The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder

Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) to explore its impact in adults with autism spectrum disorder (ASD). Among 25 adults with ASD, 19 (mean age: 20.8 years) completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation) in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT) and the Wisconsin Card Sorting Test (WCST). Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Social Responsiveness Scale (SRS). In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71) while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations

A genome-wide scan using tree-based association analysis for candidate loci related to fasting plasma glucose levels

BACKGROUND: In the analysis of complex traits such as fasting plasma glucose levels, researchers often adjust the trait for some important covariates before assessing gene susceptibility, and may at times encounter confounding among the covariates and the susceptible genes. Previously, the tree-based method has been employed to accommodate the heterogeneity in complex traits. In this study, we performed a genome-wide screen on fasting glucose levels in the offspring generation of the Framingham Heart Study provided by the Genetic Analysis Workshop 13. We defined one quantitative trait and converted it to a dichotomous trait based on a predetermined cut-off value, and performed association analyses using regression and classification trees for the two traits, respectively. A marker was interpreted as positive if at least one of its alleles exhibited association in both analyses. Our purpose was to identify candidate genes susceptible to fasting glucose levels in the presence of other covariates. The covariates entered in the analysis including sex, body mass index, and lipids (total plasma cholesterol, high density lipoprotein cholesterol, and triglycerides) of the subjects, and those of their parents. RESULTS: Four out of seven positive regions in chromosomes 1, 2, 6, 11, 16, 18, and 19 from our analyses harbored or were very close to previously reported diabetes related genes or potential candidate genes. CONCLUSION: This screen method that employed tree-based association showed promise for identifying candidate loci in the presence of covariates in genome scans for complex traits

Pilot Scheme of Health Policy in Stroke Adjuvant Acupuncture Therapy for Acute and Subacute Ischemic Stroke in Taiwan

To reduce the health care burden of strokes, the Taiwan Department of Health launched the Pilot Scheme of the Health Policy in Stroke Adjuvant Acupuncture Therapy (HPSAAT) in 2006. This cross-sectional, hospital-based, match-controlled study at Chang Gung Memorial Hospital-Kaohsiung Medical Center during 2006∼2008 retrospectively evaluated the clinical characteristics of acute and subacute ischemic stroke patients who electively joined the HPSAAT. The study also evaluated the safety and clinical benefits of adjuvant acupuncture in treating acute and subacute ischemic stroke patients. Twenty-six HPSAAT participants and 52 age-sex matched random controls were enrolled. The stroke baseline of the HPSAAT participants was more severe than the non-HPSAAT controls. Although the stroke severity closely correlates to mortality and comorbidity, this study noted no significant complications in the HPSAAT participants during the acupuncture treatment course. Adjuvant acupuncture was considered safe at the acute and subacute stages of ischemic stroke. Due to uneven baseline severity, the clinical benefits in reducing neurological deficits and functional recovery were not concluded in this study

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

Impact of impaired glomerular filtration rate and revascularization strategy on one-year cardiovascular events in acute coronary syndrome: data from Taiwan acute coronary syndrome full spectrum registry

BACKGROUND: The optimal revascularization strategy for patients with impaired glomerular filtration rate (IGFR) has not been established in acute coronary syndrome (ACS). We investigated the prognosis and impact of IGFR and invasive strategy on the cardiovascular outcomes in the ACS population. METHODS: In a Taiwan national-wide registry, 3093 ACS patients were enrolled. The invasive strategy was defined as patients with ST-elevation ACS (STE-ACS) undergoing primary angioplasty or fibrinolysis or coronary angiography with intent to revascularization performed within 72 hours of symptom onset in non-ST-elevation ACS (NSTE-ACS). IGFR was defined as an estimated GFR of less than 60 ml/min per 1.73 m(2). Primary endpoint was a composite of death, non-fatal myocardial infarction or stroke at one year. RESULTS: Patients with IGFR (n = 1226) had more comorbidities but received less evidence-based medications during admission than those without IGFR (n = 1867). The primary endpoint-free survival rate is lower in the IGFR patients, in the whole, STE-ACS and NSTE-ACS population (all log-rank tests p < 0.01). Cox regression analysis revealed IGFR subjects had higher primary endpoint after adjusting by age, sex, medication at discharge and traditional risk factors (all p < 0.01). Kaplan–Meier curves showed IGFR patients without invasive strategy had the worst outcome in the STE-ACS and NSTE-ACS population (both p < 0.01). The invasive strategies, either with early angiography only or angioplasty, were associated with reduced primary endpoints among IGFR patients in the NSTE-ACS population (both p ≦ 0.024). CONCLUSIONS: IGFR patients suffering from ACS had poor prognosis and an invasive strategy could improve cardiovascular outcome in the NSTE-ACS population

Predictive factors warrant screening for obstructive sleep apnea in COPD: a Taiwan National Survey

BACKGROUND AND OBJECTIVES: COPD and obstructive sleep apnea (OSA) share similar pathological processes and cardiovascular sequelae. Coexisting OSA in COPD – “overlap syndrome” – has worse prognosis than either condition alone, and appropriate treatment improves survival. Our objectives were to ascertain the frequency at which COPD coexists with the risk of OSA in Taiwan and to compare the risk factors, COPD symptoms, and life quality metrics between COPD subgroups with versus without risk of OSA. METHODS: We conducted a random cross-sectional national telephone survey of adults >40 years old in Taiwan. Participants fulfilling an epidemiological case definition of COPD completed a questionnaire to assess COPD symptoms and OSA risk, comorbidities, and performance of daily activities. Data from COPD cohorts with and without risk of OSA were analyzed and compared. RESULTS: Of 6,600 interviews completed, 404 subjects fit the epidemiological case definition of COPD – an overall prevalence of 6.1% in this national sample. Data on OSA risk were available for 292 of this COPD cohort, of whom 29.5% were at risk of OSA. Compared to those without risk of OSA, those with risk of OSA were significantly more likely to have hypertension or cardiovascular disease and diabetes, had significantly higher body mass index and COPD Assessment Test scores, and reported impaired work performance and leisure activities. CONCLUSION: Among adults in Taiwan who fulfill epidemiologic criteria for COPD, 29.5% have coexisting risk of OSA. Comorbid hypertension or cardiovascular disease and diabetes are common and significantly more prevalent among the COPD population at risk of OSA than those who are not. OSA screening is warranted in patients with COPD with those risk factors that are more prevalent in COPD with risk of OSA than without, to target early interventions to reduce adverse cardiovascular sequelae from overlap syndrome

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms