002 高血压及抗高血压药物与Ⅱ型糖尿病

本文采用前瞻性群体研究旨在确定降压药物的应用与继发Ⅱ型糖尿病的危险之间是否存在独立的相关性。 作者对12 550名(年龄45-64岁)无糖尿病的成年人进行全面健康评价(包括药物的使用及血压测定)。高血压判定标准为收缩压≥140mmH-g(1mmHg=0.1333 kPa)或舒张压≥90mmHg。确定高血压患者3 804例,根据使用降压药物的种类分为血管紧张素转化酶抑制剂(ACEI)162例,β阻滞剂543例,钙拮抗剂96例,噻嗪利尿剂458例,其它单一药物137例,多种药物(≥2种)934例,其余1 474例高血压患者未给予任何抗高血压药物治疗。随访3年及6年后,通过测定空腹血糖浓度[糖尿病判定标准为：空腹血糖≥126m/dl(≥7.0mmol/L)餐后血糖≥200m/dl(≥11.1mmol/L)]评价糖尿病新病例的发生率。     

Striatal creatine and glutamate/glutamine in attention-deficit/hyperactivity disorder

OBJECTIVE: The glutamatergic prefrontal-striatal pathway has been implicated previously in the neurobiology of attention-deficit/hyperactivity disorder (ADHD). We used short echo proton magnetic resonance spectroscopy (1H-MRS) to examine glutamate in the prefrontal cortex, left striatum, and, as a control area, the occipital lobe. METHOD: Thirteen treatment-na?ve ADHD children and 10 healthy comparison subjects participated. All were males between the ages of 6 to 11 years of age. Twelve ADHD subjects were scanned after 8 weeks of treatment. RESULTS: Striatal glutamate, glutamate/glutamine (Glx) and creatine concentrations were greater in the ADHD subjects at baseline as compared to controls. Only striatal creatine, not glutamate or Glx, was reduced after stimulant treatment in the ADHD patients. No significant differences between groups were noted in the remainder of the striatal metabolites or any of the occipital lobe or prefrontal cortex metabolites. CONCLUSIONS: These findings provide initial evidence of a striatal creatine/glutamatergic dysregulation in ADHD.     

Association studies of BMI and type 2 diabetes in the neuropeptide Y pathway: a possible role for NPY2R as a candidate gene for type 2 diabetes in men

The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity and its complications, including type 2 diabetes. We genotyped a set of 71 single nucleotide polymorphisms (SNPs) that capture the most common variation in NPY, PPY, PYY, NPY1R, NPY2R, and NPY5R in 2,800 individuals of recent European ancestry drawn from the near extremes of BMI distribution. Five SNPs located upstream of NPY2R were nominally associated with BMI in men (P values = 0.001-0.009, odds ratios [ORs] 1.27-1.34). No association with BMI was observed in women, and no consistent associations were observed for other genes in this pathway. We attempted to replicate the association with BMI in 2,500 men and tested these SNPs for association with type 2 diabetes in 8,000 samples. We observed association with BMI in men in only one replication sample and saw no association in the combined replication samples (P = 0.154, OR = 1.09). Finally, a 9% haplotype was associated with type 2 diabetes in men (P = 1.73 x 10(-4), OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men.     

Relation of the "hypertriglyceridemic waist" phenotype to earlier manifestations of coronary artery disease in patients with glucose intolerance and type 2 diabetes mellitus

This study tested the hypothesis that the "hypertriglyceridemic waist" phenotype (waist girth >90 cm [35.4 inches] in men and >85 cm [33.5 inches] in women, along with a plasma triglyceride concentration of >or=2.0 mmol/L [177 mg/dl]) as a covariate of metabolic syndrome features (hyperinsulinemia, hyperapolipoprotein B, and small low-density lipoprotein particles), is predictive of premature coronary artery disease (CAD) among patients with glucose intolerance or type 2 diabetes. Glucose intolerance and type 2 diabetes were assessed after an oral glucose tolerance test among 1,190 men and women using the American Diabetes Association criteria. Glycemic control was evaluated using hemoglobin A1c levels. CAD was considered present on the basis of a clinical history of retrosternal pains on exertion, electrophysiologically and clinically documented myocardial infarction, or angiographic evidence of coronary lesions. More than 53% of men (n = 103) with a waist circumference >or=90 cm (35.4 inches) and nearly 80% of women (n = 122) with a waist circumference >or=85 cm (33.5 in.) with triglyceride levels >or=2 mmol/L (177 mg/dl) were diagnosed with glucose intolerance or type 2 diabetes. Survival models revealed that those with glucose intolerance or type 2 diabetes with the "hypertriglyceridemic waist" phenotype experienced their first CAD symptoms 5 years earlier than those without this phenotype. This elevated and earlier risk of CAD was statistically significant (hazard ratio 2.0, 95% confidence interval 1.2 to 3.7, p = 0.02). In conclusion, the "hypertriglyceridemic waist" phenotype, an inexpensive and simple tool identifying subjects with metabolic syndrome features, is a significant marker of CAD manifestations occurring at an earlier age in those with glucose intolerance or type 2 diabetes.     

Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses

Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population-based case-control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one-carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73-0.96) and 0.85 (0.62-1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p-trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta-analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk.     

Temporomandibular Disorder Treatment Outcomes: Second Report of a Large-Scale Prospective Clinical Study

Longitudinal studies of outcomes for temporomandibular disorder (TMD) treatment are rarely done and even when conducted often suffer methodological weaknesses. These may include the lack of valid outcome measures for symptom changes. This second report of a long-term multi-site study of 2104 treated, 250 untreated, and 44 long-term treated TMD patients is part of a continuing effort to study TMD treatment efficacy in a very large patient population. A validated symptom measurement system, the TMJ Scale, assured a valid and uniform assessment of treatment outcomes across a large number of practices. Data indicate that untreated TMD patients do not improve spontaneously over time and that patients treated with a variety of active modalities achieve clinically and statistically significant levels of improvement with no evidence of symptom relapse after treatment completion. The use of anterior repositioning appliance therapy produced better results than flat plane splint therapy.     

Immediate Post-Concussion and Cognitive Testing (ImPACT): a systematic review of the prevalence and assessment of invalid performance

Objective: Computerized neuropsychological assessment of concussion has rapidly expanded and Immediate Post-Concussion and Cognitive Testing (ImPACT) is among the most commonly used measures in this domain. ImPACT was primarily developed for use with athletic populations but continues to expand beyond athletics to settings such as the workplace and schools where motivational dispositions may vary. The purpose of the present study was to conduct a systematic review of existing research investigating the prevalence of invalid baseline results and the effectiveness of ImPACT’s embedded invalidity indicators in detecting suspect effort.Method: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in order to systematically structure a search across four databases and analysis of studies that presented data related to the prevalence of invalid performance and/or the effectiveness of ImPACT’s embedded invalidity indicators.Results: A total of 17 studies included prevalence rates of invalid performances or examined the effectiveness of ImPACT’s invalidity indicators. Of the 17 studies, 12 included prevalence rates of invalid baseline results; and across this group of studies (after removing an outlier), the weighted prevalence rate of invalid baseline results was 6%. Four of the 17 studies examined the effectiveness of ImPACT’s embedded invalidity indicators. ImPACT’s embedded invalidity indicators correctly identified suboptimal effort in approximately 80% of individuals instructed to perform poorly and avoid detection (‘coached’) or instructed to perform poorly (‘naïve’).Conclusions: These findings raise a number of issues pertaining to the use of ImPACT. Invalid performance incidence may increase with large group versus individual administration, use in nonclinical settings, and among those with Attention Deficit-Hyperactivity Disorder or learning disability. Additionally, the older desktop version of ImPACT appears to be associated with a higher rate of invalid performances than the online version. Although ImPACT’s embedded invalidity indicators detect invalid performance at a rate of 6% on average, known group validity studies suggest that these measures miss invalid performance approximately 20% of the time when individuals purposefully underperform.