Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Adult Patients with X-Linked Hypophosphatemia.

Objective: To examine the highest certainty evidence addressing the management of X-linked hypophosphatemia (XLH) in adults to inform treatment recommendations.

Methods: We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included RCTs and observational studies of individuals 18+ with clinically or genetically confirmed XLH.

Ethical Considerations Regarding Psychedelics for Clinical Pain Research.

Psychedelics, substances with a long history of cultural and medicinal use, are experiencing a resurgence in clinical research, particularly in psychiatry. Despite their classification as Schedule I drugs, recent studies suggest therapeutic potential, particularly in treating refractory depression. With chronic pain representing a major health concern and with few non-opioid treatment options available, psychedelics are being explored as alternative treatment modalities.

Cytomegalovirus viremia and hepatitis B reactivation in patient with RET fusion-positive non-small cell lung cancer treated with pralsetinib.

Introduction: Mutated rearranged during transfection (RET) kinase is found in approximately 1-2% non-small-cell lung cancer (NSCLC) patients. These patients are typically younger, non-smokers, and have non-squamous histology. Pralsetinib is a novel RET inhibitor that showed promising efficacy and tolerability in the ARROW trial.

Do Patients With Candidemia Need an Ophthalmologic Examination?

Background: The Infectious Diseases Society of America recommends a screening dilated retinal examination by an ophthalmologist for all patients with candidemia. Conversely, the American Academy of Ophthalmology recommends against routine screening in patients with candidemia without symptoms.

Methods: In a collaborative effort between infectious diseases and ophthalmology, we examined the incidence of ocular complications in 308 patients with candidemia and subsequently measured the rate of fundoscopic examinations, risk factors for ocular complications, management changes, and outcomes.

Humeral Stem Design in Reverse Total Shoulder Arthroplasty.

Purpose Of The Review: There have been tremendous modifications to the humeral component since Paul Grammont first introduced the reverse total shoulder arthroplasty in 1985. The purpose of this article is to review historical design features and their drawbacks and to summarize the clinical outcomes of modern designs.

Recent Findings: Decreasing the neck-shaft angle and increasing humeral lateralization have helped address problems of scapular notching and limited internal and external rotation that were common with traditional designs.

Diabetes Mellitus Associated with Maternally Inherited Diabetes and Deafness (MIDD): From Pathogenic Variant to Phenotype.

Maternally inherited diabetes and deafness (MIDD) is a monogenic mitochondrial disorder caused by a pathogenic variant in the MT-TL1 gene encoding for a leucine transfer RNA. We propose a new hypothesis that explains how the MT-TL1 variant causes impaired glucose tolerance and diabetes in MIDD. We suggest that diabetes in MIDD primarily depends on a variable combination of insulin resistance and impaired beta cell function that seems more likely to occur in the presence of high skeletal muscle heteroplasmy and moderate beta cell heteroplasmy for m.

A Narrative Review of Congenital Syphilis in the United States: Innovative Perspectives on a Complex Public Health and Medical Disease.

Over the past two decades, congenital syphilis cases have risen 11-fold in the United States. While disparities across geography, race, and ethnicity exist, lack of timely screening or treatment is identified in 88% of cases nationally. Congenital syphilis is a public health and medical problem rooted in systematic and societal structural determinants of health and healthcare limitations.

Exome variant prioritization in a large cohort of hearing-impaired individuals indicates IKZF2 to be associated with non-syndromic hearing loss and guides future research of unsolved cases.

Although more than 140 genes have been associated with non-syndromic hereditary hearing loss (HL), at least half of the cases remain unexplained in medical genetic testing. One reason is that pathogenic variants are located in 'novel' deafness genes. A variant prioritization approach was used to identify novel (candidate) genes for HL.

High-Throughput Image-Based Assay for Identifying Hepatocyte Microtubule Disruption.

Disruption of microtubule stability in mammalian cells may lead to genotoxicity and carcinogenesis. The ability to screen for microtubule destabilization or stabilization is therefore a useful and efficient approach to aid in the design of molecules that are safe for human health. In this study, we developed a high-throughput 384-well assay combining immunocytochemistry with high-content imaging to assess microtubule disruption in the metabolically competent human liver cell line: HepaRG.

In Vitro Predictions of Acute Fish Toxicity for Development of Sustainable Crop Protection Products.

New agrochemicals must demonstrate safety to numerous ecological systems, including aquatic systems, and aquatic vertebrate toxicity is typically evaluated by using the in vivo acute fish toxicity (AFT) test. Here, we investigated two alternative in vitro assays using a cell line isolated from rainbow trout () gill tissue: (i) adenosine triphosphate (ATP) luminescence and (ii) cell painting. The former assay measures cytotoxicity, while the latter measures changes in cellular morphology in response to chemical exposure.

Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.

Ubiquitination is one of the most common posttranslational modifications in eukaryotic cells. Depending on the architecture of polyubiquitin chains, substrate proteins can meet different cellular fates, but our understanding of how chain linkage controls protein fate remains limited. UBL-UBA shuttle proteins, such as UBQLN2, bind to ubiquitinated proteins and to the proteasome or other protein quality control machinery elements and play a role in substrate fate determination.

Renal and multisystem effectiveness of 3.9 years of migalastat in a global real-world cohort: Results from the followME Fabry Pathfinders registry.

Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat-amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient-focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry-associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real-world setting.

Effects of hours of sleep on ImPACT concussion testing: comparing baseline with postinjury scores.

Objective: The influence of sleep on baseline and postconcussion neurocognitive performance prior to Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is poorly understood. Since ImPACT is widely used in youth sport to assess neurocognitive performance before and after head injury, it is important to delineate factors that affect testing performance. While some have reported correlations between fewer hours of sleep and lower scores on baseline tests, others have not observed any such associations.

Clinical, Neuroimaging, and Metabolic Footprint of the Neurodevelopmental Disorder Caused by Monoallelic Variants.

Background And Objectives: Hexokinase 1 (encoded by ) catalyzes the first step of glycolysis, the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate. Monoallelic variants causing a neurodevelopmental disorder (NDD) have been reported in 12 individuals.

Methods: We investigated clinical phenotypes, brain MRIs, and the CSF of 15 previously unpublished individuals with monoallelic variants and an NDD phenotype.

Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.

Ubiquitination is one of the most common post-translational modifications in eukaryotic cells. Depending on the architecture of polyubiquitin chains, substrate proteins can meet different cellular fates, but our understanding of how chain linkage controls protein fate remains limited. UBL-UBA shuttle proteins, such as UBQLN2, bind to ubiquitinated proteins and to the proteasome or other protein quality control machinery elements and play a role in substrate fate determination.

Clinical Performance of Plasma Metagenomic Sequencing in Immunocompromised Pediatric Patients.

The performance of plasma metagenomic next-generation sequencing was evaluated in an immunocompromised pediatric population. The clinical impact was limited, with management changes in 13% of cases. Moreover, organisms thought to be non-pathogenic were commonly detected.

Evaluation of KIDs List Compliance at a Children's Hospital Within a Large Academic Medical Center.

Objectives: In 2020, a list of Key Potentially Inappropriate Drugs in Pediatrics, known as the "KIDs List," was published. The objective of this analysis was to evaluate institutional compliance with the -recommendations in this publication and identify areas for improvement.

Methods: Medications in the KIDs List were compared to the institutional formulary at a large academic medical center caring for pediatric and adult patients.

Naturally occurring splice variants dissect the functional domains of BHC80 and emphasize the need for RNA analysis.

Pathogenic PHF21A variation causes PHF21A-related neurodevelopmental disorders (NDDs). Although amorphic alleles, including haploinsufficiency, have been established as a disease mechanism, increasing evidence suggests that missense variants as well as frameshift variants extending the BHC80 carboxyl terminus also cause disease. Expanding on these, we report a proposita with intellectual disability and overgrowth and a novel de novo heterozygous PHF21A splice variant (NM_001352027.