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

Objective: The current study aims to compare college adjustment and the effects of the COVID-19 pandemic on first-year students with and without ADHD. Participants: Two cohorts (pre-pandemic, during the pandemic) of first-year, undergraduate college students (N = 3,006; Mage=18.32) were recruited from a multisite research consortium across several universities. Methods: First-year participants self-reported on ADHD diagnosis and symptoms, functional impairments, and experiences transitioning to college. Results: First-year college students with and without ADHD reported significantly greater academic, daily living, and overall functional impairments during the pandemic compared to pre-pandemic. Compared to college students without ADHD, college students with ADHD reported greater functional impairment, more difficulty adjusting to the academic demands of college, and were less likely to feel valued at their institution. Conclusions: First-year college students with and without ADHD experienced greater difficulties navigating the transition to college during the pandemic. Psychosocial and academic supports to help students transition to college are needed.

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

STUDY OBJECTIVES: 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 to 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, 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. Youth with cSLE had worse sleep efficiency (73.3%) and sleep regularity index scores (55.4) compared to the healthy comparison group of youth (79.2%, 60.1, respectively). Youth with cSLE had worse pain (p = .03) and fatigue (p = .004) compared to the healthy comparison group. Negative associations were found among self-reported sleep quality, sleep satisfaction, and symptoms of pain, fatigue, and depressed mood in youth with cSLE and wake after sleep onset was positively associated with fatigue. CONCLUSIONS: Poor sleep efficiency and sleep irregularity accompanied by symptoms of pain, fatigue, and depressed mood was prevalent in youth with cSLE. Youth with lupus should be encouraged to maintain a regular sleep schedule. Since, this is the first study to incorporate objective sleep and sleep regularity measures in youth with cSLE, additional studies with objective and self-report sleep measures are needed to replicate our findings.

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. These patients presented with cutaneous tumid lupus and juvenile idiopathic arthritis plus neuroinflammatory disease, respectively. Disruption of UNC93B1-mediated regulation by these mutations led to enhanced TLR7/8 responses, and both variants resulted in systemic autoimmune or inflammatory disease when introduced into mice via genome editing. Altogether, our results implicate the UNC93B1-TLR7/8 axis in human monogenic autoimmune diseases and provide a functional resource to assess the impact of yet-to-be-reported UNC93B1 mutations.

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 15.1% of a large MTurk sample (i.e., 8500+) identified as a sexual or gender minority (SGM; e.g., lesbian, gay, bisexual, transgender, queer [LGBTQ+]). In addition, data from Study 1 showed that our youngest cohort (i.e., aged 18-25 years) reported significantly higher rates of LGBTQ+ identification (22.7%) than our oldest cohort (i.e., 65-84 years; 1.3%), suggesting that endorsement of these idnetities is increasing. Next, in Study 2 we found that psychology researchers (N = 135) tended to rate expansive sex, gender, and sexual orientation demographic variables as important in general, but were much less likely to report actually using these variables in their own studies. Moreover, younger faculty and faculty who identified as women rated these variables as more important than their colleagues. Based on our findings, we conclude that psychology researchers should use expansive sex, gender, and sexual orientation items in their studies, report these demographic variables consistently, and analyze their data by these important variables when possible. Because a substantial and growing proportion of individuals identify as LGBTQ+, and because SGM identity is related to additional life stressors, it is imperative to better understand these individuals. Various resources are offered and challenges are discussed.

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. METHODS: This proposal is the result of 4 face-to-face consensus meetings with a 27-member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data-driven decisions. The use of items for each domain as an outcome measure in an open label 12-month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique. RESULTS: After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda. CONCLUSION: We reached consensus on multiple domains and items that should be assessed in an open label, 12-month clinical juvenile SSc trial as well as a research agenda for future development.

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

Objective: 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. Method: Few studies have examined this; therefore, a qualitative study using Interpretative Phenomenological Analysis (IPA) was conducted. First- and second-year college students with ADHD participated in open-ended, one-on-one interviews (N = 11; 64% women, 91% White). Results: The two broad categories of findings included Parental Support and the Renegotiation of the Parent-Child Relationship. Participants described feeling supported by their parents in the progress toward their short- and long-term goals. Students described this support as helpful when they managed or initiated the contact, but as unhelpful when the parent was perceived as over involved. They described a strong PCR in this transition as helpful to their adjustment and enjoyed the renegotiation of the PCR in terms of their own increased autonomy and responsibility. Many additional themes and sub-themes are described herein. Conclusion: Optimal levels of involvement and support from parents in the context of a strong PCR is beneficial for adjustment to college for those with ADHD. We discuss the clinical implications of our findings, such as therapists helping families transition to college, and working with college students with ADHD on an adaptive renegotiation of the PCR in their transition to adulthood.

Circulating maternal chimeric cells have an impact on the outcome of biliary atresia.

Introduction: We aimed to quantify the DNA of maternal chimeric (MC) cells in the peripheral blood of the BA patients and investigated the impact on the outcome. Methods: Patients with progressive jaundice because of no bile flow, which necessitated liver transplantation, or who showed inadequate bile flow with or without episodes of cholangitis and progressive hepatic fibrosis and portal hypertension were classified into the poor group. Those with adequate bile flow with completely normal liver function tests beyond 2 years were classified into the good group. The qPCR were separately carried out in buffy coat samples and plasma samples, targeting the non-inherited maternal HLA alleles in the DNA samples. Results: MC-DNA was present in the buffy coat (10-328 gEq per 106 host cells) in seven patients. There was no MC-DNA in the remaining five patients. MC-DNA (214-15,331 gEq per 106 host cells) was observed in the plasma of five patients. The quantity of MC-DNA in the buffy coat showed a significant difference between the two prognostic groups (p = 0.018), whereas there was no significant difference in the quantity of MC-DNA in plasma (p = 0.205). MC-DNA in the buffy coat was significantly associated with the outcome (p = 0.028), whereas MC-DNA in the plasma did not influence the outcome (p = 0.56). Conclusions: Poor outcomes in BA were correlated with circulating maternal chimeric lymphocytes.

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. To address these issues, a conference was held in Bethesda, Maryland, from October 15-16, 2019, entitled "Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies: Overcoming the Barriers." Conference participants included people with lupus, lupus physicians, lupus clinical trialists, treatment developers from biotechnology, social scientists, patient advocacy groups, and US government representatives (The Office of Minority Health, Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration). For all these groups, the organizers of the conference purposefully included people of non-White ancestry. Decreased participation of non-White SLE patients in clinical research was evaluated through historical, societal, experiential, and pragmatic perspectives, and several interventional programs to increase non-White patient participation in SLE and non-SLE research were described and discussed. The presentations and discussions highlighted the need for changes at the societal, institutional, research team, referring physician, and patient education levels to achieve equitable ancestral representation in SLE clinical studies.

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

Objective: 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. Method: 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. Studies were screened based on the following inclusion criteria: college students with ADHD and/or LD, student characteristics as predictors, and GPA and/or retention as outcomes. Results: Twenty-one studies were included (20 quantitative studies and 1 randomized control trial). Academic regulation, academic self-efficacy, emotional regulation, ADHD symptoms, and academic and social integration predicted college success. Conclusion: Incorporating these components into interventions with students with ADHD and/or LD may enhance their success in college.

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. Expression of HERV-K transcripts were profiled in SLE leukocytes by RNA-Seq. RESULTS: Both adult and paediatric SLE patients had autoantibodies against HERV-K Env with higher titres than healthy controls or patients with Sjögren's syndrome, small- or large-vessel vasculitis, or psoriatic arthritis. Transcripts from only two HERV-K loci capable of producing Env, HERV-K102 and -K108, were detected among the 10 expressed loci in SLE patients. CONCLUSIONS: Our data reveal that HERV-K proviruses are expressed in SLE and that the HERV-K-encoded Env protein elicits an immune response in patients, particularly during active disease.

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). Sera from 100 patients with RA, plasma from 32 patients with juvenile idiopathic arthritis (JIA), and healthy adult and pediatric controls were included. Antibody reactivity was evaluated for correlations with clinical and laboratory variables of the patients. RESULTS: We replicated and expanded upon published data suggesting that patients with RA or JIA have autoantibodies against HERV-K Env, some with high titers. Anti-HERV-K antibodies correlated with cigarette smoking and with circulating myeloperoxidase-DNA complexes indicative of nonapoptotic neutrophil cell death. Further, most of the patients with RA, but not those with JIA, had autoantibodies that reacted more strongly with Env that was citrullinated by PAD4. These anticitrullinated Env autoantibodies correlated with seropositivity and tended to be higher in patients with erosive disease. CONCLUSION: Our data suggest that anti-HERV-K immunity is elevated in RA and JIA and may have a connection with pathogenic protein citrullination in RA.

IgG and IgA autoantibodies against L1 ORF1p expressed in granulocytes correlate with granulocyte consumption and disease activity in pediatric systemic lupus erythematosus.

BACKGROUND: Most patients with systemic lupus erythematosus (SLE) have IgG autoantibodies against the RNA-binding p40 (ORF1p) protein encoded by the L1 retroelement. This study tested if these autoantibodies are also present in children with pediatric SLE (pSLE) and if the p40 protein itself could be detected in immune cells. METHODS: Autoantibodies in the plasma of pSLE patients (n = 30), healthy children (n = 37), and disease controls juvenile idiopathic arthritis (JIA) (n = 32) and juvenile dermatomyositis (JDM) (n = 60), were measured by ELISA. Expression of p40 in immune cells was assessed by flow cytometry. Markers of neutrophil activation and death were quantitated by ELISA. RESULTS: IgG and IgA autoantibodies reactive with p40 were detected in the pSLE patients, but were low in healthy controls and in JIA or JDM. pSLE patients with active disease (13 of them newly diagnosed) had higher titers than the same patients after effective therapy (p = 0.0003). IgG titers correlated with SLEDAI (r = 0.65, p = 0.0001), ESR (r = 0.43, p = 0.02), and anti-dsDNA antibodies (r = 0.49, p < 0.03), and inversely with complement C3 (r = -0.55, p = 0.002) and C4 (r = -0.51, p = 0.006). p40 protein was detected in a subpopulation of CD66b+ granulocytes in pSLE, as well as in adult SLE patients. Myeloperoxidase and neutrophil elastase complexed with DNA and the neutrophil-derived S100A8/A9 were elevated in plasma from pSLE patients with active disease and correlated with anti-p40 autoantibodies and disease activity. CONCLUSIONS: Children with active SLE have elevated IgG and IgA autoantibodies against L1 p40, and this protein can be detected in circulating granulocytes in both pediatric and adult SLE patients. P40 expression and autoantibody levels correlate with disease activity. Markers of neutrophil activation and death also correlate with these autoantibodies and with disease activity, suggesting that neutrophils express L1 and are a source of p40.

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. Those with ADHD may be inadequately prepared for college. College readiness can be broken into self-determination, academic skills, and daily living skills, all of which are possible areas of deficit for individuals with ADHD, given their common characteristics. In the current study, we examined differences in college readiness in undergraduates with and without ADHD. In general, students with ADHD were found to be less prepared for college than those without ADHD, and specific areas of unpreparedness were identified. The findings support the need for intervention for students with ADHD before or early in their college careers. Further research on specific skill deficits and ameliorative steps is needed.

Prevalence of Juvenile Idiopathic Arthritis in the Alaska Native Population.

OBJECTIVE: To determine the prevalence and clinical characteristics of juvenile idiopathic arthritis (JIA) in Alaska Native children. METHODS: Potential cases of JIA were identified by querying administrative data from hospitals and clinics in the Alaska Tribal Health System for codes possibly identifying JIA. Medical record abstraction was performed to confirm criteria met for JIA, demographic and clinical characteristics, and treatment patterns. Individuals age ≤18 years with a confirmed diagnosis of JIA were included. The denominator for prevalence was the 2015 Alaska Area Indian Health Service user population age of ≤18 years. RESULTS: The unadjusted prevalence of JIA in Alaska Native children was 74.6 per 100,000 (age-adjusted 79.0 per 100,000). JIA was more common in females than males (unadjusted prevalence 105.8 versus 45.0 per 100,000). Oligoarthritis was the most common subtype (31% of cases), but polyarthritis and enthesitis-related arthritis were also common (26% and 24% of cases, respectively), with a notably high prevalence of enthesitis-related arthritis. The median age at diagnosis was 9 years. Of the combined cohort with results available, 56% were antinuclear antibody positive, 23% were rheumatoid factor positive, 19% were anti-cyclic citrullinated peptide antibody positive, and 57% had the presence of HLA-B27. Uveitis had been diagnosed in 16% of cases. CONCLUSION: The prevalence of JIA in Alaska Native children may be higher than the general US population. Enthesitis-related arthritis makes up a higher proportion of cases than in other populations described likely because of the high prevalence of HLA-B27 in this population.

Psychometric Properties of the Weiss Functional Impairment Rating Scale: Evidence for Utility in Research, Assessment, and Treatment of ADHD in Emerging Adults.

Objective: The current study examines psychometric properties of the Weiss Functional Impairment Rating Scale (WFIRS), a measure of adult ADHD-related impairment. It is a self-report questionnaire that provides a metric of overall life impairment and domain-specific dysfunction. Method: Using data from a large (N = 2,093), multi-institution sample of college students and including a subsample of collateral informants (n = 262), a series of analyses were conducted. Results: The WFIRS demonstrated robust internal reliability, cross-informant agreement on par or superior to other measures of ADHD symptomatology and impairment, and concurrent validity. The WFIRS was not shown to be uniquely associated with ADHD, as internalizing symptoms also associated with the total and domain scores. Conclusion: The use of the WFIRS in identifying ADHD-related impairment in emerging adults appears to be psychometrically supported, and will prove useful to clinicians and researchers.

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. Control groups included pediatric dental clinic patients and healthy volunteers. The primary aim was to test for an association between dental health indices and JIA; the secondary aim was to characterize the microbial profile of supragingival plaque using 16S rRNA gene sequencing. RESULTS: The study included 85 patients with JIA, 62 dental patients and 11 healthy child controls. JIA patients overall had significantly more gingival inflammation compared to dental patients, as evidenced by bleeding on probing of the gingiva, the most specific sign of active inflammation (p = 0.02). Overall, however, there was a trend towards better dental hygiene in the JIA patients compared to dental patients, based on indices for plaque, decay, and periodontitis. In the JIA patients, plaque microbiota analysis revealed bacteria belonging to genera Haemophilus or Kingella elevated, and Corynebacterium underrepresented. In poly JIA, bacteria belonging to the genus Porphyromonas was overrepresented and Prevotella was underrepresented. CONCLUSION: Increased gingival inflammation in JIA was independent of general oral health, and thus cannot be attributed to poor dental hygiene secondary to disability. The variation of microbial profile in JIA patients could indicate a possible link between gingivitis and synovial inflammation.

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. The genetics of patients with jSSc differ from women with SSc, resembling instead the genes of adult males with SSc, with additional HLA genes uniquely associated with childhood-onset disease. Current treatments are aimed at inhibiting the inflammatory aspect of disease, but important mechanisms of fibrosis regulated by dermal white adipose tissue dendritic cells may provide an avenue for targeting and potentially reversing the fibrotic stage.

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. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the unique features of the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. We discuss future directions in better understanding the pathophysiology of and how to better treat pediatric LS.