113 research outputs found

    Contaminants in Unionid Mussels from the Confluence of the Mississippi and Illinois Rivers

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    Unionid mussels were collected from three mussel beds near the confluence of the Mississippi and Illinois rivers in 2003 to evaluate concentrations of selected elements and organic compounds in three abundant species and to preliminarily investigate the relative contribution of these waterways to observed contaminant burdens. Copper (Cu), selenium (Se), and zinc (Zn) concentrations were higher and lead (Pb) concentrations were lower in Amblema plicata collected downstream of the confluence than in those collected upstream. Mean concentrations of nickel (Ni), total mercury (Hg), methylmercury (MeHg), Pb, and Zn varied by species. Concentrations of cadmium (Cd) decreased with age in A. plicata from two of three sites. Tissue concentrations of some elements, e.g., arsenic (As), Cd, Cu, Pb, Se, and Zn, were similar to or higher than those previously reported for unionid mussels from areas of contaminated sediment. Concentrations of Cd, Cu, and Zn in A. plicata were comparable to those collected from the Mississippi River approximately 450 and 900 km upstream from our study sites (Naimo et al. 1992). Although total Hg concentrations we observed were an order of magnitude lower than in that study, MeHg concentrations were above those associated with reductions in soft tissue mass in a study of Elliptio complanata (Salazar et al. 1995). A number of polychlorinated biphenyl (PCB) congeners were detected in A. plicata tissues, with 85% of detections occurring in mussels from downstream of the confluence. Concentrations of individual PCB congeners were ???33 ng/g ww and the maximum summed PCB congener concentration was 100.2 ng/g ww. Although few persistent pesticides were detected, -hexachlorocyclohexane (HCH) was detected in each of the species collected from below the confluence of the two rivers, and in A. plicata collected above it on both the Mississippi and Illinois rivers, at a maximum concentration of 103.5 ng/g ww. Aldrin, ??-HCH and dichlorodiphenyltrichloroethane (DDT) were detected in few of the specimens collected. The findings of this preliminary investigation suggest that unionid mussels from near the confluence of the Mississippi and Illinois rivers may be at risk of negative health effects of elevated exposure to certain environmental contaminants. Studies examining the health and productivity of unionid mussels from this area appear warranted.published or submitted for publicationis peer reviewe

    Controlled Assembly of Rodlike Viruses with Polymers

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    A practical method to assemble rodlike tobacco mosaic virus and bacteriophage M13 with polymers was developed, which afforded a 3D core–shell composite with morphological control

    Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity

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    Abstract Introduction Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. Methods Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. Results We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. Conclusions The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity

    New Models for Large Prospective Studies: Is There a Better Way?

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    Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the “UK Biobank,” which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which “process” expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

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    Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

    Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

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    : The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

    Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

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    To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs
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