143 research outputs found

    Comparison of body mass index and waist circumference as predictors of cardiometabolic health in a population of young Canadian adults

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    <p>Abstract</p> <p>Background</p> <p>This study aimed to investigate whether waist circumference (WC) or body mass index (BMI) is a better predictor of blood lipid concentrations among young men and women from different ethnocultural groups.</p> <p>Methods</p> <p>Participants were 1181 healthy men (n = 358) and women (n = 823) aged 20-29 years taken from the cross-sectional Toronto Nutrigenomics and Health Study. Analyses were conducted separately for men and women, and for Caucasian and East Asian ethnocultural groups. Serum triglycerides (TG) and total to HDL cholesterol ratio (TC:HDL cholesterol) were used as outcomes. Associations between the adiposity and blood lipid measures were examined using partial correlations and odds ratios derived from logistic regression models.</p> <p>Results</p> <p>WC had a stronger association with serum lipid concentrations than BMI. WC was significantly related to TG and TC:HDL cholesterol after adjusting for BMI and covariates among men and women (P ≤ 0.01). However, after adjusting for WC and covariates, BMI was not significantly associated with the two serum lipid measures. WC was a better predictor of TG and TC:HDL among all sex and ethnocultural subgroups except among East Asian women where little difference between the two measures was observed.</p> <p>Conclusions</p> <p>WC is a stronger predictor of cardiometabolic health when compared with BMI among young adults, especially among men.</p

    Possible Role of Meckel's Scan Fused with SPECT CT Imaging: Unraveling the Cause of Abdominal Pain and Obscure-Overt Gastrointestinal Bleeding

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    A 27-year-old male presented with recurrent abdominal pain and high volume hematochezia despite undergoing extensive testing and a right hemicolectomy 3 years prior for a linear bleeding ulceration in the ascending colon. Studies at the University of Michigan included esophagogastroduodenoscopy (EGD), colonoscopy and video capsule endoscopy (VCE), revealing an arteriovenous malformation (AVM) in the terminal ileum. He was hospitalized for recurrent symptoms. His presentation suggested a small bowel source of obscure-overt GI bleeding based on prior non-diagnostic colonoscopy and EGD and a bilious nasogastric lavage. Tagged red blood cell scan localized bleeding to the right lower quadrant. Colonoscopy showed fresh blood in the terminal ileum without a clear source. Angiography showed no evidence of bleeding or terminal ileal AVM. A novel Meckel's scan fused with SPECT imaging showed focal uptake in the terminal ileum. The patient underwent Meckel's diverticulectomy with sparing of adjacent bowel and has remained asymptomatic for 19 months. This case illustrates that patients with obscure-overt GI bleeding require a step-wise multi-modality diagnostic work-up. Because Meckel's scans are false-positive in 28% of adults, Meckel's scan fused with SPECT imaging may offer an approach to refine diagnostic accuracy of either scan alone, but requires further investigation. Exploratory laparotomy should be reserved as a last option and is best performed with intraoperative endoscopy

    Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium

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    Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA

    Lung cancer risk in never-smokers: a population-based case-control study of epidemiologic risk factors

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    <p>Abstract</p> <p>Background</p> <p>We conducted a case-control study in the greater Toronto area to evaluate potential lung cancer risk factors including environmental tobacco smoke (ETS) exposure, family history of cancer, indoor air pollution, workplace exposures and history of previous respiratory diseases with special consideration given to never smokers.</p> <p>Methods</p> <p>445 cases (35% of which were never smokers oversampled by design) between the ages of 20-84 were identified through four major tertiary care hospitals in metropolitan Toronto between 1997 and 2002 and were frequency matched on sex and ethnicity with 425 population controls and 523 hospital controls. Unconditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between exposures and lung cancer risk.</p> <p>Results</p> <p>Any previous exposure to occupational exposures (OR total population 1.6, 95% CI 1.4-2.1, OR never smokers 2.1, 95% CI 1.3-3.3), a previous diagnosis of emphysema in the total population (OR 4.8, 95% CI 2.0-11.1) or a first degree family member with a previous cancer diagnosis before age 50 among never smokers (OR 1.8, 95% CI 1.0-3.2) were associated with increased lung cancer risk.</p> <p>Conclusions</p> <p>Occupational exposures and family history of cancer with young onset were important risk factors among never smokers.</p

    Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes

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    Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction1. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity1,2. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments

    Previous Lung Diseases and Lung Cancer Risk: A Systematic Review and Meta-Analysis

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    In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent.A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22-1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI=1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR=1.22, 0.97-1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer

    Solvent-selective routing for centrifugally automated solid-phase purification of RNA

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    The final publication is available at Springer via https://doi.org/10.1007/s10404-014-1477-9.We present a disc-based module for rotationally controlled solid-phase purification of RNA from cell lysate. To this end, multi-stage routing of a sequence of aqueous and organic liquids into designated waste and elution reservoirs is implemented by a network of strategically placed, solvent-selective composite valves. Using a bead-based stationary phase at the entrance of the router, we show that total RNA is purified with high integrity from cultured MCF7 and T47D cell lines, human leucocytes and Haemophilus influenzae cell lysates. Furthermore, we demonstrate the broad applicability of the device through the in vitro amplification of RNA purified on-disc using RT-PCR and NASBA. Our novel router will be at the pivot of a forthcoming, fully integrated and automated sample preparation system for RNA-based analysis.Peer reviewe
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