High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis.

Objectives: Patients with RA display greater occult coronary atherosclerosis burden and experience higher cardiovascular morbidity and mortality compared with controls. We here explored whether pro-inflammatory cytokines and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, correlated with plaque burden and cardiovascular events (CVEs) in RA.

Methods: We evaluated 150 patients with 64-slice coronary CT angiography.

Randomized Trial of CPAP and Vardenafil on Erectile and Arterial Function in Men With Obstructive Sleep Apnea and Erectile Dysfunction.

Context: Erectile function is important for life satisfaction and often impaired in men with obstructive sleep apnea (OSA). Uncontrolled studies show that treating OSA with continuous positive airway pressure (CPAP) improves erectile function. Phosphodiesterase type 5 inhibitors (e.

Specific mutations in the D1-D2 linker region of VCP/p97 enhance ATPase activity and confer resistance to VCP inhibitors.

Valosin-containing protein (VCP), together with several partner proteins, extracts ubiquitinated client proteins from E3 ligase complex and facilitates their degradation through ubiquitin-proteasome system. Therefore, it plays an important role in regulating protein quality control and various cellular pathways. Recent studies also identified VCP as a lineage-specific essential gene in ovarian cancer.

A NETWORK APPROACH TO EXAMINING INJURY SEVERITY IN PEDIATRIC TBI.

Traumatic brain injury (TBI) is the leading cause of death and disability in children, and can lead to long lasting functional impairment. Many factors influence outcome, but imaging studies examining effects of individual variables are limited by sample size. Roughly 20-40% of hospitalized TBI patients experience seizures, but not all of these patients go on to develop a recurrent seizure disorder.

Multi-modal Registration Improves Group Discrimination in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) can disrupt the white matter (WM) integrity in the brain, leading to functional and cognitive disruptions that may persist for years. There is considerable heterogeneity within the patient group, which complicates group analyses. Here we present improvements to a tract identification workflow, automated multi-atlas tract extraction (autoMATE), evaluating the effects of improved registration.

Discordant patient-physician assessments of disease activity and its persistence adversely impact quality of life and work productivity in US Hispanics with rheumatoid arthritis.

Objective: This study was designed to evaluate the determinants of patient and physician global assessments (PtGA and MDGA, respectively) of disease activity, their discordance and change over 2 years in Hispanics with rheumatoid arthritis (RA). We further examined the impact of discordance and its persistence on health-related quality of life (HRQOL) and work productivity on final visit.

Methods: We studied 536 Hispanics with established RA from a single centre.

Changes of vitamin D levels and bone turnover markers after CPAP therapy: a randomized sham-controlled trial.

The aim was to investigate whether continuous positive airway pressure treatment could modulate serum vitamin D (25-hydroxyvitamin D) and bone turnover markers (collagen-type 1 cross-linked C-telopeptide, osteocalcin and N-terminal propeptide of type 1 collagen) in secondary analysis from a randomized controlled trial. Sixty-five continuous positive airway pressure-naïve male patients with obstructive sleep apnea (age = 49 ± 12 years, apnea-hypopnea index = 39.9 ± 17.

Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California.

Carnitine transporter defect (CTD; also known as systemic primary carnitine deficiency; MIM 212140) is due to mutations in the SLC22A5 gene and leads to extremely low carnitine levels in blood and tissues. Affected individuals may develop early onset cardiomyopathy, weakness, or encephalopathy, which may be serious or even fatal. The disorder can be suggested by newborn screening.

A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses.

Background: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear.

Methods: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis.

Diverging volumetric trajectories following pediatric traumatic brain injury.

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics.

Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA Domain Ubiquitination.

p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain.

Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes.

Context: Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third-trimester di-2-ethyl hexyl phthalate exposure and total testosterone (TT) concentrations. Here, we examine early-pregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes.

A structure- and chemical genomics-based approach for repositioning of drugs against VCP/p97 ATPase.

Valosin-containing protein (VCP/p97) ATPase (a.k.a.

Diverging white matter trajectories in children after traumatic brain injury: The RAPBI study.

Objective: To examine longitudinal trajectories of white matter organization in pediatric moderate/severe traumatic brain injury (msTBI) over a 12-month period.

Methods: We studied 21 children (16 M/5 F) with msTBI, assessed 2-5 months postinjury and again 13-19 months postinjury, as well as 20 well-matched healthy control children. We assessed corpus callosum function through interhemispheric transfer time (IHTT), measured using event-related potentials, and related this to diffusion-weighted MRI measures of white matter (WM) microstructure.

Muscle Derived Stem Cells Stimulate Muscle Myofiber Repair and Counteract Fat Infiltration in a Diabetic Mouse Model of Critical Limb Ischemia.

Background: Critical Limb Ischemia (CLI) affects patients with Type 2 Diabetes (T2D) and obesity, with high risk of amputation and post-surgical mortality, and no effective medical treatment. Stem cell therapy, mainly with bone marrow mesenchymal, adipose derived, endothelial, hematopoietic, and umbilical cord stem cells, is promising in CLI mouse and rat models and is in clinical trials. Their general focus is on angiogenic repair, with no reports on the alleviation of necrosis, lipofibrosis, and myofiber regeneration in the ischemic muscle, or the use of Muscle Derived Stem Cells (MDSC) alone or in combination with pharmacological adjuvants, in the context of CLI in T2D.

A multi-group confirmatory factor analyses of the LupusPRO between southern California and Filipino samples of patients with systemic lupus erythematosus.

Introduction Systemic lupus erythematosus (SLE) leads to a range of biopsychosocial health outcomes through an unpredictable and complex disease path. The LupusPRO is a comprehensive, self-report measure developed specifically for populations with SLE, which assesses both health-related quality of life and non-health related quality of life. Given its increasingly widespread use, additional research is needed to evaluate the psychometric integrity of the LupusPRO across diverse populations.

Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low.

Divergent Perceptions of Barriers to Diabetic Retinopathy Screening Among Patients and Care Providers, Los Angeles, California, 2014-2015.

Introduction: Despite availability of screening for diabetic retinopathy, testing is underused by many low-income and racial/ethnic minority patients with diabetes. We examined perceived barriers to diabetic retinopathy screening among low-income patients and their health care providers and provider staffers.

Methods: We collected survey data from 101 patients with diabetes and 44 providers and staffers at a safety-net clinic where annual diabetic retinopathy screening rates were low.

p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein-Protein Interactions.

The AAA+ ATPase p97/VCP adopts at least three conformations that depend on the binding of ADP and ATP and alter the orientation of the N-terminal protein-protein interaction (PPI) domain into "up" and "down" conformations. Point mutations that cause multisystem proteinopathy 1 (MSP1) are found at the interface of the N domain and D1-ATPase domain and potentially alter the conformational preferences of p97. Additionally, binding of "adaptor" proteins to the N-domain regulates p97's catalytic activity.

Trends in Functional Disability and Determinants of Clinically Meaningful Change Over Time in Hispanic Patients With Rheumatoid Arthritis in the US.

Objective: To identify determinants of clinically meaningful change in functional disability in low-income Hispanic patients with established rheumatoid arthritis (RA) in the US.

Methods: We evaluated 156 low-socioeconomic status, uninsured, largely immigrant Hispanic patients, collectively described as vulnerable patients, on 3 consecutive visits (baseline, 6, and 12 months followup) at a single center. Disability (Health Assessment Questionnaire [HAQ] disability index [DI]), pain (visual analog scale), and depression (Patient Health Questionnaire [PHQ-9]) were assessed each time.

Implanted Muscle-Derived Stem Cells Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes, but Their Repair Capacity Is Impaired by Their Prior Exposure to the Diabetic Milieu.

Introduction: Muscle-derived stem cells (MDSCs) and other SCs implanted into the penile corpora cavernosa ameliorate erectile dysfunction in type 1 diabetic rat models by replenishing lost corporal smooth muscle cells (SMCs) and decreasing fibrosis. However, there are no conclusive data from models of type 2 diabetes (T2D) and obesity.

Aim: To determine whether MDSCs from obese Zucker (OZ) rats with T2D at an early stage of diabetes (early diabetic SCs isolated and cultured in low-glucose medium [ED-SCs]) counteract corporal veno-occlusive dysfunction and corporal SMC loss or lipo-fibrosis when implanted in OZ rats at a late stage of diabetes and whether MDSCs from these OZ rats with late diabetes (late diabetic SCs isolated and cultured in high-glucose medium [LD-SC]) differ from ED-SCs in gene transcriptional phenotype and repair capacity.