OBJECTIVES Electronic health records (EHR) provide a valuable resource for assessing drug side-effects, but treatments are not randomly allocated in routine care creating the potential for bias. We conduct a case study using the Prior Event Rate Ratio (PERR) Pairwise method to reduce unmeasured confounding bias in side-effect estimates for two second-line therapies for type 2 diabetes, thiazolidinediones and sulfonylureas, . STUDY DESIGN and settings. Primary care data were extracted from the Clinical Practice Research Datalink (n=41871). We utilized outcomes from the period when patients took first-line metformin to adjust for unmeasured confounding. Estimates for known side-effects and a negative control outcome were compared to the ADOPT trial (n=2545). RESULTS When on metformin, patients later prescribed thiazolidinediones had greater risks of oedema, HR 95%CI 1.38 (1.13,1.68) and gastrointestinal (GI) side-effects 1.47 (1.28,1.68), suggesting the presence of unmeasured confounding. Conventional Cox regression overestimated the risk of oedema on thiazolidinediones and identified a false association with GI. The PERR Pairwise estimates were consistent with ADOPT 1.43 (1.10,1.83) vs 1.39 (1.04,1.86) respectively for oedema, and 0.91 (0.79,1.05) vs 0.94 (0.80,1.10) for GI. CONCLUSIONS The PERR Pairwise approach offers potential for enhancing post-marketing surveillance of side-effects from EHRs but requires careful consideration of assumptions. SQUAMOSA promoter binding protein-like (SPL) family plays vital regulatory roles in plant growth and development. The SPL family in climacteric fruit Carica papaya has not been reported. This study identified 14 papaya SPLs (CpSPL) from papaya genome and analyzed their sequence features, phylogeny, intron/exon structure, conserved motif, miR156-mediated posttranscriptional regulation, and expression patterns. 14 CpSPLs were clustered into 8 groups, and two distinct expression patterns were revealed for miR156-targeted and nontargeted CpSPLs in different tissues and fruit development stages. The expression changes of CpSPLs in ethephon and 1-MCP treated fruit during ripening suggested that the CpSPLs guided by CpmiR156 play crucial roles in ethylene signaling pathway. This study sheds light on the new function of SPL family in fruit development and ripening, providing insights on understanding evolutionary divergence of the members of SPL family among plant species. AIMS The aim of the study was to determine the serum levels of 25-hydroxyvitamin D and high-sensitivity C-reactive protein (hsCRP) in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine factors (including 25-hydroxyvitamin D and hsCRP) associated with MCI in elderly patients with type 2 diabetes (T2DM). METHODS A total of 194 T2DM elders were evaluated 62 subjects with MCI and 132 controls. Data was collected concerning biochemical parameters and biomarkers. RESULTS HsCRP concentration was elevated and 25-hydroxyvitamin D level was decreased in MCI patients to controls. HsCRP level was negatively correlated with 25-hydroxyvitamin D level and with MoCA score, and highly correlated with HbA1c level. The multivariable analysis indicated that less years of formal education, previous CVD and hypertension, increased number of co-morbidities, higher level of hsCRP and lower level of 25-hydroxyvitamin D, are the predisposing factors for MCI. CONCLUSIONS Higher hsCRP level and lower 25-hydroxyvitamin D may be regarded as a state of cognitive impairment in elderly patients with T2DM. Further prospective larger studies should be conducted to check the association between decreased vitamin D and risk of cognitive decline and to clarify whether this association may be mediated by systemic inflammation. One of the key challenges that we face in the 21st century is the need to feed an ever-increasing human population with increasingly limited natural resources. selleck products Even today it is estimated that roughly 1 out of 9 people in the world are undernourished, of which the most important factor is protein-energy malnutrition. By establishing microalgae as a new food and feed platform, we have the opportunity to increase the supply of these essential products to address global demands in a more efficient and environmentally sustainable way. Many types of algae are nutritionally complete foods, their yields outperform most plant crops, and there is a growing set of tools to develop improved strains of algae. Similar improvements were achieved in traditional crops through thousands of years of breeding and strain selection, whereas with the newest genetic engineering tools and advanced strain selection techniques, similar changes can be implemented in microalgae in just a few years. Here we describe different strategies that could be used to enhance the nutritional content, productivity, and organoleptic traits of algae to help drive development of this new crop. Clearly developing more efficient, sustainable, and nutritious foods and feed would be an enormous benefit for the planet, and algae represents an opportunity to develop a new crop that would complement traditional agriculture, and one that could potential result in a more efficient means to meet the world's food and feed supply. Impaired social facilitation was reported in autism spectrum disorder (ASD) children. However, behavioral analysis methods of social facilitation for ASD model have not been reported. We developed a novel breeding home cage for social facilitation. Voluntary exercise of more social C57BL/6 J mice was significantly increased in the presence of observer mouse compared to that in the absence of observer mouse. In contrast, the presence of observer mouse did not affect voluntary exercise of less social BALB/cCrSlc mice. These suggest that BALB/cCrSlc mice, a mouse model of ASD, exhibited impaired social facilitation. Our method would provide novel clues for ASD pathophysiology. Glia use multiple mechanisms to mediate potassium fluxes that support neuronal function. In addition to changes in potassium levels within synapses, these ions are dynamically dispersed through the interstitial parenchyma, perivascular spaces, leptomeninges, cerebrospinal fluid, choroid plexus, blood, vitreous, and endolymph. Neural circuits drive diversity in the glia that buffer potassium and this is reciprocal. Glia mediate buffering of potassium locally at glial-neuronal interfaces and via widespread networked connections. Control of potassium levels in the central nervous system is mediated by mechanisms operating at various loci with complexity that is difficult to model. However, major components of networked glial buffering are known. The role that potassium buffering plays in homeostasis of the CNS underlies some pathologic phenomena. An overview of potassium fluxes in the CNS is relevant for understanding consequences of pathogenic sequence variants in genes that encode potassium buffering proteins.