Plos One
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Lower levels of cognitive function have been found to be associated with higher mortality in older people, particularly in dementia, but the association in people with other mental disorders is still inconclusive. ⋯ Current study identified an association between cognitive impairment and increased mortality in older people using secondary mental health services regardless of a dementia diagnosis. Causal pathways between this exposure and outcome (for example, suboptimal healthcare) need further investigation.
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A large number of unwanted adverse events and symptoms reported by patients in clinical trials are not caused by the drug provided, since most of adverse events also occur in corresponding placebo groups. These nocebo effects also play a major role in drug discontinuation in clinical practice, negatively affecting treatment efficacy as well as patient adherence and compliance. Experimental and clinical data document a large interindividual variability in nocebo responses, however, data on psychological, biological or genetic predictors of nocebo responses are lacking. ⋯ Significantly more drug-specific as well as general side effects were reported from homozygous carriers of the Val158 variant during medication as well as placebo treatment compared to the other genotype groups. Val158/Val158 carriers also had significantly higher scores in the somatosensory amplification scale (SSAS) and the BMQ (beliefs about medicine questionnaire). Together these data demonstrate potential genetic and psychological variables predicting nocebo responses after drug and placebo intake, which might be utilized to minimize nocebo effects in clinical trials and medical practice.
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Several imaging-based indices were constructed quantitatively using the emphysema index (EI) and fibrosis score (FS) on high-resolution computed tomography (HRCT). We evaluated the ability of these indices to predict mortality compared to physiologic results. Additionally, prognostic predictive factors were compared among subgroups with biopsy-proven fibrotic idiopathic interstitial pneumonia (IIP) (biopsy-proven CPFE) and in a separate cohort with subclinical CPFE. ⋯ Recognition and stratification using CT quantification can be utilized as a prognostic predictor. Prognostic factors vary according to fibrosis severity and among cohorts of patients with biopsy-proven and subclinical CPFE.
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Since the initial publication of the International Study of Unruptured Intracranial Aneurysms (ISUIA), management of unruptured intracranial aneurysms has been mainly based on the size of the aneurysm. The contribution of morphological characteristics to treatment decisions of unruptured aneurysms has not been well studied in a systematic and location specific manner. We present a large sample of basilar artery tip aneurysms (BTA) that were assessed using a diverse array of morphological variables to determine the parameters associated with ruptured aneurysms. ⋯ Multivariate logistic regression revealed that a larger angle between the posterior cerebral arteries (P1-P1 angle, p = 0.037) was most strongly associated with aneurysm rupture after adjusting for other morphological variables. In this location specific study of BTA aneurysms, the larger the angle formed between posterior cerebral arteries was found to be a new morphological parameter significantly associated with ruptured BTA aneurysms. This is a physically intuitive parameter that can be measured easily and readily applied in the clinical setting.
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SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. ⋯ Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak.