Effects of Metformin and Weight Loss on Serum Alanine Aminotransferase Activity in the Diabetes Prevention Program

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and impaired glucose tolerance. We investigated whether metformin or changes in metabolic measurements (weight, fasting plasma glucose (FPG), or fasting insulin (FI)) improved serum alanine aminotransferase (ALT) activity, as a marker for NAFLD, in the Diabetes Prevention Program (DPP). From 1996 to 1999, 2,153 participants without marked elevations of serum ALT at baseline were randomized (1,081 to placebo, 1,072 to metformin) and treated for an average of 3.2 years. ALT increased during the first 2 years of the study, and was slightly but significantly lower in the participants randomized to metformin. In regression models adjusted for sex, baseline age, FPG, and FI, these differences remained significant, but disappeared after adjustment for weight, FPG, and FI changes at each examination. The 3‐year cumulative incidence for development of abnormal ALT concentrations was not significantly different ((mean ± s.e.) 21.4 ± 1.4% and 24.6 ± 1.4%, P = 0.11) in the metformin vs. placebo groups but was lower in individuals in both groups that lost more weight by the end of year 1 (metformin: 19.4 ± 2.4% vs. 27.5 ± 3.7%, for highest vs. lowest quartile of weight loss; placebo: 18.7 ± 3.4% vs. 28.8 ± 2.6%). Over 3 years of follow‐up in persons at high risk for development of diabetes, serum ALT was consistently lower in those treated with metformin compared with placebo. This effect was mediated by weight loss, indicating that the effects of metformin therapy on ALT is via its effects on weight.     

生物多样性价值的经济学处理：一些理论障碍及其克服

本文首先对国际生态经济学界围绕“世界生态系统功能价值计量”的方法学论争进行短简的评价,接着阐述了生物多样性价值的新的概念框架,并据此就生物多样性价值计量中尚未得到关注的问题（生物多样性价值的可计算性,价值计量方法的恰当性,价值分量的可加性和可解析性,价值误差测算）提出解决思路,本文最后讨论了两个保护经济学问题方法学构架,其一是生物多样性破坏的经济损失计算,其二是生物多样性保护工程的成本－效益体质与成本－效果分析。     

Likelihood of attending bowel screening after a negative genetic test result: the possible influence of health professionals

This study was undertaken to determine the extent to which the reported likelihood of attending future bowel screening following negative genetic testing results for familial adenomatous polyposis (FAP) varies between the type of health professional providing care and the country of testing. The study subjects were 103 unaffected adults at risk for FAP who received negative results following predictive DNA testing. Our study indicates that the reported likelihood of attending bowel screening was higher in those given results by nongenetics physicians, rather than by genetics professionals; the reported likelihood of attending bowel screening under these circumstances was also higher in the UK than in Australia. Both of these results were affected by the perceived chances of developing FAP, and, in the case of the country of testing, by the perceived accuracy of the genetic test result and the perceived seriousness of the disease. How and what health professionals communicate with patients about genetic testing may explain the differences between type of health professional and country of testing and attitudes toward bowel screening. If this is the case, training in communication may change patients' perceptions and, in turn, their behavioral intentions and actions following a negative test result.     

Anti-inflammatory response after infusion of p55 soluble tumor necrosis factor receptor fusion protein for severe sepsis

OBJECTIVES: To investigate the effects of Lenercept , a recombinant soluble TNF receptor p55 fused to an immunoglobulin heavy chain IgG1, on the balance of pro- and anti-inflammatory mediators in sepsis. DESIGN: Post hoc analysis of a subgroup of patients enrolled in a multicenter phase III, prospective, double-blind, placebo-controlled, randomized study of Lenercept in severe sepsis. SETTING: Surgical and medical intensive care units, and postoperative recovery room of a tertiary care teaching hospital. PATIENTS: A total of 57 patients were enrolled in the multicenter study in our center. Intervention: Septic patients were randomly assigned to receive either Lenercept 0.125 mg/kg or placebo. The patients were followed for up to 28 days after randomization. MEASUREMENTS AND MAIN RESULTS: Circulating levels of TNF-alpha, IL-6, TNFsR75 and IL-1Ra were measured before and after treatment. The two groups were comparable with regard to age, gender and diagnosis distribution. The total level of TNF-alpha increased significantly in treated patients, compared to patients receiving placebo. The levels of the other inflammatory mediators did not differ between the two groups CONCLUSIONS: Lenercept -treated patients experienced a protracted TNF-alpha half-life, leading to higher total TNF-alpha levels throughout the study. However, the treatment had no effects on anti-inflammatory mediators. Therefore, peripheral inflammatory processes might not have been significantly modified by the treatment. This might account for the lack of efficacy this treatment in septic patients     

石油降解细菌的表型特性和系统发育分析

从3种不同土壤中分离和纯化得到10个石油降解细菌菌株,分离菌株均为好氧菌、革兰氏阴性菌、不形成芽孢的杆菌,10个菌株均能利用中等链长的烷烃、柴油和原油作为碳源,而不能以单环芳烃和多环芳烃为碳源。根据其生理生化性状和16SrDNA序列分析结果表明,分离菌株EVA5,EVA6,EVA7,EVA8和EVA9为假单胞菌（Pseudomonas spp.）,EVA10、EVA11、EVA12、EVA13和EVA14为不动杆菌（Acinetobacter spp.）,均属于Proteobac-teria的γ亚群。     

应用杆状病毒载体在昆虫细胞系统中表达乙型肝炎病毒表面抗原基因

构建了同时带有乙型肝炎病毒表面抗原基因和大肠杆菌的β-半乳糖苷酶基因的杆状病毒转移载体质粒pVL941lacHBS。应用磷酸钙沉淀技术将pVL941lacHBS DNA转入事先用AcNPV感染过的Sf9细胞,在显色剂X-gal存在下,筛选无多角体的蓝色蚀斑。经过若干次蚀斑纯化,最后获得含乙肝病毒表面抗原基因和β-半乳糖苷酶基因的重组杆状病毒R-AcV941LS。 用R-AcV941LS感染Sf9细胞,在感染后72～96小时,用RPHA和RIA分别检测组织培养上清液和细胞裂解液中的乙型肝炎病毒表面抗原含量。结果,组织培养上清液为3.83μg/1×10~6～2×10~6细胞;细胞裂解液为4.39μg/1×10~6～2×10~6细胞。乙型肝炎病毒表面抗原的合成总量为8.22μg/1×10~6～2×10~6细胞。免疫电镜观察显示表达产物呈约22nm的球形颗粒。小鼠免疫接种实验结果表明,以R-AcV941LS感染Sf9细胞表达的乙型肝炎病毒表面抗原与在哺乳动物细胞系表达的乙型肝炎病毒表面抗原具有相近似的免疫原性。     

Association of monosodium glutamate intake with overweight in Chinese adults: the INTERMAP Study

Animal studies indicate that monosodium glutamate (MSG) can induce hypothalamic lesions and leptin resistance, possibly influencing energy balance, leading to overweight. This study examines the association between MSG intake and overweight in humans. We conducted a cross-sectional study involving 752 healthy Chinese (48.7% women), aged 40-59 years, randomly sampled from three rural villages in north and south China. The great majority of participants prepared their foods at home, without use of commercially processed foods. Diet was assessed with four in-depth multipass 24-h recalls. Participants were asked to demonstrate MSG amounts added in food preparation. Amounts shaken out were weighed by trained interviewers. Overweight was defined as BMI > or =25.0 or > or =23.0 kg/m(2)(based on World Health Organization recommendations for Asian populations). Eighty-two percent of participants were MSG users. Average intake was 0.33 g/day (s.d. = 0.40). With adjustment for potential confounders including physical activity and total energy intake, MSG intake was positively related to BMI. Prevalence of overweight was significantly higher in MSG users than nonusers. For users in the highest tertile of MSG intake compared to nonusers, the multivariable-adjusted odds ratios of overweight (BMI > or =23.0 and > or =25.0) were 2.10 (95% confidence interval, 1.13-3.90, P for trend across four MSG categories = 0.03) and 2.75 (95% confidence interval, 1.28-5.95, P = 0.04). This research provides data that MSG intake may be associated with increased risk of overweight independent of physical activity and total energy intake in humans.     

Use of Third Line Antiretroviral Therapy in Latin America

Background

Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known.

Methods

Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART.

Results

Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001).

Conclusions

Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.     

Metabolic compensation constrains the temperature dependence of gross primary production

Gross primary production (GPP) is the largest flux in the carbon cycle, yet its response to global warming is highly uncertain. The temperature dependence of GPP is directly linked to photosynthetic physiology, but the response of GPP to warming over longer timescales could also be shaped by ecological and evolutionary processes that drive variation in community structure and functional trait distributions. Here, we show that selection on photosynthetic traits within and across taxa dampens the effects of temperature on GPP across a catchment of geothermally heated streams. Autotrophs from cold streams had higher photosynthetic rates and after accounting for differences in biomass among sites, biomass‐specific GPP was independent of temperature in spite of a 20 °C thermal gradient. Our results suggest that temperature compensation of photosynthetic rates constrains the long‐term temperature dependence of GPP, and highlights the importance of considering physiological, ecological and evolutionary mechanisms when predicting how ecosystem‐level processes respond to warming.