High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Assessment and Management of Attention-Deficit/Hyperactivity Disorder: Pediatric Resident Perspectives on Training and Practice.

Attention-deficit/hyperactivity disorder (ADHD) is a common presenting concern in primary care. This study examined the relationship between pediatric residency training program characteristics and residents' ADHD knowledge, attitudes, and comfort in providing ADHD services. Given the familiarity that pediatric chief residents have with the training and experiences within their residency programs, a 30-item survey was mailed to pediatric chief residents. A total of 100 residents returned their surveys (response rate 49.5%) and were included in the descriptive quantitative and thematic qualitative analyses. The majority of participants rated their ADHD knowledge as at least average. However, approximately half of the participants were comfortable with screening, and less than half were comfortable with managing stimulant medication or behavioral treatments. Participants emphasized the importance of interprofessional collaboration, clinical experiences, and integrated ADHD education throughout training. These results emphasize the importance of improved training in screening, diagnosing, and managing ADHD to increase resident comfort regarding these practices.

Examining long-term intervention effects to promote teacher problem-solving and communication skills in the rural context.

Conjoint behavioral consultation (CBC), a teacher-parent partnership intervention, has been shown to yield immediate improvements in problem-solving skills and communication quality with parents for kindergarten through third grade teachers in rural schools. The purpose of the present study was to determine whether CBC can yield maintained effects on teacher skills and communication over a 1-year follow-up period. We used an experimental design to examine maintenance effects of CBC (nCBC = 84, nControl = 68). Outcomes were assessed four times: baseline, 12-week posttest (immediate effects), and twice during a 1-year follow-up period (maintenance effects). Longitudinal growth modeling revealed that immediate improvements in perceived problem-solving competence and communication quality with parents for teachers in the CBC condition compared to teachers in the control condition were maintained 1-year postintervention. CBC appears to support teachers' professional practices over time. Implications for enhancing families' and schools' capacities to address student behavior concerns are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Perspectives of Rural Primary Care Clinicians on Pediatric Attention-Deficit/Hyperactivity Disorder Care.

OBJECTIVE: Despite efficacious treatments, evidence-based guidelines, and increased availability of integrated behavioral health care, youth coping with attention-deficit/hyperactivity disorder (ADHD) receive suboptimal care. More research is needed to understand and address care gaps, particularly within rural health systems that face unique challenges. We conducted a qualitative study within a predominantly rural health system with a pediatric-integrated behavioral health care program to address research gaps and prepare for quality improvement initiatives, including primary care clinician (PCC) trainings and clinical decision support tools in the electronic health record (EHR). METHOD: Semistructured interviews were conducted with 26 PCCs representing clinics within the health system. Interview guides were based on the Practical Robust Implementation and Sustainability Model to elicit PCC views regarding determinants of current practices and suggestions to guide quality improvement efforts. We used thematic analysis to identify patterns of responding that were common across participants. RESULTS: PCCs identified several internal and external contextual factors as determinants of current practices. Of note, PCCs recommended increased access to continuing education trainings held in clinic over lunch and delivered in less than 30 minutes. Suggested improvements to the EHR included incorporating parent and teacher versions of the Vanderbilt Rating Scale into the EHR, documentation templates aligned with evidence-based guidelines, and alerts and suggestions to aid medication management during appointments. CONCLUSION: Future research to identify implementation strategies to help rural PCCs adopt innovations are needed given the increased responsibility for managing ADHD care and intractable gaps in access to behavioral health care in rural regions.

Alterations of host-gut microbiome interactions in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder. METHODS: We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted UPLC-MS. A four-day food diary was recorded to capture the habitual dietary pattern of study participants. FINDINGS: Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. The microbiome and metabolome profiles remained stable over six months in MS and control individuals. INTERPRETATION: Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. FUNDING: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

School-Based Interventions for Elementary School Students with Attention-Deficit/Hyperactivity Disorder.

Children with attention-deficit/hyperactivity disorder experience significant academic, social, and behavioral impairments in elementary school settings. Although psychopharmacologic treatments can improve symptomatic behaviors, these rarely are sufficient for enhancing school performance. Thus, medication should be supplemented by one or more school interventions, including behavioral strategies, academic interventions, behavioral peer interventions, organizational skills training, and self-regulation strategies. Although all of these school interventions have been found effective, classroom behavioral strategies, organizational skills training, and self-regulation strategies have the strongest empirical support. Clinicians should collaborate with school mental health professionals to encourage implementation of effective school interventions across school years.

RNA profiling of laser microdissected human trophoblast subtypes at mid-gestation reveals a role for cannabinoid signaling in invasion.

Human placental architecture is complex. Its surface epithelium, specialized for transport, forms by fusion of cytotrophoblast progenitors into multinucleated syncytiotrophoblasts. Near the uterine surface, these progenitors assume a different fate, becoming cancer-like cells that invade its lining and blood vessels. The latter process physically connects the placenta to the mother and shunts uterine blood to the syncytiotrophoblasts. Isolation of trophoblast subtypes is technically challenging. Upon removal, syncytiotrophoblasts disintegrate and invasive cytotrophoblasts are admixed with uterine cells. We used laser capture to circumvent these obstacles. This enabled isolation of syncytiotrophoblasts and two subpopulations of invasive cytotrophoblasts from cell columns and the endovascular compartment of spiral arteries. Transcriptional profiling revealed numerous genes, the placental or trophoblast expression of which was not known, including neurotensin and C4ORF36. Using mass spectrometry, discovery of differentially expressed mRNAs was extended to the protein level. We also found that invasive cytotrophoblasts expressed cannabinoid receptor 1. Unexpectedly, screening agonists and antagonists showed that signals from this receptor promote invasion. Together, these results revealed previously unseen gene expression patterns that translate to the protein level. Our data also suggested that endogenous and exogenous cannabinoids can affect human placental development.

B cell depletion changes the immune cell profile in multiple sclerosis patients: One-year report.

B cell depletion therapy has been shown to be beneficial in multiple sclerosis (MS). However, the mechanism by which B cell depletion mediates its beneficial effects in MS is still unclear. To better understand how B cell depletion may benefit patients with a disease previously thought to be primarily mediated by CD4 T cells, immune profiles were monitored in 48 patients in a phase II trial of ublituximab, a glycoengineered CD20 monoclonal antibody, at 18 time points over a year. As we previously described there was a significant shift in the percentages of T cells, NK cells, and myeloid cells following the initial dose of ublituximab, but this shift normalized within a week and these populations remained stable for the duration of the study. However, T cell subsets changed with an increase in the percentage of naïve CD4 and CD8 T cells and a decline in memory T cells. Importantly, the percentage of Th1 and CD4+GM-CSF+ T cells decreased, while the percentage of Tregs continued to increase over the year. Ublituximab not only depleted CD20+ B cells, but also CD20+ T cells. The favorable changes in the T cell subsets may contribute to the beneficial effects of B cell depletion therapy.

Alterations of the gut mycobiome in patients with MS.

BACKGROUND: The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied. METHODS: In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months. FINDINGS: The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16+ dendritic cells in pwMS. Different mycobiome profiles, defined as mycotypes, were associated with different bacterial microbiome and immune cell subsets in the blood. Initial treatment with dimethyl fumarate, a common immunomodulatory therapy which also has fungicidal activity, did not cause uniform gut mycobiome changes across all pwMS. INTERPRETATION: There is an alteration of the gut mycobiome in pwMS, compared to healthy controls. Further study is required to assess any causal association of the mycobiome with MS and its direct or indirect interactions with bacteria and autoimmunity. FUNDING: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS102633-04 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-1805-31003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG- 1907-34474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease.

The human placenta and its specialized cytotrophoblasts rapidly develop, have a compressed lifespan, govern pregnancy outcomes, and program the offspring's health. Understanding the molecular underpinnings of these behaviors informs development and disease. Profiling the extraembryonic epigenome and transcriptome during the 2nd and 3rd trimesters revealed H3K9 trimethylation overlapping deeply DNA hypomethylated domains with reduced gene expression and compartment-specific patterns that illuminated their functions. Cytotrophoblast DNA methylation increased, and several key histone modifications decreased across the genome as pregnancy advanced. Cytotrophoblasts from severe preeclampsia had substantially increased H3K27 acetylation globally and at genes that are normally downregulated at term but upregulated in this syndrome. In addition, some cases had an immature pattern of H3K27ac peaks, and others showed evidence of accelerated aging, suggesting subtype-specific alterations in severe preeclampsia. Thus, the cytotrophoblast epigenome dramatically reprograms during pregnancy, placental disease is associated with failures in this process, and H3K27 hyperacetylation is a feature of severe preeclampsia.

Academic Trajectories of College Students with and without ADHD: Predictors of Four-Year Outcomes.

Objective: Completing a college degree is associated with success in employment, financial earnings, and life satisfaction. Mental health difficulties, including attention-deficit/hyperactivity disorder (ADHD), can compromise degree completion.Method: We examined 4-year academic performance trajectories of 201 college students with ADHD (97 receiving medication [ADHD-Med], 104 not receiving medication [ADHD-NoMed]) relative to 205 non-ADHD Comparison students. Demographic (e.g., sex, race/ethnicity), psychological (e.g., self-reported depression and anxiety symptoms), and service-related (e.g., receipt of academic support) variables were included as predictors of intercept (i.e., Year 1 performance) and slope (yearly change) of semester GPA, progress toward graduation, and self-reported study skill strategies.Results: College students with ADHD obtained significantly lower GPAs (Hedge's g = -0.46 and -0.63) and reported less frequent use of study skills strategies (Hedge's g range from -1.00 to -2.28) than Comparison students. Significantly more Comparison students (59.1%) persisted through eight semesters relative to ADHD-NoMed students (49%). Multiple variables predicted outcomes with parent education, fewer depressive symptoms, better executive functioning, and receipt of high school Section 504 accommodations and college academic support services among the strongest predictors.Conclusions: Findings suggest support services for students with ADHD should begin prior to college matriculation and focus on improving executive functioning skills and depressive symptoms to increase chances of academic success.

A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis.

BACKGROUND: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. OBJECTIVE: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. METHODS: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1-4 hours on day 1 and 450-600 mg over 1-3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. RESULTS: In all cohorts (N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions (p = 0.003) and a 10.6% decrease in T2 lesion volume (p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). CONCLUSION: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.

The relationship between integrated pediatric psychology and primary care visit length, revenue, content over 24 months.

Introduction: Integrating behavioral health providers into pediatric primary care to provide behavioral health (BH) services is both effective and efficient; however, the impact of pediatric integrated services on the operational and financial outcomes of primary care provider (PCP) visits has not been thoroughly investigated. The present study examined whether length of practice integration predicts the relationship between BH content addressed in a PCP visit, visit length, and revenue generation. Method: A total of 1,209 pediatric encounters with 25 PCPs across 7 primary care offices in a predominantly rural health system were abstracted for the presence or absence of BH content, visit length, duration of integration, and revenue. χ2 analyses and the generalized linear model framework were used to address the study objectives. Results: Integration was associated with more PCP visits with a BH topic discussed at 6-11 months of integration but not at 14-24 months. Visits with a BH topic were longer than medical-only visits and shorter when a practice was integrated for 6-11 months but not at 14-24 months of integration. Public insurance and integration were associated with lower revenue generation per minute. Visit content was not associated with PCP revenue. Discussion: Results suggest a relationship between integration and the operational and financial outcomes of PCP visits. This study shows that initial efficiencies or improvements (e.g., time, cost, content) associated with integrating BH may be lost over time. Future studies should evaluate sustainability in relation to program impact. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Cytotrophoblast extracellular vesicles enhance decidual cell secretion of immune modulators via TNFα.

The placenta releases large quantities of extracellular vesicles (EVs) that likely facilitate communication between the embryo/fetus and the mother. We isolated EVs from second trimester human cytotrophoblasts (CTBs) by differential ultracentrifugation and characterized them using transmission electron microscopy, immunoblotting and mass spectrometry. The 100,000  g pellet was enriched for vesicles with a cup-like morphology typical of exosomes. They expressed markers specific to this vesicle type, CD9 and HRS, and the trophoblast proteins placental alkaline phosphatase and HLA-G. Global profiling by mass spectrometry showed that placental EVs were enriched for proteins that function in transport and viral processes. A cytokine array revealed that the CTB 100,000  g pellet contained a significant amount of tumor necrosis factor α (TNFα). CTB EVs increased decidual stromal cell (dESF) transcription and secretion of NF-κB targets, including IL8, as measured by qRT-PCR and cytokine array. A soluble form of the TNFα receptor inhibited the ability of CTB 100,000  g EVs to increase dESF secretion of IL8. Overall, the data suggest that CTB EVs enhance decidual cell release of inflammatory cytokines, which we theorize is an important component of successful pregnancy.

Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum.

In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of preterm delivery, hemorrhage, and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The messenger RNA (mRNA) encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly up-regulated molecule in PAS samples. Overexpression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up-regulate a cancer-like proinvasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.

Trisomy 21 is Associated with Caspase-2 Upregulation in Cytotrophoblasts at the Maternal-Fetal Interface.

Impaired placentation is implicated in poor perinatal outcomes associated with Trisomy 21. Earlier studies revealed abnormal cytotrophoblast differentiation along the invasive pathway as a contributing mechanism. To further elucidate the causes, we evaluated Caspase-2 expression at the protein level (immunolocalization and immunoblot) in samples from Trisomy 21 (n = 9) and euploid (n = 4) age-matched placentas. Apoptosis was investigated via the TUNEL assay. An immunolocalization approach was used to characterize Caspase-3, Fas (CD95), and Fas ligand in the same samples. Caspase-2 was significantly overexpressed in Trisomy 21 placentas, with the highest expression in villous cores and invasive cytotrophoblasts. Immunolocalization showed that Caspase-3 had a similar expression pattern as Caspase-2. Using the TUNEL approach, we observed high variability in the number of apoptotic cells in biopsies from different regions of the same placenta and among different placentas. However, Trisomy 21 placentas had more apoptotic cells, specifically in cell columns and basal plates. Furthermore, Caspase-2 co-immunolocalized with Fas (CD95) and FasL in TUNEL-positive extravillous cytotrophoblasts, but not in villous cores. These results help explain the higher levels of apoptosis among placental cells of Trisomy 21 pregnancies in molecular terms. Specifically, the co-expression of Caspase-2 and Caspase-3 with other regulators of the apoptotic process in TUNEL-positive cells suggests these molecules may cooperate in launching the observed apoptosis. Among trophoblasts, only the invasive subpopulation showed this pattern, which could help explain the higher rates of adverse outcomes in these pregnancies. In future experiments, this relationship will be further examined at a functional level in cultured human trophoblasts.

Conjoint behavioral consultation in rural schools: Do student effects maintain after 1 year?

Challenging behavior problems are common in early childhood and, if left untreated, may escalate into more severe and intractable problems in adolescence and early adulthood. This trajectory is of particular importance in rural schools, where disruptive behaviors are more prominent than in urban and suburban schools. Conjoint behavioral consultation (CBC) is a family-school partnership intervention with documented efficacy in producing immediate decreases in child problem behaviors and increases in child adaptive behaviors and social skills. The purpose of the present study was to determine whether the immediate effects of CBC maintain over a 1-year follow-up period. Participants at study enrollment were students (N = 267) and their parents, as well as both the students' original (N = 152) and subsequent (N = 135) teachers in 45 Midwest rural schools. At the time of initial study enrollment, students were assigned randomly to an active CBC intervention or "business as usual" control condition. Results demonstrated that immediate effects of parent-rated adaptive and social skills and teacher-rated school problems were maintained at the 1-year follow-up. Additionally, for parent-rated adaptive skills and teacher-rated school problems, improvements during the maintenance phase were statistically equivalent to gains in the control group. However, increases in parent-rated social skills for the control group during the follow-up phase significantly outpaced increases among the CBC group. Implications for use of CBC in rural communities, as well as future research directions, are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles. During a phase IIa clinical trial with ublituximab, a novel CD20 antibody, blood was collected from 48 MS patients at 11 time points over 24 weeks and the lymphocyte profiles were analyzed by flow cytometry. The percentage of naïve CD4+ and CD8+ T cells increased, while the percentage of both effector and central memory T cells declined. CD4+ Th1 effector cells decreased, while there was a significant increase in CD4+ regulatory T cells. The depletion of B cells had a favorable shift in the lymphocyte landscape, reducing the number of naïve T cells becoming activated and transitioning to memory T cells. The ratio of Th1 cells to CD4+ regulatory T cells declined, suggesting that immune regulation was being restored. These data suggest that loss of B cells as antigen presenting cells is a major mechanism of action for the beneficial effects of CD20 antibody therapy in MS.

First-Year GPA and Academic Service Use Among College Students With and Without ADHD.

Objective: ADHD is a chronic neurodevelopmental disorder that typically results in persistent academic difficulties over time. Although most colleges offer support services, students often do not use the available services or those to which they are entitled. The present study examined predictors of academic performance among college students with and without ADHD. In addition, the rate, predictors, and outcomes of academic service use were explored. Methods: A series of multivariate analyses of variance (MANOVAs) and regression analyses were conducted using SPSS v. 21 ® software. Results: First year college students with ADHD earned significantly lower grade point averages (GPAs) relative to students without ADHD. Additionally, ADHD combined with other disorders, but not ADHD alone, predicted higher rates of service use relative to students without ADHD. Finally, the findings suggest that typically available academic services are not independently related to GPA among first-year college students with or without ADHD. Conclusion: This study replicates previous work demonstrating significantly lower GPAs among a rigorously defined sample of students with ADHD relative to students without ADHD. Second, this study indicates that traditional predictors of college success may be less meaningful for students with ADHD relative to those without ADHD. Finally, additional research needs to be conducted regarding the use and effectiveness of academic services on college campuses.

Rates and Patterns of Comorbidity Among First-Year College Students With ADHD.

The purpose of this study was to examine rates and patterns of non-attention-deficit/hyperactivity disorder (non-ADHD) psychiatric diagnoses among a large group of 1st-year college students with and without ADHD. A total of 443 participants, including 214 men and 229 women ranging in age from 18 to 22 years of age (M = 18.2), were recruited from 9 colleges involved in a large-scale, multisite longitudinal investigation. Non-Hispanic Caucasian students represented 67.5% of the total sample. A comprehensive multimethod assessment approach was used in conjunction with expert panel review to determine both ADHD and comorbidity status. Significantly higher rates of overall comorbidity were found among college students with well-defined ADHD, with 55.0% exhibiting at least one comorbid diagnosis and 31.8% displaying two or more, relative to the corresponding rates of non-ADHD diagnoses among Comparison students, which were 11.2% and 4.0%, respectively. These differences in overall comorbidity rates were, in large part, attributable to the increased presence of depressive and anxiety disorders, especially major depressive disorder (active or in partial remission) and generalized anxiety disorder, among the students with ADHD. Within the ADHD group, differential comorbidity rates were observed as a function of ADHD presentation type and gender but not ethnic/racial diversity status. The current findings fill a gap in the literature and shed new light on the rates and patterns of comorbidity among emerging adults with ADHD in their 1st year of college. Implications for providing clinical and support services to college students with ADHD are discussed.