Towards screening Barrett’s Oesophagus: current guidelines, imaging modalities and future developments

Barrett’s oesophagus is the only known precursor to oesophageal adenocarcinoma (OAC). Although guidelines on the screening and surveillance exist in Barrett’s oesophagus, the current strategies are inadequate. Oesophagogastroduodenoscopy (OGD) is the gold standard method in screening for Barrett’s oesophagus. This invasive method is expensive with associated risks negating its use as a current screening tool for Barrett’s oesophagus. This review explores current definitions, epidemiology, biomarkers, surveillance, and screening in Barrett’s oesophagus. Imaging modalities applicable to this condition are discussed, in addition to future developments. There is an urgent need for an alternative non-invasive method of screening and/or surveillance which could be highly beneficial towards reducing waiting times, alleviating patient fears and reducing future costs in current healthcare services. Vibrational spectroscopy has been shown to be promising in categorising Barrett’s oesophagus through to high-grade dysplasia (HGD) and OAC. These techniques need further validation through multicentre trials

Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming

Endothelial barrier (EB) breaching is a frequent event during inflammation, and it is followed by the rapid recovery of microvascular integrity. The molecular mechanisms of EB recovery are poorly understood. Triggering of MHC molecules by migrating T-cells is a minimal signal capable of inducing endothelial contraction and transient microvascular leakage. Using this model, we show that EB recovery requires a CD31 receptor-induced, robust glycolytic response sustaining junction re-annealing. Mechanistically, this response involves src-homology phosphatase activation leading to Akt-mediated nuclear exclusion of FoxO1 and concomitant \u3b2-catenin translocation to the nucleus, collectively leading to cMyc transcription. CD31 signals also sustain mitochondrial respiration, however this pathway does not contribute to junction remodeling. We further show that pathologic microvascular leakage in CD31-deficient mice can be corrected by enhancing the glycolytic flux via pharmacological Akt or AMPK activation, thus providing a molecular platform for the therapeutic control of EB response

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development

Modifying Tacrolimus-related Toxicity After Liver Transplantation Comparing Life Cycle Pharma Tacrolimus Versus Extended-released Tacrolimus: A Multicenter, Randomized Controlled Trial

Background. The aim of this open-label, multicenter, randomized controlled study was to investigate whether the life cycle pharma (LCP)-tacrolimus compared with the extended-release (ER)-tacrolimus formulation results in a difference in the prevalence of posttransplant diabetes, hypertension and chronic kidney disease (CKD) at 12 mo after liver transplantation. Methods. Patients were 1:1 randomized to either of the 2 tacrolimus formulations. The primary endpoint was defined as a composite endpoint of any of 3 events: sustained (>3 mo postrandomization) posttransplant diabetes, new-onset hypertension, and/or CKD, defined as estimated glomerular filtration rate 3 m during the follow-up. Results. In total, 105 patients were included. In the intention-to-treat analysis, a statistically significant lower proportion of liver transplant recipients in the LCP-tacrolimus group reached the composite primary endpoint at 12 mo compared with the ER-tacrolimus group (50.9% [27/53], 95% confidence interval [CI], 37.9%-63.9% versus 71.2% [37/52], 95% CI, 57.7%-81.7%; risk difference: 0.202; 95% CI, 0.002-0.382; P = 0.046). No significant difference was found in the per protocol analysis. In the intention-to-treat and per protocol population, fewer liver transplant recipients in the LCP-tacrolimus group developed CKD and new-onset hypertension compared with the ER-tacrolimus group. No differences in rejection rate, graft and patient survival were found. Conclusions. A statistically significant and clinically relevant reduction in the prevalence of the composite primary endpoint was found in the LCP-tacrolimus group compared with the ER-tacrolimus group in the first year after liver transplantation with comparable efficacy

Recovery and functional outcome after radial nerve palsy in adults with a humeral shaft fracture: a multicenter prospective case series

Background: The consequences of radial nerve palsy associated with a humeral shaft fracture are unclear. The aim of this study was to examine the functional recovery of radial nerve palsy, at presentation or postoperatively, in patients with a humeral shaft fracture. Methods: Data from patients who participated in the HUMeral shaft fractures: measuring recovery after operative versus non-operative treatment (HUMMER) study, a multicenter prospective cohort study including adults with a closed humeral shaft fracture Arbeitsgemeinschaft für Osteosynthesefragen (AO) type 12A or 12B, and had radial nerve palsy at presentation or postoperatively, were extracted from the HUMMER database. The primary outcome measure was clinically assessed recovery of motor function of the radial nerve. Secondary outcomes consisted of treatment, functional outcome (Disabilities of the Arm, Shoulder, and Hand and Constant–Murley Score), pain level, quality of life (Short Form-36 and EuroQoL-5D-3L), activity resumption, and range of motion of the shoulder and elbow joint at 12 months after trauma. Results: Three of the 145 nonoperatively treated patients had radial nerve palsy at presentation. One recovered spontaneously and 1 after osteosynthesis. Despite multiple surgical interventions, the third patient had no recovery after entrapment between fracture fragments. Thirteen of the 245 operatively treated patients had radial nerve palsy at presentation; all recovered. Nine other patients had postoperative radial nerve palsy; 8 recovered. One had ongoing recovery at the last follow-up, after nerve release and suture repair due to entrapment under the plate. At 12 months, the functional outcome scores of all patients suggested full recovery regarding functional outcome, pain, quality of life, activity resumption, and range of motion. Conclusion: Radial nerve palsy in patients with a humeral shaft fracture at presentation or postoperatively functionally recovers in 94% and 89%, respectively

Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

© 2019 American Academy of Neurology. ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

Chemical composition of Turkish olive oil, Ayvalik

Although large amounts of olive oil are produced in Turkey, not much information on its chemical composition is available in the literature to date. The aim of this study was to evaluate the chemical composition of commercial olive oils produced from the Ayvalik olive cultivar in Canakkale, Turkey. Five different samples corresponding to the olive oil categories of extra virgin (conventional, extra virgin olive oil (EVOO), and organic extra virgin olive oil (OGOO) production), virgin olive oil (OO-1), ordinary virgin olive oil (OO-2) and refined olive oil (RFOO) were evaluated. Olive oils were collected from two consecutive production years. According to the free fatty acids, the absorbance values (K-232 and K-270), and peroxide values of all the samples conformed to the European standards for olive oil. The level of oleic acid was in the range of 68-73%; while the linoleic acid content was significantly lower in the refined olive oils. The tocopherol and polyphenol content was in the lower range of some European olive oils. However, pinoresinol was a major phenolic compound (5-77 mg/kg depending on the oil category). Its content was markedly higher than in many other oils, which would be a useful finding for olive oil authentication purposes