CUL3-related neurodevelopmental disorder: Clinical phenotype of 20 new individuals and identification of a potential phenotype-associated episignature.

Neurodevelopmental disorder with or without autism or seizures (NEDAUS) is a neurodevelopmental disorder characterized by global developmental delay, speech delay, seizures, autistic features, and/or behavior abnormalities. It is caused by CUL3 (Cullin-3 ubiquitin ligase) haploinsufficiency. We collected clinical and molecular data from 26 individuals carrying pathogenic variants and variants of uncertain significance (VUS) in the CUL3 gene, including 20 previously unreported cases.

The culture of care to enhance laboratory animal personnel well-being: a scoping review.

There has been intense focus on improving the quality of animal research in recent times. An emerging concept of a 'culture of care' has been proposed as another important pillar to enhance scientific quality, with staff well-being being a critical aspect. Professionals working with research animals can face moral and psychological burdens and are at risk of experiencing work-related stress.

Loss-of-function of the Zinc Finger Homeobox 4 () gene underlies a neurodevelopmental disorder.

8q21.11 microdeletions encompassing the gene encoding transcription factor ZFHX4, have previously been associated by us with a syndromic form of intellectual disability, hypotonia, decreased balance and hearing loss. Here, we report on 57 individuals, 52 probands and 5 affected family members, with protein truncating variants (n=36), (micro)deletions (n=20) or an inversion (n=1) affecting with variable developmental delay and intellectual disability, distinctive facial characteristics, morphological abnormalities of the central nervous system, behavioral alterations, short stature, hypotonia, and occasionally cleft palate and anterior segment dysgenesis.

Experiences of early career researchers: Influences on the design and reporting of animal experiments, and the practical and emotional support needed to enhance best practice methods.

While best practice methodology in animal research aims to address reproducibility and translational issues, awareness and implementation remains low. Preclinical systematic reviews have highlighted many flaws, including issues with internal validity and reporting. With early career researchers (ECRs) heavily involved in all aspects of animal experiments, it is crucial we understand what shapes their research practices.

The impact of an adapted SPIKES protocol vs routine care in the delivery of bad news to IVF patients: an exploratory pilot multicenter randomized controlled trial.

Purpose: Determine if the SPIKES method was associated with less distress and more compassion than current modes of delivering negative pregnancy test results to patients undergoing in vitro fertilization.

Methods: Twenty-seven nurses from two centers were randomized to use the modified SPIKES script or continue their standard of care; 136 patients with a negative hCG following embryo transfer were included. SPIKES nurses received 1 h of training by a study psychologist; nurses in the control group were instructed to deliver the news as done previously.

Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial- The ABC-Sepsis Trial.

Objectives: International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital.

The detection of a strong episignature for Chung-Jansen syndrome, partially overlapping with Börjeson-Forssman-Lehmann and White-Kernohan syndromes.

Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm).

The influence of undetected hemolysis on POCT potassium results in the emergency department.

Objectives: This study aimed to evaluate discrepancies in potassium measurements between point-of-care testing (POCT) and central laboratory (CL) methods, focusing on the impact of hemolysis on these measurements and its impact in the clinical practice in the emergency department (ED).

Methods: A retrospective analysis was conducted using data from three European university hospitals: Technische Universitat München (Germany), Hospital Universitario La Paz (Spain), and Erasmus University Medical Center (The Netherlands). The study compared POCT potassium measurements in EDs with CL measurements.

DNA methylation episignature and comparative epigenomic profiling for Pitt-Hopkins syndrome caused by TCF4 variants.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by pathogenic variants in TCF4, leading to intellectual disability, specific morphological features, and autonomic nervous system dysfunction. Epigenetic dysregulation has been implicated in PTHS, prompting the investigation of a DNA methylation (DNAm) "episignature" specific to PTHS for diagnostic purposes and variant reclassification and functional insights into the molecular pathophysiology of this disorder. A cohort of 67 individuals with genetically confirmed PTHS and three individuals with intellectual disability and a variant of uncertain significance (VUS) in TCF4 were studied.

Prolonged acid reflux monitoring using acid exposure time and DeMeester score: two days are not enough.

Background: Wireless pH monitoring allows for a definitive GERD diagnosis, which is essential for optimal medical or surgical management of the patient. However, there is no guideline recommendation on whether prolonged pH testing (72 or 96 h) provides additional benefit when compared to the standard 48-h testing. We aimed to assess whether prolonged pH monitoring diagnoses more patients with GERD, as well as compare the DeMeester score to acid exposure time as diagnostic criteria for GERD.

Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global DNA methylation profile.

Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 gene result in a syndromic neurodevelopmental disorder named Kleefstra syndrome.

Identification of the DNA methylation signature of Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment. MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period.

Metabolomic signatures of ideal cardiovascular health in black adults.

Plasma metabolomics profiling is an emerging methodology to identify metabolic pathways underlying cardiovascular health (CVH). The objective of this study was to define metabolomic profiles underlying CVH in a cohort of Black adults, a population that is understudied but suffers from disparate levels of CVD risk factors. The Morehouse-Emory Cardiovascular (MECA) Center for Health Equity study cohort consisted of 375 Black adults (age 53 ± 10, 39% male) without known CVD.

Validation of the MIRACLE Score for Prognostication After Out-of-hospital Cardiac Arrest.

Background: Out-of-hospital cardiac arrest (OHCA) is associated with very poor clinical outcomes. An optimal pathway of care is yet to be defined, but prognostication is likely to assist in the challenging decision-making required for treatment of this high-risk patient cohort. The MIRACLE score provides a simple method of neuro-prognostication but as yet it has not been externally validated.

Intensive care following in-hospital cardiac arrest / periarrest calls-experience from one Scottish hospital.

Background: In-hospital cardiac arrest/periarrest is a recognised trigger for consideration of admission to the intensive care unit (ICU). We aimed to investigate the rates of ICU admission following in-hospital cardiac arrest/periarrest, evaluate the outcomes of such patients and assess whether anticipatory care planning had taken place prior to the adult resuscitation team being called.

Methods: Analysis of all referrals to the ICU page-holder within our district general hospital is between 1st November 2018 and 31st May 2019.

DNA methylation episignature, extension of the clinical features, and comparative epigenomic profiling of Hao-Fountain syndrome caused by variants in USP7.

Purpose: Hao-Fountain syndrome (HAFOUS) is a neurodevelopmental disorder caused by pathogenic variants in USP7. HAFOUS is characterized by developmental delay, intellectual disability, speech delay, behavioral abnormalities, autism spectrum disorder, seizures, hypogonadism, and mild dysmorphic features. We investigated the phenotype of 18 participants with HAFOUS and performed DNA methylation (DNAm) analysis, aiming to generate a diagnostic biomarker.

A pilot study of alternative substrates in the critically Ill subject using a ketogenic feed.

Bioenergetic failure caused by impaired utilisation of glucose and fatty acids contributes to organ dysfunction across multiple tissues in critical illness. Ketone bodies may form an alternative substrate source, but the feasibility and safety of inducing a ketogenic state in physiologically unstable patients is not known. Twenty-nine mechanically ventilated adults with multi-organ failure managed on intensive care units were randomised (Ketogenic n = 14, Control n = 15) into a two-centre pilot open-label trial of ketogenic versus standard enteral feeding.

Optogenetic manipulation of BMP signaling to drive chondrogenic differentiation of hPSCs.

Optogenetics is a rapidly advancing technology combining photochemical, optical, and synthetic biology to control cellular behavior. Together, sensitive light-responsive optogenetic tools and human pluripotent stem cell differentiation models have the potential to fine-tune differentiation and unpick the processes by which cell specification and tissue patterning are controlled by morphogens. We used an optogenetic bone morphogenetic protein (BMP) signaling system (optoBMP) to drive chondrogenic differentiation of human embryonic stem cells (hESCs).

PSGL-1 Blockade Induces Classical Activation of Human Tumor-associated Macrophages.

Unlabelled: The immune suppressive microenvironment is a major culprit for difficult-to-treat solid cancers. Particularly, inhibitory tumor-associated macrophages (TAM) define the resistant nature of the tumor milieu. To define tumor-enabling mechanisms of TAMs, we analyzed molecular clinical datasets correlating cell surface receptors with the TAM infiltrate.

The impact of a reminder email on the return to care behavior of infertility patients after a first office visit: A quality improvement project.

Research Question: Prior research has determined that up to half of infertility patients attend one visit with an infertility specialist but do not return for a diagnostic workup or treatment. As part of a quality-of-care improvement project, patients who had not returned after one visit with an infertility specialist received an email which asked why they had not returned. The return to care behavior was then compared to a period of time when the email was not sent out, to answer the question as to whether or not the email had a significant impact on behavior.