Neonatal Septicemia in Nepal: Early-Onset versus Late-Onset

Introduction. Neonatal septicemia is defined as infection in the first 28 days of life. Early-onset neonatal septicemia and late-onset neonatal septicemia are defined as illnesses appearing from birth to three days and from four to twenty-eight days postnatally, respectively. Methods. In this cross-sectional study, blood samples from the suspected infants were collected and processed in the bacteriology laboratory. The growth was identified by standard microbiological protocol and the antibiotic sensitivity testing was carried out by modified Kirby-Bauer disk diffusion method. Results. Among total suspected cases, the septicemia was confirmed in 116 (12.6%) neonates. Early-onset septicemia (EOS) was observed in 82 infants and late-onset septicemia (LOS) in 34 infants. Coagulase-negative staphylococcus (CoNS) (46.6%) was the predominant Gram-positive organism isolated from EOS as well as from LOS cases followed by Staphylococcus aureus (14.6%). Acinetobacter species (9.5%) was the predominant Gram-negative organism followed by Klebsiella pneumoniae (7.7%). Conclusions. The result of our study reveals that the CoNS, Staphylococcus aureus, Acinetobacter spp., and Klebsiella pneumoniae are the most common etiological agents of neonatal septicemia. In particular, since rate of CoNS causing sepsis is alarming, prompting concern to curb the excess burden of CoNS infection is necessary

Design and Characteristics of Hydroxyapatites: Effect of Radiation

Hydroxyapatites single crystals have been investigated their applications as the laser host material. Czochralksi and flux growth methods have been utilized to achieve single crystals. Because of their bioactivities with tissues these have attracted interest for bone applications. For low temperature processing we have used several techniques. We utilized some organic melt and oriented the grains by the directional solidification method. This organic treated material has different characteristics than coarsened oxide materials. Our approach involved low temperature processing using nano-engineered powders of the material system MgO-Na2O-K2O-CaO-SrO-SiO2 and also borates were processed by sintering and grain growth. Our results indicate that substitution of calcium and strontium with some other elements such as gallium and magnesium have great potential to improve the mechanical properties of bones

Childhood Septicemia in Nepal: Documenting the Bacterial Etiology and Its Susceptibility to Antibiotics

Introduction. Children are among the most vulnerable population groups to contract illnesses. The varying microbiological pattern of septicemia warrants the need for an ongoing review of the causative organisms and their antimicrobial susceptibility pattern. Therefore, the objective of this study was to document the bacterial etiology of childhood septicemia and its antibiotic susceptibility profile. Methods. Cross-sectional type of study in 1630 suspected patients was conducted at CMCTH from January 2012 to December 2013. Blood samples were collected aseptically for culture. The organisms grown were identified by standard microbiological methods recommended by American Society for Microbiology (ASM) and subjected to antibiotic susceptibility testing by modified Kirby-Bauer disk diffusion method. Methicillin resistance was confirmed using cefoxitin and oxacillin disks methods. Results. Septicemia was detected in 172 (10.6%) cases. Among Gram-positive organisms, coagulase negative staphylococci (CoNS) were leading pathogen and Acinetobacter spp. were leading pathogen among Gram-negative isolates. Vancomycin, teicoplanin, and clindamycin were the most effective antibiotics against Gram-positive isolates while amikacin was effective against Gram-positive as well as Gram-negative isolates. Methicillin resistance was detected in 44.4% of Staphylococcus aureus. Conclusions. This study has highlighted the burden of bacterial etiology for septicemia among children in a tertiary care center of central Nepal

Quantitative tissue proteome profile reveals neutrophil degranulation and remodeling of extracellular matrix proteins in early stage gallbladder cancer

Gallbladder cancer (GBC) is an aggressive malignancy of the gastrointestinal tract with a poor prognosis. It is important to understand the molecular processes associated with the pathogenesis of early stage GBC and identify proteins useful for diagnostic and therapeutic strategies. Here, we have carried out an iTRAQ-based quantitative proteomic analysis of tumor tissues from early stage GBC cases (stage I, n=7 and stage II, n=5) and non-tumor controls (n=6) from gallstone disease (GSD). We identified 357 differentially expressed proteins (DEPs) based on ≥ 2 unique peptides and ≥ 2 fold change with p value < 0.05. Pathway analysis using the STRING database showed, ‘neutrophil degranulation’ to be the major upregulated pathway that includes proteins such as MPO, PRTN3, S100A8, MMP9, DEFA1, AZU, and ‘ECM organization’ to be the major downregulated pathway that includes proteins such as COL14A1, COL1A2, COL6A1, COL6A2, COL6A3, BGN, DCN. Western blot and/or IHC analysis confirmed the elevated expression of MPO, PRTN3 and S100A8 in early stage of the disease. Based on the above results, we hypothesize that there is an increased neutrophil infiltration in tumor tissue and neutrophil degranulation leading to degradation of extracellular matrix (ECM) proteins promoting cancer cell invasion in the early stage GBC. Some of the proteins (MPO, MMP9, DEFA1) associated with ‘neutrophil degranulation’ showed the presence of ‘signal sequence’ suggesting their potential as circulatory markers for early detection of GBC. Overall, the study presents a protein dataset associated with early stage GBC

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Investigation of dielectric behaviour in ferrofluid-ferroelectric liquid crystal nanocomposites

We demonstrate here the frequency-bias-temperature-dependent dielectric studies of ferrofluid (FF) mixed ferroelectric liquid crystals (FLCs; SCE13 and Felix017/100). As a FF, cobalt ferrite nanoparticles (similar to 9 nm) synthesised through chemical co-precipitation were used in the study. In these FF-FLCs nanocomposites, a memory (dielectric) effect is observed at room temperature, which becomes more pronounced as the temperature tends towards the smectic C* (SmC*) to smectic A (SmA) phase transitions. Moreover, in addition to the memory effect, the observed enhanced dielectric constant (epsilon') also reveals the importance of FF nanoparticles in the FLC matrix. We anticipate that, in current nanocomposites, the interaction of the AC field frequency response of FF nanoparticles with the dielectric response of FLCs could be the plausible reason for these observations

Prevalence of subclinical Vitamin K deficiency in early infancy in exclusively breast-fed term infants

Background: Late Vitamin K deficiency bleeding, is a disease of exclusively breast-fed infants attributable to poor content of Vitamin K in breast milk. We aimed to estimate the prevalence of subclinical Vitamin K deficiency, at 3 months of age in exclusively breast-fed term infants who were administered routine Vitamin K 1 mg intramuscular at birth. Methods: This prospective observational study was conducted between June 2018 and June 2020 in a Tertiary Care Teaching Hospital in Western India. Consecutive inborn infants, having received Injection Vitamin K at birth and on exclusive breast feeds attending immunization at 3 months of age were included. Half milliliter of venous blood was withdrawn for the estimation of Proteins Induced by Vitamin K Absence or Antagonist-II (PIVKA-II). Subclinical Vitamin K deficiency was defined as PIVKA-II level of more than 2 ng/mL. Results: The mean age of infants was 3.2 ± 0.2 months and the PIVKA II levels ranged from 0.19 to 10.07 ng/ml. Subclinical Vitamin K deficiency was present in 62 (32.63%) out of 190 infants. Conclusion: Significantly raised PIVKA II levels (>2 ng/mL) were detectable in 32.6% of infants after 3 months of age who had received 1 mg of Vitamin K at birth

Communicating complex forecasts:An analysis of the approach in Nepal's flood early warning system

Early warning systems have the potential to save lives and improve resilience. However, barriers and challenges remain in disseminating and communicating early warning information to institutional decision-makers, community members and individuals at risk, including unequal access, insufficient understanding, and inability to act on warning information. Research was undertaken to analyse and understand the current flood early warning system in Nepal, considering available data and forecasts, information flows, early warning dissemination, and decision-making for early action. Data were collected from key informant interviews, community-level questionnaires, and a national stakeholder workshop and qualitatively analysed. The availability and utilisation of simple and complex flood forecasts in Nepal, and their integration into dissemination, and decision support tools were reviewed, considering their impact on improving early action to increase the resilience of vulnerable communities to flooding. Results suggest that as Nepal continues to advance in hydro-meteorological forecasting capabilities, efforts are simultaneously needed to ensure these forecasts are more effectively communicated and disseminated

Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer

Abstract Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median survival- ~ 23 months) in spite of standard treatment which includes extended surgery followed by chemotherapy, radiotherapy and targeted therapy. This study aims at understanding the underlying molecular processes associated with LN metastasis in GBC. Here, we used iTRAQ-based quantitative proteomic analysis using tissue cohort comprising of primary tumor of LN negative GBC (n = 3), LN positive GBC (n = 4) and non-tumor controls (Gallstone disease, n = 4), to identify proteins associated with LN metastasis. A total of 58 differentially expressed proteins (DEPs) were found to be specifically associated with LN positive GBC based on the criteria of p value ≤ 0.05, fold change ≥ 2 and unique peptides ≥ 2. These include the cytoskeleton and associated proteins such as keratin, type II cytoskeletal 7 (KRT7), keratin type I cytoskeletal 19 (KRT19), vimentin (VIM), sorcin (SRI) and nuclear proteins such as nucleophosmin Isoform 1 (NPM1), heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 (HNRNPA2B1). Some of them are reported to be involved in promoting cell invasion and metastasis. Bioinformatic analysis of the deregulated proteins in LN positive GBC using STRING database identified ‘neutrophil degranulation’ and ‘HIF1 activation’ to be among the top deregulated pathways. Western blot and IHC analysis showed a significant overexpression of KRT7 and SRI in LN positive GBC in comparison to LN negative GBC. KRT7, SRI and other proteins may be further explored for their diagnostics and therapeutic applications in LN positive GBC

AMMI and GGE biplot analysis of yield performance of wheat genotypes under irrigated, heat stress and heat drought environments

Wheat is the third most important cereal crop in Nepal. The impact of global warming is threatening global wheat production and food security. The terminal heat stress reduces the grain quality of wheat. However, the drought is affecting more than 15% of global wheat productivity. To find out the stable and high- yielding wheat genotype the experiment was carried out in Rupandehi, Nepal with twenty genotypes under three different environmental conditions namely heat drought, heat stress and irrigated in an alpha lattice design with two replications in each environment. The AMMI (Additive mean effect multiplicative interaction) biplot analysis shows differences in 20 different genotypes in terms of yield and stability. The analysis of variance model showed the share of GE (genotype and environment) interaction in the variation in grain yield of twenty wheat genotypes. The grain yield of genotype varied significantly with environmental impact (p ). The AMMI stability value (ASV) examined NL1387 as the most stable line. The tested environments were discriminative for genotype and showed negative correlation between them. The GGE biplot analysis was conducted to find out the best performing line under different environments and the stable line in diverse environments. The NL1420 was found stable genotype in all three tested environment. The NL1376 line is most ideal ranking first in the ranking biplot. The mean versus stability model indicated NL1369 and NL1376 as elite genotypes and NL 1404, BL4919 and NL1387 can be recommended as new cultivars