EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

The zettabyte era is in our DNA.

This Perspective surveys the critical computational challenges associated with in vitro DNA-based data storage. As digital data expand exponentially, traditional storage media are becoming less viable, making DNA a promising solution due to its density and durability. However, numerous obstacles remain, including error correction, data retrieval from large volumes of noisy reads, and scalability.

Parental magnetic resonance imaging for the evaluation of fetuses with brain anomalies.

Aim: To evaluate the role of parental magnetic resonance imaging (MRI) in assessing fetuses with suspected brain anomalies and its use in prenatal counselling.

Method: A retrospective, multicentre chart review was conducted on fetuses who underwent brain MRI because of suspected brain abnormalities between January 2008 and December 2022, with one or both parents who underwent brain MRI (MRI-Trio) as part of prenatal counselling. Clinical and demographic data were collected, including fetal and parental MRI findings, prenatal counselling outcomes, genetic testing results, family and previous pregnancy history, neurological examinations of the born children up to 24 months of age, and autopsy reports of fetuses from terminated pregnancies.

The impact of preoperative breast MRI on the therapeutic management of breast cancer patients.

Background: The role of preoperative breast MRI to evaluate the extent of disease in breast cancer patients is considered controversial. We aimed at assessing the effect of breast MRI on the management of newly diagnosed breast cancer.

Materials: A retrospective review of 202 consecutively seen patients who were newly diagnosed with breast cancer and who underwent preoperative breast MRIs at Assuta Ashdod between June 1, 2017, and June 1, 2020.

Autosomal Dominant, Long-Standing Dysglycemia in 2 Families with Unique Phenotypic Features.

We describe 2 families with 5 members from 2 generations whose clinical and laboratory characteristics over up to 15 years were consistent with dysglycemia/impaired glucose tolerance. In both families (2 probands and 3 family members), long-term follow-up excluded diabetes type 1 and type 2. Diabetes type 1 antibodies were persistently negative and C-peptide levels were normal.

Novel phenotype associated with homozygous likely pathogenic variant in the POP1 gene.

The biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomalies.

Riboflavin-responsive lipid-storage myopathy in elderly patients.

There are scarce reports of riboflavin-responsive lipid storage myopathy in elderly patients with onset in their sixties. We describe three elderly patients with riboflavin-responsive lipid-storage myopathy. All three patients (aged 67-71 years on first examination) had subacute onset of neck extensors and proximal limb weakness progressing to inability to rise from a sitting position or to walk.

Discontinuation of benzodiazepines and Z-drugs in hospitalised population at the age of 60 and above. An open-label randomized controlled trial.

Background: Treating insomnia with hypnotic drugs in elderly patients has many adverse effects. This study aims to assess the effect of two discontinuation methods of hypnotic drugs during acute hospitalization.

Methods: We conducted an open-label randomized controlled trial that included participants aged 60 and above taking benzodiazepines or Z-Drugs for at least 3 months as a treatment for insomnia and were admitted to the hospital.

Design of optimal labeling patterns for optical genome mapping via information theory.

Motivation: Optical genome mapping (OGM) is a technique that extracts partial genomic information from optically imaged and linearized DNA fragments containing fluorescently labeled short sequence patterns. This information can be used for various genomic analyses and applications, such as the detection of structural variations and copy-number variations, epigenomic profiling, and microbial species identification. Currently, the choice of labeled patterns is based on the available biochemical methods and is not necessarily optimized for the application.

Utility of genetic testing in children with leukodystrophy.

Background: Leukodystrophies are monogenic disorders primarily affecting the white matter. We aimed to evaluate the utility of genetic testing and time-to-diagnosis in a retrospective cohort of children with suspected leukodystrophy.

Methods: Medical records of patients who attended the leukodystrophy clinic at the Dana-Dwek Children's Hospital between June 2019 and December 2021 were retrieved.

Diagnosis of fetal cortical abnormalities by new reference charts for assessment of sylvian fissure biometry.

Objective: To develop novel fetal reference ranges for the characterization of the normal appearance of the Sylvian fissures (SF) along gestation and to apply them to fetuses with cortical abnormalities affecting the SF.

Methods: In this cross-sectional study, we used three-dimensional sonographic multiplanar reformatting (3D-MPR) to examine the fetal SF. Normal development was assessed in the second and third trimesters.

Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.

Background And Purpose: Medullary tegmental cap dysplasia is a rare brainstem malformation, first described and defined by James Barkovich in his book from 2005 as an anomalous mass protruding from the posterior medullary surface. We describe the neuroimaging, clinical, postmortem, and genetic findings defining this unique malformation.

Materials And Methods: This is a multicenter, international, retrospective study.

Characterization of alternative mRNA splicing in cultured cell populations representing progressive stages of human fetal kidney development.

Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme-a transient kidney-specific progenitor state-undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms' tumor that mimics normal kidney development.

Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature.

Purpose: Pathogenic variants in genes involved in the epigenetic machinery are an emerging cause of neurodevelopment disorders (NDDs). Lysine-demethylase 2B (KDM2B) encodes an epigenetic regulator and mouse models suggest an important role during development. We set out to determine whether KDM2B variants are associated with NDD.

Juvenile mucopolysaccharidosis plus disease caused by a missense mutation in VPS33A.

A rare and fatal disease resembling mucopolysaccharidosis in infants, is caused by impaired intracellular endocytic trafficking due to deficiency of core components of the intracellular membrane-tethering protein complexes, HOPS, and CORVET. Whole exome sequencing identified a novel VPS33A mutation in a patient suffering from a variant form of mucopolysaccharidosis. Electron and confocal microscopy, immunoblotting, and glycosphingolipid trafficking experiments were undertaken to investigate the effects of the mutant VPS33A in patient-derived skin fibroblasts.

"Virtual patch clamp analysis" for predicting the functional significance of pathogenic variants in sodium channels.

Objective: Opening of voltage-gated sodium channels is crucial for neuronal depolarization. Proper channel opening and influx of Na through the ion pore, is dependent upon binding of Na ion to a specific amino-acid motif (DEKA) within the pore. In this study we used molecular dynamic simulations, an advanced bioinformatic tool, to research the dysfunction caused by pathogenic variants in SCN1a, SCN2a and SCN8a genes.

Anti-Tumorigenic Effect of a Novel Derivative of 2-Hydroxyoleic Acid and the Endocannabinoid Anandamide on Neuroblastoma Cells.

Modulation of the endogenous cannabinoid system has been suggested as a potential anticancer strategy. In the search for novel and less toxic therapeutic options, structural modifications of the endocannabinoid anandamide and the synthetic derivative of oleic acid, Minerval (HU-600), were done to obtain 2-hydroxy oleic acid ethanolamide (HU-585), which is an HU-600 derivative with the anandamide side chain. We showed that treatment of SK-N-SH neuroblastoma cells with HU-585 induced a better anti-tumorigenic effect in comparison to HU-600 as evidenced by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide assay, colony-forming assay, and migration assay.

The effect of ivermectin on the viral load and culture viability in early treatment of nonhospitalized patients with mild COVID-19 - a double-blind, randomized placebo-controlled trial.

Objectives: Ivermectin, an antiparasitic agent, also has antiviral properties. In this study, we aimed to assess whether ivermectin has anti-SARS-CoV-2 activity.

Methods: In this double-blinded trial, we compared patients receiving ivermectin for 3 days versus placebo in nonhospitalized adult patients with COVID-19.

Accessory heads of the biceps brachii muscle: A systematic review and meta-analysis.

The anatomy of the biceps brachii muscle has been a subject of interest to many researchers. In particular, the presence of one or more accessory heads has been reported to be the most common variation of the biceps brachii muscle. In fact, contemporary knowledge is quite inconsistent and lacks a definitive summary.