Sec6 mutations and the Drosophila exocyst complex

To allow a detailed analysis of exocyst function in multicellular organisms, we have generated sec6 mutants in Drosophila. We have used these mutations to compare the phenotypes of sec6 and sec5 in the ovary and nervous system, and we find them to be similar. We also find that Sec5 is mislocalized in sec6 mutants. Additionally, we have generated an epitope-tagged Sec8 that localized with Sec5 on oocyte membranes and was mislocalized in sec5 and sec6 germ-line clones. This construct further revealed a genetic interaction of sec8 and sec5. These data, taken together, provide new information about the organization of the exocyst complex and suggest that Sec5, Sec6 and Sec8 act as a complex, each member dependent on the others for proper localization and function

Interference of anti-nuclear antibodies on determination of anti-neutrophil cytoplasmic antibodies in patients suspected of vasculitis: a case series

Anti-neutrophil cytoplasmic antibodies (ANCA) are mainly associated with medium and small vessel vasculitis. Two main methodologies currently available for detection of these antibodies are indirect immunofluorescence (IIF) and monospecific proteinase 3 (PR3) and myeloperoxidase (MPO) based immunoassays. However, well-defined guidelines regarding mode of testing for ANCA in laboratories still don’t exist, leading to problems in diagnosis and further patient management. Anti-neutrophil cytoplasmic antibodies testing by IIF and enzyme linked immunosorbent assay (ELISA) often pose a significant challenge in diseases other than vasculitis and in overlapping autoimmune conditions. Anti-neutrophil cytoplasmic antibodies reporting by IIF can be challenging in certain circumstances. This case series aims to discuss four cases with probable interference of anti-nuclear antibodies (ANA) during ANCA testing by IIF resulting in ANCA false positivity. All four cases on subsequent reflex testing by line immunoassay (LIA) for PR3, MPO and glomerular basement membrane (GBM) antigens proved otherwise. While analysing for the presence of ANCA by IIF, the possible interference of ANA leading to a false positive ANCA result should be kept in mind and alternative methods of testing like ELISA, extended granulocyte based IIF assays with MPO and PR3 coated beads, etc., should also be advised. Probability of atypical ANCA in diseases other than vasculitis should also be considered in case of ambiguous results

Spectroscopic and biochemical correlations during the course of human lens aging

BACKGROUND: With age, the human lens accumulates variety of substances that absorbs and fluorescence, which explains the color of yellow, brunescent and nigrescent cataract in terms of aging. The aim of this study was to assess lens fluorophores with properties comparable to those of advanced glycated end products (AGEs) in relation to age in human lenses. These fluorescent compounds are believed to be involved in the development of cataract. METHODS: Spectroscopic (UV-Vis-NIR) and fluorescence photography (CCD-Digital based image analysis) studies were carried out in randomly selected intact human lenses (2–85 years). AGE-like fluorophores were also measured in water soluble and insoluble (alkali soluble) fractions of human lenses (20–80 years). RESULTS: Our experimental findings suggest that there was a progressive shift in the absorbance characteristic of intact lens in the range of λ(210 nm)-λ(470 nm). A relative increase in the absorptivity at λ((511–520 nm)), with age, was also observed. In addition, the ratio of absorptivity at λ((511–520 nm)) versus the maximum absorbance recorded at blue-end cut-off (210–470 nm) was also found to increase, with age. The fluorescent intensity in the intact lens at both UV-B (λ(Ex312 nm)) and UV-A (λ(Ex365 nm)) were found to be positively correlated (r(2 )= 0.91 & 0.94, respectively; Confidence interval 95%) upto 50 years of age. In addition, a concomitant changes in AGE- like fluorophores were also observed in the processed lens samples (soluble and insoluble fractions) along the age. A significant increase in the concentration of AGE- like fluorophores, both in intact and processed lens was observed during the period of 40 – 50 years. CONCLUSION: Based on the present investigation, it was concluded that significant changes do occur in the AGE-like fluorophores of human lenses during the period of 40–50 years

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

An assessment of immediate newborn care readiness and availability in Nepal

Background Global neonatal mortality necessitates access to immediate newborn care interventions. In Nepal, disparities persist in the readiness and availability of newborn care services within health facilities. Objective This study aimed to assess this status and compare facilities that had implemented an intensive newborn resuscitation capacity building and retention programme in the past five years with those that had not. Methods Our observational cross-sectional study involved 154 health facilities across Nepal. Through on-site inspections and maternal log reviews, we evaluated the immediate newborn care readiness and availability. Results The mean immediate newborn care intervention availability score of 52.8% (SE = 21.5) and the readiness score averaged 79.6% (SE = 12.3). Encouragingly, 96% of facilities ensured newborns were dried and wrapped for warmth, and 69.9% provided newborn resuscitation. Practices such as delayed cord clamping (42.0%), skin-to-skin contact (28.6%), and early breastfeeding (63.5%) showed room for improvement. Only 16.1% of health facilities administered Vitamin K1 prophylaxis.Domain-specific scores demonstrated a high level of facility readiness in infrastructure (97.5%), medicine, equipment, and supplies (90.6%), and staff training (90.9%), but a lower score for neonatal resuscitation aids (28.8%). Disparities in readiness and availability were evident, with rural areas and the Madhesh province reporting lower scores. Variations among health facility types revealed provincial and private hospitals outperforming local-level facilities. A positive association was observed between the LDSC/SSN mentoring programme and both the readiness and availability of immediate newborn care services. Conclusion This study highlights the gap between healthcare facility readiness and the actual availability of immediate newborn care interventions in Nepal. Addressing disparities and barriers, particularly in rural areas and local-level facilities, is crucial for improving neonatal survival. The positive link between the LDSC/SSN programme and service availability and facility readiness emphasises the significance of targeted training and mentorship programmes in enhancing newborn care across Nepal

Extraction, purification and characterization of polyphenoloxidase from peel and pulp

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Clinical and serological evaluation of gastrointestinal profile by line immunoassay (LIA) in a group of patients attending tertiary care hospital of Bihar: An observational study

Objectives: the evaluation of Clinical and serological auto-antibodies against gastrointestinal tract by gastrointestinal profile using LIA in a group of patients who have attended AIIMS Patna for symptoms suggestive of gastrointestinal disorder. Material and methods:This was a retrospective study on all samples (130-150) received for gastrointestinal profile to be done in Biochemistry central lab for a study period of May 2019 to January 2020(9 months). A total of approximately 50 samples positive or equivocal for antibodies against IF, Gliadin, ASCA, PCA and tTg antigen were analysed further for clinical data.  Results: In our study 56% and 44% female were participated most of the patients was 30-40 years followed by 20-30 years .The most common symptom Weight loss 48% was found in our study and  followed by Chronic/intermittent diarrhea 46%, weakness 24%, Abdominal pain 20%,constipation 18%, Abdominal discomfort and vomiting.We found 32% patients had below 11micromol/L iron and 54% patients had below 12gm/100ml Hb means suffring from anaemia.The ASCA positive status was a predictor for Crohn s disease(CD). in our study out of 50 patients 20% was ASCA+,2% ASCA++,4% ASCA+++and 4% ASCAwas positive. In our study on the basis of the histological diagnosis, PCA+ patients were14%, PCA++ patients 6%, PCA+++patients 12% and PCA Equivocal 4% was found.Tissue transglutaminase (tTG) has been identified as the autoantigen in CD. Out of 50 patients 28% tTG +,2% tTG ++,12% tTG +++,2% tTG Equivocal was found. Conclusion: The evaluation of Clinical and serological auto-antibodies against gastrointestinal tract by gastrointestinal profile using LIA was beneficial for identification of  the gastrointestinal diseases of the patients . Keywords: gastrointestinal, immunoassay, clinical, patient