CodonBERT large language model for mRNA vaccines.

mRNA-based vaccines and therapeutics are gaining popularity and usage across a wide range of conditions. One of the critical issues when designing such mRNAs is sequence optimization. Even small proteins or peptides can be encoded by an enormously large number of mRNAs. The actual mRNA sequence can have a large impact on several properties, including expression, stability, immunogenicity, and more. To enable the selection of an optimal sequence, we developed CodonBERT, a large language model (LLM) for mRNAs. Unlike prior models, CodonBERT uses codons as inputs, which enables it to learn better representations. CodonBERT was trained using more than 10 million mRNA sequences from a diverse set of organisms. The resulting model captures important biological concepts. CodonBERT can also be extended to perform prediction tasks for various mRNA properties. CodonBERT outperforms previous mRNA prediction methods, including on a new flu vaccine data set.

Predicting non-initiation of care and dropout in a blended care CBT intervention: Impact of early digital engagement, sociodemographic, and clinical factors.

Objective: This study examines predictors of non-initiation of care and dropout in a blended care CBT intervention, with a focus on early digital engagement and sociodemographic and clinical factors. Methods: This retrospective cohort analysis included 3566 US-based individuals who presented with clinical levels of anxiety and depression and enrolled in a blended-care CBT (BC-CBT) program. The treatment program consisted of face-to-face therapy sessions via videoconference and provider-assigned digital activities that were personalized to the client's presentation. Multinomial logistic regression and Cox proportional hazard survival analysis were used to identify predictors of an increased likelihood of non-initiation of therapy and dropout. Results: Individuals were more likely to cancel and/or no-show to their first therapy session if they were female, did not disclose their ethnicity, reported poor financial status, did not have a college degree, endorsed more presenting issues during the onboarding triage assessment, reported taking antidepressants, and had a longer wait time to their first appointment. Of those who started care, clients were significantly more likely to drop out if they did not complete the digital activities assigned by their provider early in treatment, were female, reported more severe depressive symptoms at baseline, reported taking antidepressants, and did not disclose their ethnicity. Conclusions: Various sociodemographic and clinical predictors emerged for both non-initiation of care and for dropout, suggesting that clients with these characteristics may benefit from additional attention and support (especially those with poor early digital engagement). Future research areas include targeted mitigation efforts to improve initiation rates and curb dropout.

Examining the Impact of Digital Components Across Different Phases of Treatment in a Blended Care Cognitive Behavioral Therapy Intervention for Depression and Anxiety: Pragmatic Retrospective Study.

BACKGROUND: Depression and anxiety incur significant personal and societal costs. Effective psychotherapies exist, such as cognitive behavioral therapy (CBT); however, timely access to quality care is limited by myriad barriers. Blended care therapy models incorporate traditional face-to-face therapy with scalable, digital components of care, expanding the reach of evidence-based care. OBJECTIVE: The aim of this study is to determine the effectiveness of a blended care CBT program (BC-CBT) in real-world settings and examine the unique impacts of the (1) digital components of care (video lessons and digital exercises) and (2) phase of treatment (early versus late) in decreasing symptoms of anxiety and depression. METHODS: This retrospective cohort analysis included 3401 US-based individuals enrolled in a BC-CBT program, who presented with clinical levels of depression and/or anxiety. The treatment program consisted of regular therapy sessions augmented by clinician-assigned digital video lessons and exercises. A growth curve model incorporating time-varying covariates examined the relationship between engagement with BCT components (ie, therapy sessions, digital video lessons, and digital exercises) during the early (weeks 0-7) and late (weeks 8-15) phases of treatment, and weekly symptom reports on depression and anxiety measures. RESULTS: On average, a significant decline in depression and anxiety symptoms was observed during the initial weeks of treatment (P<.001), with a continued, though slower, decline over subsequent weeks (P<.001). Each session completed was associated with significant decreases in anxiety (b=-0.72) and depression (b=-0.83) in the early phase, as well as in the late phase (anxiety, b=-0.47; depression, b=-0.27). Significant decreases in anxiety (b=-0.15) and depression (b=-0.12) were observed for time spent on video lessons (measured in 10-minute intervals) in the early phase of treatment. Engaging with exercises was associated with statistically significant increases in anxiety symptoms (b=0.03) during the early phase of treatment. However, sensitivity analyses examining the effects of exercises in isolation revealed significant decreases in anxiety (b=-0.05) in the early phase, suggesting a potential suppression effect in the larger model. CONCLUSIONS: Using a retrospective cohort design, therapy sessions and digital video lessons were uniquely predictive of improvements in depression and anxiety symptoms, and their effects were modulated based on the phase of treatment (early vs late). Future research should investigate whether other treatment variables, such as therapeutic alliance or familiarity with technology, are related to differential effects on various components of care.

Outcomes of a Blended Care Coaching Program for Clients Presenting With Moderate Levels of Anxiety and Depression: Pragmatic Retrospective Study.

BACKGROUND: Depression and anxiety are leading causes of disability worldwide, but access to quality mental health care is limited by myriad factors. Cognitive-behavioral coaching is rooted in evidence-based principles and has the potential to address some of these unmet care needs. Harnessing technology to facilitate broader dissemination within a blended care model shows additional promise for overcoming barriers to care. OBJECTIVE: The aim of this study is to evaluate the outcomes of a blended care coaching (BCC) program for clients presenting with moderate levels of anxiety and depression in real-world settings. METHODS: This study examined retrospective data from US-based individuals (N=1496) who presented with moderate levels of depression and anxiety symptoms and who received blended care coaching services. Using a short-term framework, clients met with coaches via a secure video conference platform and also received digital video lessons and exercises. To evaluate the effectiveness of the BCC program, mixed effects modeling was used to examine growth trajectories of anxiety and depression scores over the course of care. RESULTS: Out of the total sample of 1496 clients, 75.9% (n=1136) demonstrated reliable improvement, and 88.6% (n=1326) recovered based on either the Generalized Anxiety Disorder-7 scale (anxiety) or Patient Health Questionnaire-9 (depression). On average, clients exhibited a significant decline in anxiety and depression symptoms during the initial weeks of coaching, with a continued decline over subsequent weeks at a lower rate. Engaging in a coaching session was associated with lower anxiety (b=-1.04) and depression (b=-0.79) symptoms in the same week, as well as lower anxiety (b=-0.74) and depression (b=-0.91) symptoms the following week (P<.001). CONCLUSIONS: The BCC program demonstrated strong outcomes in decreasing symptomology for clients presenting with moderate levels of anxiety and depression. When clients received coaching sessions, significant decreases in symptoms were observed, reflecting the importance of session attendance. Additionally, the steepest declines in symptoms tended to occur during the initial weeks of coaching, emphasizing the importance of client buy-in and early engagement. Collectively, these findings have implications for addressing unmet mental health care needs in a more accessible, cost-effective manner.

Longitudinal trajectory and predictors of change in family accommodation during exposure therapy for pediatric OCD.

Family accommodation (FA) is key in the maintenance of OCD. However, most studies are cross-sectional, and have not identified long-term trajectories and correlates of FA changes over treatment. This study investigated changes in clinician-rated FA over 10 sessions of cognitive behavioral therapy (CBT) for 142 children with OCD, as well as several key predictors/correlates: (a) clinician-rated OCD symptom severity, (b) child- and parent-rated functional impairment, (c) parent-rated treatment expectancies, and (d) child- and parent-rated therapeutic alliance. Multi-level models indicated that FA changed significantly during treatment, with gains maintained over 6-months. Baseline clinician-rated OCD severity did not predict changes in FA. Significant interactions indicated that children with higher child- and parent-rated impairment exhibited greater FA improvements over treatment (versus children with lower impairment). Child- and parent-rated therapeutic alliance and parent-rated expectancies did not predict FA changes. Finally, FA mediated the relationship between OCD severity and parent- (but not child-) rated impairment. Reverse mediation models were also significant. Findings indicate that CBT can successfully reduce FA (a) even if children experience high OCD severity and interference in school, relationships, and family life, and (b) regardless of non-specific factors like treatment expectancies and alliance. FA reductions are an important mechanism mediating treatment response.

Knowledge and competency standards for specialized cognitive behavior therapy for pediatric obsessive-compulsive disorder.

Although exposure-based cognitive behavior therapy (CBT) and pharmacotherapy have demonstrated efficacy for obsessive-compulsive disorder (OCD), the lack of clinicians effectively trained in these treatments significantly limit effective intervention options for affected youth. This is very unfortunate since child onset is reported by 50% of adults with OCD. To ameliorate this serious global issue the 14 nation International Obsessive-Compulsive Disorders Accreditation Task Force (ATF) of The Canadian Institute for Obsessive Compulsive Disorders (CIOCD) has developed knowledge and competency standards recommended for specialized treatments for OCD through the lifespan. Currently available guidelines are considered by experts to be essential but insufficient because there are not enough clinicians with requisite knowledge and competencies to effectively treat OCD. This manuscript presents knowledge and competency standards recommended for specialized cognitive behavior therapy (CBT) for pediatric OCD, derived from comprehensive literature review and expert synthesis. In addition to standards covering the elements of individual CBT-based assessment and treatment, family and school interventions are addressed given the critical role these domains play in the psychosocial development of youths. The ATF standards presented in these phase two papers will be foundational to the upcoming development of certification (individuals) and accreditation (sites) for specialized treatments in OCD through the lifespan.

Prevalence, severity, and clinical correlates of food neophobia in Salvadorian youth.

Food neophobia (FN) describes problematic fear-based avoidance/restriction of novel foods. Using the novel parent-reported Measure of Food Neophobia (MFN), the authors examined FN symptoms and impairment in 305 Salvadorian children and explored clinical correlates. Factor analysis supported the MFN's designed structure to inquire about FN symptoms and FN impairment. At least one FN symptom was observed in 91% of the sample; however, only 9% were rated as having moderate or greater impairment. Demographic variables were not associated with FN; however, FN was positively correlated with internalizing, externalizing, inattention, health anxiety, and obsessive-compulsive symptoms. Inattention symptoms and health anxiety emerged as significant predictors of FN symptoms, while FN symptoms were the only significant predictor of FN impairment. The present study supports the MFN and provides information about FN in a general population, including the prevalence of clinically significant symptoms and association with psychological domains. Continued investigation of FN is still needed.

Development, Acceptability, and Feasibility of a Digital Module for Coping with COVID-19 Distress: Pragmatic Retrospective Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic and the measures to help contain it have taken a significant toll on mental health. Blended care psychotherapy combining provider-led care with digital tools can help alleviate this toll. This study describes the development of digital activities designed to teach cognitive-behavioral skills for coping with COVID-19 distress, and evaluates initial acceptability and feasibility data. Materials and Methods: Using a pragmatic retrospective cohort design, data from 664 U.S.-based individuals enrolled in blended care psychotherapy were analyzed. Descriptive analyses summarized acceptability for the digital activities. Ordinal logistic regression analyses were conducted on a subsample (n = 162) to explore the association between clients' attitudes toward the digital lesson and reported practice of skills in the exercise. Results: The majority of clients completed the assigned digital lesson and exercise. Clients reported finding the lesson valuable and relevant for coping with COVID-19 distress, and they intended to apply the skills to their lives. Higher agreement with these attitude questions was associated with a significantly greater number of skills practiced on the digital exercise. Discussion: Clients who were assigned a cognitive-behaviorally oriented digital lesson and/or exercise within a blended care model largely engaged with the materials and found them valuable. Clients with more positive attitudes about the digital lesson reported using more coping skills. Conclusions: Digital modules that teach specific skills for coping with COVID-19 can be integrated into treatment and minimize provider burden. Future study should investigate the clinical impact of these digital activities on psychiatric symptoms and personalizing the content.

Synthesis of low immunogenicity RNA with high-temperature in vitro transcription.

The use of synthetic RNA for therapeutics requires that the in vitro synthesis process be robust and efficient. The technology used for the synthesis of these in vitro-transcribed RNAs, predominantly using phage RNA polymerases (RNAPs), is well established. However, transcripts synthesized with RNAPs are known to display an immune-stimulatory activity in vivo that is often undesirable. Previous studies have identified double-stranded RNA (dsRNA), a major by-product of the in vitro transcription (IVT) process, as a trigger of cellular immune responses. Here we describe the characterization of a high-temperature IVT process using thermostable T7 RNAPs to synthesize functional mRNAs that demonstrate reduced immunogenicity without the need for a post-synthesis purification step. We identify features that drive the production of two kinds of dsRNA by-products-one arising from 3' extension of the run-off product and one formed by the production of antisense RNAs-and demonstrate that at a high temperature, T7 RNAP has reduced 3'-extension of the run-off product. We show that template-encoded poly(A) tailing does not affect 3'-extension but reduces the formation of the antisense RNA by-products. Combining high-temperature IVT with template-encoded poly(A) tailing prevents the formation of both kinds of dsRNA by-products generating functional mRNAs with reduced immunogenicity.

The Impact of Treatment Expectations on Exposure Process and Treatment Outcome in Childhood Anxiety Disorders.

This study examined the relationship between caregivers' and youths' treatment expectations and characteristics of exposure tasks (quantity, mastery, compliance) in cognitive-behavioral therapy (CBT) for childhood anxiety. Additionally, compliance with exposure tasks was tested as a mediator of the relationship between treatment expectations and symptom improvement. Data were from youth (N = 279; 7-17 years old) enrolled in the Child/Adolescent Anxiety Multimodal Study (CAMS) and randomized to cognitive-behavioral therapy (CBT) or the combination of CBT and sertraline for the treatment of separation anxiety disorder, generalized anxiety disorder, and social phobia. Caregivers and youth independently reported treatment expectations prior to randomization, anxiety was assessed pre- and post-treatment by independent evaluators blind to treatment condition, and exposure characteristics were recorded by the cognitive-behavioral therapists following each session. For both caregivers and youths, more positive expectations that anxiety would improve with treatment were associated with greater compliance with exposure tasks, and compliance mediated the relationship between treatment expectations and change in anxiety symptoms following treatment. Additionally, more positive parent treatment expectations were related to a greater number and percentage of sessions with exposure. More positive youth treatment expectations were associated with greater mastery during sessions focused on exposure. Findings underscore the importance of addressing parents' and youths' treatment expectations at the outset of therapy to facilitate engagement in exposure and maximize therapeutic gains.

Pseudouridinylation of mRNA coding sequences alters translation.

Chemical modifications of RNAs have long been established as key modulators of nonprotein-coding RNA structure and function in cells. There is a growing appreciation that messenger RNA (mRNA) sequences responsible for directing protein synthesis can also be posttranscriptionally modified. The enzymatic incorporation of mRNA modifications has many potential outcomes, including changing mRNA stability, protein recruitment, and translation. We tested how one of the most common modifications present in mRNA coding regions, pseudouridine (Ψ), impacts protein synthesis using a fully reconstituted bacterial translation system and human cells. Our work reveals that replacing a single uridine nucleotide with Ψ in an mRNA codon impedes amino acid addition and EF-Tu GTPase activation. A crystal structure of the Thermus thermophilus 70S ribosome with a tRNAPhe bound to a ΨUU codon in the A site supports these findings. We also find that the presence of Ψ can promote the low-level synthesis of multiple peptide products from a single mRNA sequence in the reconstituted translation system as well as human cells, and increases the rate of near-cognate Val-tRNAVal reacting on a ΨUU codon. The vast majority of Ψ moieties in mRNAs are found in coding regions, and our study suggests that one consequence of the ribosome encountering Ψ can be to modestly alter both translation speed and mRNA decoding.

Hoarding Symptoms in Children and Adolescents With Obsessive-Compulsive Disorder: Clinical Features and Response to Cognitive-Behavioral Therapy.

OBJECTIVE: Although adult hoarding disorder is relatively common and often debilitating, few studies have examined the phenomenology of pediatric hoarding. We examined the clinical phenomenology and response to cognitive-behavioral therapy (CBT) treatment in youths with a diagnosis of obsessive-compulsive disorder (OCD) with and without hoarding symptoms. Age was tested as a moderator across analyses, given prior findings that the impact of hoarding symptoms may not become apparent until adolescence. METHOD: Youths (N = 215; aged 7-17 years) with OCD pursuing evaluation and/or treatment at a university-based specialty clinic participated in the current study. Presence of hoarding symptoms was assessed as part of a larger battery. Data from a subset of youths (n = 134) who received CBT were included in treatment response analyses. RESULTS: Youths with hoarding symptoms did not differ from those without hoarding symptoms with respect to overall OCD symptom severity and impairment. Youths with hoarding met criteria for more concurrent diagnoses, including greater rates of internalizing and both internalizing/externalizing, but not externalizing-only, disorders. Youths with and without hoarding symptoms did not significantly differ in rate of response to CBT. Age did not moderate any of these relationships, suggesting that the presence of hoarding symptoms was not associated with greater impairments across the clinical presentation of OCD or its response to treatment by age. CONCLUSION: We found no evidence that hoarding is associated with greater OCD severity or poorer treatment response in affected youth. Theoretical and clinical implications of these findings, including future directions for research on testing developmental models of hoarding across the lifespan, are discussed.

Comorbid Psychopathology and the Clinical Profile of Family Accommodation in Pediatric OCD.

Family accommodation (FA) has been linked with myriad negative outcomes in pediatric obsessive-compulsive disorder (OCD), but extant literature has yielded differential relationships between FA and clinical variables of interest. Consequently, this study examined the phenomenology, clinical profile, and effects of comorbid psychopathology on FA to better understand these behaviors. A total of 150 youths and their caregivers completed clinician- and self-reported measures at a baseline visit for a larger randomized controlled trial. Sociodemographic variables were not associated with FA, but specific types of OCD symptom clusters were. Higher OC-symptom severity and functional impairment were associated with increased FA. Comorbid anxiety disorders moderated the relationship between OC-symptom severity and FA, but comorbid attention deficit hyperactivity, oppositional defiant, and mood disorders did not. Internalizing and externalizing problems both mediated the relationship between FA and functional impairment. These findings provide clinical implications for important treatment targets and factors that may impact FA.

Development and Psychometric Evaluation of the Children's Yale-Brown Obsessive-Compulsive Scale Second Edition.

OBJECTIVE: To develop and examine the psychometric properties of the Children's Yale-Brown Obsessive-Compulsive Scale Second Edition (CY-BOCS-II) in children and adolescents with obsessive-compulsive disorder (OCD). METHOD: Youth with OCD (N = 102; age range 7-17 years), who were seeking treatment from 1 of 2 specialty OCD treatment centers, participated in the study. The CY-BOCS-II was administered at an initial assessment, and measures of OCD symptom severity, anxiety and depressive symptoms, behavioral and emotional problems, and global functioning were administered. Inter-rater and test-retest reliabilities were assessed on a subsample of participants (n = 50 and n = 31, respectively) approximately 1 week after intial assessment. RESULTS: The CY-BOCS-II demonstrated moderate-to-strong internal consistency (α = 0.75-0.88) and excellent inter-rater (intraclass correlation coefficient = 0.86-0.92) and test-retest (intraclass correlation coefficient = 0.95-0.98) reliabilities across all scales. Construct validity was supported by strong correlations with clinician-rated measures of OCD symptom severity and moderate correlations with measures of anxiety symptoms. Exploratory factor analysis showed a 2-factor structure, which was generally inconsistent with its adult counterpart, the Yale-Brown Obsessive-Compulsive Scale Second Edition. CONCLUSION: Initial findings support the CY-BOCS-II as a reliable and valid measure of obsessive-compulsive symptoms in youth.

A Review of Tics Presenting Subsequent to Traumatic Brain Injury.

PURPOSE OF REVIEW: This review summarizes case reports of patients with tics emerging subsequent to traumatic brain injury (TBI), with respect to demographics, post-TBI symptoms, tic onset latency and topography, clinical history, neuroimaging results and treatment outcome. RECENT FINDINGS: Patients were 22 adults and 3 youth. Trauma onset appeared to fall mostly in adulthood. Two-thirds of patients were male and head trauma was related to motor vehicle accidents in most cases. Loss of consciousness was reported in just below half (48.0%) of cases. Associated physical and cognitive symptoms (e.g., impaired memory, reduced sensory perception, poor balance, muscle weakness, attention problems, aggression/impulsivity, obsessions and compulsions, depression and anxiety) were commonly reported. The latency between head trauma and tic onset varied, but generally ranged from one day post-trauma to approximately one year post-trauma. Sole presentation of motor tics was common, with rostral to caudal development of motor tics in other cases. Simple and/or complex vocal tics were present in several cases, often emerging after motor tics. Post-trauma obsessive-compulsive symptoms were noted in five cases (20.0%). A personal or family history of tics was reported in four cases. Damage to the basal ganglia, ventricular system, and temporal region was observed across ten patients (40.0%). Pharmacological intervention varied, with tic symptoms deemed to have significantly or somewhat improved in 12 cases (48.0%). A comparison of post-TBI symptoms in youth with head trauma history relative to those with peripheral injury suggests tic symptoms are not a common post-TBI symptom in youth. SUMMARY: Ultimately, there has been limited study on the link between traumatic brain injury and tic expression, and methodological issues preclude the ability to draw definitive conclusions regarding this relationship. Nevertheless, findings do suggest there may be heterogeneity in brain dysfunction associated with tic expression. Future case reports should utilize more systematic and thorough assessment of TBI and tics using validated measures, evaluate medication effects using single-case designs, and perform more longitudinal follow-up of cases with repeated neuroimaging.

The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans.

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.

Comparing OCD-affected youth with and without religious symptoms: Clinical profiles and treatment response.

BACKGROUND: Childhood obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric condition, with varied symptom presentations that have been differentially associated with clinical characteristics and treatment response. One OCD symptom cluster of particular interest is religious symptoms, including fears of offending religious figures/objects; patients affected by these symptoms have been characterized as having greater overall OCD severity and poorer treatment response. However, the extant literature primarily examines this symptom subtype within adults, leaving a gap in our understanding of this subtype in youth. METHOD: Consequently, this study examined whether presence of religious symptoms in OCD-affected children and adolescents (N = 215) was associated with greater clinical impairments across OCD symptoms and severity, insight, other psychiatric comorbidity, family variables, or worse treatment response. RESULTS: Results found that youth with religious OCD symptoms presented with higher OCD symptom severity and exhibited more symptoms in the aggressive, sexual, somatic, and checking symptom cluster, as well as the symmetry, ordering, counting, and repeating cluster. Religious OCD symptoms were also significantly associated with poorer insight and higher family expressiveness. No differences in treatment response were observed in youths with versus without religious OCD symptoms. CONCLUSION: Ultimately, youths with religious OCD symptoms only differed from their OCD-affected counterparts without religious symptoms on a minority of clinical variables; this suggests they may be more comparable to youths without religious OCD symptoms than would be expected based on the adult OCD literature and highlights the importance of examining these symptoms within a pediatric OCD sample.

Editorial Perspective: Exposures in cognitive behavior therapy for pediatric obsessive-compulsive disorder: addressing common clinician concerns.

Professional organizations and expert consensus recommend the use of exposure-based cognitive-behavioral therapy (CBT) to treat pediatric obsessive-compulsive disorder (OCD), but a sizable proportion of clinicians possess hesitancy regarding the use of exposures in treatment. Most notably, this hesitancy relates to concerns about negative patient and parent reactions to exposures. Accordingly, we examine three commonly reported clinician concerns regarding negative patient/parent reactions (e.g. treatment attrition, therapeutic relationship, and treatment satisfaction) among youths receiving exposure-based CBT compared to a nonexposure-based treatment. Based on our findings, there is no empirical support that exposure-based CBT precipitates adverse consequences in treatment (e.g. treatment attrition, poor therapeutic relationship, low treatment satisfaction) relative to nonexposure-based interventions. These results corroborate existing OCD expert recommendations for the use of exposure-based CBT and provide information to mitigate clinicians' concerns about the potentially iatrogenic impact of exposures when treating pediatric OCD. We briefly present best practice recommendations for implementing exposure-based CBT in pediatric OCD patients.

Quality of life and burden in caregivers of youth with obsessive-compulsive disorder presenting for intensive treatment.

BACKGROUND: Pediatric obsessive-compulsive disorder (OCD) is associated with deleterious familial effects; caregivers are often enmeshed in the disorder and can experience considerable burden and decreased quality of life (QoL). Consequently, this study examined burden and QoL in caregivers of youth with OCD enrolled in an intensive outpatient or partial hospitalization program. METHOD: The relationships between caregiver QoL and burden and the following variables were investigated: OCD symptom severity, functioning (youth functional impairment, general family functioning), family (family accommodation, parental relationship satisfaction, positive aspects of caregiving), and comorbid psychopathology (caregiver anxiety and depressive symptoms, youth internalizing and externalizing behaviors). Seventy-two child and caregiver dyads completed clinician- and self-rated questionnaires. RESULTS: Components of caregiver QoL correlated with caregiver-rated functional impairment, family accommodation, youth externalizing behaviors, and caregiver psychopathology. Aspects of caregiver burden correlated with child OCD symptom severity, functional impairment related to OCD, as well as caregiver and child comorbid psychopathology. Caregiver depressive symptoms predicted caregiver QoL, and caregiver depressive symptoms and child externalizing symptoms both predicted caregiver burden. Caregiver burden did not mediate the relationship between obsessive-compulsive symptom severity and caregiver QoL. CONCLUSION: Ultimately, elucidating factors associated with increased caregiver burden and poorer QoL is pertinent for identifying at-risk families and developing targeted interventions.

The Conserved Intron Binding Protein EMB-4 Plays Differential Roles in Germline Small RNA Pathways of C. elegans.

Proper regulation of the germline transcriptome is essential for fertility. In C. elegans, germline homeostasis hinges on a complex repertoire of both silencing and activating small RNA pathways, along with RNA processing. However, our understanding of how fundamental RNA processing steps intersect with small RNA machineries in the germline remains limited. Here, we link the conserved intron binding protein, EMB-4/AQR/IBP160, to the CSR-1 and HRDE-1 nuclear 22G-RNA pathways in the C. elegans germline. Loss of emb-4 leads to distinct alterations in CSR-1- versus HRDE-1-associated small RNA and mRNA transcriptomes. Our transcriptome-wide analysis shows that EMB-4 is enriched along pre-mRNAs of nearly 8,000 transcripts. While EMB-4 complexes are enriched for both intronic and exonic sequences of HRDE-1 targets, CSR-1 pathway targets are enriched for intronic, but not exonic, sequences. These data suggest that EMB-4 could contribute to a molecular signature that distinguishes the targets of these two germline small RNA pathways.