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1.
Environ Epidemiol ; 4(4): e0106, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33154986

RESUMO

Background: Behavioral effects of prenatal exposure to mixtures of essential and toxic metals are incompletely understood. Methods: We investigated neurodevelopmental effects of prenatal metal exposures in the New Hampshire Birth Cohort Study, a prospective birth cohort. We measured metals (As, Cu, Mn, Pb, Se, Zn) in maternal prenatal and postnatal toenails and infant toenails, reflecting exposures during periconception and early pregnancy, mid pregnancy, and late pregnancy and early neonatal life, respectively. Mothers completed the Social Responsiveness Scale, 2nd ed. (SRS-2) and the Behavior Assessment System for Children, 2nd ed. (BASC-2) to assess their child's neurobehavior at 3 years. We used mean field variational Bayes for lagged kernel machine regression to investigate associations of toenail metal concentrations with SRS-2 Total Scores and BASC-2 composite scores (SRS-2: n = 371; BASC-2: n = 318). Results: Infant toenail Mn was associated with poorer performance on multiple BASC-2 composite scores. Maternal postnatal toenail As was associated with worse scores on the BASC-2 Internalizing Problems and Behavioral Symptoms Index. Associations with Mn were generally stronger in males, and associations with As were generally stronger in females. Other metals, including Pb, were weakly or inconsistently associated with BASC-2 outcomes, and there were no strong associations of individual metals and SRS-2 Total Scores. We observed suggestive evidence of interaction between As and Se for SRS-2 Total Scores and BASC-2 Adaptive Skills, though overall evidence of interactions between metals was weak. Conclusion: Our results support the hypothesis that exposure to Mn and As in mid to late pregnancy may be neurodevelopmentally harmful.

2.
BMC Med Genomics ; 13(1): 162, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126877

RESUMO

BACKGROUND: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset. METHODS: To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data. RESULTS: Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR 1.24, P = 3.15 × 10-15), as the top marker to predict age of lung cancer onset. CONCLUSIONS: From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.

3.
BioData Min ; 13: 16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042226

RESUMO

Background: Throughout their lifespans, humans continually interact with the microbial world, including those organisms which live in and on the human body. Research in this domain has revealed the extensive links between the human-associated microbiota and health. In particular, the microbiota of the human gut plays essential roles in digestion, nutrient metabolism, immune maturation and homeostasis, neurological signaling, and endocrine regulation. Microbial interaction networks are frequently estimated from data and are an indispensable tool for representing and understanding the conditional correlation between the microbes. In this high-dimensional setting, zero-inflation and unit-sum constraint for relative abundance data pose challenges to the reliable estimation of microbial interaction networks. Methods and Results: To identify the microbial interaction network, the zero-inflated latent Ising (ZILI) model is proposed which assumes the distribution of relative abundance relies only on finite latent states and provides a novel way to solve issues induced by the unit-sum and zero-inflation constrains. A two-step algorithm is proposed for the model selection of ZILI. ZILI is evaluated through simulated data and subsequently applied to an infant gut microbiota dataset from New Hampshire Birth Cohort Study. The results are compared with results from Gaussian graphical model (GGM) and dichotomous Ising model (DIS). Providing ZILI is the true data-generating model, the simulation studies show that the two-step algorithm can identify the graphical structure effectively and is robust to a range of parameter settings. For the infant gut microbiota dataset, the final estimated networks from GGM and ZILI turn out to have significant overlap in which the ZILI tends to select the sparser network than those from GGM. From the shared subnetwork, a hub taxon Lachnospiraceae is identified whose involvement in human disease development has been discovered recently in literature. Conclusions: Constrains induced by relative abundance of microbiota such as zero inflation and unit sum render the conditional correlation analysis unreliable for conventional methods such as GGM. The proposed optimal categoricalization based ZILI model provides an alternative yet elegant way to deal with these difficulties. The results from ZILI have reasonable biological interpretation. This model can also be used to study the microbial interaction in other body parts.

4.
Muscle Nerve ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33006184

RESUMO

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. Head trauma was associated with increased ALS risk (adjusted odds ratio [OR] 1.60 95% confidence interval [CI] 1.04-2.45), with significantly greater effects for injuries occurring 10 or more years prior to symptom onset (P = .037). ALS risk was increased for those reporting severe electrical burns (adjusted OR 2.86, 95% CI 1.37-6.03), with odds ratios highest for burns after age 30 (OR 3.14), and for burns 10 or more years prior to symptom onset (OR 3.09). Hobbies involving lead were the most strongly associated with ALS risk (adjusted OR 2.92, 95% CI 1.45-5.91). Exposures to lead 20 or more years prior to diagnosis had larger effect sizes compared to those occurring more recently. Holding a job in mechanics, painting, or construction was associated with ALS. The identification of these specific environmental factors associated with ALS highlight the need for future prospective and laboratory studies to assess causality, biological mechanisms, and find prevention or treatment opportunities.

5.
J Clin Psychiatry ; 81(6)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049805

RESUMO

OBJECTIVE: Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD). One prior study using US Department of Veterans Affairs (VA) medical records data to compare these agents found no differences in symptom reduction in clinical practice. The current study addresses several weaknesses in that study, including limited standardization of treatment duration, inability to account for prior treatment receipt, use of an outdated symptomatic assessment for PTSD, and lack of functional outcome. METHODS: A total of 834 VA outpatients were identified with DSM-5 clinical diagnoses of PTSD between October 2016 and March 2018 who initiated one of the medications and met prespecified criteria for treatment duration and dose, combined with baseline and endpoint DSM-5 PTSD Checklist (PCL-5) measurements. Twelve-week acute-phase changes in PCL-5 score and remission of PTSD symptoms were compared among patients receiving the different medications, as was use of acute psychiatric services in the subsequent 6-month continuation phase. RESULTS: In the acute phase, patients improved by a mean of 6.8-10.1 points on the PCL-5 and 0.0%-10.9% achieved remission of PTSD symptoms. Those taking venlafaxine were significantly more likely to achieve remission (P = .008 vs fluoxetine and P < .0001 vs paroxetine, sertraline, and topiramate). In the continuation phase, there were no differences in acute psychiatric care use between medications. Those who continued their medication were less likely to use acute psychiatric services (HR = 0.55; P = .03). CONCLUSIONS: There may be an advantage to venlafaxine over other agents in achieving acute-phase remission for DSM-5 PTSD in routine clinical practice, but this finding requires further study. Regardless of the agent chosen, medication cessation during the continuation phase is associated with a higher risk of acute psychiatric care use.

6.
Sci Signal ; 13(648)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900880

RESUMO

The reciprocal regulation of phosphoprotein phosphatases (PPPs) by protein kinases is essential to cell cycle progression and control, particularly during mitosis for which the role of kinases has been extensively studied. PPPs perform much of the serine/threonine dephosphorylation in eukaryotic cells and achieve substrate selectivity and specificity through the interaction of distinct regulatory subunits with conserved catalytic subunits in holoenzyme complexes. Using a mass spectrometry-based chemical proteomics approach to enrich, identify, and quantify endogenous PPP holoenzyme complexes combined with kinase profiling, we investigated the phosphorylation-dependent regulation of PPP holoenzymes in mitotic cells. We found that cyclin-dependent kinase 1 (CDK1) phosphorylated a threonine residue on the catalytic subunit of the phosphatase PP2A, which disrupted its holoenzyme formation with the regulatory subunit B55. The consequent decrease in the dephosphorylation of PP2A-B55 substrates promoted mitotic entry. This direct phosphorylation by CDK1 was in addition to a previously reported indirect mechanism, thus adding a layer to the interaction between CDK1 and PP2A in regulating mitotic entry.

7.
J Behav Med ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915350

RESUMO

There is an elevated risk of suicide among people living in rural areas, and the rural-urban disparity in death by suicide is growing in the general United States population. The department of Veterans Affairs (VA) implemented programs targeting rural health in 2007 and suicide prevention in 2008. Rural-urban differences in suicide rates among VA users have not been examined since 2010. We sought to understand whether the rural-urban disparity in suicide risk among VA users decreased during a time of contemporaneous VA efforts to improve access to mental health care for rural Veterans and to improve the effectiveness of mental health services at preventing suicide. We performed a retrospective cohort study examining differences in the raw and adjusted annual suicide rate among rural and urban VA users between 2003 and 2017. All VHA users 2003-2017. Descriptive statistics are presented for all VHA users in 2017. This includes 6,120,355 unique VA users, 32.0% (n = 1,955,935) of whom lived at a rural address. Raw rates of death by suicide were higher in rural VA users than urban VA users overall (33.3 vs. 29.1 deaths per 100,000 population) and across years, but the age, sex, and race-adjusted rates converged in 2005. White VA users had over triple the rate of death by suicide as black VA users, and lived disproportionally in rural areas. The rural-urban suicide disparity among VA users persists. However, the disparity appears to be driven by differences in the racial composition of rural and urban patients, which were not accounted for in prior studies.

8.
Breast Cancer Res Treat ; 183(2): 403-410, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32656723

RESUMO

PURPOSE: Little is known about the three-dimensional shape of breast cancer. Implicit to approaches that localize the center of the tumor for breast-conserving surgery (BCS) of non-palpable cancers is the assumption that breast cancers are spherical about a central point, which may not be accurate. METHODS: Pre-operative supine breast MRI images were obtained of 83 breast cancer patients undergoing partial mastectomy using supine MRI-guided resection techniques. Three-dimensional (3D) tumor models were derived after radiologists outlined tumor edges on successive MRI slices. Ideal resection volumes were determined by adding 1 cm in every dimension to the actual tumor volume. Geometrically defined parameters were used to define tumor shapes and associations between clinical variables and shapes were examined. RESULTS: Seventy-five patients had invasive cancer. Breast cancers were categorized into four tumor shapes: 34% of tumors were discoidal, 29% segmental, 19% spherical, and 18% irregular. If hypothetical spherical excisions were performed, non-spherical cases would excise 143% more tissue than the ideal resection volume. When the 3D shape of each tumor was provided to the surgeon during MR-guided BCS, the percentage of tissue overexcised in non-spherical cases was significantly less (143% vs. 66%, p < 0.001). CONCLUSIONS: Information obtained from a supine MRI can be used to generate 3D tumor models and rapidly classify breast tumor shapes. The vast majority of invasive cancers and DCIS are not spherical. Knowledge of tumor shape may allow surgeons to excise breast cancer more precisely.

9.
Front Pharmacol ; 11: 742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528287

RESUMO

Background: The incidence of obesity-associated decline in male fertility has increased over the years. Lycium barbarum polysaccharide (LBP), a natural plant polysaccharide extracted from the Chinese herb L. barbarum has shown promising therapeutic effects in overcoming the same. Aim: This study aimed to investigate the protective effect of LBP on the testes of obese mice. Methods: Following administration of LBP to high-fat diet-induced obese mice for 35 days, serum, sperm, and testis samples were obtained for subsequent experiments. Biochemical analysis and sex hormone content determination were performed to observe changes in glycolipid metabolism and testosterone levels, respectively, in the blood. Hematoxylin and eosin staining were carried out to assess the pathological changes in the testicular tissue. Oxidative stress levels were detected using enzyme-linked immunosorbent assay and expression levels of endoplasmic reticulum stress markers were determined using western blot in the testicular tissue. Results: Our results suggested that LBP reduced glucose levels and insulin resistance, increased testosterone levels and insulin sensitivity, and decreased testicular oxidative stress and pathological damage in obese mice. In addition, LBP down-regulated the expression of p-eIF2α, GRP78, and CHOP in the testicular tissues of obese mice. Conclusion: Our results show that LBP is a potential novel drug for preventing male infertility caused by obesity.

10.
Breast Cancer Res Treat ; 182(3): 665-677, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32562118

RESUMO

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a "liquid biopsy" for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1-3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 ± 11.81% (mean ± SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).

11.
Artigo em Inglês | MEDLINE | ID: mdl-32394096

RESUMO

We sought to develop a quality standard for the prescription of antidepressants for posttraumatic stress disorder (PTSD) that is both consistent with the underlying evidence supporting antidepressants as a treatment for PTSD and associated with the best levels of symptom improvement. We quantified antidepressant initiation during the first year of PTSD treatment in a 10-year national cohort of Department of Veterans Affairs (VA) users, and compared outcomes in a subgroup who completed patient-reported outcome measurement (PROM) as part of routine practice. We added progressively stringent measurement requirements. Prescribing quality for PTSD in the VA was stable over time. Use of PROM was rare in the case of antidepressant treatment, limiting our assessment of outcomes.

12.
Adm Policy Ment Health ; 47(4): 648, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32314128

RESUMO

The original version of this article unfortunately contained a mistake. The co-author name was incorrectly published with the middle initial in the author list.

13.
Psychol Med ; : 1-10, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32063248

RESUMO

BACKGROUND: This study evaluated whether natural language processing (NLP) of psychotherapy note text provides additional accuracy over and above currently used suicide prediction models. METHODS: We used a cohort of Veterans Health Administration (VHA) users diagnosed with post-traumatic stress disorder (PTSD) between 2004-2013. Using a case-control design, cases (those that died by suicide during the year following diagnosis) were matched to controls (those that remained alive). After selecting conditional matches based on having shared mental health providers, we chose controls using a 5:1 nearest-neighbor propensity match based on the VHA's structured Electronic Medical Records (EMR)-based suicide prediction model. For cases, psychotherapist notes were collected from diagnosis until death. For controls, psychotherapist notes were collected from diagnosis until matched case's date of death. After ensuring similar numbers of notes, the final sample included 246 cases and 986 controls. Notes were analyzed using Sentiment Analysis and Cognition Engine, a Python-based NLP package. The output was evaluated using machine-learning algorithms. The area under the curve (AUC) was calculated to determine models' predictive accuracy. RESULTS: NLP derived variables offered small but significant predictive improvement (AUC = 0.58) for patients that had longer treatment duration. A small sample size limited predictive accuracy. CONCLUSIONS: Study identifies a novel method for measuring suicide risk over time and potentially categorizing patient subgroups with distinct risk sensitivities. Findings suggest leveraging NLP derived variables from psychotherapy notes offers an additional predictive value over and above the VHA's state-of-the-art structured EMR-based suicide prediction model. Replication with a larger non-PTSD specific sample is required.

14.
Adm Policy Ment Health ; 47(3): 451-467, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31853686

RESUMO

We sought to develop a quality standard for the delivery of psychotherapy for posttraumatic stress disorder (PTSD) that is both consistent with the underlying evidence supporting psychotherapy as a treatment for PTSD and associated with the best levels of symptom improvement. We quantified psychotherapy receipt during the initial year of PTSD treatment in a 10-year national cohort of Department of Veterans Affairs (VA) users who completed patient-reported outcome measurement as part of routine practice. We added progressively stringent measurement requirements. The most stringent requirement was associated with superior outcomes. Quality of psychotherapy for PTSD in the VA improved over time.

15.
Environ Epidemiol ; 3(5)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31844832

RESUMO

Background: In utero exposure to individual metals may impact fetal growth, though little is known about the effects of exposure to metal mixtures. Therefore, we investigated joint effects of in utero exposure to a mixture of As (arsenic), Mn (manganese), and Pb (lead) on newborn outcomes in a United States population. Methods: Concentrations of As, Mn, and Pb were determined in maternal postpartum toenail samples, a biomarker of in utero exposure, from 989 maternal-infant pairs (492 females and 497 males). Newborns' anthropometric characteristics, including head circumference, length, and weight, were obtained from medical records. The joint effects of the three metals were modeled using Bayesian kernel machine regression and linear regression. Both sex-combined and sex-stratified statistical analyses were performed. Results: We observed an inverted-U-shape association between maternal toenail Mn concentrations and newborn head circumference, particularly among female infants. Concentrations of Pb were related to reduced head circumference, weight, and length, especially among females at lower concentrations of the other metals. Overall, toenail As concentrations were related to reduced head circumference, especially among males, and an increase in birth length and weight among females. We found little evidence of As interactions with other metals within the mixture. Conclusions: Our findings suggest that in utero metal mixture exposures may influence birth outcomes, and that such relations may differ by infant sex.

16.
Comput Biol Med ; 114: 103417, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31521894

RESUMO

Examining the effects of exogenous exposures on complex metabolic processes poses the unique challenge of identifying interactions among a large number of metabolites. Recent progress in the quantification of the metabolome through mass spectrometry (MS) and nuclear magnetic resonance (NMR) has given rise to high-dimensional biomedical data of specific metabolites that can be leveraged to study their effects in humans. These metabolic interactions can be evaluated using probabilistic graphical models (PGMs), which define conditional dependence and independence between components within and between heterogeneous biomedical datasets. This method allows for the detection and recovery of valuable but latent information that cannot be easily detected by other currently existing methods. Here, we develop a PGM method, referred to as an "Integrated Gaussian Graphical Model (IGGM)", to incorporate exposure concentrations of seven trace elements-arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd), zinc (Zn), selenium (Se) and copper (Cu-into metabolic networks. We first conducted a simulation study demonstrating that the integration of trace elements into metabolomics data can improve the accuracy of detecting latent interactions of metabolites impacted by exposure in the network. We tested parameters such as sample size and the number of neighboring metabolites of a chosen trace element for their impact on the accuracy of detecting metabolite interactions. We then applied this method to measurements of cord blood plasma metabolites and placental trace elements collected from newborns in the New Hampshire Birth Cohort Study (NHBCS). We found that our approach can identify latent interactions among metabolites that are related to trace element concentrations. Application to similarly structured data may contribute to our understanding of the complex interplay between exposure-related metabolic interactions that are important for human health.


Assuntos
Metaboloma/fisiologia , Metabolômica/métodos , Modelos Estatísticos , Simulação por Computador , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Redes e Vias Metabólicas , Metais Pesados/análise , Metais Pesados/toxicidade , Distribuição Normal , Placenta/química , Gravidez , Oligoelementos/análise
17.
J Eval Clin Pract ; 25(4): 689-699, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31115137

RESUMO

RATIONALE: Identifying predictors of improvement amongst patients receiving routine treatment for post-traumatic stress disorder (PTSD) could provide information about factors that influence the clinical effectiveness of guideline-concordant care. This study builds on prior work by accounting for delivery of specific evidence-based treatments (EBTs) for PTSD while identifying potential predictors of clinical improvement using patient-reported outcomes measurement. METHOD: Our sample consisted of 2 643 US Department of Veterans Affairs (VA) outpatients who initiated treatment for PTSD between 2008 and 2013 and received at least four PTSD checklist (PCL) measurements over 12 weeks. We obtained PCL data as well as demographic, diagnostic, and health services use information from the VA corporate data warehouse. We used latent trajectory analysis to identify classes of patients based on PCL scores, then determined demographic, diagnostic, and treatment predictors of membership in each class. RESULTS: Patients who met our PCL-based inclusion criteria were far more likely than those who did not receive EBTs. We identified two latent trajectories of PTSD symptoms. Patients in the substantial improvement group (25.9%) had a mean decrease in PCL score of 16.24, whereas patients in the modest improvement group improved by a mean of 8.09 points. However, there were few differences between the groups, and our model to predict group membership was only slightly better than chance (area under the curve [AUC] = 0.55). Of the 64 covariates we tested, the only robust individual predictor of improvement was gender, with men having lower odds of being in the substantial improvement group compared with women (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.58-0.96). CONCLUSION: VA patients with PTSD can realize significant improvement in routine clinical practice. Although available medical records-based variables were generally insufficient to predict improvement trajectory, this study did indicate that men have lower odds of substantial improvement than women.


Assuntos
Medicina Baseada em Evidências , Serviços de Saúde Mental/normas , Administração dos Cuidados ao Paciente , Guias de Prática Clínica como Assunto , Transtornos de Estresse Pós-Traumáticos , Adulto , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/normas , Preferência do Paciente , Medidas de Resultados Relatados pelo Paciente , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/terapia , Resultado do Tratamento , Estados Unidos , Saúde dos Veteranos/estatística & dados numéricos
18.
Front Physiol ; 10: 432, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068831

RESUMO

miRNAs are small non-coding RNAs modulating gene expression, and variants in miRNA genes are involved in the pathogenesis of ischemic stroke (IS). However, the effect of miR-34a polymorphisms on IS susceptibility has rarely been reported. In the present study, we investigated the association between rs12128240, rs2666433, and rs6577555 of the miR-34a gene and IS susceptibility. Snapshot assay was used to detect miR-34a polymorphisms in 548 IS patients and 560 controls. Relative expression of miR-34a was measured by quantitative real-time PCR. We found that rs2666433 was associated with a significantly increased risk of IS (AA vs. GG: OR = 1.61, 95% CI = 1.05-2.52, P = 0.031; AA vs. GG+GA: OR = 1.58, 95% CI = 1.05-2.45, P = 0.026). For the IS subtypes, rs2666433 was associated with large artery atherosclerosis (AA vs. GG: OR = 2.09, 95% CI = 1.16-3.51, P = 0.007; AA vs. GG+GA: OR = 2.02, 95% CI = 1.15-3.33, P = 0.007; A vs. G: OR = 1.36, 95% CI = 1.07-1.81, P = 0.021). Additionally, the level of miR-34a was significantly up-regulated in IS patients compared to the controls (P < 0.001), and patients with rs2666433 AA genotype had a higher level of miR-34a than those with GG+GA genotypes (P < 0.001). Furthermore, increased level of homocysteine was observed in IS patients compared to the controls (P < 0.001), especially in patients carrying the rs2666433AA genotype compared to those carrying the rs2666433 GG+GA genotypes (P < 0.001). However, no significant association between rs12128240 or rs6577555 and IS was found. Collectively, our study found the association between miR-34a polymorphisms and the risk of IS among the Chinese population. The results may provide an explanation for etiology of IS and a potential biomarker or therapeutic target for IS. HIGHLIGHTS-MiR-34a rs2666433 polymorphism was associated with an increased risk of ischemic stroke.-The level of miR-34a was significantly up-regulated in ischemic stroke patients compared with controls, and patients with rs2666433 AA genotype had a higher level miR-34a than those with GG+GA genotypes.-Furthermore, increased level of homocysteine was showed in IS patients compared to controls, and in patients carrying the rs2666433AA compared to those carrying the rs2666433 GG+GA.

19.
AIDS ; 33(9): 1449-1454, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30932961

RESUMO

OBJECTIVE: Evidence suggests damage to brain auditory pathways, rather than inner ear damage, underlies the hearing difficulties HIV+ individuals report. But, antiretroviral therapy (ART) may affect the hearing system and also lead to hearing complaints. DESIGN: Longitudinal study of HIV+ and HIV- individuals in Dar es Salaam Tanzania. A subset of this cohort started ART while in the study allowing the effects of ART to be studied directly. METHODS: The ability to hear quiet sounds (pure-tone audiometry), cochlear outer hair cell function [distortion-product otoacoustic emissions (DPOAEs)], and gaps-in-noise detection thresholds (a central auditory processing test) were assessed at each visit. Visits were scheduled for 6-month intervals, but the number and spacing of visits varied. In the group that started ART while in the study, 107 HIV+ individuals had audiometric thresholds, 98 had DPOAEs, and 98 had gap measurements suitable for analysis. Data were analyzed using a linear mixed model with time and starting ART as fixed effects and individual participant repeated measures as random effects. RESULTS: Starting ART did not affect audiometric or gap detection thresholds. The slope of the DPOAE amplitude vs. time relationship was more negative after starting ART but did not differ from the HIV- group. Gap thresholds were higher in the HIV+ group. CONCLUSION: ART did not affect audiometric thresholds significantly suggesting common ART drugs are not major ototoxins. The gap detection results from the study show effects on central auditory processing in HIV+ individuals, supporting the origin of HIV-related hearing complaints in the central auditory system.


Assuntos
Encefalopatias/complicações , Infecções por HIV/complicações , Perda Auditiva/etiologia , Perda Auditiva/fisiopatologia , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Criança , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Tanzânia , Adulto Jovem
20.
Sensors (Basel) ; 19(3)2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717339

RESUMO

In driver training, the correct observation of the trainees' operation is the key to ensure the training quality. The operation of the vehicle can be expressed by the vehicle state changes. This paper proposes a driver training model based on a multiple-embedded-sensor net. Six vehicle state parameters are identified as the critical features of the reverse parking machine learning model and represented quantitatively. A multiple-embedded-sensor net-based system mounted on a real vehicle is developed to collect the actual data of the six critical features. The data collected at the same time are bound together and encapsulated into a vector and sequenced by time with a label given by the multiple-embedded-sensor net. All vectors are evaluated by subjective assessment conclusions from experienced driving instructors and the positive ones are used as the training data of the model. The trained model can remind the driver of the next correct operation during training, and can also analyze the improvements after the training. The model has achieved good results in practical application. The experiments prove the validity and reliability of the proposed driver training model.

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