophysical characteristics, epitope diversity, IgA competition profiles and transcytosis activity in cell and human primary lung tissue models. Making use of this diverse VHH panel, we studied the relationship between biophysical and functional properties of anti-pIgR binders targeting different domains and epitopes of pIgR. These VHH molecules will serve as excellent tools for studying pIgR-mediated transport of biologics and for delivering multispecific IgG antibodies into mucosal lumen, where they can target and neutralize mucosal antigens.

CX3CR1 has been identified as a highly attractive target for several therapeutic interventions. Despite this potential, no potent antagonists, either small molecule or monoclonal antibody, have been identified. Here we describe the lead finding and engineering approach that lead to the identification of BI 655088, a potent biotherapeutic antagonist to CX3CR1. BI 655088 is a potent CX3CR1 antagonist that, upon therapeutic dosing, significantly inhibits plaque progression in the standard mouse model of atherosclerosis. BI 655088 represents a novel and highly selective biotherapeutic that could reduce inflammation in the atherosclerotic plaque when added to standard of care treatment including statins, which could result in a significant decrease in atherothrombotic events in patients with existing cardiovascular disease.

BACKGROUND:The utility of ex vivo Magnetic resonance imaging proton density fat fraction (MRI-PDFF) in donor liver fat quantification is unknown. PURPOSE:To evaluate the diagnostic accuracy and utility in predicting early allograft dysfunction (EAD) of ex vivo MRI-PDFF measurement of fat in deceased donor livers using histology as the gold standard. METHODS:We performed Ex vivo, 1.5 Tesla MRI-PDFF on 33 human deceased donor livers before implantation, enroute to the operating room. After the exclusion of 4 images (technical errors), 29 MRI images were evaluable. Histology was evaluable in 27 of 29 patients. EAD was defined as a peak value of aminotransferase >2000 IU/mL during the first week or an INR of ≥1.6 or bilirubin ≥10 mg/dL at day 7. RESULTS:MRI-PDFF values showed a strong positive correlation (Pearson's correlation coefficient) when histology (macro-steatosis) was included (r = 0.78, 95% confidence interval 0.57-0.89, p

Swimming learning was temporarily suspended, as well as the learning process that should be face-to-face, changed to an online learning process that requires educators to be able to produce a learning innovation to maintain student achievement. This is what underlies the research which aims to analyze the impact of YouTube-assisted learning on the understanding of concepts and swimming speed of elementary school students. The design of this study was a quasi-experimental design in the form of a posttest control group design. the population of this study was 48. The data collection process used was the test and documentation method. The data analysis method of this research is descriptive analysis and inferential statistical analysis with manova. The results showed that youtube-based learning had a positive and significant impact both simultaneously and partially on the understanding of the concept and swimming speed of students, this was indicated by the sig value. < 0.05. From the results of descriptive data, research results are also obtained in the form of the variable speed of students is more influenced by youtube-based learning than the variable understanding of the concept. So, it can be recommended that youTube-based learning can be used as an innovative learning for swimming.

Introduction: Accurate assessment of fluid status in hemodialysis patients presents a significant challenge. Nephrologists have long relied on dry weight estimation based solely on clinical parameters to decide the ultrafiltration volume for patients with end-stage kidney disease on dialysis. However, this method is far from accurate and many patients recurrently suffer from signs and symptoms of fluid overload or circulatory collapse from overaggressive ultrafiltration. Invasive methods such as measurement of central venous pressure cannot be used routinely. We evaluated the usefulness of inferior vena cava (IVC) diameter measured by handheld ultrasound in the estimation of fluid status in patients before and after hemodialysis. Materials and Methods: Clinical assessment included patients’ symptoms, weight, blood pressure, heart rate, and presence of edema before and after dialysis session. Dry weight was assessed based on the above parameters. Each patient underwent measurement of inferior vena cava before and after hemodialysis. The anteroposterior IVC diameter (IVCD) was measured 1.5 cm below the diaphragm in the hepatic segment in supine position during normal inspiration and expiration. Results: Thirty hemodialysis patients (mean age 51.6±18.03 years) were evaluated in outpatient dialysis unit. Following hemodialysis mean IVCe (IVC diameter in expiration) decreased from 1.40±0.38 to 0.91±0.30 cm (p

Summary: The major objective of this study was to understand the molecular basis of how sarcolipin uncoupling of SERCA regulates muscle oxidative metabolism. Using genetically engineered sarcolipin (SLN) mouse models and primary muscle cells, we demonstrate that SLN plays a crucial role in mitochondrial biogenesis and oxidative metabolism in muscle. Loss of SLN severely compromised muscle oxidative capacity without affecting fiber-type composition. Mice overexpressing SLN in fast-twitch glycolytic muscle reprogrammed mitochondrial phenotype, increasing fat utilization and protecting against high-fat diet-induced lipotoxicity. We show that SLN affects cytosolic Ca2+ transients and activates the Ca2+/calmodulin-dependent protein kinase II (CamKII) and PGC1α axis to increase mitochondrial biogenesis and oxidative metabolism. These studies provide a fundamental framework for understanding the role of sarcoplasmic reticulum (SR)-Ca2+ cycling as an important factor in mitochondrial health and muscle metabolism. We propose that SLN can be targeted to enhance energy expenditure in muscle and prevent metabolic disease. : Maurya et al. report that sarcolipin, a regulator of the SERCA pump, promotes mitochondrial biogenesis and oxidative phenotype in muscle. Loss of SLN decreases fat oxidation, whereas overexpression of SLN in muscle provides resistance against diet-induced lipotoxicity. By increasing cytosolic Ca2+ transients, SLN activates the CamKII-PGC1α signaling pathway to promote mitochondrial biogenesis. Keywords: skeletal muscle, sarcolipin, SERCA, mitochondrial biogenesis, Ca2+ signaling, oxidative metabolism, lipotoxicity, primary muscle myotubes, CamKII, PGC1α

PCNSL (primary central nervous system lymphoma) is a chemosensitive and radiosensitive tumor, and early diagnosis has a significant impact on management. Unlike many other brain tumors, radical surgical excision of PCNSLs is not indicated because these lesions are highly infiltrative and even partial resection leads to a bad prognosis. The goal of this study is to highlight the unusual radiological presentation of PCNSLs and increase the awareness, familiarity, and global database of our observations that pose a challenge on management.

Abstract Background Multidrug-resistant (MDR) Gram-negative bacterial species are an increasingly dangerous public health threat, and are now endemic in many areas of South Asia. However, there are a lack of comprehensive data from many countries in this region determining historic and current MDR prevalence. Enterotoxigenic Escherichia coli (ETEC) is a leading cause of both acute infant diarrhea and traveler’s diarrhea in Nepal. The MDR prevalence and associated resistance mechanisms of ETEC isolates responsible for enteric infections in Nepal are largely unknown. Methods A total of 265 ETEC isolates were obtained from acute diarrheal samples (263/265) or patient control samples (2/265) at traveler’s clinics or regional hospitals in Nepal from 2001 to 2016. Isolates were screened for antibiotic resistance, to include extended spectrum beta-lactamase (ESBL) production, via the Microscan Automated Microbiology System. ETEC virulence factors, specifically enterotoxins and colonization factors (CFs), were detected using multiplex PCR, and prevalence in the total isolate population was compared to ESBL-positive isolates. ESBL-positive isolates were assessed using multiplex PCR for genetic markers potentially responsible for observed resistance. Results A total of 118/265 (44.5%) ETEC isolates demonstrated resistance to ≥2 antibiotics. ESBL-positive phenotypes were detected in 40/265 isolates, with isolates from 2008, 2013, 2014, and 2016 demonstrating ESBL prevalence rates of 1.5, 34.5, 31.2, and 35.0% respectively. No difference was observed in overall enterotoxin characterization between the total ETEC and ESBL-positive populations. The CFs CS2 (13.6%), CS3 (25.3%), CS6 (30.2%), and CS21 (62.6%) were the most prevalent in the total ETEC population. The ESBL-positive ETEC isolates exhibited a higher association trend with the CFs CS2 (37.5%), CS3 (35%), CS6 (42.5%), and CS21 (67.5%). The primary ESBL gene identified was bla CTX-M-15 (80%), followed by bla SHV-12 (20%) and bla CTX-M-14 (2.5%). The beta-lactamase genes bla TEM-1 (40%) and bla CMY-2 (2.5%) were also identified. It was determined that 42.5% of the ESBL-positive isolates carried multiple resistance genes. Conclusion Over 30% of ETEC isolates collected post-2013 and evaluated in this study demonstrated ESBL resistance. Persistent surveillance and characterization of enteric ETEC isolates are vital for tracking the community presence of MDR bacterial species in order to recommend effective treatment strategies and help mitigate the spread of resistant pathogens.

Limitations of observation data cause analysis and prediction of precipitation is difficult. One way to overcome such limitations is the use of satellite data such as GSMaP, but satellite data needs to be validated before use. This study aims to validate GSMaP rainfall data on observation data in Bali and Nusa Tenggara. Through monthly time series analysis, GSMaP rainfall data tend to have smaller value than observation data, but it has similar data pattern in each region with rain pattern that occurs in November to March (NDJFM). While validation between GSMaP satellite rainfall data and observation using Pearson and RMSE correlation and MBE at each location showed strong positive correlation value (> 0.5), correlation value obtained from each location from 0.82 to 0.93 with RMSE value from 2.08 to 5.51 and MBE values ??from 0.23 to 0.89, this indicates that GSMaP satellite data is valid and can be used to fill in empty data especially in 5 observation areas ie Denpasar, Ampenan, Sumbawa Besar, Bima and Kupang.

Human-monkey conflicts reached crisis proportions in Sri Lanka over the last 10 years due to extensive deforestation to promote rapid economic growth and agricultural expansion. This resulted in complaints from the public with demands for Sri Lanka’s Department of Wildlife Conservation (DWC) to solve the problem without delay. Caught between political pressure and public outcry, the DWC’s efforts to deal with the crisis gradually fell into disarray. To overcome this, the SPEARS Foundation--, offered to help the DWC to develop a strategic plan to deal with human-monkey conflicts. This plan was developed through a series of workshops and submitted to the Ministry of Sustainable Development and Wildlife in March 2016 for approval. During and after the development of the strategy, some of its key elements were implemented by the SPEARS Foundation. One of these elements was documenting details of human-monkey conflict from letters of complaint received by DWC. This information was used to initiate a series of field surveys to identify sites suitable for long-term protection of monkeys and other wildlife. When these areas are identified they would be designated as community conservation areas (CCAs), and managed by local stakeholders on a sustainable basis under the supervision of DWC. Establishing CCAs is a new paradigm for Sri Lanka to conserve wildlife while benefitting local communities. Its details were presented in the strategic plan submitted to the government. In this paper, we present the information obtained from the letters of complaint received by DWC and discuss its details. In subsequent reports, we will discuss the results of our field surveys to identify areas suitable for the establishment of CCAs.

Abstract Exclusion from the mainstream financial world is a burden on the poor of many countries. The proliferation of new mobile and online financial services, such as e-banking, money transfers, and payment processing has the potential to provide access to basic financial products and services to financially excluded people. The purpose of this study was to investigate the effects of the growth of mobile phone and Internet use on financial inclusion in the South Asian Association for Regional Cooperation (SAARC) countries from 2004 to 2014. We applied principal component analysis to construct a financial inclusion index that served as a proxy variable for the accessibility of financial services in the SAARC countries. Using three different models-the fixed effect, random effect, and panel correction standard errors models-this study discovered a positive and significant relationship between the growth of financial inclusion and expansion of both mobile phone and Internet services. Moreover, an empirical study of the control variables showed that the levels of income and education were positively associated with financial inclusion, whereas the size of the rural population and unemployment were negatively related to financial inclusion. In addition, the empirical estimates posit a unidirectional causal flow from the growth of mobile and Internet services to expanded financial inclusion in the SAARC countries.

Background: The right to health is a fundamental part of human rights. Ensuring right to health is not straightforward; there are several challenges. Factors such as capacity of right holders and duty-bearers and practices of providing and utilizing services among others determine to ensure health rights for the whole population. Objective: The objective of this paper is to analyze whether the health policies and programs follow a human rights-based approach (HRBA) and assess the situation of rights to health among the poor and vulnerable population. Methods: The study assessed domestic instruments against human rights policies and analyzed the implementation status of the policies and programs. An analytical case study method is used by utilizing qualitative and quantitative data. Results: Around 90% medicines are available in the facilities; however, 22% of health worker posts are vacant. Persistence of unequal distribution of health facilities, high out-of-pocket payment, and cultural and language barriers does not ensure accessibility of health services. Acceptability of health-care services in terms of utilization rate and client satisfaction is improved after introduction of new policy. Nepal has made significant progress in improving maternal mortality ratio, infant/child mortality, immunization rates, and life expectancy at birth. Conclusions: Although a progressive realization of the right to health is being achieved, more efforts are still needed to follow HRBA so as to achieve quality and equity in health-care services.

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets.

We consider the properties of a specific distribution of mixed quantum states of arbitrary dimension that can be biased towards a specific mean purity. In particular, we analyze mixtures of Haar-random pure states with Dirichlet-distributed coefficients. We analytically derive the concentration parameters required to match the mean purity of the Bures and Hilbert–Schmidt distributions in any dimension. Numerical simulations suggest that this value recovers the Hilbert–Schmidt distribution exactly, offering an alternative and intuitive physical interpretation for ensembles of Hilbert–Schmidt-distributed random quantum states. We then demonstrate how substituting these Dirichlet-weighted Haar mixtures in place of the Bures and Hilbert–Schmidt distributions results in measurable performance advantages in machine-learning-based quantum state tomography systems and Bayesian quantum state reconstruction. Finally, we experimentally characterize the distribution of quantum states generated by both a cloud-accessed IBM quantum computer and an in-house source of polarization-entangled photons. In each case, our method can more closely match the underlying distribution than either Bures or Hilbert–Schmidt distributed states for various experimental conditions.

A variety of strategies are used to construct algorithms for solving equations. However, higher order derivatives are usually assumed to calculate the convergence order. More importantly, bounds on error and uniqueness regions for the solution are also not derived. Therefore, the benefits of these algorithms are limited. We simply use the first derivative to tackle all these issues and study the ball analysis for two sixth order algorithms under the same set of conditions. In addition, we present a calculable ball comparison between these algorithms. In this manner, we enhance the utility of these algorithms. Our idea is very general. That is why it can also be used to extend other algorithms as well in the same way.

Ribosomes assemble through the hierarchical addition of proteins to a ribosomal RNA scaffold. Here the authors use three-color single-molecule FRET to show how the dynamics of the rRNA dictate the order in which multiple proteins assemble on the 5′ domain of the E. coli 16S rRNA.

Abstract Background This study revisits the clinico-epidemiology and serological patterns of rickettsioses in the central region of Sri Lanka and highlights the need of advanced diagnostics for precise identification of species responsible for rickettsioses. Methods The patients treated for rickettsioses between November 2009 and October 2011 were recruited for the study from Teaching Hospital, Peradeniya. Clinical characteristics and serology results were used for diagnosis. Results Study included 210 patients (mean age 44 years ± 3.2) and of them 188 (90%) had positive IgG and/or IgM sero-reactivity for spotted fever group (SFG). Of them, 134 had IgG titre ≥1/256 for SFG and presented with fever and skin rash. They also had headache [n = 119 (89%)], myalgia [n = 103 (77%)], arthralgia [n = 89 (66%)] of large joints, conjunctival injections [n = 83 (62%)], thrombocytopenia (n = 78.58%), anaemia (n = 14.10%), leukocytosis [n = 35 (26%)], leucopenia [n = 17 (13%)], elevated aspartate transaminase [n = 69 (52%)] and alanine transaminase [n = 73 (55%)]. Conclusions Predominance of SFG rickettsioses are reiterated, possibly transmitted by ticks. Joint disease is common with occasional fern leaf skin necrosis. Changing socio-economic conditions, vegetations, contact with domestic and wild animals, abundance of vectors would have contributed for emergence and sustenance of SFG in the region. Further research is needed to identify the causative agents and the mode of transmission.

When surgical decompression of cervical spine is considered, multilevel cervical corpectomy with long strut grafts is the preferred treatment. This procedure is used in a variety of pathologies including degenerative disease, tumors, trauma and infection. Corpectomy with interbody grafting helps in adequate spinal canal and neural decompression compared to multilevel discectomy, which could be difficult as well as inadequate. Fibular/iliac strut grafts are used for reconstruction along with a stabilizing hardware in this procedure. So far, complete imaging spectrum of complications exclusive to strut graft has not been reported in the literature. This pictorial essay presents complications exclusive to the strut graft, utility of advanced imaging in diagnosis and a brief note on the clinical management of complications.

Abstract Ambient pressure in situ synchrotron-based spectroscopic techniques have been correlated to illuminate atomic-level details of bond breaking and formation during the hydrolysis of a chemical warfare nerve agent simulant over a polyoxometalate catalyst. Specifically, a Cs8[Nb6O19] polyoxoniobate catalyst has been shown to react readily with dimethyl methylphosphonate (DMMP). The atomic-level transformations of all reactant moieties, the [Nb6O19]8− polyanion, its Cs+ counterions, and the DMMP substrate, were tracked under ambient conditions by a combination of X-ray absorption fine structure spectroscopy, Raman spectroscopy, and X-ray diffraction. Results reveal that the reaction mechanism follows general base (in contrast to specific base) hydrolysis. Together with computational results, the work demonstrates that the ultimate fate of DMMP hydrolysis at the Cs8[Nb6O19] catalyst is strong binding of the (methyl) methylphosphonic acid ((M)MPA) product to the polyanions, which ultimately inhibits catalytic turnover.

Background: Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods: Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings: Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation: The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. Funding: Bill & Melinda Gates Foundation.

Enveloped viruses like Coronavirus acquire their envelope from the host cell membrane which is a bilayer of phospholipid interspersed with cholesterol molecules and proteins. Viruses enter their host cell by coming in contact with their specific receptors. Experiments have shown that when cell membranes are depleted of cholesterol in vitro by Methyl beta cyclodextrin (MβCD) these Coronaviruses are not able to enter the host cell membrane by the process of receptor mediated endocytosis. Statin inhibits HMG Co-A reductase, a key enzyme in the Mevalonate pathway resulting into either very low or no production of endogenous cholesterol by the human cells. This results into upregulation of LDL-R in the cell membrane which may lead to more cholesterol getting incorporated into the cell membrane through LDL-C from the plasma creating greater number of lipid rafts suitable for entry of enveloped viruses by receptor-mediated endocytosis.

Introduction: Gall bladder carcinoma is not a common disease. The overall prevalence is low worldwide. It is a highly malignant tumor with a poor prognosis. The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. The carcinoma gall bladder is 2-6 times more common in females compared to males and its incidence increases with increasing age. Aggressive surgical management and preoperative adjuvant therapy have helped to prolong survival in patients with gallbladder cancer. We conducted a study with an aim to evaluate the clinicopathological aspect of the disease in patients of gall bladder cancer managed in our surgical department. Methods: Data were recorded retrospectively by reviewing the charts of the patients who were diagnosed and treated for carcinoma gall bladder in Patan hospital from Aug 2017 to Aug 2019. Results: Thirty patients were included in the study. Twenty (66.7%) were female and ten (33.33%) were males. Age ranged from 36 to 83 years with the median age of presentation at 63.5 yrs. Curative treatment was possible in 43.33% of the patients, among them 12 had radical surgery and one had cholecystectomy alone for the T1a stage. All other (56.6%) required palliative treatment. One patient developed liver metastasis within six months of radical excision. Conclusions: The majority of the patients present with an advanced disease which makes it less chance for curative surgical resection. Since only palliative care is possible in an advanced stage, early detection and curative treatment are advisable.

Introduction: Pilonidal sinus is a common disease. Various surgical techniques for management of sacrococcygeal pilonidal sinus have been described. Among them, the most commonly used is the rhomboid excision with the Limberg flap. With this technique of flattening the natal cleft and tension-free repair is made using a wide, well-vascularized flap. It is reported the best treatment methods, with 0-16 % of surgical area-related complications and a recurrence rate of 0-5 %. We conducted a study to evaluate the patient’s profile and outcomes of the patients of pilonidal sinus treated with rhomboid excision and Limberg flap reconstruction at our center. Methods: Data were recorded retrospectively by reviewing the charts of patients who underwent rhomboid excision and Limberg flap operation for sacrococcygeal pilonidal sinus from September 2015 to September 2019. Results: Thirty-four patients were included in the study. Twenty-nine (85.4%) were males and 5 (14.7%) were females. The mean age was 25.29 years (range 17-40 years). Mean hospital stay was 4.5 days (range 3 – 7 days. Nine (26.5%) patients had surgical site infections. Two patients (5.9%) had a recurrence. Conclusion: Limberg flap for reconstruction after rhomboid excision of pilonidal sinus is an effective and feasible technique with good outcome.

The thoracic kidney is the rarest form of an ectopic kidney that usually present on the left thorax and twice more common in males. No case has been reported from Nepal and very few cases are reported worldwide. We report a 24 years-old female with right thoracic kidney with Bochdalek hernia diagnosed incidentally. We have included clinico-radiological and surgical findings of the case with a review of the literature.

The paper analyses the contributions to Journal of Learning for Development (JL4D) from volume one to five using bibliometrics and content analysis techniques. Analysing the 91 papers in various categories of JL4D, the paper identifies authorship pattern, topics covered, research methods used, types of documents used in citations, core journals and the median age of citations to JL4D. The finding of the study reveals that JL4D has created a niche for itself as a specialised research journal focusing on innovations in learning contributing to development.

Introduction: Coronary Artery Disease (CAD) is the most important reason of morbidity and mortality worldwide. Measurement of coronary calcification with the help of CT-based Coronary Calcium Score (CCS) is a considerable indicator of coronary atherosclerosis and correlates well with the risk for future cardiovascular events. Aim: To evaluate the relationship between CCS and the presence of significant CAD in low to intermediate risk in Indian subjects with cardiac chest pain undergoing CT Coronary Angiography (CTCA). In addition, we sought to identify the additive value of the CCS to the traditional Framingham Risk Score (FRS) in an Indian population. Materials and Methods: Multi-centric prospective study was conducted in subjects referred for CTCA due to cardiac chest pain. Patients were excluded if they had Coronary Artery Bypass Graft (CABG), Percutaneous Transluminal Coronary Angiography (PTCA), previous myocardial infarction and other CTCA contraindications. Scans were performed on a 128-slice MDCT with contemporary protocols. CCS and CAD severity were classified as per Society of Cardiovascular Computed Tomography (SCCT) guidelines. Significant CAD (>70% stenosis of epi-cardial coronary artery or >50% of left main coronary artery). FRS was calculated to predict long term risk of CAD. Results: We enrolled a total of 306 subjects (52±9 years; 59% males). The mean CCS was 79±10 AU. Significant CAD was present in 44 of the 99 subjects (44%) with a CCS=0 who were classified as low risk by FRS and 16 of 20 subjects (80%) who had an intermediate risk FRS and a CCS=0 AU had significant CAD on CTCA. There was no correlation between FRS and presence of significant CAD. Conclusion: Unlike Western countries, low CCS have poor correlation with absence of CAD in this population, whereas in the present study there was no relation between FRS and presence of CAD.

Background and aimsThis article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.MethodsIn May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.ResultsThese recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.ConclusionsPruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

Low-income and middle-income countries are struggling with a growing epidemic of non-communicable diseases. To achieve the Sustainable Development Goals, their healthcare systems need to be strengthened and redesigned. The Starfield 4Cs of primary care—first-contact access, care coordination, comprehensiveness and continuity—offer practical, high-quality design options for non-communicable disease care in low-income and middle-income countries. We describe an integrated non-communicable disease intervention in rural Nepal using the 4C principles. We present 18 months of retrospective assessment of implementation for patients with type II diabetes, hypertension and chronic obstructive pulmonary disease. We assessed feasibility using facility and community follow-up as proxy measures, and assessed effectiveness using singular ‘at-goal’ metrics for each condition. The median follow-up for diabetes, hypertension and chronic obstructive pulmonary disease was 6, 6 and 7 facility visits, and 10, 10 and 11 community visits, respectively (0.9 monthly patient touch-points). Loss-to-follow-up rates were 16%, 19% and 22%, respectively. The median time between visits was approximately 2 months for facility visits and 1 month for community visits. ‘At-goal’ status for patients with chronic obstructive pulmonary disease improved from baseline to endline (p=0.01), but not for diabetes or hypertension. This is the first integrated non-communicable disease intervention, based on the 4C principles, in Nepal. Our experience demonstrates high rates of facility and community follow-up, with comparatively low lost-to-follow-up rates. The mixed effectiveness results suggest that while this intervention may be valuable, it may not be sufficient to impact outcomes. To achieve the Sustainable Development Goals, further implementation research is urgently needed to determine how to optimise non-communicable disease interventions.

Background Chronic obstructive pulmonary disease accounts for a significant portion of the world’s morbidity and mortality, and disproportionately affects low/middle-income countries. Chronic obstructive pulmonary disease management in low-resource settings is suboptimal with diagnostics, medications and high-quality, evidence-based care largely unavailable or unaffordable for most people. In early 2016, we aimed to improve the quality of chronic obstructive pulmonary disease management at Bayalpata Hospital in rural Achham, Nepal. Given that quality improvement infrastructure is limited in our setting, we also aimed to model the use of an electronic health record system for quality improvement, and to build local quality improvement capacity.Design Using international chronic obstructive pulmonary disease guidelines, the quality improvement team designed a locally adapted chronic obstructive pulmonary disease protocol which was subsequently converted into an electronic health record template. Over several Plan-Do-Study-Act cycles, the team rolled out a multifaceted intervention including educational sessions, reminders, as well as audits and feedback.Results The rate of oral corticosteroid prescriptions for acute exacerbations of chronic obstructive pulmonary disease increased from 14% at baseline to >60% by month 7, with the mean monthly rate maintained above this level for the remainder of the initiative. The process measure of chronic obstructive pulmonary disease template completion rate increased from 44% at baseline to >60% by month 2 and remained between 50% and 70% for the remainder of the initiative.Conclusion This case study demonstrates the feasibility of robust quality improvement programmes in rural settings and the essential role of capacity building in ensuring sustainability. It also highlights how individual quality improvement initiatives can catalyse systems-level improvements, which in turn create a stronger foundation for continuous quality improvement and healthcare system strengthening.

Scientific argumentation is a higher-order thinking skill that is a major focus in education in the 21st century. This is a skill that plays an important role in knowledge construction which in reality is rarely implemented in science learning. The facts show that most students have low scientific argumentation skills and still need to be improved. In improving scientific argumentation skills, the learning design used must give students more opportunities to build and criticize arguments, make claims, and use evidence in the process of reasoning based on inquiry activities. Based on the results of previous research, it is known that inquiry-based learning has extraordinary potential in developing students' scientific argumentation skills. Interestingly, no research has been found that reveals the effect of inquiry-based online learning on students' scientific argumentation skills. Therefore, this study aims to determine the impact of inquiry-based online learning with a virtual laboratory on students' scientific argumentation skills. This study uses a onegroup pretest-posttest design with n-gain analysis. The results of this study indicate that the application of inquiry-based online learning with a virtual laboratory can improve students' scientific argumentation skills. Uniquely, this only significantly impacts the claim, evidence, and reasoning components, but not the counterclaim and rebuttal components.

The plaster-casting method to create a scoliosis brace consists of mould generation and rectification to obtain the desired orthosis geometry. Alternative methods entail the use of 3D scanning and CAD/CAM. However, both manual and digital design entirely rely on the orthotist expertise. Characterisation of the rectification process is needed to ensure that digital designs are as efficient as plaster-cast designs. Three-dimensional scans of five patients, pre-, and post-rectification plaster moulds were obtained using a Structure Mark II scanner. Anatomical landmark positions, transverse section centroids, and 3D surface deviation analyses were performed to characterise the rectification process. The rectification process was characterised using two parameters. First, trends in the external contours of the rectified moulds were found, resulting in lateral tilt angles of 81 ± 3.8° and 83.3 ± 2.6° on the convex and concave side, respectively. Second, a rectification ratio at the iliac crest (0.23 ± 0.04 and 0.11 ± 0.02 on the convex and concave side, respectively) was devised, based on the pelvis width to estimate the volume to be removed. This study demonstrates that steps of the manual rectification process can be characterised. Results from this study can be fed into software to perform automatic digital rectification.

In this article, we suggest the local analysis of a uni-parametric third and fourth order class of iterative algorithms for addressing nonlinear equations in Banach spaces. The proposed local convergence is established using an ω-continuity condition on the first Fréchet derivative. In this way, the utility of the discussed schemes is extended and the application of Taylor expansion in convergence analysis is removed. Furthermore, this study provides radii of convergence balls and the uniqueness of the solution along with the calculable error distances. The dynamical analysis of the discussed family is also presented. Finally, we provide numerical explanations that show the suggested analysis performs well in the situation where the earlier approach cannot be implemented.

We study the local convergence of a family of fifth and sixth convergence order derivative free methods for solving Banach space valued nonlinear models. Earlier results used hypotheses up to the seventh derivative to show convergence. However, we only use the first divided difference of order one as well as the first derivative in our analysis. We also provide computable radius of convergence, error estimates, and uniqueness of the solution results not given in earlier studies. Hence, we expand the applicability of these methods. The dynamical analysis of the discussed family is also presented. Numerical experiments complete this article.