208 research outputs found

    Exposure to Household Air Pollution from Biomass-Burning Cookstoves and HbA1c and Diabetic Status Among Honduran Women

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    Household air pollution from biomass cookstoves is estimated to be responsible for more than two and a half million premature deaths annually, primarily in low and middle‐income countries where cardiometabolic disorders, such as Type II Diabetes, are increasing. Growing evidence supports a link between ambient air pollution and diabetes, but evidence for household air pollution is limited. This cross‐sectional study of 142 women (72 with traditional stoves and 70 with cleaner‐burning Justa stoves) in rural Honduras evaluated the association of exposure to household air pollution (stove type, 24‐hour average kitchen and personal fine particulate matter [PM2.5] mass and black carbon) with glycated hemoglobin (HbA1c) levels and diabetic status based on HbA1c levels. The prevalence ratio (PR) per interquartile range increase in pollution concentration indicated higher prevalence of prediabetes/diabetes (vs normal HbA1c) for all pollutant measures (eg, PR per 84 ÎŒg/m3 increase in personal PM2.5, 1.49; 95% confidence interval [CI], 1.11‐2.01). Results for HbA1c as a continuous variable were generally in the hypothesized direction. These results provide some evidence linking household air pollution with the prevalence of prediabetes/diabetes, and, if confirmed, suggest that the global public health impact of household air pollution may be broader than currently estimated

    Exposure to household air pollution from biomassĂą burning cookstoves and HbA1c and diabetic status among Honduran women

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    Household air pollution from biomass cookstoves is estimated to be responsible for more than two and a half million premature deaths annually, primarily in low and middleĂą income countries where cardiometabolic disorders, such as Type II Diabetes, are increasing. Growing evidence supports a link between ambient air pollution and diabetes, but evidence for household air pollution is limited. This crossĂą sectional study of 142 women (72 with traditional stoves and 70 with cleanerĂą burning Justa stoves) in rural Honduras evaluated the association of exposure to household air pollution (stove type, 24Ăą hour average kitchen and personal fine particulate matter [PM2.5] mass and black carbon) with glycated hemoglobin (HbA1c) levels and diabetic status based on HbA1c levels. The prevalence ratio (PR) per interquartile range increase in pollution concentration indicated higher prevalence of prediabetes/diabetes (vs normal HbA1c) for all pollutant measures (eg, PR per 84Ă‚Â ĂŽÂŒg/m3 increase in personal PM2.5, 1.49; 95% confidence interval [CI], 1.11Ăą 2.01). Results for HbA1c as a continuous variable were generally in the hypothesized direction. These results provide some evidence linking household air pollution with the prevalence of prediabetes/diabetes, and, if confirmed, suggest that the global public health impact of household air pollution may be broader than currently estimated.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145588/1/ina12484_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145588/2/ina12484.pd

    RTOG/NRG 1115 Quality of Life of Phase III Dose Escalated Radiation Therapy (RT) and Standard Androgen Deprivation Therapy (ADT) with GnRH Agonist vs. Dose Escalated RT and ADT with GnRH Agonist and Orteronel (TAK-700) for Men with High-Risk Prostate

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    Purpose/Objective(s): Quality of life (QOL) was assessed with the hypothesis that QOL and fatigue scores would not differ significantly between the ADT + RT (Arm A) and the experimental group receiving ADT + RT + oreteronel (Arm B). Materials/Methods: In both arms, ADT with GnRH agonist was given for 24 mos, and dose escalated RT started 8-10 wks after initiation of ADT. In Arm B, oreteronel was given BID for 24 mos. QOL was measured with Expanded Prostate Cancer Index Composite (EPIC) and EQ-5D global QOL assessment. EPIC has 4 domains: bowel, urinary, sexual, and hormonal. EQ-5D index score was calculated using health states obtained from 5 dimensions, and a visual analog score (VAS). For EPIC, EQ-5D index and VAS, higher scores indicate better QOL. Fatigue was measured by the 7-item Patient-Reported Outcome Measurement Information System (PROMIS) short form. Total score is standardized into a T-score with mean of 50 and standard deviation of 10 with higher score representing more fatigue. Change scores, calculated as follow-up minus baseline, were compared between arms. Longitudinal analysis using repeated measures mixed effects models was conducted (prior to ADT [baseline], one wk prior to starting RT, last wk of RT, and 1 and 2.5 yrs after initiation of therapy). Results: Of 231 eligible patients, 196 consented to QOL, 102 on Arm A and 94 on Arm B. Compliance prior to start of RT and end of RT was 83%. At 1 and 2.5 yrs, 80% and 62% of pts, respectively, completed the EPIC. There were no differences between any EPIC domain between arms from the start of RT through the end of follow-up. Men on oreteronel had a significantly greater decline in bowel score prior to starting RT then control patients (-6.12, 95% confidence interval [CI]: -9.24, -3.01 vs. -1.93, 95% CI: -4.48, 0.63, respectively, p=0.038). Arm B patients also had a statistically significant and clinically meaningful worse change in urinary score vs control from baseline to pre-RT (-2.33, 95% CI: -5.02, 0.36 vs. 1.38, 95% CI: -1.07, 3.83, respectively, p=0.043). No other timepoints were significant. The only sig. between arm difference in EPIC sexual and hormonal scores was also at pre-RT in favor of Arm A over Arm B; p=0.024 and p=0.0024 respectively). Fatigue was also greater in the oreteronel patients prior to starting RT (3.81, 95% CI: 1.88, 5.74 vs. 1.18, 95% CI: -0.23, 2.60, p=0.028). Conclusion: The addition of oreteronel to RT and ADT resulted in greater declines in QOL prior to the start of RT but did not result in significant differences at any other time points. Although oreteronel development has been halted, the QOL results are encouraging for other drugs in this class that remain under investigation. In ongoing prospective trials, QOL impacts should be measured in conjunction with changes in clinical outcome and survival. This project was supported by grants UG1CA189867, U10CA180868, U10CA180822 from the National Cancer Institute and Takeda Pharmaceutical

    Impact of gaming disorder on first episode psychosis patients' evolution: Protocol for a multicentered prospective study.

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    The objective of this study is to underline the impact of Gaming Disorder on the clinical evolution of patients with First Episode Psychosis. The specific aims of the study are to determine the prevalence of gaming disorder among those patients and assess the consequences of gaming on their clinical trajectory. This is a prospective multicenter cohort study that will enrol 800 patients diagnosed with a first episode psychosis, with a follow-up period of up to 3 years. Using a systematic screening procedure for gaming disorder, the clinical staff will assess patients gaming habits at admission and every 6 months thereafter. Information from patients' medical records will also be extracted using the same timeframe. The patients' characteristics at admission and during follow-up will be presented in the form of descriptive statistics and compared between different subgroups of patients using uni- and multivariate logistic regression models. Repeated measures ANCOVA will also be performed to analyse the impact of gaming disorders on patients' clinical path as assessed by the Positive and Negative Syndrome Scale and the Clinical Global Impression scale, considering covariates such as psychiatric diagnosis, pharmacological treatment, age, sex/gender, and duration of untreated psychosis. These findings will guide the development of prevention, detection, and treatment strategies for the comorbidity between gaming disorder and first episode psychosis, ultimately improving the patients' recovery

    Assessing exposure in epidemiologic studies to disinfection by-products in drinking water: report from an international workshop.

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    The inability to accurately assess exposure has been one of the major shortcomings of epidemiologic studies of disinfection by-products (DBPs) in drinking water. A number of contributing factors include a) limited information on the identity, occurrence, toxicity, and pharmacokinetics of the many DBPs that can be formed from chlorine, chloramine, ozone, and chlorine dioxide disinfection; b) the complex chemical interrelationships between DBPs and other parameters within a municipal water distribution system; and c) difficulties obtaining accurate and reliable information on personal activity and water consumption patterns. In May 2000, an international workshop was held to bring together various disciplines to develop better approaches for measuring DBP exposure for epidemiologic studies. The workshop reached consensus about the clear need to involve relevant disciplines (e.g., chemists, engineers, toxicologists, biostatisticians and epidemiologists) as partners in developing epidemiologic studies of DBPs in drinking water. The workshop concluded that greater collaboration of epidemiologists with water utilities and regulators should be encouraged in order to make regulatory monitoring data more useful for epidemiologic studies. Similarly, exposure classification categories in epidemiologic studies should be chosen to make results useful for regulatory or policy decision making

    Kinesin expands and stabilizes the GDP-microtubule lattice

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    Kinesin-1 is a nanoscale molecular motor that walks towards the fast-growing (plus) ends of microtubules, hauling molecular cargo to specific reaction sites in cells. Kinesin-driven transport is central to the self-organization of eukaryotic cells and shows great promise as a tool for nano-engineering1. Recent work hints that kinesin may also play a role in modulating the stability of its microtubule track, both in vitro2,3 and in vivo4, but the results are conflicting5,6,7 and the mechanisms are unclear. Here, we report a new dimension to the kinesin–microtubule interaction, whereby strong-binding state (adenosine triphosphate (ATP)-bound and apo) kinesin-1 motor domains inhibit the shrinkage of guanosine diphosphate (GDP) microtubules by up to two orders of magnitude and expand their lattice spacing by ~1.6%. Our data reveal an unexpected mechanism by which the mechanochemical cycles of kinesin and tubulin interlock, and so allow motile kinesins to influence the structure, stability and mechanics of their microtubule track

    Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia

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    Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel Îł-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis
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