Mutations in Genes Encoding Subunits of the RNA Exosome as a Potential Novel Cause of Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) in association with RNA exosome encoding mutations has only recently been recognized. Here, we present an infant (female) with an mutation (c.230_232del p.

Therapeutic communication improves patient comfort during venipuncture in children: a single-blinded intervention study.

The aim of this study was to examine whether therapeutic communication improves children's comfort during venipuncture compared to standard communication. This study was registered in the Dutch trial register (NL8221), December 10, 2019. This single-blinded interventional study was carried out in an outpatient clinic of a tertiary hospital.

FriendlyClearMap: an optimized toolkit for mouse brain mapping and analysis.

Background: Tissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratory's use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2's CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment.

Stereoselective ketamine effect on cardiac output: a population pharmacokinetic/pharmacodynamic modelling study in healthy volunteers.

Background: Ketamine has cardiac excitatory side-effects. Currently, data on the effects of ketamine and metabolite concentrations on cardiac output are scarce. We therefore developed a pharmacodynamic model derived from data from a randomised clinical trial.

Retinal oximetry with a prototype handheld oximeter during hyperoxia.

Purpose: Retinal oximetry measures oxygen saturation in retinal vessels. With the introduction of a mobile handheld prototype oximeter, this technique will become available for a broader patient population including bedridden patients and newborn babies. The objective is to determine the sensitivity of this handheld oximeter in room air and during isocapnic hyperoxia.

Biventricular function in exercise during autonomic (thoracic epidural) block.

Background: Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia (TEA) was previously shown to reduce right and left ventricular systolic function and effective pulmonary arterial elastance. At conditions of constant paced heart rate, cardiac output and systemic hemodynamics were unchanged. In this study, we further investigated the effect of cardiac sympathicolysis during physical stress and increased oxygen demand.

Prevalence of DNA of regular occupants in vehicles.

People will deposit, redistribute and remove biological traces when they interact with their environment. Understanding the dynamics of trace DNA is crucial to assess both the optimal sampling strategy to recover traces and the relevance of DNA evidence in the context of a case. This paper addresses the prevalence of DNA of drivers, passengers, and unknown individuals in vehicles.

Deep neuromuscular block does not improve surgical conditions in patients receiving sevoflurane anaesthesia for laparoscopic renal surgery.

Background: Deep neuromuscular block is associated with improved working conditions during laparoscopic surgery when propofol is used as a general anaesthetic. However, whether deep neuromuscular block yields similar beneficial effects when anaesthesia is maintained using volatile inhalation anaesthesia has not been systematically investigated. Volatile anaesthetics, as opposed to intravenous agents, potentiate muscle relaxation, which potentially reduces the need for deep neuromuscular block to obtain optimal surgical conditions.

EHMT1 regulates Parvalbumin-positive interneuron development and GABAergic input in sensory cortical areas.

Mutations in the Euchromatic Histone Methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a rare form of intellectual disability (ID) with strong autistic traits and sensory processing deficits. Proper development of inhibitory interneurons is crucial for sensory function. Here we report a timeline of Parvalbumin-positive (PV) interneuron development in the three most important sensory cortical areas in the Ehmt1 mouse.

Reduced postoperative pain using Nociception Level-guided fentanyl dosing during sevoflurane anaesthesia: a randomised controlled trial.

Background: The majority of postoperative patients report moderate to severe pain, possibly related to opioid underdosing or overdosing during surgery. Objective guidance of opioid dosing using the Nociception Level (NOL) index, a multiparameter artificial intelligence-driven index designed to monitor nociception during surgery, may lead to a more appropriate analgesic regimen, with effects beyond surgery. We tested whether NOL-guided opioid dosing during general anaesthesia results in less postoperative pain.

Pharmacokinetics of ketamine and its major metabolites norketamine, hydroxynorketamine, and dehydronorketamine: a model-based analysis.

Background: Recent studies show activity of ketamine metabolites, such as hydroxynorketamine, in producing rapid relief of depression-related symptoms and analgesia. To improve our understanding of the pharmacokinetics of ketamine and metabolites norketamine, dehydronorketamine, and hydroxynorketamine, we developed a population pharmacokinetic model of ketamine and metabolites after i.v.

Effect of treatment on cognitive and attention problems in children with narcolepsy type 1.

Study Objectives: To ascertain the presence of cognitive and attention problems in treatment naïve children with narcolepsy type 1 (NT1) and to explore whether children recently diagnosed with NT1 improve with respect to cognition and attention problems 1 year after regular treatment for NT1.

Methods: A total of 15 treatment naïve children (7-15 years) with recently diagnosed NT1 were recruited from three sleep medicine centers in the Netherlands. The control group consisted of 15 healthy children, being frequency matched on age and gender.

Opioid utility function: methods and implications.

Opioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse and addiction, sedation and potentially lethal respiratory depression (RD). Consequently, opioid treatment requires careful evaluation in terms of benefit on the one hand and harm on the other. Considering benefit and harm from an economic perspective, opioid treatment should lead to profit maximization with decision theory defining utility as (profit - loss).

Safety of sugammadex for reversal of neuromuscular block.

: Sugammadex is a modified cyclodextrin that is able to reverse neuromuscular block induced by aminosteroidal neuromuscular blocking drugs. Compared to reversal with neostigmine, it reverses neuromuscular block quicker and more predictable and without cholinergic side effects. However, there have been concerns about sugammadex ability to bind other drugs and its effects on QT interval and clotting times.

Reversal of Partial Neuromuscular Block and the Ventilatory Response to Hypoxia: A Randomized Controlled Trial in Healthy Volunteers.

What We Already Know About This Topic: The ventilatory response to hypoxia is a critical reflex that is impaired by neuromuscular blocking drugs. However, the degree to which this reflex is restored after reversal of blockade is unknown.

What This Article Tells Us That Is New: Despite full reversal of neuromuscular blockade at the thumb using different drug classes, this hypoxic chemoreflex is not fully restored.

Opioid-induced respiratory depression in humans: a review of pharmacokinetic-pharmacodynamic modelling of reversal.

Background: Opioids are potent painkillers but come with serious adverse effects ranging from addiction to potentially lethal respiratory depression. A variety of drugs with separate mechanisms of action are available to prevent or reverse opioid-induced respiratory depression (OIRD).

Methods: The authors reviewed human studies on reversal of OIRD using models that describe and predict the time course of pharmacokinetics (PK) and pharmacodynamics (PD) of opioids and reversal agents and link PK to PD.

Nociception-guided versus Standard Care during Remifentanil-Propofol Anesthesia: A Randomized Controlled Trial.

Background: The multidimensional index of nociception, the nociception level, outperforms blood pressure and heart rate in detection of nociceptive events during anesthesia. We hypothesized that nociception level-guided analgesia reduces opioid consumption and suboptimal anesthesia events such as low blood pressure and use of vasoactive medication.

Methods: In this single-blinded randomized study, 80 American Society of Anesthesiologists class I-III adult patients of either sex, scheduled for major abdominal procedures under remifentanil/propofol anesthesia by target-controlled infusion, were included.

Targeting relevant sampling areas for human biological traces: Where to sample displaced bodies for offender DNA?

Sampling strategy is one of the deciding factors in DNA typing success rates. Small amounts of bodily fluid traces and (skin) contact traces are currently not visualized in standard forensic practice. Trace recovery is usually based on the information available in a particular case and on the experience and 'forensic common sense' applied by the trace recovery expert.

Effects of Thoracic Epidural Anesthesia on Neuronal Cardiac Regulation and Cardiac Function.

Cardiac sympathetic blockade with high-thoracic epidural anesthesia is considered beneficial in patients undergoing major surgery because it offers protection in ischemic heart disease. Major outcome studies have failed to confirm such a benefit, however. In fact, there is growing concern about potential harm associated with the use of thoracic epidural anesthesia in high-risk patients, although underlying mechanisms have not been identified.

Sharing data on DNA transfer, persistence, prevalence and recovery: Arguments for harmonization and standardization.

Sharing data between forensic scientists on DNA transfer, persistence, prevalence and recovery (TPPR) is crucial to advance the understanding of these issues in the criminal justice community. We present the results of a collaborative exercise on reporting forensic genetics findings given activity level propositions. This exercise outlined differences in the methodology that was applied by the participating laboratories, as well as limitations to the use of published data on DNA TPPR.

The use of surgical rating scales for the evaluation of surgical working conditions during laparoscopic surgery: a scoping review.

Introduction: Surgical rating scales (SRSs) enable the surgeon to uniformly quantify surgical working conditions. They are increasingly used as a primary outcome in studies evaluating the effect of anaesthesia or surgery-related interventions on the quality of the surgical work field. SRSs are especially used in laparoscopic surgery due to a renewed interest in deep neuromuscular block.

Handheld Retinal Oximetry in Healthy Young Adults.

Purpose: The objective of this study was to measure the relative retinal oxygen saturation with a prototype, mobile handheld oximeter in upright and supine position and to compare these measurements to the gold standard Oxymap T1 retinal oximeter in upright position. A handheld oximeter is needed for measurements of infants with retinopathy of prematurity as well as acutely injured and bedridden adults.

Methods: Healthy volunteers (age 18-35) were recruited at the Leiden University Medical Center.