PTBP1 acts as a dominant repressor of the aberrant tissue-specific splicing of ISCU in hereditary myopathy with lactic acidosis.

Background: Hereditary myopathy with lactic acidosis (HML) is an autosomal recessive disease caused by an intron mutation in the iron-sulfur cluster assembly (ISCU) gene. The mutation results in aberrant splicing, where part of the intron is retained in the final mRNA transcript, giving rise to a truncated nonfunctional ISCU protein. Using an ISCU mini-gene system, we have previously shown that PTBP1 can act as a repressor of the mis-splicing of ISCU, where overexpression of PTBP1 resulted in a decrease of the incorrect splicing.

Coenzyme Q10 in acute influenza.

Objectives: The goal of this investigation was to determine if acute influenza infection is associated with depletion of CoQ10 compared to healthy controls and to determine any associations between CoQ10 levels and illness severity and inflammatory biomarkers.

Patients And Methods: We analyzed serum CoQ10 concentrations of patients with acute influenza enrolled in a randomized clinical trial prior to study drug administration. Patients were enrolled at a single urban tertiary care center over 3 influenza seasons (December 27, 2013 to March 31, 2016).

Extracorporeal cardiopulmonary resuscitation for cardiac arrest: A systematic review.

Aim: To assess the use of extracorporeal cardiopulmonary resuscitation (ECPR), compared with manual or mechanical cardiopulmonary resuscitation (CPR), for out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) in adults and children.

Methods: The PRISMA guidelines were followed. We searched Medline, Embase, and Evidence-Based Medicine Reviews for randomized clinical trials and observational studies published before May 22, 2018.

Metabolic and functional changes in transgender individuals following cross-sex hormone treatment: Design and methods of the GEnder Dysphoria Treatment in Sweden (GETS) study.

Background: Although the divergent male and female differentiation depends on key genes, many biological differences seen in men and women are driven by relative differences in estrogen and testosterone levels. Gender dysphoria denotes the distress that gender incongruence with the assigned sex at birth may cause. Gender-affirming treatment includes medical intervention such as inhibition of endogenous sex hormones and subsequent replacement with cross-sex hormones.

Ubiquinol (Reduced Coenzyme Q10) and Cellular Oxygen Consumption in Patients Undergoing Coronary Artery Bypass Grafting.

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting.

CYP3A4*22 Impairs the Elimination of Ticagrelor, But Has No Significant Effect on the Bioactivation of Clopidogrel or Prasugrel.

CYP3A enzymes participate in the elimination of ticagrelor and the bioactivation of clopidogrel and prasugrel. We studied the effects of functional CYP3A genetic variants (CYP3A4*22; rs35599367 and CYP3A5*3; rs776746) on the pharmacokinetics and pharmacodynamics of ticagrelor, clopidogrel, and prasugrel. Six healthy volunteers with the CYP3A4*1/*22 and CYP3A5*3/*3 genotype (CYP3A4*22 carriers), eight with the CYP3A4*1/*1 and CYP3A5*1/*3 genotype (CYP3A5 expressors), and 11-13 with the CYP3A4*1/*1 and CYP3A5*3/*3 genotypes (controls) ingested single doses of ticagrelor, clopidogrel, and prasugrel on separate occasions.

Minimally Invasive Ponto Surgery Versus the Linear Incision Technique With Soft Tissue Preservation for Bone Conduction Hearing Implants: A Multicenter Randomized Controlled Trial.

Objective: To compare the surgical outcomes of the Minimally Invasive Ponto Surgery (MIPS) technique with those of the linear incision technique with soft-tissue preservation for bone-anchored hearing systems (BAHS).

Design: Sponsor-initiated multicenter, open, randomized, controlled clinical trial.

Setting: Maastricht University Medical Centre, Ziekenhuisgroep Twente and Medisch Centrum Leeuwarden, all situated in The Netherlands.

Modelling study of soil C, N and pH response to air pollution and climate change using European LTER site observations.

Current climate warming is expected to continue in coming decades, whereas high N deposition may stabilize, in contrast to the clear decrease in S deposition. These pressures have distinctive regional patterns and their resulting impact on soil conditions is modified by local site characteristics. We have applied the VSD+ soil dynamic model to study impacts of deposition and climate change on soil properties, using MetHyd and GrowUp as pre-processors to provide input to VSD+.

In-hospital cardiac arrest: are we overlooking a key distinction?

Purpose Of Review: To review the epidemiology, peri-arrest management, and research priorities related to in-hospital cardiac arrest (IHCA) and explore key distinctions between IHCA and out-of-hospital cardiac arrest (OHCA) as they pertain to the clinician and resuscitation scientist.

Recent Findings: IHCA is a common and highly morbid event amongst hospitalized patients in the United States. As compared with patients who experience an OHCA, patients who experience an IHCA tend to have more medical comorbidities, have a witnessed arrest, and be attended to by professional first responders.

Neighborhood characteristics, bystander automated external defibrillator use, and patient outcomes in public out-of-hospital cardiac arrest.

Background: Automated external defibrillators (AEDs) can be used by bystanders to provide rapid defibrillation for patients with out-of-hospital cardiac arrest (OHCA). Whether neighborhood characteristics are associated with AED use is unknown. Furthermore, the association between AED use and outcomes has not been well characterized for all (i.

ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A>G and c.5461-10T>C cause Stargardt disease due to defective splicing.

Purpose: Inherited retinal dystrophies (IRDs) represent a group of progressive conditions affecting the retina. There is a great genetic heterogeneity causing IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a disease with early onset, central visual impairment, frequent appearance of yellowish flecks and mutations in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene.

The care of patients assessed as not in need of emergency ambulance care - Registered nurses' lived experiences.

Aim: The aim of this study was to describe the care of patients assessed as not in need of emergency ambulance care, from Registered Nurse's lived experiences.

Background: Non-emergency patients in need of ambulance care are described as vulnerable and patients in ambulance care have earlier been found to be dependent on the Registered Nurse. However, little is known about the care of non-emergency patients in the ambulance setting, from the perspective of Registered Nurses.

Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury.

There are no effective therapies available currently to ameliorate loss of function for patients with spinal cord injuries (SCIs). In addition, proposed treatments that demonstrated functional recovery in animal models of acute SCI have failed almost invariably when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration.

Derivation and Internal Validation of a Mortality Prediction Tool for Initial Survivors of Pediatric In-Hospital Cardiac Arrest.

Objectives: To develop a clinical prediction score for predicting mortality in children following return of spontaneous circulation after in-hospital cardiac arrest.

Design: Observational study using prospectively collected data.

Setting: This was an analysis using data from the Get With The Guidelines-Resuscitation registry between January 2000 and December 2015.

Clopidogrel Carboxylic Acid Glucuronidation is Mediated Mainly by UGT2B7, UGT2B4, and UGT2B17: Implications for Pharmacogenetics and Drug-Drug Interactions.

The antiplatelet drug clopidogrel is metabolized to an acyl--d-glucuronide, which causes time-dependent inactivation of CYP2C8. Our aim was to characterize the UDP-glucuronosyltransferase (UGT) enzymes that are responsible for the formation of clopidogrel acyl--d-glucuronide. Kinetic analyses and targeted inhibition experiments were performed using pooled human liver and intestine microsomes (HLMs and HIMs, respectively) and selected human recombinant UGTs based on preliminary screening.

Effects of Genetic Variants on Carboxylesterase 1 Gene Expression, and Clopidogrel Pharmacokinetics and Antiplatelet Effects.

Several single nucleotide variations (SNVs) affect carboxylesterase 1 (CES1) activity, but the effects of genetic variants on CES1 gene expression have not been systematically investigated. Therefore, our aim was to investigate effects of genetic variants on CES1 gene expression in two independent whole blood sample cohorts of 192 (discovery) and 88 (replication) healthy volunteers and in a liver sample cohort of 177 patients. Furthermore, we investigated possible effects of the found variants on clopidogrel pharmacokinetics (n = 106) and pharmacodynamics (n = 46) in healthy volunteers, who had ingested a single 300 mg or 600 mg dose of clopidogrel.

Bystander automated external defibrillator use and clinical outcomes after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

Aim: To systematically review studies comparing bystander automated external defibrillator (AED) use to no AED use in regard to clinical outcomes in out-of-hospital cardiac arrest (OHCA), and to provide a descriptive summary of studies on the cost-effectiveness of bystander AED use.

Methods: We searched Medline, Embase, the Web of Science, and the Cochrane Library for randomized trials and observational studies published before June 1, 2017. Meta-analyses were performed for patients with all rhythms, shockable rhythms, and non-shockable rhythms.

The ghost of pandemics past: revisiting two centuries of influenza in Sweden.

Previous influenza pandemics are usually invoked in pandemic preparedness planning without a thorough analysis of the events surrounding them, what has been called the 'configuration' of epidemics. Historic pandemics are instead used to contrast them to the novelty of the coming imagined plague or as fear of a ghost-like repetition of the past. This view of pandemics is guided by a biomedical framework that is ahistorical and reductionist.

Cytochrome c in patients undergoing coronary artery bypass grafting: A post hoc analysis of a randomized trial.

Purpose: To establish whether plasma cytochrome c is detectable in patients undergoing cardiac surgery, whether cytochrome c levels are associated with lactate/inflammatory markers/cellular oxygen consumption, and whether cytochrome c levels are associated with clinical outcomes.

Materials And Methods: This was an observational sub-study of a randomized trial comparing thiamine to placebo in patients undergoing coronary artery bypass grafting. Patients had blood drawn before, after, and again 6h after surgery.

Quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome Criteria as Predictors of Critical Care Intervention Among Patients With Suspected Infection.

Objectives: The Sepsis III clinical criteria for the diagnosis of sepsis rely on scores derived to predict inhospital mortality. In this study, we introduce the novel outcome of "received critical care intervention" and investigate the related predictive performance of both the quick Sequential Organ Failure Assessment and the Systemic Inflammatory Response Syndrome criteria.

Design: This was a single-center, retrospective analysis of electronic health records.

Titan's ionosphere: A survey of solar EUV influences.

Effects of solar EUV on positive ions and heavy negative charge carriers (molecular ions, aerosol, and/or dust) in Titan's ionosphere are studied over the course of almost 12 years, including 78 flybys below 1400 km altitude between TA (October 2004) and T120 (June 2016). The Radio and Plasma Wave Science/Langmuir Probe-measured ion charge densities (normalized by the solar zenith angle) show statistically significant variations with respect to the solar EUV flux. Dayside charge densities increase by a factor of ≈2 from solar minimum to maximum, while nightside charge densities are found to anticorrelate with the EUV flux and decrease by a factor of ≈3-4.

The knowledge desired by emergency medical service managers of their ambulance clinicians - A modified Delphi study.

Aim: The aim of the study was to identify the types of knowledge that Swedish Emergency Medical Service (EMS) managers considered desirable in their Ambulance Clinicians.

Background: Emergency medical service managers are responsible for organisational tasking and in this are dependent on the knowledge possessed by their ambulance clinicians. It would therefore be of value to explore EMS managers' approach to this knowledge.