Morphological characteristics of the sinus node on postmortem tissue

The sinus node is an intensively researched structure in terms of anatomical, histological, electrophysiological, molecular and genetic approach. For postmortem diagnosis it is still difficult to investigate due to a still reduced accessibility. In this study we tried and succeed to apply molecular biology techniques on postmortem tissues in order to widen the range of postmortem forensic investigation and provide information related to the diagnostic of cardiac arrhythmia. We described the stages of this investigation, with dissection, preservation and analysis that included classical histology, immunohistochemistry, confocal microscope, microdissection, RIN testing, mRNA expression obtaining a precise morphofunctional location of the sinus node

Introduction to Computational Media

Curatorial note from Digital Pedagogy in the Humanities: Yanni Loukissas’s syllabus documents the required introductory course in the Georgia Institute of Technology’s computational media major. The major is designed with a both/and pedagogy of code in mind; students take courses in both computer science and the humanities so as to develop a deep and nuanced understanding of the computer as a medium. The Introduction to Computational Media course represents the students’ first exposure to this synthesis and asks students to explore the history and theory of computation through a series of six focused projects. Each project employs a different programming language and has a different end product—including a data visualization, narrative bot, or procedural poem. Any one of these projects might be incorporated into another course as a capstone element, but the syllabus is most valuable as a whole, because it leads students toward a syncretic understanding of the computer as an expressive form

Trial-by-Trial Adjustments of Cognitive Control Following Errors and Response Conflict are Altered in Pediatric Obsessive Compulsive Disorder

Background: Impairments of cognitive control have been theorized to drive the repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from early in the course of illness. However, it remains unclear whether altered trial-by-trial adjustments of cognitive control characterize young patients. To test this hypothesis, we determined whether trial-by-trial adjustments of cognitive control are altered in children with OCD, relative to healthy controls. Methods: Forty-eight patients with pediatric OCD and 48 healthy youth performed the Multi-Source Interference Task. Two types of trial-by-trial adjustments of cognitive control were examined: post-error slowing (i.e., slower responses after errors than after correct trials) and post-conflict adaptation (i.e., faster responses in high-conflict incongruent trials that are preceded by other high-conflict incongruent trials, relative to low-conflict congruent trials). Results: While healthy youth exhibited both post-error slowing and post-conflict adaptation, patients with pediatric OCD failed to exhibit either of these effects. Further analyses revealed that patients with low symptom severity showed a reversal of the post-conflict adaptation effect, whereas patients with high symptom severity did not show any post-conflict adaptation. Conclusion: Two types of trial-by-trial adjustments of cognitive control are altered in pediatric OCD. These abnormalities may serve as early markers of the illness

Chronic medication does not affect hyperactive error responses in obsessive-compulsive disorder

Patients with obsessive-compulsive disorder (OCD) show an increased error-related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder-specific.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79361/1/j.1469-8986.2010.00988.x.pd

Linking protein to phenotype with Mendelian Randomization detects 38 proteins with causal roles in human diseases and traits

To efficiently transform genetic associations into drug targets requires evidence that a particular gene, and its encoded protein, contribute causally to a disease. To achieve this, we employ a three-step proteome-by-phenome Mendelian Randomization (MR) approach. In step one, 154 protein quantitative trait loci (pQTLs) were identified and independently replicated. From these pQTLs, 64 replicated locally-acting variants were used as instrumental variables for proteome-by-phenome MR across 846 traits (step two). When its assumptions are met, proteome-by-phenome MR, is equivalent to simultaneously running many randomized controlled trials. Step 2 yielded 38 proteins that significantly predicted variation in traits and diseases in 509 instances. Step 3 revealed that amongst the 271 instances from GeneAtlas (UK Biobank), 77 showed little evidence of pleiotropy (HEIDI), and 92 evidence of colocalization (eCAVIAR). Results were wide ranging: including, for example, new evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia, and a new finding that intestinal fatty acid binding protein (FABP2) abundance contributes to the pathogenesis of cardiovascular disease. We also demonstrated confirmatory evidence for the causal role of four further proteins (FGF5, IL6R, LPL, LTA) in cardiovascular disease risk

Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding

Micafungin, a new echinocandin antifungal agent, has been widely used for the treatment of various fungal infections in human populations. Micafungin is predominantly cleared by biliary excretion and it binds extensively to plasma proteins (>99.5%). Micafungin body weight-adjusted clearance is higher in neonates than in adults, but the mechanisms underlying this difference are not understood. Previous work had revealed the roles of sinusoidal uptake (Na+-taurocholate co-transporting peptide, NTCP; organic anion transporting polypeptide, OATP) as well as canalicular efflux (bile salt export pump, BSEP; breast cancer resistance protein, BCRP) transporters in micafungin hepatobiliary elimination. In the present study, the relative protein expression of hepatic transporters was compared between liver homogenates from neonates and adults. Also, the extent of micafungin binding to serum from neonates and adults was measured in vitro. The results indicate that relative expression levels of NTCP, OATP1B1/3, BSEP, BCRP, and MRP3 were similar in neonates and in adults. However, micafungin fraction unbound (fu) in neonatal serum was about 8-fold higher than in adult serum (0.033 ± 0.012 versus 0.004 ± 0.001, respectively). While there was no evidence for different intrinsic hepatobiliary clearance of micafungin between neonates and adults, our data suggest that age-dependent serum protein binding of micafungin is responsible for its higher clearance in neonates compared to adults

Failure to rescue patients after emergency laparotomy for large bowel perforation: analysis of the National Emergency Laparotomy Audit (NELA).

BACKGROUND: Past studies have highlighted variation in in-hospital mortality rates among hospitals performing emergency laparotomy for large bowel perforation. The aim of this study was to investigate whether failure to rescue (FTR) contributes to this variability. METHODS: Patients aged 18 years or over requiring surgery for large bowel perforation between 2013 and 2016 were extracted from the National Emergency Laparotomy Audit (NELA) database. Information on complications were identified using linked Hospital Episode Statistics data and in-hospital deaths from the Office for National Statistics. The FTR rate was defined as the proportion of patients dying in hospital with a recorded complication, and was examined in hospitals grouped as having low, medium or high overall postoperative mortality. RESULTS: Overall, 6413 patients were included with 1029 (16.0 per cent) in-hospital deaths. Some 3533 patients (55.1 per cent) had at least one complication: 1023 surgical (16.0 per cent) and 3332 medical (52.0 per cent) complications. There were 22 in-hospital deaths following a surgical complication alone, 685 deaths following a medical complication alone, 150 deaths following both a surgical and medical complication, and 172 deaths with no recorded complication. The risk of in-hospital death was high among patients who suffered either type of complication (857 deaths in 3533 patients; FTR rate 24.3 per cent): 172 deaths followed a surgical complication (FTR-surgical rate 16.8 per cent) and 835 deaths followed a medical complication (FTR-medical rate of 25.1 per cent). After adjustment for patient characteristics and hospital factors, hospitals grouped as having low, medium or high overall postoperative mortality did not have different FTR rates (P = 0.770). CONCLUSION: Among patients having emergency laparotomy for large bowel perforation, efforts to reduce the risk of in-hospital death should focus on reducing avoidable complications. There was no evidence of variation in FTR rates across National Health Service hospitals in England