204 research outputs found

    Elegance persists in the purification of K+ channels

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    Alcohol as a Risk Factor for Type 2 Diabetes: A systematic review and meta-analysis

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    OBJECTIVE - To clarify the dose-response relationship between alcohol consumption and type 2 diabetes.RESEARCH DESIGN AND METHODS - A systematic computer-assisted and hand search was conducted to identify relevant articles with longitudinal design and quantitative measurement of alcohol consumption. Adjustment was made for the sick-quitter effect. We used fractional polynomials in a meta-regression to determine the dose-response relationships by sex and end point using lifetime abstainers as the reference group.RESULTS - The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76-1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71-1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52-0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83-1.26]).CONCLUSIONS - Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women

    Using ELISPOT to Expose False Positive Skin Test Conversion in Tuberculosis Contacts

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    BACKGROUND: Repeat tuberculin skin tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. We evaluated whether an ELISPOT test could identify tuberculosis (TB) contacts with boosting of immunity to non-tuberculous mycobacterial exposure. METHODOLOGY/PRINCIPAL FINDINGS: We conducted tuberculin and ELISPOT tests in 1665 TB contacts: 799 were tuberculin test negative and were offered a repeat test after three months. Those with tuberculin test conversion had an ELISPOT, chest X-ray and sputum analysis if appropriate. We compared converters with non-converters, assessed the probability of each of four combinations of ELISPOT results over the two time points and estimated boosting with adjustment for ELISPOT sensitivity and specificity. 704 (72%) contacts had a repeat tuberculin test; 176 (25%) had test conversion, which increased with exposure to a case (p = 0.002), increasing age (p = 0.0006) and BCG scar (p = 0.06). 114 tuberculin test converters had ELISPOT results: 16(14%) were recruitment positive/follow-up positive, 9 (8%) positive/negative, 34 (30%) negative/positive, and 55 (48%) were negative/negative. There was a significant non-linear effect of age for ELISPOT results in skin test converters (p = 0.038). Estimates of boosting ranged from 32%–41% of skin test converters with increasing age. Three converters were diagnosed with TB, two had ELISPOT results: both were positive, including one at recruitment. CONCLUSIONS/SIGNIFICANCE: We estimate that approximately one third of tuberculin skin test conversion in Gambian TB case contacts is due to boosting of immunity to non-tuberculous mycobacterial exposure. Further longitudinal studies are required to confirm whether ELISPOT can reliably identify case contacts with tuberculin test conversion that would benefit most from prophylactic treatment

    Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease

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    BACKGROUND: Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women. METHODS: A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO(2 )and transcutaneous PCO(2 )(tcCO(2)) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA. RESULTS: Thirteen patients completed the trial. At baseline, the average ± SD of SaO(2 )mean was 90.6 ± 3.2 % and the median of SaO(2 )nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 ± 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO(2 )median was 6.0 ± 0.9 kPa and decreased with MPA by 0.9 ± 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO(2 )nadir and tcCO(2 )median also during REM sleep. Three weeks after cessation of MPA, the SaO(2 )mean remained 1.4 ± 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO(2 )nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO(2 )mean and SaO(2 )nadir during sleep with MPA were inversely associated with baseline SaO(2 )mean (r = -0.70, p = 0.032) and baseline SaO(2 )nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO(2 )mean, SaO(2 )nadir and tcCO(2 )levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables. CONCLUSION: MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO(2 )values. Long-term studies in females are warranted
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