Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans.

Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen.

College during COVID-19: The pandemic's effect on college adjustment in first year students with ADHD.

The current study aims to compare college adjustment and the effects of the COVID-19 pandemic on first-year students with and without ADHD. Two cohorts (pre-pandemic, during the pandemic) of first-year, undergraduate college students ( = 3,006; =18.32) were recruited from a multisite research consortium across several universities.

Sleep deficiency and symptoms of pain, fatigue, and depressed mood in youth with and without childhood systemic lupus erythematosus.

Study Objectives: We undertook a study to describe and compare sleep deficiency and symptoms of pain, fatigue, and depressed mood in youth with childhood systemic lupus erythematosus (cSLE) to a healthy comparison group of youth and test the associations between sleep and symptoms of pain, fatigue, and depressed mood in youth with cSLE.

Methods: Forty-three youth (23 youth with cSLE; 20 age- and sex-matched healthy youth) wore actigraphs and completed sleep diaries for 10 days and completed self-report questionnaires on sleep quality, pain, fatigue, and depressed mood.

Results: On average, both groups had a total sleep time of less than 7 hours.

Sex, Gender, and Sexual Orientation in Psychological Research: Exploring Data Trends & Researcher Opinions.

Psychology researchers have historically neglected variables related to sex, gender, and sexual orientation, leading to the erasure of sex, gender, and sexual orientation in research, which limits the generalizability of psychological findings. We argue that these important variables need to be considered more consistently by researchers across psychology subdisciplines. In Study 1 we found that 15.

Transitioning to college with ADHD: a qualitative examination of parental support and the renegotiation of the parent-child relationship.

In the transition to college, students with Attention-Deficit/Hyperactivity Disorder (ADHD) often face difficulties. Parental support may aid in the successful adjustment to college, and a strong parent-child relationship (PCR) may optimize the balance between autonomy and support necessary during this transition. Few studies have examined this; therefore, a qualitative study using Interpretative Phenomenological Analysis (IPA) was conducted.

Proposed Response Parameters for Twelve-Month Drug Trial in Juvenile Systemic Sclerosis: Results of the Hamburg International Consensus Meetings.

Objective: Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes.

Autoantibodies against the envelope proteins of endogenous retroviruses K102 and K108 in patients with systemic lupus erythematosus correlate with active disease.

Objectives: To determine if patients with systemic lupus erythematosus (SLE), a disease characterised by elevated type I interferons reminiscent of anti-viral immunity, have expression of human endogenous retrovirus K (HERV-K) proviruses capable of producing envelope (Env) protein, as well as associated autoantibodies against the Env protein.

Methods: ELISAs were conducted with recombinant Env protein and sera from SLE patients with active (n=60) or inactive (n=49) disease, healthy controls (n=47), other rheumatic disorders (n=59), as well as plasma from paediatric lupus patients with active (n=30) or inactive (n=30) disease, and 17 healthy children. Antibody reactivity was evaluated for correlations with clinical and laboratory parameters of the patients.

Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope Protein in Patients With Rheumatoid Arthritis.

Objective: Autoantibodies against proteins encoded by human endogenous retrovirus K (HERV-K) have been reported in patients with rheumatoid arthritis (RA), but their relevance, if any, has remained unresolved. We revisited this question and tested if such autoantibodies may react with citrullinated epitopes on the envelope (Env) protein of HERV-K.

Methods: Immunoblotting and ELISAs were conducted with unmodified Env protein and with Env citrullinated by protein arginine deiminase 4 (PAD4).

Promoting academic success in college students with ADHD and LD: A systematic literature review to identify intervention targets.

College students with attention-deficit/hyperactivity disorder (ADHD) and/or a learning disorder (LD) are at higher risk for not attaining a bachelor's degree. The purpose is to identify the predictors of academic success in college for students with ADHD and/or LD using a systematic review of the literature. Academic Search Premier, Education Full Text, Education Source, Education Resources Information Center, Teacher Reference Center, PsycINFO, PsycArticles, and Primary Search and relevant journals were searched using PRISMA guidelines.

College Readiness: Differences Between First-Year Undergraduates With and Without ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattentive, hyperactive, and impulsive behaviors. Impairment in individuals diagnosed with ADHD is significant; one such domain of impairment is achieving a college education. College students with ADHD tend to have lower grade point averages, take longer to graduate, and have higher dropout rates than individuals without ADHD.

Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies.

Non-White people are more likely to develop systemic lupus erythematosus (SLE) yet are underrepresented in SLE clinical trials. The efficacy and safety of drugs may be influenced by ancestry, and ancestrally diverse study populations are necessary to optimize treatments across the full spectrum of patients. However, barriers to entry into clinical trials are amplified in non-White populations.

Oral health and plaque microbial profile in juvenile idiopathic arthritis.

Background: The oral microbiota has been implicated in the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. This study tested for associations between oral health, microbial communities and juvenile idiopathic arthritis (JIA).

Methods: A cross-sectional exploratory study of subjects aged 10-18 years with oligoarticular, extended oligoarticular and polyarticular JIA was conducted.

Immunopathogenesis of Juvenile Systemic Sclerosis.

Juvenile-onset systemic sclerosis (jSSc) is a rare and severe autoimmune disease with associated life-threatening organ inflammation and evidence of fibrosis. The organ manifestations of jSSc resemble adult SSc, but with better outcomes and survival. The etiology of jSSc appears to reflect adult-onset SSc, with similar inflammatory mediators and autoantibodies, but with a significant population of children with uncharacterized anti-nuclear antibodies.

Immunopathogenesis of Pediatric Localized Scleroderma.

Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining.

Parental Perception of Dietary Intervention in Juvenile Idiopathic Arthritis.

To evaluate the prevalence of special diet adoption in juvenile idiopathic arthritis (JIA) and parental perceptions of efficacy. An online survey was distributed over a year to nearly 20,000 individuals. Responses from 261 parents of patients with JIA were received.

Relationship Between Esophageal Abnormalities on Fluoroscopic Esophagram and Pulmonary Function Testing in Juvenile Systemic Sclerosis.

Objective: Juvenile systemic sclerosis (SSc) is a disabling autoimmune condition that affects multiple organs in addition to skin, notably the gastrointestinal and pulmonary systems. The relationship between esophageal abnormalities and pulmonary disease in juvenile SSc is not well understood. We describe associations between radiologic esophageal abnormalities and pulmonary function.

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.

Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk.

Clinical Characteristics and Factors Associated With Disability and Impaired Quality of Life in Children With Juvenile Systemic Sclerosis: Results From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.

Objective: To investigate clinical manifestations of juvenile systemic sclerosis (SSc; scleroderma), including disease characteristics and patient quality of life, using the multinational Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry.

Methods: Patients with juvenile SSc were prospectively enrolled between 2010 and 2013. The diagnosis of juvenile SSc was determined by the enrolling pediatric rheumatologist, with the requirement for disease onset prior to age 18 years.

Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis.

Objective: Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% of children with JIA have rheumatoid factor (RF)-positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with those of RA and selected other JIA categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies.

Soluble CD40L is associated with increased oxidative burst and neutrophil extracellular trap release in Behçet's disease.

Background: Studies have suggested that soluble factors in plasma from patients with active (aBD) and inactive (iBD) Behçet's disease (BD) stimulate neutrophil function. Soluble CD40 ligand (sCD40L) is an important mediator of inflammation in BD. Its expression and effect on neutrophil oxidative burst and neutrophil extracellular trap (NET) release have not been characterized.