The FOXP3+ Pro-Inflammatory T Cell: A Potential Therapeutic Target in Crohn's Disease.

BACKGROUND & AIMS: The incidence of Crohn's disease (CD) continues to increase worldwide. The contribution of CD4+ cell populations remains to be elucidated. We aimed to provide an in-depth transcriptional assessment of CD4+ T cells driving chronic inflammation in CD. METHODS: We performed single-cell RNA-sequencing in CD4+ T cells isolated from ileal biopsies of patients with CD compared with healthy individuals. Cells underwent clustering analysis, followed by analysis of gene signaling networks. We overlapped our differentially expressed genes with publicly available microarray data sets and performed functional in vitro studies, including an in vitro suppression assay and organoid systems, to model gene expression changes observed in CD regulatory T (Treg) cells and to test predicted therapeutics. RESULTS: We identified 5 distinct FOXP3+ regulatory Treg subpopulations. Tregs isolated from healthy controls represent the origin of pseudotemporal development into inflammation-associated subtypes. These proinflammatory Tregs displayed a unique responsiveness to tumor necrosis factor-α signaling with impaired suppressive activity in vitro and an elevated cytokine response in an organoid coculture system. As predicted in silico, the histone deacetylase inhibitor vorinostat normalized gene expression patterns, rescuing the suppressive function of FOXP3+ cells in vitro. CONCLUSIONS: We identified a novel, proinflammatory FOXP3+ T cell subpopulation in patients with CD and developed a pipeline to specifically target these cells using the US Food and Drug Administration-approved drug vorinostat.

Interleukin 21 Drives a Hypermetabolic State and CD4+ T-Cell-Associated Pathogenicity in Chronic Intestinal Inflammation.

BACKGROUND & AIMS: Incapacitated regulatory T cells (Tregs) contribute to immune-mediated diseases. Inflammatory Tregs are evident during human inflammatory bowel disease; however, mechanisms driving the development of these cells and their function are not well understood. Therefore, we investigated the role of cellular metabolism in Tregs relevant to gut homeostasis. METHODS: Using human Tregs, we performed mitochondrial ultrastructural studies via electron microscopy and confocal imaging, biochemical and protein analyses using proximity ligation assay, immunoblotting, mass cytometry and fluorescence-activated cell sorting, metabolomics, gene expression analysis, and real-time metabolic profiling utilizing the Seahorse XF analyzer. We used a Crohn's disease single-cell RNA sequencing dataset to infer the therapeutic relevance of targeting metabolic pathways in inflammatory Tregs. We examined the superior functionality of genetically modified Tregs in CD4+ T-cell-induced murine colitis models. RESULTS: Mitochondria-endoplasmic reticulum appositions, known to mediate pyruvate entry into mitochondria via voltage-dependent anion channel 1 (VDAC1), are abundant in Tregs. VDAC1 inhibition perturbed pyruvate metabolism, eliciting sensitization to other inflammatory signals reversible by membrane-permeable methyl pyruvate supplementation. Notably, interleukin (IL) 21 diminished mitochondria-endoplasmic reticulum appositions, resulting in enhanced enzymatic function of glycogen synthase kinase 3 ß, a putative negative regulator of VDAC1, and a hypermetabolic state that amplified Treg inflammatory response. Methyl pyruvate and glycogen synthase kinase 3 ß pharmacologic inhibitor (LY2090314) reversed IL21-induced metabolic rewiring and inflammatory state. Moreover, IL21-induced metabolic genes in Tregs in vitro were enriched in human Crohn's disease intestinal Tregs. Adoptively transferred Il21r-/- Tregs efficiently rescued murine colitis in contrast to wild-type Tregs. CONCLUSIONS: IL21 triggers metabolic dysfunction associated with Treg inflammatory response. Inhibiting IL21-induced metabolism in Tregs may mitigate CD4+ T-cell-driven chronic intestinal inflammation.

Effectiveness of Robotics in Stroke Rehabilitation to Accelerate Upper Extremity Function: Systematic Review.

Objective: To examine the effectiveness of robot-assisted therapy (RAT) combined with conventional therapy (CT) compared to CT alone in accelerating upper extremity (UE) recovery poststroke. Data Sources. We searched five databases: Ovid, MEDLINE, CINAHL, PubMed, and Scopus Study Selection. Studies were selected for this review using the following inclusion criteria: randomized controlled trials of adults, RAT combined with CT compared to CT, and Fugl-Meyer Assessment (FMA) as an outcome measure. Studies focused on children with neurological impairments, and studies that used RAT to facilitate lower extremity recovery and/or improve gait were excluded. Data Extraction. The initial search yielded 3,019 citations of articles published between January 2011 and May 2021. Fourteen articles met the inclusion criteria. Randomization, allocation sequence concealment, blinding, and other biases were assessed. Data Synthesis. Current evidence suggests that the use of RAT along with CT may accelerate upper extremity recovery, measured by FMA, in the beginning of rehabilitation. However, the progress fades over time. More empirical research is needed to validate this observation. Also, the findings related to cost-benefit analyses of RAT are inconclusive. Conclusions: It is unclear whether RAT accelerates UE recovery poststroke when used in conjunction with conventional therapy. Given the capital and maintenance costs involved in developing and delivering RAT, more controlled studies examining the effectiveness and cost-benefit analysis of RAT are needed before it can be used widely. This trial is registered with CRD42021270824.

Preclinical development of 1B7/CD3, a novel anti-TSLPR bispecific antibody that targets CRLF2-rearranged Ph-like B-ALL.

Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. Further, 1B7/CD3 was shown to induce potent T cell activation and tumor lytic activity in both cell lines and primary B-ALL patient samples. Using humanized cell- or patient-derived xenograft models, 1B7/CD3 treatment was shown to trigger dose-dependent tumor remission or growth inhibition across donors as well as induce T cell activation and expansion. Pharmacokinetic studies in murine models revealed 1B7/CD3 to exhibit a prolonged half-life. Finally, toxicology studies using cynomolgus monkeys found that the maximum tolerated dose of 1B7/CD3 was ≤1 mg/kg. Overall, our preclinical data provide the framework for the clinical evaluation of 1B7/CD3 in patients with CRLF2-rearranged B-ALL.

G9a Modulates Lipid Metabolism in CD4 T Cells to Regulate Intestinal Inflammation.

BACKGROUND & AIMS: Although T-cell intrinsic expression of G9a has been associated with murine intestinal inflammation, mechanistic insight into the role of this methyltransferase in human T-cell differentiation is ill defined, and manipulation of G9a function for therapeutic use against inflammatory disorders is unexplored. METHODS: Human naive T cells were isolated from peripheral blood and differentiated in vitro in the presence of a G9a inhibitor (UNC0642) before being characterized via the transcriptome (RNA sequencing), chromatin accessibility (assay for transposase-accessible chromatin by sequencing), protein expression (cytometry by time of flight, flow cytometry), metabolism (mitochondrial stress test, ultrahigh performance liquid chromatography-tandem mas spectroscopy) and function (T-cell suppression assay). The in vivo role of G9a was assessed using 3 murine models. RESULTS: We discovered that pharmacologic inhibition of G9a enzymatic function in human CD4 T cells led to spontaneous generation of FOXP3+ T cells (G9a-inibitors-T regulatory cells [Tregs]) in vitro that faithfully reproduce human Tregs, functionally and phenotypically. Mechanistically, G9a inhibition altered the transcriptional regulation of genes involved in lipid biosynthesis in T cells, resulting in increased intracellular cholesterol. Metabolomic profiling of G9a-inibitors-Tregs confirmed elevated lipid pathways that support Treg development through oxidative phosphorylation and enhanced lipid membrane composition. Pharmacologic G9a inhibition promoted Treg expansion in vivo upon antigen (gliadin) stimulation and ameliorated acute trinitrobenzene sulfonic acid-induced colitis secondary to tissue-specific Treg development. Finally, Tregs lacking G9a expression (G9a-knockout Tregs) remain functional chronically and can rescue T-cell transfer-induced colitis. CONCLUSION: G9a inhibition promotes cholesterol metabolism in T cells, favoring a metabolic profile that facilitates Treg development in vitro and in vivo. Our data support the potential use of G9a inhibitors in the treatment of immune-mediated conditions including inflammatory bowel disease.

Diagnostic accuracy of Achenbach scales in detecting youths' substance use disorders.

It is vital to identify substance use disorders (SUDs) in youths and adults early and accurately. Previous studies have investigated the validity and reliability of the Achenbach Child Behavior Checklist (CBCL) and Youth Self Report (YSR) for other related anxiety, mood, and behavior problems. The present study tested if the CBCL and YSR substance use items can discriminate adolescents with versus without a SUD diagnosis accurately enough to justify clinical application within an evidence-based assessment framework. N = 422 outpatient adolescents (age 9-18) and their caregivers completed semistructured diagnostic interviews. Caregivers completed CBCL, and adolescents completed the YSR. K-SADS-PL + diagnoses indicated that 34 youths met Diagnostic and Statistical Manual (DSM)-IV criteria for SUDs. Receiver Operating Characteristics (ROC) models estimated the likelihood of having Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (KSADS-PL) + SUDs based on substance use scores of CBCL or YSR. Scores on all scales significantly identified KSADS-PL-diagnosed SUDs in adolescents: Area under the curve (AUCCBCL = .90, p < .0005; AUCYSR = .84, p < .0005). There was no significant difference in the accuracy comparing each informant used separately; CBCL showed incremental value above the YSR report when both were included in logistic regression models. CBCL and YSR substance items demonstrated diagnostic and clinical utility in identifying SUDs in adolescents. Findings suggest that Achenbach Scales could be a valuable intake instrument in detecting adolescents SUDs. A supplemental clinical vignette illustrates the clinical application of the study findings. It will be important for future research to replicate use of these measures across varying clinical scenarios and settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Systemic erythematosus lupus and pregnancy outcomes in a Colombian cohort.

OBJECTIVE: Pregnant women with SLE have higher probabilities of maternal complications. SLE during pregnancy has alternating patterns of remission and flare-ups; however, most pregnant SLE patients tend to worsen with associated poor obstetric and perinatal outcomes. This study aimed to describe obstetric outcomes in pregnant women with SLE. METHODS: This retrospective study was performed between 2011 and 2020 at a highly complex referral health center in Cali, Colombia. Pregnant women with a diagnosis of SLE were included. Demographic, clinical, and laboratory features and obstetric and fetal outcomes, including intensive care unit (ICU) characteristics, were evaluated. RESULTS: Forty-eight pregnant women with SLE were included. The median age was 29 (25-33.7) years. The SLE diagnosis was made before pregnancy in 38 (79.1%) patients, with a median disease duration of 46 (12-84) months. Thirteen (27.1%) patients had lupus nephritis. Preterm labor (34, 70.8%), preeclampsia (25, 52%), and preterm rupture of membranes (10, 20.8%) were the most common obstetric complications. A relationship between a greater systemic lupus erythematosus pregnancy disease activity index (SLEPDAI) and the development of hypertensive disorders during pregnancy was established (preeclampsia = p < 0.0366; eclampsia = p < 0.0153). A relationship was identified between lupus nephritis (LN) and eclampsia (p < 0.01), preterm labor (p < 0.045), and placental abruption (p < 0.01). Seventeen (35.4%) patients required ICU admission; 52.9% of them were due to AID activity, 17.6% for cardiovascular damage, 11.7% for septic shock, and 5.8% for acute kidney failure. Fetal survival was 89.5% (N = 43/48). Among the live births, two (4.2%) newborns were diagnosed with neonatal lupus, and two (4.2%) were diagnosed with congenital heart block. One maternal death was registered due to preeclampsia and intraventricular hemorrhage. CONCLUSIONS: This study is the first to describe SLE during pregnancy in Colombia. SLE was the most prevalent AID in this cohort, and complications included preterm labor, preeclampsia, and postpartum hemorrhage. A higher SLEPDAI and lupus nephritis predicted adverse maternal outcomes.

Dyslexia knowledge, perceived preparedness, and professional development needs of in-service educators.

The purpose of this study was to investigate New Jersey educators' dyslexia knowledge and misconceptions, professional development perceptions and needs, and perceived preparedness regarding teaching students with dyslexia. A second purpose was to investigate what factors predicted New Jersey educators' knowledge about dyslexia. A total of 705 in-service educators completed a survey about their dyslexia knowledge, perceived preparedness, and professional development perceptions. Participants had accurate overall knowledge about dyslexia, but some prevailing misconceptions were still present. The greatest predictor of dyslexia knowledge was years of experience in working with students with dyslexia. Reading specialists, educators with greater perceived preparedness and those educators who had training in multi-sensory approaches to instruction had significantly more dyslexia knowledge than other educators. Approximately half of the participants felt prepared to teach students with dyslexia and that working with students with dyslexia prepared them the most. Participants perceived that multi-sensory approaches were the most effective professional development and their undergraduate education was the least effective. Most participants were in support of further professional development on the topic of dyslexia. Implications for in-service educators' professional development and future research directions are discussed.

BMI1 maintains the Treg epigenomic landscape to prevent inflammatory bowel disease.

FOXP3+ Tregs are expanded within the inflamed intestine of human Crohn's disease, yet FOXP3-mediated gene repression within these cells is lost. The polycomb repressive complexes play a role in FOXP3 target gene regulation, but deeper mechanistic insight is incomplete. We have now specifically identified the polycomb-repressive complex 1 (PRC1) family member, BMI1 in the regulation of a proinflammatory enhancer network in both human and murine Tregs. Using human Tregs and lamina propria T cells, we inferred PRC1 to regulate Crohn's associated gene networks through assays of chromatin accessibility. Conditional deletion of BMI1 in murine FOXP3+ cells led to systemic inflammation. BMI1-deficient Tregs beared a TH1/TH17-like phenotype as assessed by assays of genome wide transcription, chromatin accessibility and proteomic techniques. Finally, BMI1 mutant FOXP3+ cells did not suppress colitis in the adoptive transfer model of human inflammatory bowel disease. We propose that BMI1 plays an important role in enforcing Treg identity in vitro and in vivo. Loss of Treg identity via genetic or transient BMI1 depletion perturbs the epigenome and converts Tregs into Th1/Th17-like proinflammatory cells, a transition relevant to human Crohn's disease associated CD4+ T cells.

Optimizing Engagement in Behavioral Parent Training: Progress Toward a Technology-Enhanced Treatment Model.

Low-income families are more likely to have a child with an early-onset Behavior Disorder (BD); yet, socioeconomic strain challenges engagement in Behavioral Parent Training (BPT). This study follows a promising pilot to further examine the potential to cost-effectively improve low-income families' engagement in and the efficiency of BPT. Low-income families were randomized to (a) Helping the Noncompliant Child (HNC; McMahon & Forehand, 2003), a weekly, mastery-based BPT program that includes both the parent and child or (b) Technology-Enhanced HNC (TE-HNC), which includes all of the standard HNC components plus a parent mobile application and therapist web portal that provide between-session monitoring, modeling, and coaching of parent skill use with the goal of improved engagement in the context of financial strain. Relative to HNC, TE-HNC families had greater homework compliance and mid-week call participation. TE-HNC completers also required fewer weeks to achieve skill mastery and, in turn, to complete treatment than those in HNC without compromising parent satisfaction with treatment; yet, session attendance and completion were not different between groups. Future directions and clinical implications are discussed.

Deregulation of Long Intergenic Non-coding RNAs in CD4+ T Cells of Lamina Propria in Crohn's Disease Through Transcriptome Profiling.

BACKGROUND: The aetiology of Crohn's disease [CD] involves immune dysregulation in a genetically susceptible individual. Genome-wide association studies [GWAS] have identified 200 loci associated with CD, ulcerative colitis, or both, most of which fall within non-coding DNA regions. Long non-coding RNAs [lncRNAs] regulate gene expression by diverse mechanisms and have been associated with disease activity in inflammatory bowel disease. However, disease-associated lncRNAs have not been characterised in pathogenic immune cell populations. METHODS: Terminal ileal samples were obtained from 22 CD patients and 13 controls. RNA from lamina propria CD4+ T cells was sequenced and long intergenic non-coding RNAs [lincRNAs] were detected. Overall expression patterns, differential expression [DE], and pathway and gene enrichment analyses were performed. Knockdown of novel lincRNAs XLOC_000261 and XLOC_000014 was performed. Expression of Th1 or Th17-associated transcription factors, T-bet and RORγt, respectively, was assessed by flow cytometry. RESULTS: A total of 6402 lincRNAs were expressed, 960 of which were novel. Unsupervised clustering and principal component analysis showed that the lincRNA expression discriminated patients from controls. A total of 1792 lincRNAs were DE, and 295 [79 novel; 216 known] mapped to 267 of 5727 DE protein-coding genes. The novel lincRNAs were enriched in inflammatory and Notch signalling pathways [p <0.05]. Furthermore, DE lincRNAs in CD patients were more frequently found in DNA regions with known inflammatory bowel disease [IBD]-associated loci. The novel lincRNA XLOC_000261 negatively regulated RORγt expression in Th17 cells. CONCLUSIONS: We describe a novel set of DE lincRNAs in CD-associated CD4+ cells and demonstrate that novel lincRNA XLOC_000261 appears to negatively regulate RORγt protein expression in Th17 cells.

BPT for Early-Onset Behavior Disorders: Examining the Link Between Treatment Components and Trajectories of Child Internalizing Symptoms.

Behavioral Parent Training (BPT) is the standard of care for early-onset Behavior Disorders (BDs). Preliminary evidence suggests that BPT may also lead to improvement in comorbid symptomatology, particularly internalizing problems, in children with BDs, yet less is currently known about how BPT produces such cascading effects. To begin to address this gap in the literature, trajectory analyses were used to examine the link between treatment components of one mastery-based BPT program, Helping the Noncompliant Child (HNC), and child internalizing symptoms over the course of treatment. Findings revealed that parental use of the Attends skill (i.e., parental description of child activity with warmth and enthusiasm) over time was significantly associated with decreases in trajectories of child internalizing symptoms across treatment. Further probing of these effects revealed that parent use of average or above-average levels of Attends across treatment sessions led to significant reductions in child internalizing symptoms by Sessions 7 to 10 of treatment. Consistent with the movement toward a modular approach to the treatment of children, findings highlight the importance of identifying particular BPT skills that can be used in treatment to target multiple comorbid child symptom clusters. Clinical implications and future directions are discussed.

Medical Providers and Harm Reduction Views on Pre-Exposure Prophylaxis for HIV Prevention Among People Who Inject Drugs.

Despite high pre-exposure prophylaxis (PrEP) acceptability among people who inject drugs (PWID) and PrEP providers, PrEP uptake is low and little is known about how to promote PrEP among PWID. This qualitative study with providers in North Carolina explored views on PrEP delivery approaches for PWID. Interviewers conducted semistructured interviews with 10 PrEP providers and 10 harm reduction (HR) providers. Interviews were transcribed and analyzed. Many participants expressed acceptability for providing PrEP referrals at syringe exchange sites, stationing PrEP providers at syringe exchange sites to provide PrEP prescriptions, and providing standing orders for PrEP at syringe exchange sites. Barriers were identified, including low PrEP awareness and limited resources. Many advocated for co-location of HR and PrEP services and scaled-up outreach services. PrEP providers emphasized maintenance of clinical requirements, while HR providers emphasized flexibility when treating PWID. Promoting PrEP uptake and adherence among PWID likely requires integration of HR and PrEP services.

Disruption of FOXP3-EZH2 Interaction Represents a Pathobiological Mechanism in Intestinal Inflammation.

Background & Aims: Forkhead box protein 3 (FOXP3)+ regulatory T cell (Treg) dysfunction is associated with autoimmune diseases; however, the mechanisms responsible for inflammatory bowel disease pathophysiology are poorly understood. Here, we tested the hypothesis that a physical interaction between transcription factor FOXP3 and the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is essential for gene co-repressive function. Methods: Human FOXP3 mutations clinically relevant to intestinal inflammation were generated by site-directed mutagenesis. T lymphocytes were isolated from mice, human blood, and lamina propria of Crohn's disease (CD) patients and non-CD controls. We performed proximity ligation or a co-immunoprecipitation assay in FOXP3-mutant+, interleukin 6 (IL6)-treated or CD-CD4+ T cells to assess FOXP3-EZH2 protein interaction. We studied IL2 promoter activity and chromatin state of the interferon γ locus via luciferase reporter and chromatin-immunoprecipitation assays, respectively, in cells expressing FOXP3 mutants. Results: EZH2 binding was abrogated by inflammatory bowel disease-associated FOXP3 cysteine 232 (C232) mutation. The C232 mutant showed impaired repression of IL2 and diminished EZH2-mediated trimethylation of histone 3 at lysine 27 on interferon γ, indicative of compromised Treg physiologic function. Generalizing this mechanism, IL6 impaired FOXP3-EZH2 interaction. IL6-induced effects were reversed by Janus kinase 1/2 inhibition. In lamina propria-derived CD4+T cells from CD patients, we observed decreased FOXP3-EZH2 interaction. Conclusions: FOXP3-C232 mutation disrupts EZH2 recruitment and gene co-repressive function. The proinflammatory cytokine IL6 abrogates FOXP3-EZH2 interaction. Studies in lesion-derived CD4+ T cells have shown that reduced FOXP3-EZH2 interaction is a molecular feature of CD patients. Destabilized FOXP3-EZH2 protein interaction via diverse mechanisms and consequent Treg abnormality may drive gastrointestinal inflammation.

The Role of Histone Methyltransferases and Long Non-coding RNAs in the Regulation of T Cell Fate Decisions.

T cell lineage decisions are critical for the development of proper immune responses to pathogens as well as important for the resolution of inflammatory responses. This differentiation process relies on a combination of intrinsic and extrinsic factors converging upon epigenetic regulation of transcriptional networks relevant to specific T cell lineages. As these biochemical modifications represent therapeutic opportunities in cancer biology and autoimmunity, implications of writers and readers of epigenetic marks to immune cell differentiation and function are highly relevant. Given the ready adoption of histone methyltransferase inhibitors in the clinic, we focus this review on the role of three histone modifying complexes: PRC-1, PRC-2, and G9A in modulating T cell fate decisions. Furthermore, we explore the role of long non-coding RNAs in regulating these processes, and discuss recent advances and challenges of implementing epigenetic therapies into clinical practice.

The Role of the Histone Methyltransferase Enhancer of Zeste Homolog 2 (EZH2) in the Pathobiological Mechanisms Underlying Inflammatory Bowel Disease (IBD).

Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have shown previously that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2Δ/ΔFOXP3+). We find that EZH2 deficiency in FOXP3+ T cells results in lethal multiorgan autoimmunity. We further demonstrate that EZH2Δ/ΔFOXP3+ T cells lack a regulatory phenotype in vitro and secrete proinflammatory cytokines. Of special interest, EZH2Δ/ΔFOXP3+ mice develop spontaneous inflammatory bowel disease. Guided by these results, we assessed the FOXP3 and EZH2 gene networks by RNA sequencing in isolated intestinal CD4+ T cells from patients with Crohn's disease. Gene network analysis demonstrates that these CD4+ T cells display a Th1/Th17-like phenotype with an enrichment of gene targets shared by FOXP3 and EZH2. Combined, these results suggest that the inflammatory milieu found in Crohn's disease could lead to or result from deregulation of FOXP3/EZH2-enforced T cell gene networks contributing to the underlying intestinal inflammation.

Physical activity differences for college students with disabilities.

BACKGROUND: Previous literature suggests that individuals with disabilities have increased rates of obesity and decreased participation in physical activity contributing to overall higher incidence of secondary health conditions compared to the general population without disabilities. OBJECTIVE/HYPOTHESIS: The purpose of this research study was to examine the differences in physical activity rates for college students with Attention Deficit Hyperactivity Disorder (ADHD) and Learning Disabilities (LD). METHODS: A secondary analysis was utilized to examine differences in physical activity rates based on disability, gender, and factors influencing participation in physical activity. The 2011 Fall National College Health Assessment was used as the reference group with a sample of 27,774 students. Multiple independent samples t-tests were utilized in this research. RESULTS: The results of this study indicated that physical activity for college students with disabilities does not have significant variations compared to those without disabilities. However, gender influences participation in physical activity for this population. CONCLUSIONS: This research helps in narrowing the research gap in this topic through analysis of the college population with ADHD and LD. This paper concludes with implications that could benefit the health status of this population.

Genetic and Clinical Features of Medullary Thyroid Carcinoma: The Experience of a Single Center in Costa Rica.

Background. Activating mutations in the RET gene leads to medullary thyroid carcinoma (MTC). Guidelines encourage performing RET analysis in subjects with hereditary and sporadic disease. Materials and Methods. Design. Observational, case series report study. Patients. Subjects diagnosed with MTC, with a thyroidectomy performed in a single center in Costa Rica between the years 2006 and 2015. Diagnosis and Follow-Up. Pre- and postoperative calcitonin, RET mutation, and neck ultrasound and tomography were obtained. Results. 21 subjects with histological diagnosis of MTC were followed up. The average age at diagnosis was 52.0 ± 15.7 years. The preoperative mean value of calcitonin was 1340 ± 665 pg/mL. Evidence of RET mutation was found in 26.3% of the patients, with only 2 of them grouped in the same kindred. We found statistically significant differences in mean ages between mutated (38.4 ± 20.2 y) versus nonmutated RET gene (54.6 ± 11.8 y, p = 0.04). There were no significant differences regarding tumor size, metastases, and surgical reintervention. Conclusions. We report the results of RET mutation analysis in subjects with MTC in a single center of Costa Rica. The availability of this tool increases the probability of identifying familial MTC, with the benefit of detecting affected subjects and their relatives at an earlier age.