Summer temperature variability and long-term survival among elderly people with chronic disease

Time series studies show that hot temperatures are associated with increased death rates in the short term. In light of evidence of adaptation to usual temperature but higher deaths at unusual temperatures, a long-term exposure relevant to mortality might be summertime temperature variability, which is expected to increase with climate change. We investigated whether the standard deviation (SD) of summer (June-August) temperatures was associated with survival in four cohorts of persons over age 65 y with predisposing diseases in 135 US cities. Using Medicare data (1985-2006), we constructed cohorts of persons hospitalized with chronic obstructive pulmonary disease, diabetes, congestive heart failure, and myocardial infarction. City-specific yearly summer temperature variance was linked to the individuals during follow-up in each city and was treated as a time-varying exposure. We applied a Cox proportional hazard model for each cohort within each city, adjusting for individual risk factors, wintertime temperature variance, yearly ozone levels, and long-term trends, to estimate the chronic effects on mortality of long-term exposure to summer temperature SD, and then pooled results across cities. Mortality hazard ratios ranged from 1.028 (95% confidence interval, 1.013- 1.042) per 1 °C increase in summer temperature SD for persons with congestive heart failure to 1.040 (95% confidence interval, 1.022-1.059) per 1 °C increase for those with diabetes. Associations were higher in elderly persons and lower in cities with a higher percentage of land with green surface. Our data suggest that long-term increases in temperature variability may increase the risk of mortality in different subgroups of susceptible older populations.     

Induction and quantification of prefrontal cortical network plasticity using 5 Hz rTMS and fMRI

Neuronal plasticity is crucial for flexible interaction with a changing environment and its disruption is thought to contribute to psychiatric diseases like schizophrenia. High‐frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool to increase local excitability of neurons and induce short‐time functional reorganization of cortical networks. While this has been shown for the motor system, little is known about the short‐term plasticity of networks for executive cognition in humans. We examined 12 healthy control subjects in a crossover study with fMRI after real and sham 5 Hz rTMS to the right dorsolateral prefrontal cortex (DLPFC). During scanning, subjects performed an n‐back working memory (WM) task and a flanker task engaging cognitive control. Reaction times during the n‐back task were significantly shorter after rTMS than after sham stimulation. RTMS compared with sham stimulation caused no activation changes at the stimulation site (right DLPFC) itself, but significantly increased connectivity within the WM network during n‐back and reduced activation in the anterior cingulate cortex during the flanker task. Reduced reaction times after real stimulation support an excitatory effect of high‐frequency rTMS. Our findings identified plastic changes in prefrontally connected networks downstream of the stimulation site as the substrate of this behavioral effect. Using a multimodal fMRI‐rTMS approach, we could demonstrate changes in cortical plasticity in humans during executive cognition. In further studies this approach could be used to study pharmacological, genetic and disease‐related alterations. Hum Brain Mapp 35:140–151, 2014. © 2012 Wiley Periodicals, Inc.     

Synthesis of α-hydroxy ketones and vicinal (R,R)-diols by Bacillus clausii DSM 8716T butanediol dehydrogenase

α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716^T (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn²⁺ (1 mM) increases BcBDH''s activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.

Reduction of symmetric or asymmetric vicinal diketones with BcBDH leads to the synthesis of either α-hydroxyketones or vicinal diols.     

CD28 and CD57 define four populations with distinct phenotypic properties within human CD8+ T cells

After repeated antigen exposure, both memory and terminally differentiated cells can be generated within CD8⁺ T cells. Although, during their differentiation, activated CD8⁺ T cells may first lose CD28, and CD28⁻ cells may eventually express CD57 as a subsequent step, a population of CD28⁺CD57⁺(DP) CD8⁺ T cells can be identified in the peripheral blood. How this population is distinct from CD28⁻CD57⁻(DN) CD8⁺ T cells, and from the better characterized non-activated/early-activated CD28⁺CD57⁻ and senescent-like CD28⁻CD57⁺ CD8⁺ T cell subsets is currently unknown. Here, RNA expression of the four CD8⁺ T cell subsets isolated from human PBMCs was analyzed using microarrays. DN cells were more similar to “early” highly differentiated cells, with decreased TNF and IFN-γ production, impaired DNA damage response and apoptosis. Conversely, increased apoptosis and expression of cytokines, co-inhibitory, and chemokine receptors were found in DP cells. Higher levels of DP CD8⁺ T cells were observed 7 days after Hepatitis B vaccination, and decreased levels of DP cells were found in rheumatoid arthritis patients. More DP and DN CD8⁺ T cells were present in the bone marrow, in comparison with PBMCs. In summary, our results indicate that DP and DN cells are distinct CD8⁺ T cell subsets displaying defined properties.     

Hypouricemia: what the practicing rheumatologist should know about this condition

Clinical Rheumatology - We presented an update in the field of hypouricemia, which is defined as a serum urate concentration of < 2 mg/dL (119 μmol/L), for the...