254 research outputs found

    Table_1_Tick bite-induced alpha-gal syndrome and immunologic responses in an alpha-gal deficient murine model.xlsx

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    IntroductionAlpha-Gal Syndrome (AGS) is a delayed allergic reaction due to specific IgE antibodies targeting galactose-α-1,3-galactose (α-gal), a carbohydrate found in red meat. This condition has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases estimated just in the United States alone. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate the levels of specific IgE. However, the precise mechanism by which tick bites influence the host’s immune system and contribute to the development of AGS remains poorly understood. This study investigates various factors related to ticks and the host associated with the development of AGS following a tick bite, using mice with a targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism.MethodsLone-star tick (Amblyomma americanum) and gulf-coast tick (Amblyomma maculatum) nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess the host immune response. Antibody responses in sensitized mice were also determined.ResultsOur results showed a significant increase in the total IgE, IgG1, and α-gal IgG1 antibodies titers in the lone-star tick-sensitized AGKO mice compared to the gulf-coast tick-sensitized mice. Pork challenge in Am. americanum -sensitized mice led to a decline in body temperature after the meat challenge. Gene expression analysis revealed that Am. americanum bites direct mouse immunity toward Th2 and facilitate host sensitization to the α-gal antigen.ConclusionThis study supports the hypothesis that specific tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions or AGS, thereby providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.</p

    Predicting the impact of climate change on range and genetic diversity patterns of the endangered endemic Nilgiri tahr (Nilgiritragus hylocrius) in the western Ghats, India

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    [Context] Climate change is considered an important factor affecting the distribution and genetic diversity of species. While many studies have described the influence of climate change on population structure at various scales, little is known about the genetic consequences of a changing climate on endemic species.[Objectives] To assess possible changes in the distribution and genetic structure of the endangered Nilgiri tahr (Nilgiritragus hylocrius), which is endemic to the Western Ghats in India, under climate change and human disturbances.[Methods] We integrated tahr occurrence and nuclear DNA data with environmental geo-datasets to project the response of tahr populations to future climate change with respect to its distribution, genetic diversity and population structure. We screened the environmental variables using MaxEnt to identify a manageable set of predictors to be used in an ensemble approach, based on ten species distribution modelling techniques, to quantify the current tahr distribution. We then projected the distribution and genetic structure under two climate change scenarios.[Results] We found that suitable habitat for tahr (9,605 km2) is determined predominantly by a combination of climatic, human disturbance and topographic factors that result in a highly fragmented habitat throughout its distribution range in the Western Ghats. Under the severe high emissions RCP8.5 scenario tahr populations may lose more than half of their available habitat (55.5%) by 2070. Application of spatial Bayesian clustering suggests that their current genetic structure comprise four genetic clusters, with three of them reflecting a clear geographic structure. However, under climate change, two of these clusters may be lost, and in the future a homogenization of the genetic background of the remaining populations may arise due to prevalence of one gene pool cluster in the remaining populations.[Conclusions] Our interdisciplinary approach that combines niche modelling and genetic data identified the climate refugia (i.e., the remaining stable habitats that overlap with the current suitable areas), where the tahr populations would be restricted to small, isolated and fragmented areas. Essential factors to avert local extinctions of vulnerable tahr populations are a reduction of human disturbances, dispersal of tahr between fragmented populations, and the availability of corridors.This research was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India, and by a German Research Foundation (DFG) fellowship awarded to RK (project number 273837911).Peer reviewe

    Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

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    Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

    Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysisResearch in context

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    Summary: Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≄100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–GuĂ©rin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17–25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82–7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58–7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48–11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23–2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98–3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≄75%), but the sensitivity was below the target of ≄75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p = 0.68 for QFT-GIT). Interpretation: IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results. Funding: YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council [MC_UU_00004/07]

    Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis

    No full text
    Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≄100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–GuĂ©rin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17–25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82–7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58–7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48–11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23–2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98–3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≄75%), but the sensitivity was below the target of ≄75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p = 0.68 for QFT-GIT). Interpretation: IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results. Funding: YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom ( RP-PG-0217-20009). MQ was supported by the Medical Research Council [ MC_UU_00004/07]

    Does the etiology, phenomenology and motor subtype of delirium differ when it occurs in patients with an underlying dementia?: A multi-site, international study

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    Objectives: To compare the etiology, phenomenology and motor subtype of delirium in patients with and without an underlying dementia. Methods: A combined dataset (n = 992) was collated from two databases of older adults (>65 years) from liaison psychiatry and palliative care populations in Ireland and India. Phenomenology and severity of delirium were analysed using the Delirium Symptom Rating Scale Revised (DRS-R98) and contributory etiologies for the delirium groups were ascertained using the Delirium Etiology Checklist (DEC). Delirium motor subtype was documented using the abbreviated version of the Delirium Motor Subtype Scale (DMSS4). Results: Delirium superimposed on dementia (DSD) showed greater impairment in short term memory, long term memory and visuospatial ability than the delirium group but showed significantly less perceptual disturbance, temporal onset and fluctuation. Systemic infection, cerebrovascular and other Central nervous system etiology were associated with DSD while metabolic disturbance, organ insufficiency and intracranial neoplasm were associated with the delirium only group. Conclusion: The etiology and phenomenology of delirium differs when it occurs in the patient with an underlying dementia. We discuss the implications in terms of identification and management of this complex condition.</p

    Mass Cytometry reveals unique phenotypic patterns associated with subclonal diversity and outcomes in multiple myeloma

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    Abstract Multiple myeloma (MM) remains an incurable plasma cell (PC) malignancy. Although it is known that MM tumor cells display extensive intratumoral genetic heterogeneity, an integrated map of the tumor proteomic landscape has not been comprehensively evaluated. We evaluated 49 primary tumor samples from newly diagnosed or relapsed/refractory MM patients by mass cytometry (CyTOF) using 34 antibody targets to characterize the integrated landscape of single-cell cell surface and intracellular signaling proteins. We identified 13 phenotypic meta-clusters across all samples. The abundance of each phenotypic meta-cluster was compared to patient age, sex, treatment response, tumor genetic abnormalities and overall survival. Relative abundance of several of these phenotypic meta-clusters were associated with disease subtypes and clinical behavior. Increased abundance of phenotypic meta-cluster 1, characterized by elevated CD45 and reduced BCL-2 expression, was significantly associated with a favorable treatment response and improved overall survival independent of tumor genetic abnormalities or patient demographic variables. We validated this association using an unrelated gene expression dataset. This study represents the first, large-scale, single-cell protein atlas of primary MM tumors and demonstrates that subclonal protein profiling may be an important determinant of clinical behavior and outcome

    Challenges in Accessing and Delivering Maternal and Child Health Services during the COVID-19 Pandemic: A Cross-Sectional Rapid Survey from Six States of India

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    Background/Objectives: Globally, the COVID-19 pandemic and its prevention and control policies have impacted maternal and child health (MCH) services. This study documents the challenges faced by patients in accessing MCH services, and the experiences of health care providers in delivering those services during the COVID-19 outbreak, explicitly focusing on the lockdown period in India. Methods: A cross-sectional study (rapid survey) was conducted in 18 districts from 6 states of India during March to June, 2020. The sample size included 540 MCH patients, 18 gynaecologists, 18 paediatricians, 18 district immunisation officers and 108 frontline health workers. Bivariate analysis and multivariable analysis were used to assess the association between sociodemographic characteristics, and challenges faced by the patients. Results: More than one-third of patients (n = 212; 39%) reported that accessing MCH services was a challenge during the lockdown period, with major challenges being transportation-related difficulties (n = 99; 46%) unavailability of hospital-based services (n = 54; 23%) and interrupted outreach health services (n = 39; 18.4%). The supply-side challenges mainly included lack of infrastructural preparedness for outbreak situations, and a shortage of human resources. Conclusions/Recommendations: A holistic approach is required that focuses on both preparedness and response to the outbreak, as well reassignment and reinforcement of health care professionals to continue catering to and maintaining essential MCH services during the pandemic

    Very high particulate pollution over northwest India captured by a high-density in situ sensor network

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    Abstract Exposure to particulate matter less than 2.5 ”m in diameter (PM2.5) is a cause of concern in cities and major emission regions of northern India. An intensive field campaign involving the states of Punjab, Haryana and Delhi national capital region (NCR) was conducted in 2022 using 29 Compact and Useful PM2.5 Instrument with Gas sensors (CUPI-Gs). Continuous observations show that the PM2.5 in the region increased gradually from < 60 ”g m−3 in 6–10 October to up to 500 ”g m−3 on 5–9 November, which subsequently decreased to about 100 ”g m−3 in 20–30 November. Two distinct plumes of PM2.5 over 500 ”g m−3 are tracked from crop residue burning in Punjab to Delhi NCR on 2–3 November and 10–11 November with delays of 1 and 3 days, respectively. Experimental campaign demonstrates the advantages of source region observations to link agricultural waste burning and air pollution at local to regional scales

    Impact of Long-Term Conservation Agriculture Practices on Phosphorus Dynamics under Maize-Based Cropping Systems in a Sub-Tropical Soil

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    Over the past decade, scientific studies have increasingly concentrated on the effects of global phosphorus (P) scarcity on food security. A comprehensive strategy that considers demand reduction and recycling possibilities is needed to address the global P scarcity. Reduced tillage along with crop residue retention could decrease fixation of P in soil, improve labile P content and enhance organic-P (Po) buildup and its mineralization by phosphatases; this could be an extra benefit of conservation agriculture (CA) in soils. To study the impact of long-term CA on soil organic and inorganic P fractions and their distribution, a long-term field trial was conducted under a maize-based cropping system with different tillage (zero tillage (ZT), permanent bed (PB) and conventional till (CT) and cropping system (maize–wheat–mungbean (MWMb), maize–chickpea–sesbania (MCS), maize–mustard–mungbean (MMuMb) and maize–maize–sesbania (MMS)). Phosphorus dynamics were studied through sequential fractionation (organic and inorganic P) at 0–5 and 5–15 cm soil depth. The findings showed that a higher amount of soluble and loosely bound P (SL-P) was detected in ZT among the inorganic P fractions, whereas iron-bound P (Fe-P), aluminum-bound P (Al-P), reductant soluble P (RES-P) and calcium-bound P (Ca-P) were found higher in CT in both soil depths. Among Organic-P fractions, moderately labile and non-labile Po was found higher in PB and ZT but, in the case of labile Po, it was found insignificant with respect to tillage operations. Significant synergistic effects of winter legume (chickpea) with summer legumes (sesbania and mungbean) in crop rotation were observed on SL-P, Labile Po, Humic acid-Po, Alkaline phosphatase and MBP at 0–5 and 5–15 cm soil depths. Given the potential relevance of understanding P dynamics for efficient P management in long-term conservation agriculture practices, our findings offers critical new insight for the P management for sustainable development
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