Neurodevelopmental Disorder Caused by Deletion of , a lncRNA Gene.

encodes a human long noncoding RNA (lncRNA) adjacent to , a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here, we report our findings in three unrelated children with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination - a phenotype that is distinct from the phenotypes of patients with haploinsufficiency.

Diabetic Endothelial Cell Glycogen Synthase Kinase 3β Activation Induces VCAM1 Ectodomain Shedding.

Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been found to be associated with poor cardiovascular disease (CVD) outcomes, supporting VCAM1's role as a potential diagnostic marker and therapeutic target.

Breakthrough COVID-19 Infections in the US: Implications for Prolonging the Pandemic.

The incidence of COVID-19 breakthrough infections-an infection that occurs after you have been vaccinated-has increased in frequency since the Delta and now Omicron variants of the SARS-CoV-2 coronavirus have become the dominant strains transmitted in the United States (US). Evidence suggests that individuals with breakthrough infections, though rare and expected, may readily transmit COVID-19 to unvaccinated populations, posing a continuing threat to the unvaccinated. Here, we examine factors contributing to breakthrough infections including a poor immune response to the vaccines due to the fact of advanced age and underlying comorbidities, the natural waning of immune protection from the vaccines over time, and viral variants that escape existing immune protection from the vaccines.

Serotonin Toxicity Precipitated by Tramadol in the Setting of Polypharmacy: A Case of Serotonin Syndrome.

Serotonin syndrome (SS), a potentially life-threatening condition, typically occurs due to polypharmacy and interaction with multiple serotonergic agents. The case presented here is based on a serotonin syndrome (SS) diagnosis, precipitated by newly prescribed tramadol in conjunction with previously prescribed serotonergic medications. A 79-year-old woman receiving combined citalopram and trazodone for major depressive disorder alongside oxycodone for chronic pain developed generalized weakness, tremors, altered mentation, episodic auditory and visual hallucinations, fever, tachypnea, tachycardia, and diaphoresis a few days after tramadol was prescribed for pain.

Coordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region.

E74-like factor 5 (ELF5) and ETS-homologous factor (EHF) are epithelial selective ETS family transcription factors (TFs) encoded by genes at chr11p13, a region associated with cystic fibrosis (CF) lung disease severity. EHF controls many key processes in lung epithelial function so its regulatory mechanisms are important. Using CRISPR/Cas9 technology, we removed three key cis-regulatory elements (CREs) from the chr11p13 region and also activated multiple open chromatin sites with CRISPRa in airway epithelial cells.

Chromatin Remodeling Proteins in Epilepsy: Lessons From -Associated Epilepsy.

The chromodomain helicase DNA-binding (CHD) family of proteins are ATP-dependent chromatin remodelers that contribute to the reorganization of chromatin structure and deposition of histone variants necessary to regulate gene expression. CHD proteins play an important role in neurodevelopment, as pathogenic variants in , , , and have been associated with a range of neurological phenotypes, including autism spectrum disorder (ASD), intellectual disability (ID) and epilepsy. Pathogenic variants in are associated with developmental epileptic encephalopathy (DEE) in humans, however little is known about how these variants contribute to this disorder.

Regulatory dynamics of 11p13 suggest a role for EHF in modifying CF lung disease severity.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), but are not good predictors of lung phenotype. Genome-wide association studies (GWAS) previously identified additional genomic sites associated with CF lung disease severity. One of these, at chromosome 11p13, is an intergenic region between Ets homologous factor (EHF) and Apaf-1 interacting protein (APIP).

Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ.

Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy.

Genotype-Specific Interaction of Latent TGFβ Binding Protein 4 with TGFβ.

Latent TGFβ binding proteins are extracellular matrix proteins that bind latent TGFβ to form the large latent complex. Nonsynonymous polymorphisms in LTBP4, a member of the latent TGFβ binding protein gene family, have been linked to several human diseases, underscoring the importance of TGFβ regulation for a range of phenotypes. Because of strong linkage disequilibrium across the LTBP4 gene, humans have two main LTBP4 alleles that differ at four amino acid positions, referred to as IAAM and VTTT for the encoded residues.

Genetic Modifiers for Neuromuscular Diseases.

Neuromuscular diseases, which encompass disorders that affect muscle and its innervation, are highly heritable. Genetic diagnosis now frequently pinpoints the primary mutation responsible for a given neuromuscular disease. However, the results from genetic testing indicate that neuromuscular disease phenotypes may vary widely, even in individuals with the same primary disease-causing mutation.

Second cistron in CACNA1A gene encodes a transcription factor mediating cerebellar development and SCA6.

The CACNA1A gene, encoding the voltage-gated calcium channel subunit α1A, is involved in pre- and postsynaptic Ca(2+) signaling, gene expression, and several genetic neurological disorders. We found that CACNA1A coordinates gene expression using a bicistronic mRNA bearing a cryptic internal ribosomal entry site (IRES). The first cistron encodes the well-characterized α1A subunit.

LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy.

Objective: Duchenne muscular dystrophy (DMD) displays a clinical range that is not fully explained by the primary DMD mutations. Ltbp4, encoding latent transforming growth factor-β binding protein 4, was previously discovered in a genome-wide scan as a modifier of murine muscular dystrophy. We sought to determine whether LTBP4 genotype influenced DMD severity in a large patient cohort.

Prevalence of 25-hydroxyvitamin D deficiency in an urban general internal medicine academic practice.

Vitamin D deficiency has received increased academic interest because of its association with many common disease processes. The goal of our study was to document the prevalence of vitamin D deficiency. A retrospective chart review of 25-hydroxyvitamin D (ng/mL) levels at the University of Tennessee Health Science Center was conducted on general internal medicine patients over an 18-month period.

Residential proximity to toxic release sites and the implications for low birth weight and premature delivery.

The objective of the study discussed in this article was to evaluate the impact of residential proximity to toxic release sites (TRS) and potential implications for low birth weight (LBW) and premature delivery in Shelby County, Tennessee women. The sample (N = 369) included pregnant women who participated in the Blues Project (2007-2009). ArcGIS was used to map the mother's residence at delivery and distance from each of the 10 TRS.

Screening of Brazilian families with primary dystonia reveals a novel THAP1 mutation and a de novo TOR1A GAG deletion.

The TOR1A and THAP1 genes were screened for mutations in a cohort of 21 Brazilian patients with Primary torsion dystonia (PTD). We identified a de novo delGAG mutation in the TOR1A gene in a patient with a typical DYT1 phenotype and a novel c.1A > G (p.

Prevalence of 25-hydroxyvitamin D deficiency in an urban general internal medicine academic practice.

Vitamin D deficiency has received increased academic interest because of its association with many common disease processes. The goal of our study was to document the prevalence of vitamin D deficiency. A retrospective chart review of 25-hydroxyvitamin D (ng/ml) levels at the University of Tennessee Health Science Center was conducted on general internal medicine patients over an 18-month period.

Compass: the direction for professional nursing development at a tertiary acute care facility.

In this article, the author discusses a professional nursing development model used at one facility, including the model's outcomes over a 3-year period and its further direction. This model, called Compass, has been useful for the professional development and retention of nursing staff.

Patterns of sexual and erectile dysfunction and response to treatment in patients receiving androgen deprivation therapy for prostate cancer.

Objective: To investigate the incidence of patient-reported erectile (ED) and sexual dysfunction and response to treatment in men after the induction of androgen deprivation therapy (ADT) for prostate cancer, as ADT-induced changes in serum testosterone can result in changes in libido and sexual function.

Patients And Methods: We retrospectively reviewed patients receiving ADT for prostate cancer at our institution between January 1989 and July 2005; those receiving only neoadjuvant ADT were excluded. Variables included age, race, body mass index, prostate-specific antigen level before ADT, Gleason sum, clinical stage, ADT type (medical vs surgical) and schedule (continuous vs intermittent), previous treatment for prostate cancer, presence of pre-existing or new-onset diabetes mellitus (DM), and presence of ED before ADT.

Development and validation of SIMS: an instrument for measuring quality of life of adults with sickle cell disease.

In recent years, there has been a growing interest in the assessment of quality of life (QOL) issues, particularly in chronic debilitating conditions. Several instruments have been developed, tested, and validated in the general population and in other chronic diseases; however, few studies have examined QOL issues in adults with sickle cell disease (SCD). We developed Sickle Cell Impact Measurement Scale (SIMS), an instrument for measuring the QOL of adults with SCD.

Risk of new-onset diabetes mellitus and worsening glycaemic variables for established diabetes in men undergoing androgen-deprivation therapy for prostate cancer.

OBJECTIVE To investigate the incidence of new-onset diabetes mellitus (NODM) and of worsening glycaemic control in established DM after starting androgen-deprivation therapy (ADT) for prostate cancer, as ADT is associated with altered body composition, potentially influencing insulin sensitivity. PATIENTS AND METHODS We retrospectively reviewed patients receiving ADT for prostate cancer at our institution between January 1989 and July 2005; those with incomplete information and those receiving only neoadjuvant ADT were excluded. Variables examined included age, race, body mass index (BMI), pretreatment prostate-specific antigen, Gleason sum, clinical stage, ADT type (medical vs surgical) and schedule (continuous vs intermittent), presence of pre-existing DM, serum glucose and glycosylated haemoglobin (HbA1c) levels before and after ADT, and receipt of vitamin D or bisphosphonate supplementation.

Osteoporosis and fractures after androgen deprivation initiation for prostate cancer.

Introduction: Androgen deprivation therapy (ADT) is widely utilized for treatment of localized and advanced prostate cancer (CaP). ADT is associated with increased rates of osteoporosis; however, its impact on fracture risk is not completely understood. We investigated incidence and predisposing factors for osteoporosis and fractures in a large, contemporary, single institution series of patients treated with ADT for CaP.