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ic samples over the past several years. Copyright © 2020 Naberhaus, Krull, Arruda, Arruda, Sahin, Schwartz, Burrough, Magstadt, Matias Ferreyra, Gatto, Meiroz de Souza Almeida, Wang and Kreuder.Hypertension, particularly midlife high blood pressure, has been related to a higher risk of cognitive decline and dementia, including Alzheimer disease. However, these associations are complex and not fully elucidated. Cerebral small vessel disease emerges as one of the most important causes. Several observational studies have shown the potential beneficial role of antihypertensive treatment in preventing cognitive decline. However, randomized clinical trials (RCTs) have shown controversial results without proving nor disproving the association. On the other hand, in very elderly or frail people some studies have observed a relationship between low blood pressure and worse cognitive function. The optimal systolic and diastolic blood pressure values for protecting cognitive function, especially in elderly people, are not known. Copyright © 2020 Sierra.Metabolic adaption is crucial for the heart to sustain its contractile activity under various physiological and pathological conditions. At the molecular level, the changes in energy demand impinge on the expression of genes encoding for metabolic enzymes. Among the major components of an intricate transcriptional circuitry, peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) plays a critical role as a metabolic sensor, which is responsible for the fine-tuning of transcriptional responses to a plethora of stimuli. Cumulative evidence suggests that energetic impairment in heart failure is largely attributed to the dysregulation of PGC-1α. In this review, we summarize recent studies revealing how PGC-1α is regulated by a multitude of mechanisms, operating at different regulatory levels, which include epigenetic regulation, the expression of variants, post-transcriptional inhibition, and post-translational modifications. We further discuss how the PGC-1α regulatory cascade can be impaired in the failing heart. Copyright © 2020 Oka, Sabry, Cawley and Warren.The DNA binding domains of Androgen/Glucocorticoid receptors (AR/GR), members of class I steroid receptors, bind as a homo-dimer to a cis-regulatory element. These response elements are arranged as inverted repeat (IR) of hexamer "AGAACA", separated with a 3 base pairs spacer. DNA binding domains of the Androgen receptor, AR-DBDs, in addition, selectively recognize a direct-like repeat (DR) arrangement of this hexamer. A chimeric AR protein, termed SPARKI, in which the second zinc-binding motif of AR is swapped with that of GR, however, fails to recognize DR-like elements. By molecular dynamic simulations, we identify how the DNA binding domains of the wild type AR/GR, and also the chimeric SPARKI model, distinctly interact with both IR and DR response elements. AR binds more strongly to DR than GR binds to IR elements. A SPARKI model built from the structure of the AR (SPARKI-AR) shows significantly fewer hydrogen bond interactions in complex with a DR sequence than with an IR sequence. Moreover, a SPARKI model based on the structure of the GR (SPARKI-GR) shows a considerable distortion in its dimerization domain when complexed to a DR-DNA whereas it remains in a stable conformation in a complex with an IR-DNA. The diminished interaction of SPARKI-AR with and the instability of SPARKI-GR on DR response elements agree with SPARKI's lack of affinity for these sequences. The more GR-like binding specificity of the chimeric SPARKI protein is further emphasized by both SPARKI models binding even more strongly to IR elements than observed for the DNA binding domain of the GR. Copyright © 2020 Bagherpoor Helabad, Volkenandt and Imhof.Cancer cachexia affects about 80% of advanced cancer patients, it is linked to poor prognosis and to date, there is no efficient treatment or cure. The syndrome leads to progressive involuntary loss of muscle and fat mass induced by systemic inflammatory processes. The role of the white adipose tissue (WAT) in the onset and manifestation of cancer cachexia gained importance during the last decade. WAT wasting is not only characterized by increased lipolysis and release of free fatty acids (FFA), but in addition, owing to its high capacity to produce a variety of inflammatory factors. The aim of this study was to characterize plasma lipid profile of cachectic patients and to correlate the FA composition with circulating inflammatory markers; finally, we sought to establish whether the fatty acids released by adipocytes trigger and/or contribute to local and systemic inflammation in cachexia. The study selected 65 patients further divided into 3 groups control (N); weight stable cancer (WSC); and cachectic cancer (CC). The plasma FA profile was significantly different among the groups and was positively correlated with pro-inflammatory cytokines expression in the CC patients. Therefore, we propose that saturated to unsaturated FFA ratio may serve as a means of detecting cachexia. Copyright © 2020 Riccardi, das Neves, de Matos-Neto, Camargo, Lima, Radloff, Alves, Costa, Tokeshi, Otoch, Maximiano, de Alcantara, Colquhoun, Laviano and Seelaender.Ketones provide an alternative brain fuel and may be neuroprotective in older people. Little is known of how to optimize the ketogenic effect of C80-C100 medium chain triglyceride supplement (kMCT). Metabolic switching (MS) from glucose to ketones as a fuel may have metabolic benefits but has not been extensively studied in humans. The objective of the present study was to use an 8 h metabolic study day protocol to assess the influence of typical components of MS, including a kMCT supplement, low-carbohydrate meal and meal timing, on blood ketones, glucose, insulin and free fatty acids (FFA). Lipopolysaccharides manufacturer In one test, the effect of age was also investigated. Over the 8 h metabolic study day, two 10 g doses of the kMCT increased the plasma ketone response by 19% while reducing overall glycemia by 12% without altering insulin or FFA levels. Moreover, a single early meal (breakfast but no lunch) potentiated the ketogenic effect of MS over 8 h, compared to a single delayed meal (lunch but no breakfast). Age and the low carbohydrate meal did not affect the ketones response. We conclude that an 8-h test period can be used to assess metabolic changes during short-term MS. kMCT provide a robust short-term increase in ketones and might enhance the metabolic effectiveness of short-term or intermittent fasting as a component of MS. Copyright © 2020 Vandenberghe, St-Pierre, Fortier, Castellano, Cuenoud and Cunnane.Transcriptomic technologies are constantly changing and improving, resulting in an ever increasing understanding of gene expression in health and disease. These technologies have been used to investigate the pathological changes occurring in the joints of rheumatoid arthritis patients, leading to discoveries of disease mechanisms, and novel potential therapeutic targets. Microarrays were initially used on both whole tissue and cell subsets to investigate research questions, with bulk RNA sequencing allowing for further elaboration of these findings. A key example is the classification of pathotypes in rheumatoid arthritis using RNA sequencing that had previously been discovered using microarray and histology. Single-cell sequencing has now delivered a step change in understanding of the diversity and function of subpopulations of cells, in particular synovial fibroblasts. Future technologies, such as high resolution spatial transcriptomics, will enable step changes integrating single cell transcriptomic and geographic data to provide an integrated understanding of synovial pathology. Copyright © 2020 Carr, Turner, Major, Scheel-Toellner and Filer.Objectives Studies have proven that improving patients' acceptance of chronic pain could be an effective therapy for alleviating pain and other symptoms. Our objectives were to investigate the correlation between chronic pain acceptance and clinical variables in ankylosing spondylitis (AS), and the prediction role of chronic pain acceptance for biologics treatment. Methods First, 167 AS patients were recruited to complete a series of questionnaires, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Chronic Pain Acceptance Questionnaire (CPAQ), Hospital Anxiety and Depression Scale (HADS), and Tampa Scale for Kinesiophobia (TSK). Bivariate correlation analysis was utilized to investigate the correlation between pain acceptance and clinical variables. Based on the level of chronic pain acceptance and serum C-reactive protein (CRP), patients were separated into four subgroups. Then, another 68 patients initiating anti-tumor necrosis fflect physical and psychological status. Clinicians should identify high-risk patients with low chronic pain acceptance and high levels of serum CRP, and give psychological and pharmacological intervention promptly. Moreover, the combination of baseline chronic pain acceptance and serum CRP level could be used to predict the treatment response in AS patients initiating biologics treatment. Copyright © 2020 Li, Liu, Sheng, Yin, Wu and Xu.Objectives To study the balance between the supply and need for rheumatology care in Austria. In addition, to investigate rheumatologists' work-hours, the amount of time rheumatologists dedicate to care for patients with rheumatic and musculoskeletal diseases (RMD), with non-RMD problems, and other professional activities such as research, teaching, and administration. Methods A questionnaire covering aspects of professional activities was sent to all 215 rheumatologists registered with the Austrian Medical Association. The data collected was set in relation to the need calculated on the basis of recommendations put forward by the German society of rheumatology. Results 149 of the 215 rheumatologists (69.0%) responded. Median weekly working time was 50 h (IQR 45-60). 47.4% of the working time was spent for care of patients with RMD. The remaining time was dedicated to patients with non-rheumatic diseases (19.6%), research and teaching (8.4%), and administration (24.5%). The number of full-time equivalents (FTE, based on a 40-h work-week) available for rheumatology care, thus, was calculated to be 178.5. Based on disease prevalence/incidence estimates and on the time allocation results of this survey, our study resulted in a need of 4.29 rheumatologists per 100.000 adult inhabitants (301.79 for an adult population of 7.03 × 106). Conclusion The study demonstrated a substantial mismatch between the available supply and the need for rheumatology care. The results of our study are a conservative estimate, which should be taken into consideration for future healthcare workforce planning. In particular, the rising need for rheumatologists should be met by increasing the numbers of those specialists. Copyright © 2020 Puchner, Vavrovsky, Pieringer, Hochreiter and Machold.Objective This study aimed at clarifying the prevalence, risk factors, outcome, and outcome-related factors of acute exacerbation of interstitial lung disease (AE-ILD) in patients with idiopathic inflammatory myopathy (IIM). Methods Data of IIM patients who were admitted to the First Affiliated Hospital of Zhejiang University (FAHZJU) from September 2007 to September 2019 were retrospectively collected. And the IIM patients with AE-ILD formed the case group. In addition, age and sex matched IIM patients without AE-ILD were randomly selected to constitute the control group. A 12 case-control study and intragroup analysis were performed to identify risk factors for development of AE-ILD in IIM patients and unfavorable short-term outcome in AE-ILD patients through comparison, univariate and multivariate logistic regression analysis. Results AE-ILD occurred in 64 out of 665 IIM patients (9.6%) with a short-term mortality rate of 39.1%. And the 64 IIM patients with AE-ILD formed the case group. Besides, 128 age and sex matched IIM patients without AE-ILD were randomly selected to constitute the control group.