Health Literacy Does Not Control Underage Alcohol Use Through the COVID19 Outbreak

Insulin resistance and altered hepatic mitochondrial function are central features of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD), but the etiological role of these processes in disease progression remains unclear. Here we investigated the molecular links between insulin resistance, mitochondrial remodeling, and hepatic lipid accumulation.
Hepatic insulin sensitivity, endogenous glucose production, and mitochondrial metabolic fluxes were determined in wild-type, obese (ob/ob) and pioglitazone-treatment obese mice using a combination of radiolabeled tracer and stable isotope NMR approaches. Mechanistic studies of pioglitazone action were performed in isolated primary hepatocytes, whilst molecular hepatic lipid species were profiled using shotgun lipidomics.
Livers from obese, insulin-resistant mice displayed augmented mitochondrial content and increased tricarboxylic acid cycle (TCA) cycle and pyruvate dehydrogenase (PDH) activities. Insulin sensitization with pioglitazone mitigated pyruvate-driven TCA cycle activity and PDH activation via both allosteric (intracellular pyruvate availability) and covalent (PDK4 and PDP2) mechanisms that were dependent on PPARγ activity in isolated primary hepatocytes. Improved mitochondrial function following pioglitazone treatment was entirely dissociated from changes in hepatic triglycerides, diacylglycerides, or fatty acids. Instead, we highlight a role for the mitochondrial phospholipid cardiolipin, which underwent pathological remodeling in livers from obese mice that was reversed by insulin sensitization.
Our findings identify targetable mitochondrial features of T2D and NAFLD and highlight the benefit of insulin sensitization in managing the clinical burden of obesity-associated disease.
Our findings identify targetable mitochondrial features of T2D and NAFLD and highlight the benefit of insulin sensitization in managing the clinical burden of obesity-associated disease.
Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments.
In this review, the latest clinical data on nuclear hormone- and peptide hormone-based drug candidates for NASH are reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear and peptide strategies.
Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities.
Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities.
Studies on the effects of manipulation under anesthesia (MUA) for primary stiff shoulder when different comorbidities are present are lacking. Our aim was to assess how comorbidities influence the recovery speed and clinical outcomes after MUA.
Between April 2013 and September 2018, 281 consecutive primary stiff shoulders in the frozen phase treated with MUA were included in this study. We investigated the comorbidities of patients and divided them into the control (n = 203), diabetes mellitus (DM) (n = 32), hyperlipidemia (n = 26), and thyroid disorder (n = 20) groups. The range of motion (ROM) and clinical scores for each group before MUA and 1 week, 6 weeks, and 3 months after MUA were comparatively analyzed. We identified the ROM recovery time after MUA and the responsiveness to MUA. Then, subjects were subdivided into early and late recovery groups based on their recovery time and into successful and nonsuccessful MUA groups based on their responsiveness to MUA.
Significant improvements in ROM and as DM. If patients have comorbidities, then they should be informed before MUA that the comorbidity could affect the outcomes of treatment.
The ROM recovery speed and responsiveness to MUA for primary stiff shoulder were poorer for the DM and thyroid disorder groups than for the control group. In particular, compared with any other disease, outcomes were poorer when the comorbidity was DM. If patients have comorbidities, then they should be informed before MUA that the comorbidity could affect the outcomes of treatment.
In the treatment of unstable olecranon fractures, anatomically preshaped locking plates exhibit superior biomechanical results compared with tension band wiring. However, posterior plating (PP) still is accompanied by high rates of plate removal because of soft-tissue irritation and discomfort. Meanwhile, low-profile plates precontoured for collateral double plating (DP) are available and enable muscular soft-tissue coverage combined with angular-stable fixation. The goal of this study was to biomechanically compare PP with collateral DP for osteosynthesis of unstable osteoporotic fractures.
A comminuted displaced Mayo type IIB fracture was created in 8 osteoporotic pairs of fresh-frozen human cadaveric elbows. Pair-wise angular stable fixation was performed by either collateral DP or PP. see more Biomechanical testing was conducted as a pulling force to the triceps tendon in 90° of elbow flexion. Cyclical load changes between 10 and 300 N were applied at 4 Hz for 50,000 cycles. Afterward, the maximum load was raised by 0.