Barrerabisgaard0115

The powerful antidiabetic actions of the CNS leptin-melanocortin system are capable of normalizing plasma glucose even in the absence of insulin and involve interactions of multiple neuronal populations and intracellular signaling pathways. Although the links between the CNS leptin-melanocortin system and its chronic effects on peripheral tissue glucose metabolism are still uncertain, they are independent of insulin action, activation of the autonomic nervous system, or the PTA axis. Unraveling the pathways that contribute to the powerful antidiabetic effects of the CNS leptin-melanocortin system may provide novel therapeutic approaches for diabetes mellitus.Objective To compare the clinical, radiographic, and histological healing patterns between the immediate and delayed applications of bone morphogenetic protein-2 (BMP-2) in damaged extraction sockets in dogs. Materials and methods The distal roots of the fourth premolars of the mandible were extracted bilaterally in five beagle dogs, and buccal bone defects (4 mm wide and 9 mm high) were surgically created. Collagenated biphasic calcium phosphate (CBCP) soaked for 10 min in 100 μL of BMP-2 solution was applied immediately to the defect site in the control group. In the test group, the BMP-2 solution of same dose was injected into the grafted site 2 weeks after grafting with a saline-soaked CBCP. The dogs were sacrificed 2 weeks later. Clinical, histological, and radiographic analyses were followed. Results Swelling and inflammatory reactions were predominantly observed in the control group at 2 weeks. The area of new bone formation was significantly larger in the control group compared with the test group (10.8 ± 7.0 mm2 [mean ± SD] and 6.3 ± 3.1 mm2, respectively; p = 0.043). No significant difference was found in ridge width at 2 mm, 4 mm and 6 mm below the lingual bone crest between the control (2.6 ± 1.0 mm, 3.2 ± 0.9 mm and 4.5 ± 0.5 mm, respectively) and test group (3.3 ± 1.0 mm, 3.7 ± 1.3 mm and 4.2 ± 1.0 mm; all p > 0.05). Conclusions Delayed application of BMP-2 2 weeks after surgery did not show any advantage over immediate application of BMP-2 in terms of new bone formation. Clinical relevance This study suggests that it might be better to apply BMP-2 immediately in alveolar ridge preservation, instead of delayed application, in order to enhance new bone formation.Background The benefit of ischemic postconditioning (IPostC) might be the throttled inflow following cold ischemia. The current study investigated advantage and mechanisms of IPostC in healthy and fatty rat livers. Methods Male SD rats received a high-fat diet to induce fatty livers. Isolated liver perfusion was performed after 24 h ischemia at 4 °C as well as in vivo experiments after 90 min warm ischemia. The so-called follow-up perfusions served to investigate the hypothesis that medium from IPostC experiments is less harmful. Lactate dehydrogenase (LDH), transaminases, different cytokines, and gene expressions, respectively, were measured. Results Fatty livers showed histologically mild inflammation and moderate to severe fat storage. IPostC reduced LDH and TXB2 in healthy and fatty livers and increased bile flow. LDH, TNF-α, and IL-6 levels in serum decreased after warm ischemia + IPostC. The gene expressions of Tnf, IL-6, Ccl2, and Ripk3 were downregulated in vivo after IPostC. Conclusions IPostC showed protective effects after ischemia in situ and in vivo in healthy and fatty livers. Restricted cyclic inflow was an important mechanism and further suggested involvement of necroptosis. IPostC represents a promising and easy intervention to improve outcomes after transplantation.Background and aims A network meta-analysis showed that low-cost optimization of existing resources was as effective as distal add-on devices in increasing adenoma detection rate (ADR). We assessed the impacts of water exchange (WE), Endocuff, and cap colonoscopy on ADR and advanced adenoma detection rate (AADR). We hypothesized that WE may be superior at improving ADR and AADR. Methods The literature was searched for all randomized controlled trials (RCTs) that reported ADR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing ADR and AADR of each method using air insufflation (AI) as the control and reported the odds ratios with 95% confidence interval. Performances were ranked based on P-score. Results Twenty-one RCTs met inclusion criteria. Fourteen RCTs also reported AADR. Both WE [1.46 (1.20-1.76)] and Endocuff [1.39 (1.17-1.66)] significantly increase ADR, while cap has no impact on ADR [1.00 (0.82-1.22)]. P-scores for WE (0.88), Endocuff (0.79), cap (0.17), and AI (0.17) suggest WE has the highest ADR. WE [1.38 (1.12-1.70)], but not Endocuff [0.96 (0.76-1.21)] or cap [1.06 (0.85-1.32)], significantly increases AADR. P-scores for WE (0.98), cap (0.50), AI (0.31), and Endocuff (0.21) suggest WE is more effective at increasing AADR. The results did not change after adjusting for age, proportion of males, and withdrawal time. Conclusion WE may be the modality of choice to maximally improve ADR and AADR.Unfortunately, the 3rd coauthor name has been published incorrectly in the original publication.Cobalt chloride can create hypoxia-like state in vitro (referred to as chemical hypoxia). Several studies have suggested that chemical hypoxia may cause deleterious effects on myogenesis. The intrinsic underlying mechanisms of myoblast differentiation, however, are not fully understood. Here, we show that cobalt chloride strongly suppresses myoblast differentiation in a dose-dependent manner. The impaired myoblast differentiation is accompanied by downregulation of myogenic regulatory factor myogenin. WH-4-023 in vitro Under chemical hypoxia, myogenin stability is decreased at mRNA and protein levels. A muscle-specific E3 ubiquitin ligase MAFbx, which can target myogenin protein for proteasomal degradation, is upregulated along with changes in Akt/Foxo and AMPK/Foxo signaling pathways. A proteasome inhibitor completely prevents cobalt chloride-mediated decrease in myogenin protein. These results suggest that cobalt chloride might modulate myogenin expression at post-transcriptional and post-translational levels, resulting in the failure of the myoblasts to differentiate into myotubes.Non-coding RNAs represent a significant proportion of the human genome. After having been considered as 'junk' for a long time, non-coding RNAs are now well established as playing important roles in maintaining cellular homeostasis and functions. Some non-coding RNAs show cell- and tissue-specific expression patterns and are specifically deregulated under pathological conditions (e.g. cancer). Therefore, non-coding RNAs have been extensively studied as potential biomarkers in the context of different diseases with a focus on microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) for several years. Since their discovery, miRNAs have attracted more attention than lncRNAs in research studies; however, both families of non-coding RNAs have been established to play an important role in gene expression control, either as transcriptional or post-transcriptional regulators. Both miRNAs and lncRNAs can regulate key genes involved in the development of cancer, thus influencing tumour growth, invasion, and metastasis by increasing the activation of oncogenic pathways and limiting the expression of tumour suppressors. Furthermore, miRNAs and lncRNAs are also emerging as important mediators in drug-sensitivity and drug-resistance mechanisms. In the light of these premises, a number of pre-clinical and early clinical studies are exploring the potential of non-coding RNAs as new therapeutics. The aim of this review is to summarise the latest knowledge of the use of miRNAs and lncRNAs as therapeutic tools for cancer treatment.Background There is limited information about acute phase renal replacement therapy (RRT) for maintenance hemodialysis patients after the onset of cerebrovascular disease. This study aimed to investigate which modality of renal replacement therapy is currently selected in practice. Methods We conducted a mail-based survey in 317 dialysis facilities that were certified by three academic societies that focus on dialysis, neurology, and neurosurgery in Japan. Results We received responses from 103 facilities (32.5%). In cases of cerebral infarction (CI) and intracerebral hemorrhage (ICH), more than 80% of the facilities selected only intermittent RRT, and 22.3% (CI)/8.7% (ICH) of the facilities selected intermittent HD which is the same setting in normal conditions. Although continuous hemodiafiltration and peritoneal dialysis are recommended in the Japanese guidelines, these were selected in only a few facilities 16.5% and 0% in CI, 16.5% and 1% in ICH, respectively. RRT on the day of onset tended to be avoided, irrespective of the duration following the last HD session. Furthermore, physicians preferred to modify anticoagulants and reduce dialysis performance in the acute phase. Conclusion This questionnaire survey uncovered a gap between guidelines and actual practice, even in hospitals accredited as educational facility, which is a novel and important finding. Further studies with larger sample sizes are needed to determine the optimal modality of RRT for the acute phase of cerebrovascular disease.Purpose of review To summarize epidemiology, pathophysiology, prognostic relevance, and treatment options of coronary artery disease (CAD) when coupled with severe aortic stenosis (SAS). In regard to treatment options, we focused on the most recently adopted therapeutic approaches and on the future perspectives in light of the latest percutaneous and surgical technical improvements in the field of both CAD and SAS management. Recent findings Nowadays, SAS is the most common valve disease requiring intervention, either surgical or percutaneous. On the other side, CAD is one of the leading causes of death in the developed countries. CAD and degenerative SAS share several predisposing factors and are often concurrently found in clinical practice. Despite in the last years the transcatheter aortic valve replacement (TAVR) has been deeply changing the therapeutic approach to SAS, the correct management of patients with concomitant CAD remains controversial due to limited and heterogeneous data in the literature. Coronary revascularization is often performed in patients with concomitant CAD and SAS. Complete surgical approach is still the standard of care according to international guidelines. However, in light of the recent results of TAVR trials, the therapeutic approach is expected to change. To date, percutaneous coronary intervention performed before TAVR is safe and feasible even if the optimal timing for revascularization remains debated. Due to the great complexity of the patients affected by SAS and CAD and until unquestionable truths will come from large randomized trials, the role of the Heart Team in the decision-making process is of primary importance to guarantee the best tailored therapeutic strategy for the single patient.Fetal well-being during labor is usually assessed by visual analysis of a fetal heart rate (FHR) tracing. Our primary objective was to evaluate the ability of automated heart rate variability (HRV) analysis methods, including our new fetal stress index (FSI), to predict neonatal acidosis. 552 intrapartum recordings were analyzed. The analysis occurred in the last 90 min before birth and was conducted during two 5-min intervals (i) a stable period of FHR and (ii) the period corresponding to the maximum FSI value. For each period, we computed the mean FHR, FSI, short-term variability (STV), and long-term variability (LTV). Visual FHR interpretation was performed using the FIGO classification. The population was separated into two groups (i) an acidotic group with an arterial pH at birth ≤ 7.10 and a control group. Prediction of a neonatal pH ≤ 7.10 was assessed by computing the receiver-operating characteristic area under the curve (AUC). FHR, FSI, STV, and LTV did not differ significantly between groups during the stable period.