35232 research outputs found
Sort by
Changes in circulating MicroRNAs-99/100 and reductions of visceral and ectopic fat depots in response to lifestyle interventions: The CENTRAL trial.
No full textBACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs and important post-transcriptional regulators of gene expression. Adipose tissue is a major source of circulating miRNAs; adipose-related circulating miRNAs may regulate body fat distribution and glucose metabolism. OBJECTIVES: We investigated how changes in adipose-related circulating microRNAs-99/100 (miR-99/100) in response to lifestyle interventions were associated with improved body fat distribution and reductions of diabetogenic ectopic fat depots among adults with abdominal obesity. DESIGN: This study included adults with abdominal obesity from an 18-month diet and physical activity intervention trial. Circulating levels of miR-99a-5p, miR-99b-5p, and miR-100-5p were measured at baseline and 18 months; changes in these miRNAs in response to the interventions were evaluated. The primary outcomes were changes in abdominal (visceral [VAT], deep subcutaneous [DSAT], superficial subcutaneous [SSAT]) adipose tissue (cm2) (n = 144). The secondary outcomes were changes in ectopic fat accumulation in the liver (n = 141) and pancreas (n = 143). RESULTS: Greater decreases in miR-100-5p were associated with more reductions of VAT (β per 1 SD decrease: -9.63 [SE 3.13]; P = 0.0025], DSAT (β -5.48 [2.36]; P = 0.0218), SSAT (β -4.64 [1.68]; P = 0.0067), and intrahepatic fat percentage (β -1.54 [0.49]; P = 0.0023) after the interventions. Similarly, participants with greater decrease in miR-99a-5p had larger 18-month reductions of VAT (β -10.12 [3.31] per 1 SD decrease; P = 0.0027) and intrahepatic fat percentage (β -1.28 [0.52]; P = 0.015). Further, decreases in circulating miR-99b-5p (β per 1 SD decrease: -0.44 [0.21]; P = 0.038) and miR-100-5p (β -0.50 [0.23]; P = 0.033) were associated with a decrease in pancreatic fat percentage, as well as improved glucose metabolism and insulin secretion at 18 months. CONCLUSIONS: Decreases in circulating miR-99-5p/100-5p levels induced by lifestyle interventions were related to improved body fat distribution and ectopic fat accumulation. Our study suggests that changes in circulating adipose-related miR-99-5p/100-5p may be linked to reducing diabetogenic fat depots in patients with abdominal obesity
Preliminary study of lithium tetraborate doped with Cu and in for external dosimetry.
No full textA potentially tissue-equivalent dosimeter based on lithium tetraborate co-doped with Cu and In was successfully synthesized in two steps melting process. Basic material properties were characterized using Differential scanning calorimetry, X-ray diffraction, and Fourier Transform Infrared Spectroscopy, the dosimetric properties using Thermoluminescence. The highest sensitivity was observed for dopant concentrations of 0.1% Cu and 0.5% In. Tmax-Tstop analysis revealed the existence of eight individual peaks in the composite TL glow curve, which was confirmed by computerized glow curve deconvolution. A linear dose-response was seen up to about 30 Gy, for higher doses saturation effects occurred. The minimum detectable dose was estimated at about 670 μGy. TL peaks, with peak temperature above 150 °C faded to values between 3.3 and 14.9% of the respective of initial values after 70 days storage
Federated disentangled representation learning for unsupervised brain anomaly detection.
No full textWith the advent of deep learning and increasing use of brain MRIs, a great amount of interest has arisen in automated anomaly segmentation to improve clinical workflows; however, it is time-consuming and expensive to curate medical imaging. Moreover, data are often scattered across many institutions, with privacy regulations hampering its use. Here we present FedDis to collaboratively train an unsupervised deep convolutional autoencoder on 1,532 healthy magnetic resonance scans from four different institutions, and evaluate its performance in identifying pathologies such as multiple sclerosis, vascular lesions, and low- and high-grade tumours/glioblastoma on a total of 538 volumes from six different institutions. To mitigate the statistical heterogeneity among different institutions, we disentangle the parameter space into global (shape) and local (appearance). Four institutes jointly train shape parameters to model healthy brain anatomical structures. Every institute trains appearance parameters locally to allow for client-specific personalization of the global domain-invariant features. We have shown that our collaborative approach, FedDis, improves anomaly segmentation results by 99.74% for multiple sclerosis, 83.33% for vascular lesions and 40.45% for tumours over locally trained models without the need for annotations or sharing of private local data. We found out that FedDis is especially beneficial for institutes that share both healthy and anomaly data, improving their local model performance by up to 227% for multiple sclerosis lesions and 77% for brain tumours
Rising hemoglobin A1c in the nondiabetic range predicts progression of type 1 diabetes as well as oral glucose tolerance tests.
No full textOBJECTIVE: Biomarkers predicting risk of type 1 diabetes (stage 3) among children with islet autoantibodies are greatly needed to prevent diabetic ketoacidosis and facilitate prevention therapies. RESEARCH DESIGN AND METHODS: Children in the prospective The Environmental Determinants of Diabetes in the Young (TEDDY) study (n = 707) with confirmed diabetes-associated autoantibodies (GAD antibody, IA-2A, and/or insulin autoantibody) and two or more HbA1c measurements were followed to diabetes or median age 11.1 years. Once confirmed autoantibody positive, HbA1c was measured quarterly. Cox models and receiver operative characteristic curve analyses revealed the prognostic utility for risk of stage 3 on a relative HbA1c increase from the baseline visit or an oral glucose tolerance test (OGTT) 2-h plasma glucose (2-hPG). This HbA1c approach was then validated in the Type 1 Diabetes TrialNet Pathway to Prevention Study (TrialNet) (n = 1,190). RESULTS: A 10% relative HbA1c increase from baseline best marked the increased risk of stage 3 in TEDDY (74% sensitive; 88% specific). Significant predictors of risk for HbA1c change were age and HbA1c at the baseline test, genetic sex, maximum number of autoantibodies, and maximum rate of HbA1c increase by time of change. The multivariable model featuring a HbA1c ≥10% increase and these additional factors revealed increased risk of stage 3 in TEDDY (hazard ratio [HR] 12.74, 95% CI 8.7-18.6, P < 0.0001) and TrialNet (HR 5.09, 95% CI 3.3-7.9, P < 0.0001). Furthermore, the composite model using HbA1c ≥10% increase performed similarly to an OGTT 2-hPG composite model (TEDDY area under the curve [AUC] 0.88 and 0.85, respectively) and to the HbA1c model in TrialNet (AUC 0.82). CONCLUSIONS: An increase of ≥10% in HbA1c from baseline is as informative as OGTT 2-hPG in predicting risk of stage 3 in youth with genetic risk and diabetes-associated autoantibodies
Impaired myocardial mitochondrial respiration in humans with prediabetes: A footprint of prediabetic cardiomyopathy.
No full textSafety and efficacy of all-comers treated with paclitaxel-coated balloon for below the knee intervention.
No full textOBJECTIVES: Data on PCB for below the knee (BTK) angioplasty exhibited conflicting efficacy results and previous meta-analyses suggested an increased mortality and amputation risk highlighting the need for further research. The aim of this study was to investigate safety and efficacy of Paclitaxel coated balloons (PCB) for BTK interventions in a real-world cohort. METHODS: Within a single-center cohort study 552 consecutive patients were included undergoing BTK interventions with and without PCB use. Two-year safety and efficacy results were compared in unadjusted and propensity score matched (PSM) analysis. RESULTS: BTK interventions were performed in 157 patients with PCB angioplasty (100% Lutonix 0.014" drug coated balloon; Bard Lutonix, New Hope, Minnesota, USA) and 395 patients with plain old balloon angioplasty (POBA). The majority of interventions (>70%) were performed for chronic limb threatening ischemia (CLTI). Mean lesion length was 20.8±12.6cm. 61.2% in the PCB and 66.7% in the POBA group were occlusions. In the PCB group, more procedures were performed for restenotic lesions compared to POBA (28.5 vs. 17.2%). In PSM analysis (128 matched pairs), the primary efficacy endpoint was freedom from clinically-driven target lesion revascularization (CD TLR), which occurred in 70.1% in the PCB and 73.1% in the POBA group at 1 year (p=.85; McNemar Test). Survival analysis suggested lower rates of major amputations in the PCB group in unadjusted (94.4%±2.1 vs. 89.2%±1.9 in the POBA group) and PSM analyses (97.2%±1.6 vs. 89.3%±3.5) through 2 years, while no differences were seen for CD TRL and all-cause mortality between the groups. CONCLUSION: In this all-comer analysis, PCB was found to be safe for BTK interventions with a signal towards lower amputation rates but no benefit was seen for repeat revascularization
Summary of radiation research society online 67th annual meeting, symposium on "Radiation and circulatory effects".
No full textPURPOSE: This article summarizes a number of presentations from a session on "Radiation and Circulatory Effects" held during the Radiation Research Society Online 67th Annual Meeting, October 3-6 2021. MATERIALS AND METHODS: Different epidemiological cohorts were analyzed with various statistical means common in epidemiology. The cohorts included the one from the U.S. Million Person Study and the Canadian Fluoroscopy Cohort Study. In addition, one of the contributions in our article relies on results from analyses of the Japanese atomic bomb survivors, Russian emergency and recovery workers and cohorts of nuclear workers. The Canadian Fluoroscopy Cohort Study data were analyzed with a larger series of linear and nonlinear dose-response models in addition to the linear no-threshold (LNT) model. RESULTS AND CONCLUSIONS: The talks in this symposium showed that low/moderate acute doses at low/moderate dose rates can be associated with an increased risk of CVD, although some of the epidemiological results for occupational cohorts are equivocal. The usually only limited availability of information on well-known risk factors for circulatory disease (e.g. smoking, obesity, hypertension, diabetes, physical activity) is an important limiting factor that may bias any observed association between radiation exposure and detrimental health outcome, especially at low doses. Additional follow-up and careful dosimetric and outcome assessment are necessary and more epidemiological and experimental research is required. Obtaining reliable information on other risk factors is especially important
Human genetic defects in SRP19 and SRPRA cause severe congenital neutropenia with distinctive proteome changes.
No full textThe mechanisms of coordinated changes in proteome composition and their relevance for the differentiation of neutrophil granulocytes are not well studied. Here, we discover two novel human genetic defects in SRPRA and SRP19, constituents of the mammalian co-translational targeting machinery and characterize their role in neutrophil granulocyte differentiation. We systematically study the proteome of neutrophil granulocytes from patients with variants in the signal recognition particle (SRP) genes, HAX1, and ELANE and identify global as well as specific proteome aberrations. Using in vitro differentiation of human induced pluripotent stem cells and in vivo zebrafish models, we study the effects of SRP-deficiency on neutrophil granulocyte development. In a heterologous cell-based inducible protein expression system, we validate the effects conferred by SRP dysfunction for selected proteins that we identified in our proteome screen. Thus, SRP-dependent protein processing, intracellular trafficking and homeostasis are critically important for the differentiation of neutrophil granulocytes
A metabolic and mitochondrial angle on aging.
No full textThe increasingly aged human population (mainly in developed countries) represents a significant scientific achievement and privilege associated with medical, social, and economic progress. However, it also poses several challenges to national health and social care systems. The uncoupling of biological evolution with the vast and fast technical progress achieved by humanity has minimized the role of natural selection and rendered aging almost an undesirable physiological event that most people desire to delay as much as possible. All this has been challenging modern gerontology to focus on potential strategies to extend the lifespan, but primarily to mitigate the negative thoughts often associated with aging and aged individuals
