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Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.The aim of this study was to assess the risk of hospitalization associated with the concomitant prescription of 10 highly prevalent drug-drug interactions (DDIs) among all individuals aged ≥65 residing in Bologna's area, Italy. We used incidence density sampling, and the effect of current (last month) and past (≥30 days before) exposure to DDI was investigated through conditional multivariable logistic regression analysis. Two DDIs were associated with increased hospitalization due to DDI related conditions ACE-inhibitors/ diuretics plus glucocorticoids (current DDI OR 2.36, 95% CI 1.94-2.87; past DDI OR 1.36, 95% CI 1.12-1.65) and antidiabetic therapy plus current use of fluoroquinolones (OR 4.43, 95% CI 1.61-11.2). Non-Steroidal Anti-inflammatory Drugs (NSAIDs) increased the risk of re-bleeding in patients taking Selective Serotonin Reuptake Inhibitors (OR 5.56, 95% CI 1.24-24.9), while no significant effect was found in those without a history of bleeding episodes. Concomitant prescription of NSAIDs and ACE-inhibitors/diuretics in patients with a history of high-risk conditions was infrequent. Within the pattern of drug prescriptions in the older population of Bologna's area, we distinguished DDIs with actual clinical consequences from others that might be considered generally safe. Observed prescribing habits of clinicians reflect awareness of potential interactions in patients at risk.In this study, we established a simple and practical tool for early identification of potentially high-risk individuals among elderly COVID-19 patients. Included were 2106 laboratory-confirmed COVID-19 patients aged 60 years and above in 30 provinces of mainland China. Using discrimination (the area under the receiver-operator characteristic curve [AUC]) and calibration (Hosmer-Lemeshow goodness-of-fit test and calibration plots), a nomogram for predicting critically ill cases was developed, and its performance was examined using an internal validation cohort (444 patients) and external cohort (770 patients). The proportion of critically ill patients was 11.8% (248/2106). The most common symptoms at the onset of illness were fever (66.6%), cough (34.1%), fatigue (23.3%), and expectoration (23.6%). Older age, history of chronic obstructive pulmonary disease, fever, fatigue, shortness of breath, and lymphocyte percentage lower than 20% at admission were associated with increased risk of becoming critically ill. The AUCs for the six-variable-based nomogram were 0.77 (95% CI 0.73-0.82), 0.73 (95% CI 0.67-0.79), and 0.77 (95% CI 0.71-0.83) in the development, internal validation, and external validation cohorts, respectively. This six-variable-based nomogram could potentially serve as a practical and reliable tool for early identification of elderly COVID-19 patients at high risk of becoming critically ill.The contribution of dysregulated mitochondrial gene expression and consequent imbalance in biogenesis is not well understood in metabolic disorders such as insulin resistance and obesity. The ribosomal RNA maturation protein PTCD1 is essential for mitochondrial protein synthesis and its reduction causes adult-onset obesity and liver steatosis. We used haploinsufficient Ptcd1 mice fed normal or high fat diets to understand how changes in mitochondrial biogenesis can lead to metabolic dysfunction. We show that Akt-stimulated reduction in lipid content and upregulation of mitochondrial biogenesis effectively protected mice with reduced mitochondrial protein synthesis from excessive weight gain on a high fat diet, resulting in improved glucose and insulin tolerance and reduced lipid accumulation in the liver. However, inflammation of the white adipose tissue and early signs of fibrosis in skeletal muscle, as a consequence of reduced protein synthesis, were exacerbated with the high fat diet. We identify that reduced mitochondrial protein synthesis and OXPHOS biogenesis can be recovered in a tissue-specific manner via Akt-mediated increase in insulin sensitivity and transcriptional activation of the mitochondrial stress response.Aging and age-related neurodegeneration are among the major challenges in modern medicine because of the progressive increase in the number of elderly in the world population. Nutrition, which has important long-term consequences for health, is an important way to prevent diseases and achieve healthy aging. The beneficial effects of Vigna unguiculata on metabolic disorders have been widely documented. Here, we show that an aqueous extract of V. unguiculata beans delays senescence both in Saccharomyces cerevisiae and Drosophila melanogaster, in a Snf1/AMPK-dependent manner. Consistently, an increased expression of FOXO, SIRT1, NOTCH and heme oxygenase (HO) genes, already known to be required for the longevity extension in D. melanogaster, is also shown. Preventing α-synuclein self-assembly is one of the most promising approaches for the treatment of Parkinson's disease (PD), for which aging is a risk factor. In vitro aggregation of α-synuclein, its toxicity and membrane localization in yeast and neuroblastoma cells are strongly decreased in the presence of bean extract. In a Caenorhabditis elegans model of PD, V. unguiculata extract substantially reduces the number of the age-dependent degeneration of the cephalic dopaminergic neurons. Our findings support the role of V. unguiculata beans as a functional food in age-related disorders.Voxel-based morphometry (VBM) analysis of nuclear Magnetic Resonance Imaging (MRI) data allows the identification of medial temporal lobe (MTL) atrophy and is widely used to assist the diagnosis of Alzheimer's disease (AD). However, its reliability in the clinical environment has not yet been confirmed. To determine the credibility of VBM, amyloid positron emission tomography (PET) and VBM studies were compared retrospectively. Patients who underwent Pittsburgh Compound B (PiB) PET were retrospectively recruited. Ninety-seven patients were found to be amyloid negative and 116 were amyloid positive. MTL atrophy in the PiB positive group, as quantified by thin sliced 3D MRI and VBM software, was significantly more severe (p =0.0039) than in the PiB negative group. Corticosterone However, data histogram showed a vast overlap between the two groups. The area under the ROC curve (AUC) was 0.646. MMSE scores of patients in the amyloid negative and positive groups were also significantly different (p = 0.0028), and the AUC was 0.672.
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