Dichloroacetate improves mitochondrial function, physiology, and morphology in FBXL4 disease models.

Pathogenic variants in the human F-box and leucine-rich repeat protein 4 (FBXL4) gene result in an autosomal recessive, multisystemic, mitochondrial disorder involving variable mitochondrial depletion and respiratory chain complex deficiencies with lactic acidemia. As no FDA-approved effective therapies for this disease exist, we sought to characterize translational C. elegans and zebrafish animal models, as well as human fibroblasts, to study FBXL4-/- disease mechanisms and identify preclinical therapeutic leads.

Mortality in Neuromuscular Early Onset Scoliosis Following Spinal Deformity Surgery.

Background: The purpose of this study was to report mortality and associated risk factors in neuromuscular early onset scoliosis following spinal deformity surgery.

Methods: This is a multicenter retrospective cohort study of patients with cerebral palsy (CP), spinal muscular atrophy, myelodysplasia, muscular dystrophy, or myopathy undergoing index spine surgery from 1994 to 2020. Mortality risk was calculated up to 10 years postoperatively.

Is It Time for a Patient-Centered Quality Measure of Asthma Control?

Quality measures play a prominent role in the US health care system. They are used to monitor and report performance across health plans, providers, and health systems and are a foundational element of value-based payment. Measuring the quality of asthma care has been challenging because of a lack of reliable data to assess clinical processes and track patient-specific outcomes.

Economic Evidence for US Asthma Self-Management Education and Home-Based Interventions.

The health and economic burden of asthma in the United States is substantial. Asthma self-management education (AS-ME) and home-based interventions for asthma can improve asthma control and prevent asthma exacerbations, and interest in health care-public health collaboration regarding asthma is increasing. However, outpatient AS-ME and home-based asthma intervention programs are not widely available; economic sustainability is a common concern.

Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu₅).

Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Starting from an acetylene-based lead from high throughput screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe further refinements leading to both dihydronaphthyridinone and tetrahydronaphthyridine mGlu5 PAMs containing an alkoxy-based linkage as an acetylene replacement.

Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.

We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis.

Public health interventions for asthma: an umbrella review, 1990-2010.

Context: Asthma is a chronic respiratory disease increasingly prevalent in the U.S., particularly among children and certain minority groups.

Effectiveness of home-based, multi-trigger, multicomponent interventions with an environmental focus for reducing asthma morbidity: a community guide systematic review.

Context: Asthma exacerbations are commonly triggered by exposure to allergens and irritants within the home. The purpose of this review was to evaluate evidence that interventions that target reducing these triggers through home visits may be beneficial in improving asthma outcomes. The interventions involve home visits by trained personnel to conduct two or more components that address asthma triggers in the home.

A model-driven approach to qualitatively assessing the added value of community coalitions.

Community-based coalitions are commonly formed to plan and to carry out public health interventions. The literature includes evaluations of coalition structure, composition, and functioning; evaluations of community-level changes achieved through coalition activities; and the association between coalition characteristics and various indicators of success. Little information is available on the comparative advantage or "added value" of conducting public health interventions through coalitions as opposed to less structured collaborative mechanisms.

A community-based strategy for improving asthma management and outcomes for preschoolers.

Although almost one in ten (8.6%) preschool children has been diagnosed with asthma, few asthma management programs are designed for parents of preschool children. The Asthma Basics for Children program addressed this need in 2003-2008 by implementing a multi-layered approach that offered educational activities to center staff, parents, and children and PACE training to physicians in 31 Northern Manhattan daycare centers.

Conceptual framework of the Controlling Asthma in American Cities Project.

The Controlling Asthma in American Cities Project (CAACP) was designed to improve the control of asthma in inner-city populations of children with a disparate burden of symptoms and adverse outcomes. As with many chronic diseases, asthma is the manifestation of multiple biologic, environmental, and social determinants. In addition to appropriate medical management, individuals with asthma must have logistical, financial, and cultural access to environments that allow avoidance of asthma triggers and encourage good asthma management practices.

Considerations and challenges for planning a public health approach to asthma.

Addressing asthma from a public health perspective is a relatively new concept for which the literature provides little guidance. A public health approach seeks to decrease the burden of asthma and improve health outcomes at the population level, such as communities, cities, or states, by reaching large numbers of individuals with effective interventions and at reasonable cost. Projects designed to achieve a measureable impact at the population level are fundamentally different from projects or interventions designed to improve outcomes among individuals.

The prototypical ranitidine analog JWS-USC-75-IX improves information processing and cognitive function in animal models.

This study was designed to evaluate further a prototypical ranitidine analog, JWS-USC-75-IX, [(3-[[[2-[[(5-dimethylaminomethyl)-2-furanyl]methyl]thio]ethyl]amino]-4-nitropyridazine, JWS], for neuropharmacologic properties that would theoretically be useful for treating cognitive and noncognitive behavioral symptoms of neuropsychiatric disorders. JWS was previously found to inhibit acetylcholinesterase (AChE) activity, serve as a potent ligand at muscarinic M₂ acetylcholine receptors, and elicit positive effects on spatial learning, passive avoidance, and working memory in rodents. In the current study, JWS was evaluated for binding activity at more than 60 neurotransmitter receptors, transporters, and ion channels, as well as for inhibitory activity at AChE and butyrylcholinesterase (BChE).

Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity.

Modulators of metabotropic glutamate receptor subtype 5 (mGluR5) may provide novel treatments for multiple central nervous system (CNS) disorders, including anxiety and schizophrenia. Although compounds have been developed to better understand the physiological roles of mGluR5 and potential usefulness for the treatment of these disorders, there are limitations in the tools available, including poor selectivity, low potency, and limited solubility. To address these issues, we developed an innovative assay that allows simultaneous screening for mGluR5 agonists, antagonists, and potentiators.

HIV-associated nephropathy: Epidemiology, pathogenesis, and treatment.

Initially described in 1984, human immunodeficiency virus-associated nephropathy (HIVAN) has now become a common disease within the HIV-seropositive population. It is a focal segmental glomerulosclerosis causing rapid deterioration of renal function. It is the most common cause of chronic renal disease in HIV patients and occurs almost exclusively in blacks.