2,683 research outputs found

    Spirits, iconoclasts and the borders of the market in urban Vietnam

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    This study takes as its object a goddess called the Lady of the Realm, whose shrine is in a rural area in the southern part of Vietnam. This goddess provides a valuable window onto changes underway in reform-era Vietnam for in recent years she has become the focus of a major pilgrimage and the controversial object of much commentary and debate

    Coronary artery bypass grafting in non–dialysis-dependent mild-to-moderate renal dysfunction

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    AbstractObjectives: The effect of mild-to-moderate elevation of preoperative serum creatinine levels on morbidity and mortality from coronary artery bypass grafting has not been investigated in a large multivariable model incorporating preoperative and intraoperative variables. Our first objective was to ascertain the effect of a mild-to-moderate elevation in the preoperative serum creatinine level on the need for mechanical renal support; the duration of special care and total postoperative stay; the occurrence of infective, respiratory, and neurologic complications; and hospital mortality. Our second objective was to ascertain which patient variables contributed to an increase in the serum creatinine level in association with coronary artery bypass grafting. Methods: A total of 1427 patients who had no known pre-existing renal disease and who were undergoing first-time coronary artery bypass grafting with cardiopulmonary bypass were recruited for the study. Patients were divided, on the basis of preoperative serum creatinine level, into 3 groups as follows: creatinine level of less than 130 μmol · L–1; creatinine level of 130 to 149 μmol · L–1; and creatinine level of 150 μmol · L–1 or greater. A multivariable stepwise logistic regression analysis was used, and variables significant at the 5% level were included when developing the final multivariable models. Results: Multivariable analysis showed that elevation of the preoperative serum creatinine level to 130 μmol · L–1 or greater increased the likelihood of needing mechanical renal support postoperatively (P <.001), as well as the need for postoperative special care (P <.001) and total hospital stay (P <.001). In-hospital mortality was also significantly elevated as the preoperative creatinine level rose to 130 to 149 μmol · L–1 (P =.045) and to 150 μmol · L–1 or greater (P <.001). It was further observed that patients with preoperative serum creatinine levels of 130 to 149 μmol · L–1 (P =.02), patients with preoperative serum creatinine levels of 150 μmol · L–1 or greater (P =.001), hypertensive patients (P =.007), patients with angina of New York Heart Association class III or greater (P =.001), patients having a nonelective operation (P =.002), and patients having a prolonged cardiopulmonary bypass time (P =.008) had a significantly greater increase in the serum creatinine level as a result of coronary artery bypass grafting. Of particular note was the finding that the method of myocardial protection (cardioplegia or crossclamp fibrillation) did not significantly influence in-hospital mortality, need for mechanical renal support, or special care or total postoperative hospital stay. Conclusions: A mild elevation (130-149 μmol · L–1) in the preoperative serum creatinine level significantly increases the need for mechanical renal support, the duration of special care and total postoperative stay, and the in-hospital mortality. As the preoperative serum creatinine level increases further (≥150 μmol · L–1), this effect is more pronounced. No significant difference in outcome was observed between the use of cardioplegia or crossclamp fibrillation for myocardial protection. (J Thorac Cardiovasc Surg 2001;121:1083-9

    Death receptor 3 regulates distinct pathological attributes of acute versus chronic murine allergic lung inflammation

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    The Death Receptor 3 (DR3)/Tumour Necrosis Factor-like cytokine 1A (TL1A) axis stimulates effector T cells and type 2 innate lymphocytes (ILC2) that trigger cytokine release and drive disease pathology in several inflammatory and autoimmune diseases, including murine models of acute allergic lung inflammation (ALI). The aim of this study was to elucidate the role of DR3 in chronic ALI compared to acute ALI, using mice genetically deficient in the DR3 gene (DR3ko). Results showed DR3 expression in the lungs of wild-type mice was up-regulated following induction of acute ALI and this increased expression was maintained in chronic disease. DR3ko mice were resistant to cellular accumulation within the alveolar passages in acute, but not chronic ALI. However, DR3ko mice displayed reduced immuno-histopathology and goblet cell hyperplasia; hallmarks of the asthmatic phenotype; in chronic, but not acute ALI. These data suggest DR3 is a potential therapeutic target, involved in temporally distinct aspects of ALI progression and pathogenesis

    Allele-Specific Chromatin Immunoprecipitation Studies Show Genetic Influence on Chromatin State in Human Genome

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    Several recent studies have shown a genetic influence on gene expression variation, including variation between the two chromosomes within an individual and variation between individuals at the population level. We hypothesized that genetic inheritance may also affect variation in chromatin states. To test this hypothesis, we analyzed chromatin states in 12 lymphoblastoid cells derived from two Centre d'Etude du Polymorphisme Humain families using an allele-specific chromatin immunoprecipitation (ChIP-on-chip) assay with Affymetrix 10K SNP chip. We performed the allele-specific ChIP-on-chip assays for the 12 lymphoblastoid cells using antibodies targeting at RNA polymerase II and five post-translation modified forms of the histone H3 protein. The use of multiple cell lines from the Centre d'Etude du Polymorphisme Humain families allowed us to evaluate variation of chromatin states across pedigrees. These studies demonstrated that chromatin state clustered by family. Our results support the idea that genetic inheritance can determine the epigenetic state of the chromatin as shown previously in model organisms. To our knowledge, this is the first demonstration in humans that genetics may be an important factor that influences global chromatin state mediated by histone modification, the hallmark of the epigenetic phenomena

    Do cladistic and morphometric data capture common patterns of morphological disparity?

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    The distinctly non-random diversity of organismal form manifests itself in discrete clusters of taxa that share a common body plan. As a result, analyses of disparity require a scalable comparative framework. The difficulties of applying geometric morphometrics to disparity analyses of groups with vastly divergent body plans are overcome partly by the use of cladistic characters. Character-based disparity analyses have become increasingly popular, but it is not clear how they are affected by character coding strategies or revisions of primary homology statements. Indeed, whether cladistic and morphometric data capture similar patterns of morphological variation remains a moot point. To address this issue, we employ both cladistic and geometric morphometric data in an exploratory study of disparity focussing on caecilian amphibians. Our results show no impact on relative intertaxon distances when different coding strategies for cladistic characters were used or when revised concepts of homology were considered. In all instances, we found no statistically significant difference between pairwise Euclidean and Procrustes distances, although the strength of the correlation among distance matrices varied. This suggests that cladistic and geometric morphometric data appear to summarize morphological variation in comparable ways. Our results support the use of cladistic data for characterizing organismal disparity

    A novel dietary intervention reduces circulatory branched-chain amino acids by 50%: A pilot study of relevance for obesity and diabetes

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    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Elevated circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are associated with obesity and type 2 diabetes (T2D). Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans. We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall en-ergy/protein intake. Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two. The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096). We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes

    Earlier seasonal onset of intense Mesoscale Convective Systems in the Congo Basin since 1999

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    Mesoscale Convective Systems (MCSs) produce some of the most intense rainfall on the planet, and their response to climate variability and change is rather uncertain. Under global warming, increased water vapour is expected to intensify the most extreme rain events and enhance flood frequency. However, MCS dynamics are also sensitive to other atmospheric variables, most notably, wind shear. Here we build on a recent study showing strong MCS intensification in the African Sahel, and examine evidence of similar trends elsewhere in tropical Africa. Using satellite data, we find a remarkable increase post‐1999 in intense MCS frequency over the Congo Basin during the month of February. This earlier onset of the spring rainy season has been accompanied by strong increases in the February meridional temperature gradient and associated wind shear. This supports the hypothesis that contrasts in warming across the continent can drive important decadal‐scale trends in storm intensity

    Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

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    BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. RESULTS: Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP) array, including loss of heterozygosity (LOH) and copy number alterations (CNA), for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT) software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q), including 20 novel LOH regions (10 kb to 4.26 Mb). Fifteen CNA-loss regions (200 kb to 4.3 Mb) and 36 CNA-gain regions (200 kb to 9.3 Mb) were also identified. CONCLUSION: These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC

    Paracetamol reduces influenza-induced immunopathology in a mouse model of infection without compromising virus clearance or the generation of protective immunity

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    Background: Seasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies are of limited efficacy, and during a pandemic outbreak would only be available to a minority of the global population. Over-the-counter medicines are routinely taken by individuals suffering from influenza, but few studies have been conducted to determine their effectiveness in reducing pulmonary immunopathology or the influence they exert upon the generation of protective immunity. Methods: A mouse model of influenza infection was utilised to assess the efficacy of paracetamol (acetaminophen) in reducing influenza-induced pathology and to examine whether paracetamol affects generation of protective immunity. Results: Administration (intraperitoneal) of paracetamol significantly decreased the infiltration of inflammatory cells into the airway spaces, reduced pulmonary immunopathology associated with acute infection and improved the overall lung function of mice, without adversely affecting the induction of virus-specific adaptive responses. Mice treated with paracetamol exhibited an ability to resist a second infection with heterologous virus comparable with that of untreated mice. Conclusions: Our results demonstrate that paracetamol dramatically reduces the morbidity associated with influenza but does not compromise the development of adaptive immune responses. Overall, these data support the utility of paracetamol for reducing the clinical symptoms associated with influenza virus infection
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