Assessment of PULP score in predicting 30-day perforated duodenal ulcer morbidity, and comparison of its performance with Boey and ASA, a retrospective study

Background: /aim: Scores commonly employed to risk stratify perforated peptic ulcer patients include ASA (American Society of Anesthesiologists), Boey and peptic ulcer perforation score (PULP). However, few studies assessed and compared the accuracy indices of these three scores in predicting post PPU repair 30-day morbidity. We assessed accuracy indices of PULP, and compared them to Boey and ASA in predicting post perforated duodenal (PDU) ulcer repair 30-day morbidity. Methods: Retrospective chart review of all PDU patients (perforated duodenal ulcers only) at the largest two hospitals in Qatar (N = 152). Data included demographic, clinical, laboratory, operative, and post repair 30-day morbidity. Area under the Curve (AUC), sensitivity and specificity were computed for each of the 3 scores. Multivariate logistic regression assessed the accuracy indices of each score. Results: All patients were males (M age 37.41 years). Post PDU repair 30-day morbidity was 10.5% (16 morbidities). Older age, higher ASA (?3), Boey (?1) or PULP (?8) scores, shock on admission and preoperative comorbidities; and conversely, lower hemoglobin and albumin were all positively significantly associated with higher post PDU 30-day morbidity. PULP displayed the largest AUC (72%), and was the only score to significantly predict 30-day morbidity. The current study is the first to report the sensitivity and specificity of these three scores for post PDU repair 30-day morbidity; and first to assess accuracy indices for PULP in predicting post PDU repair 30-day morbidity. Conclusion: PULP score had the largest AUC and was the only score to significantly predict post PDU repair 30-day morbidity.Scopu

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. OBJECTIVES: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. METHODS: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age 50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age

Competing endogenous rna networks as biomarkers in neurodegenerative diseases

Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases

European regulatory agenices should employ full time statisticians

No abstract available

Targeting Methylglyoxal in Diabetic Kidney Disease Using the Mitochondria-Targeted Compound MitoGamide.

Diabetic kidney disease (DKD) remains the number one cause of end-stage renal disease in the western world. In experimental diabetes, mitochondrial dysfunction in the kidney precedes the development of DKD. Reactive 1,2-dicarbonyl compounds, such as methylglyoxal, are generated from sugars both endogenously during diabetes and exogenously during food processing. Methylglyoxal is thought to impair the mitochondrial function and may contribute to the pathogenesis of DKD. Here, we sought to target methylglyoxal within the mitochondria using MitoGamide, a mitochondria-targeted dicarbonyl scavenger, in an experimental model of diabetes. Male 6-week-old heterozygous Akita mice (C57BL/6-Ins2-Akita/J) or wildtype littermates were randomized to receive MitoGamide (10 mg/kg/day) or a vehicle by oral gavage for 16 weeks. MitoGamide did not alter the blood glucose control or body composition. Akita mice exhibited hallmarks of DKD including albuminuria, hyperfiltration, glomerulosclerosis, and renal fibrosis, however, after 16 weeks of treatment, MitoGamide did not substantially improve the renal phenotype. Complex-I-linked mitochondrial respiration was increased in the kidney of Akita mice which was unaffected by MitoGamide. Exploratory studies using transcriptomics identified that MitoGamide induced changes to olfactory signaling, immune system, respiratory electron transport, and post-translational protein modification pathways. These findings indicate that targeting methylglyoxal within the mitochondria using MitoGamide is not a valid therapeutic approach for DKD and that other mitochondrial targets or processes upstream should be the focus of therapy

The MINERν\nuA Data Acquisition System and Infrastructure

MINER$\nu$A (Main INjector ExpeRiment $\nu$-A) is a new few-GeV neutrino cross section experiment that began taking data in the FNAL NuMI (Fermi National Accelerator Laboratory Neutrinos at the Main Injector) beam-line in March of 2010. MINER$\nu$A employs a fine-grained scintillator detector capable of complete kinematic characterization of neutrino interactions. This paper describes the MINER$\nu$A data acquisition system (DAQ) including the read-out electronics, software, and computing architecture.Comment: 34 pages, 16 figure

Single neutral pion production by charged-current νˉμ\bar{\nu}_\mu interactions on hydrocarbon at ⟨Eν⟩=\langle E_\nu \rangle = 3.6 GeV

Single neutral pion production via muon antineutrino charged-current interactions in plastic scintillator (CH) is studied using the \minerva detector exposed to the NuMI low-energy, wideband antineutrino beam at Fermilab. Measurement of this process constrains models of neutral pion production in nuclei, which is important because the neutral-current analog is a background for $\bar{\nu}_e$ appearance oscillation experiments. The differential cross sections for $\pi^0$ momentum and production angle, for events with a single observed $\pi^0$ and no charged pions, are presented and compared to model predictions. These results comprise the first measurement of the $\pi^0$ kinematics for this process.Comment: 6 pages, 5 figures, submitted to Physics Letters

Vascular histone deacetylation by pharmacological HDAC inhibition

HDAC inhibitors can regulate gene expression by post-translational modification of histone as well as nonhistone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action. However, little is known of the extent of genome-wide changes in cells stimulated by the hydroxamic acids, TSA and SAHA. In this article, we map vascular chromatin modifications including histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation-mediated gene expression is often associated with modification of other lysine residues, we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). RNA sequencing indicates the differential expression of ∼30% of genes, with almost equal numbers being up- and down-regulated. We observed broad deacetylation and gene expression changes conferred by TSA and SAHA mediated by the loss of EP300/CREBBP binding at multiple gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation by pharmacological HDAC inhibition