Safety and efficacy of viltolarsen in ambulatory and nonambulatory males with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by mutations in the dystrophin gene, causing motor and pulmonary function decline. Viltolarsen is indicated for patients with dystrophin gene mutations amenable to exon 53 skipping. Here, we report safety, motor function, and the first pulmonary function results from the open-label, phase II Galactic53 trial of viltolarsen (NCT04956289).

Monomeric myeloperoxidase is a specific biomarker for early-stage ovarian cancer.

Ovarian cancer cells are known to express myeloperoxidase (MPO), an oxidant-producing enzyme with a 150 kDa homodimer, consisting of two identical monomers connected by a disulfide bond. Here, we aim to validate monomeric MPO (mMPO) as a biomarker for the early detection of ovarian cancer. Human ovarian cancer cells, sera from patients at various stages, sera from non-cancer inflammatory gynecological diseases, and healthy volunteers were used.

Findings from the Longitudinal CINRG Becker Natural History Study.

Background: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype.

Objective: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials.

Impact of the COVID-19 Pandemic on a Clinical Trial: A Quantitative Report on Study Engagement and Strategies.

Introduction: The COVID-19 pandemic impacted clinical research worldwide potentially altering research findings. The study purpose was to measure the effect of the pandemic on recruitment, retention, assessment, and intervention completion rates.

Methods: Enrollment and participation data from a clinical trial evaluating efficacy of a physical therapy intervention for high-risk preterm infants were compared across 3 pandemic periods (February 2019 through November 2021).

Factors Influencing Receipt and Type of Therapy Services in the NICU.

Understanding the type and frequency of current neonatal intensive care unit (NICU) therapy services and predictors of referral for therapy services is a crucial first step to supporting positive long-term outcomes in very preterm infants. This study enrolled 83 very preterm infants (<32 weeks, gestational age mean 26.5 ± 2.

Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study.

Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased dystrophin levels in patients with DMD. Presented here are completed study results of > 4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]).

Effect of a NICU to Home Physical Therapy Intervention on White Matter Trajectories, Motor Skills, and Problem-Solving Skills of Infants Born Very Preterm: A Case Series.

Infants born very preterm (VPT; ≤29 weeks of gestation) are at high risk of developmental disabilities and abnormalities in neural white matter characteristics. Early physical therapy interventions such as Supporting Play Exploration and Early Development Intervention (SPEEDI2) are associated with improvements in developmental outcomes. Six VPT infants were enrolled in a randomised clinical trial of SPEEDI2 during the transition from the neonatal intensive care unit to home over four time points.

Hereditary motor and sensory neuropathy type VIA with optic nerve pallor in two sisters with pathologic myopia: a case series and review.

Purpose: Hereditary Motor Sensory Neuropathy Type VIA with Optic Atrophy (HMSN6A) is a rare variant subtype of mitofusin 2 () associated Charcot-Marie-Tooth disease, with ophthalmic manifestations largely limited to optic atrophy. We report a case series of two sisters with HMSN6A corresponding to known variants in the gene. The proband's mother, maternal aunt, and maternal grandfather were also reportedly affected with the condition, although not examined at our institution.

Binding of Intracellular Myeloperoxidase to αV/β1 Integrin Serves as a Mechanism of Survival in Epithelial Ovarian Cancer.

We were the first to report that epithelial ovarian cancer (EOC) cells and tissues express myeloperoxidase (MPO) that is known to play a role in immune surveillance and inflammation by myeloid cells. Additionally, we reported that MPO is colocalized with inducible nitric oxide synthase (iNOS), a key pro-oxidant enzyme, and plays a key role in regulating apoptosis in EOC cells. Whereas myeloid cells express MPO in a dimeric form, intriguingly, here we report the unique expression of only the monomeric form of MPO in EOC cells, tissues, and blood of an ovarian cancer patient.

Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a rare, genetic disease caused by mutations in the DMD gene resulting in an absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, has been shown to increase endogenous dystrophin levels. Herein, long-term (>2 years) functional outcomes in viltolarsen treated patients were compared to a matched historical control group.

TRPV4 mutations causing mixed neuropathy and skeletal phenotypes result in severe gain of function.

Objective: Distinct dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) typically cause nonoverlapping diseases of either the neuromuscular or skeletal systems. However, accumulating evidence suggests that some patients develop mixed phenotypes that include elements of both neuromuscular and skeletal disease. We sought to define the genetic and clinical features of these patients.

Eye manifestations in the intellectual disability syndrome.

The -intellectual disability syndrome is a rare disorder of the cellular transcriptome that prevents proper t-RNA splicing. This disorder interrupts cellular function and leads to an accumulation of RNA fragments, producing a constellation of symptoms including dysmorphic facies, hypotonia, microcephaly, and short stature. Eye manifestations have been reported but not well characterized.

Talcum powder induces malignant transformation in normal human primary ovarian epithelial cells.

Background: Several studies have linked perineal use of talcum powder to increased risk of ovarian cancer (OC). Here, we determined that exposure to talcum powder induces malignant transformation in human normal ovarian cells.

Methods: Human primary ovarian epithelial cells (HPOE), ovarian epithelial cells (HOSEpiC), and primary fibroblasts (NF) were treated with either 100 or 500 μg/mL of talcum powder or titanium dioxide (TiO2) as a particulate control for 72 hours before assessment with a cell transformation assay and p53 and Ki-67 immunohistochemistry.

Child Neurology: Hypotonia and Delayed Teeth Eruption in a 2-Year-Old Girl.

POLR3-related disorders are rare hypomyelinating leukodystrophies associated with hypodontia. We present a female patient, who was referred to pediatric neurology at 2 years of age for tremor, low tone, and motor delays. In addition, she was noted to have a delay in her teeth eruption and myopia.

Longitudinal Changes in the Sensorimotor Pathways of Very Preterm Infants During the First Year of Life With and Without Intervention: A Pilot Study.

: Evaluate longitudinal changes in brain microstructure and volumes in very preterm infants during the first year of life with and without intervention.: Descriptive pilot study.: Five preterm infants in a three-arm clinical trial, one SPEEDI Early, two SPEEDI Late, and two usual care.

Aggressive vertebral hemangioma masquerading as neurological disease in a pediatric patient.

Aggressive hemangioma is a rare vertebral lesion in pediatric patients which can present with deteriorating neurological function. It can mimic malignancy on imaging, particularly as it regularly has an extrasosseous soft tissue component. We present a case of a 13-year-old male who presented with a three month history of lower extremity weakness that was found to have an infiltrative mass at T10 with associated cord compression from epidural extension of the lesion.

Preference for and reinforcing efficacy of different types of attention in preschool children.

It is unknown whether and to what extent common types of attention delivered in early childhood environments are preferred by and function as reinforcers for young children. We assessed children's preference for commonly delivered types of attention across 31 preschool-aged participants (Experiment 1). Next, we conducted a reinforcer assessment (Experiment 2) and a progressive-ratio assessment (Experiment 3) to (a) validate the results of the preference assessment and (b) determine the relative reinforcing efficacy of each type of attention.

Multi-Omics Identifies Circulating miRNA and Protein Biomarkers for Facioscapulohumeral Dystrophy.

The development of therapeutics for muscle diseases such as facioscapulohumeral dystrophy (FSHD) is impeded by a lack of objective, minimally invasive biomarkers. Here we identify circulating miRNAs and proteins that are dysregulated in early-onset FSHD patients to develop blood-based molecular biomarkers. Plasma samples from clinically characterized individuals with early-onset FSHD provide a discovery group and are compared to healthy control volunteers.

The CINRG Becker Natural History Study: Baseline characteristics.

We performed an observational, natural history study of males with in-frame dystrophin gene deletions causing Becker muscular dystrophy (BMD). A prospective natural history study collected longitudinal medical, strength, and timed function assessments. Eighty-three participants with genetically confirmed BMD were enrolled (age range 5.

Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.

Importance: An unmet need remains for safe and efficacious treatments for Duchenne muscular dystrophy (DMD). To date, there are limited agents available that address the underlying cause of the disease.

Objective: To evaluate the safety, tolerability, and efficacy of viltolarsen, a novel antisense oligonucleotide, in participants with DMD amenable to exon 53 skipping.

Efficacy of Supporting Play Exploration and Early Development Intervention in the First Months of Life for Infants Born Very Preterm: 3-Arm Randomized Clinical Trial Protocol.

Objective: The aim of this project is to study the effect of a physical therapist intervention provided in the first months of life on developmental outcomes of infants born very preterm. Secondary aims are to investigate the impact of intervention timing on the efficacy and impact of the intervention on infants with and without cerebral palsy.

Methods: This study is a multisite longitudinal controlled trial comparing developmental outcomes from infants in the Supporting Play, Exploration, and Early Development Intervention (SPEEDI)_Late or SPEEDI_Early group to a usual care group.

Heat Shock Protein 60 (HSP60) Serves as a Potential Target for the Sensitization of Chemoresistant Ovarian Cancer Cells.

HSP60 is a mitochondrial chaperone protein that is associated with decreased overall survival of ovarian cancer patients. We determined whether targeting HSP60 with its monoclonal antibody would induce cytotoxicity in sensitive and chemoresistant ovarian cancer cells and whether it is synergistic when combined with chemotherapeutic drugs. Epithelial ovarian cancer (EOC) cells and their docetaxel- or cisplatin-resistant counterparts were utilized.