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AIM: There is concern that the provision of the clinical high risk for psychosis (CHR) label is stigmatizing. Prior research suggests people have nuanced reactions to feedback involving the CHR label, including a positive experience receiving feedback and improvement in negative emotions (e.g., shame), while also exhibiting concerns about self-perception and perceptions from others related to the label. The current pilot study aimed to evaluate whether individuals at CHR showed changes in emotional and stigma-related experiences following a CHR psychoeducation intervention, BEGIN: Brief Educational Guide for Individuals in Need. METHOD: Participants at CHR (N = 26) identified via the Structured Interview for Psychosis-Risk Syndromes completed the Mental Health Attitudes Interview measuring symptom-related and CHR label-related stigma at pre- and post-intervention. RESULTS: Stigma did not increase and participants had greater positive emotions (e.g., feeling hopeful and relieved), post-BEGIN. CONCLUSION: This study suggests that standardized CHR psychoeducation does not increase stigma in individuals at CHR.
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Grape and grape derived products contain many bioactive phenolics which have a variety of impacts on health. Following oral ingestion, the phenolic compounds and their metabolites may be detectable in human urine. However, developing a reliable method for the analysis of phenolic compounds in urine is challenging. In this work, we developed and validated a new high-throughput, sensitive and reproducible analytical method for the simultaneous analysis of 31 grape phenolic compounds and metabolites using Oasis PRiME HLB cleanup for sample preparation combined with ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). Using this new method, the accuracy achieved was 69.3 % â¼ 134.9 % (except for six compounds), and the recovery achieved was 52.4 % â¼ 134.7 % (except for two very polar compounds). For each of the 31 target analytes, the value of intra-day precision was less than 14.3 %. The value of inter-day precision was slightly higher than intra-day precision, with a range of 0.7 % â¼ 19.1 %. We report for the first time on the effect of gender and BMI on the accuracy and recovery of human urine samples, and results from analysis of variance (ANOVA), and principal component analysis (PCA) indicated there was no difference in the value of accuracy and recovery between different gender or BMI (>30) using our purposed cleanup and UHPLC-QqQ-MS/MS method. Overall, this newly developed method could serve as a powerful tool for analyzing grape phenolic compounds and metabolites in human urine samples.
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Polifenoles , Espectrometría de Masas en Tándem , Vitis , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Vitis/química , Polifenoles/orina , Reproducibilidad de los Resultados , Masculino , Femenino , Modelos Lineales , Límite de Detección , Adulto , Ensayos Analíticos de Alto Rendimiento/métodosRESUMEN
BACKGROUND: Clubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is poorly understood and variants in known clubfoot disease genes account for only a small portion of the heritability. METHODS: Exome sequence data were generated from 1190 non-syndromic clubfoot cases and their family members from multiple ethnicities. Ultra-rare variant burden analysis was performed comparing 857 unrelated clubfoot cases with European ancestry with two independent ethnicity-matched control groups (1043 in-house and 56 885 gnomAD controls). Additional variants in prioritised genes were identified in a larger cohort, including probands with non-European ancestry. Segregation analysis was performed in multiplex families when available. RESULTS: Rare variants in 29 genes were enriched in clubfoot cases, including PITX1 (a known clubfoot disease gene), HOXD12, COL12A1, COL9A3 and LMX1B. In addition, rare variants in posterior HOX genes (HOX9-13) were enriched overall in clubfoot cases. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry. Among these, 3 are de novo and 22 show variable penetrance, including 4 HOXD12 variants that segregate with clubfoot. CONCLUSION: We report HOXD12 as a novel clubfoot disease gene and demonstrate a phenotypic expansion of known disease genes (myopathy gene COL12A1, Ehlers-Danlos syndrome gene COL9A3 and nail-patella syndrome gene LMX1B) to include isolated clubfoot.
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Pie Equinovaro , Secuenciación del Exoma , Proteínas de Homeodominio , Femenino , Humanos , Masculino , Pie Equinovaro/genética , Pie Equinovaro/patología , Exoma/genética , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Linaje , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: Personal recovery refers to a person's pursuit of a full, meaningful life despite the potentially debilitating impact of a mental illness. An evidence base describing personal recovery among people at risk for developing a mental illness is lacking, limiting the potential for mental health services to support personal recovery. To address this gap, the authors synthesized the extant research describing personal recovery among people at risk for developing a mental illness. METHODS: A systematic search of several literature databases (MEDLINE, Embase, APA PsycInfo, Web of Science Core Collection, and Cochrane Library) was conducted to retrieve qualitative and case studies and first-person accounts. The Joanna Briggs Institute guidelines for systematic reviews were followed. Included studies reported on participants at variable risk for developing a schizophrenia spectrum, bipolar, major depressive, or borderline personality disorder. Articles were retrieved through a librarian-assisted search and through use of additional strategies (e.g., expert consultation). Abstracts were screened by the research team, and themes were developed by using thematic synthesis. RESULTS: The 36 included articles were synthesized, and six themes were generated: difficulties and challenges; establishing an understanding of, and finding ways to cope with, one's mental health challenges; reestablishing a sense of agency and personhood; receiving support from people and services, as well as restoring relationships; reestablishing hope, meaning, and purpose; and overcoming stigma and destigmatizing mental illness in others. CONCLUSIONS: These findings provide a conceptual foundation that can guide future research on personal recovery and clinical interventions that foster it among people at risk for mental illness.
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Trastornos Mentales , Humanos , Investigación CualitativaRESUMEN
Individuals at clinical high risk for psychosis (CHR) report a strong desire for psychoeducation, and clinical guidelines recommend psychoeducation in early psychosis care. Although several CHR psychoeducation models have been developed, additional research is needed to establish the effectiveness of these models. The goal of this study was to conduct a pilot trial of the Brief Educational Guide for Individuals in Need (BEGIN). BEGIN is a brief structured psychoeducation intervention designed to educate CHR individuals on symptoms and treatment options. We conducted a feasibility and pilot study of 25 CHR individuals (60% female, Mage = 20.6, 64% non-White, 52% Hispanic/Latino) identified via the Structured Interview for Psychosis Risk Syndromes. Qualitative interviews were administered to learn about their experience and analyzed using iterative thematic analysis. Participants (n = 12) completed pre- and post-BEGIN self-report measures to assess factors that influence treatment engagement, including CHR knowledge and motivation for therapy. Data were analyzed using Hedges' g effect sizes and paired samples t tests. The intervention completion rate (83%) and therapeutic alliance were high. Qualitative themes and quantitative measures converged on similar results showing how CHR individuals were impacted by receiving psychoeducation via BEGIN, including increased CHR knowledge (g = 1.37), competence to monitor symptoms (g = 0.53), hope (g = 0.87), and motivation for therapy (g = 0.46). This study demonstrated the feasibility, acceptability, and potential benefits of the BEGIN CHR psychoeducation model, including enhancing motivation for treatment. The flexible but standardized format can facilitate BEGIN's implementation and dissemination.This pilot study found that the Brief Educational Guide for Individuals in Need (BEGIN), a standardized five-session psychoeducation intervention for individuals at clinical high risk for psychosis (CHR), was feasible, acceptable, and enhanced mental health literacy and motivation for subsequent treatment. Clinicians can utilize the BEGIN intervention to ensure the empathic provision of psychoeducation when disclosing patients' CHR status. Future research with a larger sample will establish efficacy and the development of a clinician training to facilitate implementation (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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STUDY DESIGN: Prospective multicenter study data were used for model derivation and externally validated using retrospective cohort data. OBJECTIVE: Derive and validate a prognostic model of benefit from bracing for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) demonstrated the superiority of bracing over observation to prevent curve progression to the surgical threshold; 42% of untreated subjects had a good outcome, and 28% progressed to the surgical threshold despite bracing, likely due to poor adherence. To avoid over-treatment and to promote patient goal setting and adherence, bracing decisions (who and how much) should be based on physician and patient discussions informed by individual-level data from high-quality predictive models. MATERIALS AND METHODS: Logistic regression was used to predict curve progression to <45° at skeletal maturity (good prognosis) in 269 BrAIST subjects who were observed or braced. Predictors included age, sex, body mass index, Risser stage, Cobb angle, curve pattern, and treatment characteristics (hours of brace wear and in-brace correction). Internal and external validity were evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n=299) through estimates of discrimination and calibration. RESULTS: The final model included age, sex, body mass index, Risser stage, Cobb angle, and hours of brace wear per day. The model demonstrated strong discrimination ( c -statistics 0.83-0.87) and calibration in all data sets. Classifying patients as low risk (high probability of a good prognosis) at the probability cut point of 70% resulted in a specificity of 92% and a positive predictive value of 89%. CONCLUSION: This externally validated model can be used by clinicians and families to make informed, individualized decisions about when and how much to brace to avoid progression to surgery. If widely adopted, this model could decrease overbracing of AIS, improve adherence, and, most importantly, decrease the likelihood of spinal fusion in this population.
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Escoliosis , Humanos , Adolescente , Escoliosis/terapia , Estudios Retrospectivos , Estudios Prospectivos , Pronóstico , Tirantes , Resultado del Tratamiento , Progresión de la EnfermedadRESUMEN
ChatGPT (Generative Pre-Trained Transformer) is a large language model (LLM), which comprises a neural network that has learned information and patterns of language use from large amounts of text on the internet. ChatGPT, introduced by OpenAI, responds to human queries in a conversational manner. Here, we aimed to assess whether ChatGPT could reliably produce accurate references to supplement the literature search process. We describe our March 2023 exchange with ChatGPT, which generated thirty-five citations, two of which were real. 12 citations were similar to actual manuscripts (e.g., titles with incorrect author lists, journals, or publication years) and the remaining 21, while plausible, were in fact a pastiche of multiple existent manuscripts. In June 2023, we re-tested ChatGPT's performance and compared it to that of Google's GPT counterpart, Bard 2.0. We investigated performance in English, as well as in Spanish and Italian. Fabrications made by LLMs, including erroneous citations, have been called "hallucinations"; we discuss reasons for which this is a misnomer. Furthermore, we describe potential explanations for citation fabrication by GPTs, as well as measures being taken to remedy this issue, including reinforcement learning. Our results underscore that output from conversational LLMs should be verified.
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Comunicación , Psiquiatría , Humanos , Lenguaje , Suplementos Dietéticos , AlucinacionesRESUMEN
Suicidal ideation (SI) is prevalent among individuals at clinical high-risk for psychosis (CHR). Natural language processing (NLP) provides an efficient method to identify linguistic markers of suicidality. Prior work has demonstrated that an increased use of "I", as well as words with semantic similarity to "anger", "sadness", "stress" and "lonely", are correlated with SI in other cohorts. The current project analyzes data collected in an SI supplement to an NIH R01 study of thought disorder and social cognition in CHR. This study is the first to use NLP analyses of spoken language to identify linguistic correlates of recent suicidal ideation among CHR individuals. The sample included 43 CHR individuals, 10 with recent suicidal ideation and 33 without, as measured by the Columbia-Suicide Severity Rating Scale, as well as 14 healthy volunteers without SI. NLP methods include part-of-speech (POS) tagging, a GoEmotions-trained BERT Model, and Zero-Shot Learning. As hypothesized, individuals at CHR for psychosis who endorsed recent SI utilized more words with semantic similarity to "anger" compared to those who did not. Words with semantic similarity to "stress", "loneliness", and "sadness" were not significantly different between the two CHR groups. Contrary to our hypotheses, CHR individuals with recent SI did not use the word "I" more than those without recent SI. As anger is not characteristic of CHR, findings have implications for the consideration of subthreshold anger-related sentiment in suicidal risk assessment. As NLP is scalable, findings suggest that language markers may improve suicide screening and prediction in this population.
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Trastornos Psicóticos , Suicidio , Humanos , Adolescente , Ideación Suicida , Lingüística , Lenguaje , Factores de RiesgoRESUMEN
Psychoeducation is recommended in the treatment of patients with schizophrenia and has been shown to improve satisfaction with mental health service and treatment adherence, reduce relapse and hospital readmission rates, and enhance functioning and quality of life. Youth at clinical high risk for psychosis (CHR) may also benefit from receiving psychoeducation as part of their treatment. The goal of this study was to conduct a scoping review to map out the existing literature on psychoeducation for CHR individuals, including content, utilization, and benefits, in order to identify areas for future research and clinical care. Following PRISMA guidelines, we conducted a systematic search of electronic databases (MEDLINE, Embase, PsycINFO, Scopus, and Web of Science Core Collection) to identify literature through 02/25/2022 that provided data or significant commentary about the provision of psychoeducation to CHR individuals. After screening titles and abstracts, four co-authors assessed full-text articles for eligibility. Thirty-three studies were included in the review. Psychoeducation is recommended in the treatment of CHR individuals, is a preferred treatment option among CHR individuals, and many CHR programs report offering psychoeducation. However, details about the psychoeducational content and method of delivery are notably absent from recommendations and reports on the provision of CHR psychoeducation in real-world settings. We identified two brief and structured CHR psychoeducation interventions and one longer-term psychoeducational multifamily group model for CHR that show feasibility and promise, though they have not yet undergone randomized trials to evaluate effectiveness of the psychoeducation. We also identified several comprehensive CHR interventions that included an explicit psychoeducation module, though the unique role of the psychoeducational component is unknown. Despite being recommended as a critical component of treatment for CHR individuals and preferred by CHR individuals, the ways in which psychoeducation are being delivered to CHR individuals in real-world practice is still largely ambiguous. Rigorous evaluations of psychoeducation treatment models are needed, as well as investment from clinical programs to facilitate the implementation and dissemination of standardized psychoeducation for CHR individuals.
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Trastornos Psicóticos , Esquizofrenia , Adolescente , Humanos , Satisfacción Personal , Calidad de Vida , Esquizofrenia/terapia , Cumplimiento y Adherencia al TratamientoRESUMEN
OBJECTIVES: To examine the effectiveness and complication rates in age- and size-appropriate patients with either stable or unstable fracture patterns treated with elastic stable intramedullary nailing (ESIN). DESIGN: Retrospective case series. SETTING: Academic tertiary care children's hospital. PATIENTS/PARTICIPANTS: This was a consecutive series of 106 preadolescent children with femoral shaft fractures. The mean age of the patients was 8.0 years (range, 4.0-16.0 years). INTERVENTION: All children were treated by retrograde ESIN. MAIN OUTCOME MEASURES: Fractures were categorized as either length stable or unstable. Length stability and complications were assessed. A subset of patients with final full-length, standing x-rays was also evaluated. RESULTS: We analyzed 63 stable and 43 length unstable fractures. The mean age and weight of the patients with stable and unstable fractures were similar. There was no difference in complication rates between groups (χ2(1) = 0.00, P = 0.99). There was no difference (t(96.93) = 0.53, P = 0.59) in femoral shaft length change. Leg length discrepancies as assessed by full-length standing radiographs at follow-up were similar (χ2(2) = 1.52, P = 0.47). CONCLUSIONS: Preadolescent children younger than 10 years do not experience increased complications after ESIN of length unstable femur fractures [odds ratio (OR) = 1.68 (0.18-16.87), P = 0.65]. Length unstable femur fractures are not at increased risk of more complications [OR = 0.90 (0.26-2.92), P = 0.87], early femoral shortening [OR = (0.42-2.02), P = 0.85], or leg length discrepancy [OR = (0.13-1.56), P = 0.21] when treated with ESIN. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for complete description of levels of evidence.
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Fracturas del Fémur , Fijación Intramedular de Fracturas , Humanos , Niño , Preescolar , Adolescente , Fijación Intramedular de Fracturas/efectos adversos , Estudios Retrospectivos , Diáfisis/cirugía , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fémur/cirugía , Diferencia de Longitud de las Piernas/etiologíaAsunto(s)
Investigación Biomédica , Ortopedia , Humanos , Prótesis e Implantes , Encuestas y CuestionariosRESUMEN
Background: The COVID-19 pandemic is expected to increase stress and mental health symptoms. We present the case of a young man at risk for psychosis who has paradoxically shown symptomatic and functional improvement as a result of circumstances produced by COVID-19. These changes were unexpected given the client's persistent mental health struggles in the year leading up to the COVID-19 outbreak in the United States and the expectation of an exacerbation of psychotic-like symptoms. Methods: This report is based on clinical assessments and the client's first-person account during the height of the pandemic when stay at home orders were in place. Results: During the pandemic, the client demonstrated increased agency by taking on more responsibility at home and obtaining part-time employment. He showed improvement in his mood and relationships with others, had less symptom-related distress, and significantly reduced his cannabis use. The client interpreted these improvements in terms of changing his mindset toward more adaptive thoughts and engaging in healthy coping skills such as praying, reading, and healthy eating. Conclusions: This case highlights the importance of fostering agency in clients during a time of crisis and ensuring that clinicians be aware of potential biases about mental health symptom exacerbation.
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Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2), which encodes a skeletal muscle-specific actin binding protein essential for sarcomere function, cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function. Transient overexpression of the 4 variants also disrupted the morphogenesis of mouse myotubes in vitro and negatively affected zebrafish muscle development in vivo. We used transient overexpression assays in zebrafish to characterize 2 potentially novel TPM2 variants and 1 recurring variant that we identified in patients with DA (V129A, E139K, A155T, respectively) and found these variants caused musculoskeletal defects similar to those of known pathogenic variants. The consistency of musculoskeletal phenotypes in our assays correlated with the severity of clinical phenotypes observed in our patients with DA, suggesting disrupted myogenesis is a potentially novel pathomechanism of TPM2 disorders and that our myogenic assays can predict the clinical severity of TPM2 variants.
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Miopatías Nemalínicas , Miopatías Estructurales Congénitas , Animales , Humanos , Ratones , Desarrollo de Músculos/genética , Miopatías Nemalínicas/metabolismo , Miopatías Estructurales Congénitas/metabolismo , Tropomiosina/genética , Pez CebraRESUMEN
BACKGROUND: Congenital vertical talus (CVT), also known as "rocker-bottom foot", is a rare foot deformity associated with a dislocation of the talonavicular joint. Although genetic causes of CVT have been described in single isolated and syndromic families, whole-exome sequencing (WES) of large cohorts have not yet been reported. METHODS: In this study, 62 probands with CVT were evaluated for likely causative single nucleotide variants (SNVs) and copy number variants (CNVs) using WES. Segregation of variants within families was determined by Sanger sequencing. RESULTS: In this cohort, CVT occurred as an isolated anomaly in 75.8% (47/62) and was familial in 19.3% (12/62) of cases. Analysis of WES data led to the identification of likely causative variants in known disease genes in 30.6% (19/62) of all CVT probands. More than one proband had likely causative SNVs in TSHZ1, GDF5, and LMX1B. Only two probands had likely causative CNVs: a chromosome 12q13.13 deletion of the 5' HOXC gene cluster, and a chromosome 18q22.3q23 deletion involving TSHZ1. Familial CVT was strongly predictive of identifying a molecular diagnosis [75% (9/12) of familial cases compared to 20% (10/50) of non-familial cases (Chi-square test, P-value = 0.0002)]. There was no difference in the solved rate based on isolated or syndromic presentation, unilateral or bilateral affectation, or sex. CONCLUSIONS: CVT is genetically heterogeneous and more often caused by SNVs than CNVs. There is a high yield of WES in familial CVT cases (â¼75%). Additional research is needed to identify the causes of sporadic CVT, which had much lower solved rates.
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Pie Plano , Deleción Cromosómica , Variaciones en el Número de Copia de ADN , Exoma/genética , Humanos , Linaje , Secuenciación del ExomaRESUMEN
Resilience research has documented the ability to cope with traumatic and stressful situations and/or retain functioning given certain risk factors in the context of psychosis. In this study, we conducted the first systematic review of the literature on psychosis-like experiences (PLEs) and resilience. Fifteen articles (from 11 unique study samples) from 10 countries were included in this systematic review, with a total of 11,937 unique study participants. Inclusion criteria were broad, capturing a wide range of individuals with PLEs who have not yet experienced threshold psychosis, such as individuals in the general population with elevated self-reports of PLEs, as well as clinical groups diagnosed by clinician interviews (i.e., clinical- or ultra-high-risk for psychosis [CHR or UHR]). For this review, studies needed to include research aims and empirical research related to resilience, and use an established or author-defined measure of psychological and/or social resilience. Data reporting quality was assessed with the Strengthening the Reporting of Observational Studies in Epidemiology and place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, social capital (PROGRESS) guidelines. Study aims and measurement of key variables varied widely, and all studies were cross-sectional. In 73% of the studies, resilience was inversely associated with PLEs or psychosis risk status (e.g., CHR or UHR). Results related to specific resilience subscales were mixed. Author-defined resilience was typically related to internal/psychological resources. Future research, particularly longitudinal research involving multidimensional measurement of resilience (e.g., internal and external factors), along with well-defined theoretical models, are necessary before drawing firm conclusions on resilience and PLEs. We propose a dynamic, multifaceted, developmentally appropriate, and culturally sensitive model of resilience for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Trastornos Psicóticos , Adaptación Psicológica , Etnicidad , Humanos , Trastornos Psicóticos/epidemiología , Factores de Riesgo , AutoinformeRESUMEN
Clubfoot or talipes equinovarus deformity is one of the most common anomalies affecting the lower extremities. This review provides an update on the outcomes of various treatment options used to correct clubfoot. The ultimate goal in the treatment of clubfoot is to obtain a fully functional and pain-free foot and maintain a long-term correction. The Ponseti method is now considered the gold standard of treatment for primary clubfoot. Relapse is common after primary treatment with the Ponseti method, and other interventions are discussed that are used to provide for long-term successful outcomes.
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Pie Equinovaro , Moldes Quirúrgicos , Pie Equinovaro/terapia , Pie , Humanos , Lactante , Recurrencia , Resultado del TratamientoRESUMEN
AIM: Identification of individuals with psychosis risk (PR) through screening and specialized assessment is becoming more widespread in an effort to promote early intervention and improve recovery outcomes. PR individuals report interest in psychoeducation, though such interventions are currently lacking. Our goal was to develop a structured PR psychoeducation intervention grounded in theory and stakeholder feedback. METHODS: By following a step-by-step intervention development model, we identified relevant conceptual frameworks, developed the content and format, and obtained stakeholder feedback. This process resulted in a 5-session PR psychoeducation intervention, Brief Educational Guide for Individuals in Need (BEGIN), with content conveyed visually via a slideshow presentation. PR individuals (n = 5) and parents of PR individuals (n = 5) reviewed BEGIN's content and format, and provided feedback through semi-structured qualitative interviews. Major themes were identified through iterative thematic analysis. RESULTS: PR individuals and parents had a positive impression of BEGIN's materials and step-by-step format and psychoeducation about the PR condition. They indicated that the intervention was likely to encourage agency. PR participants emphasized the importance of a patient's decision regarding whether their family member(s) should participate in BEGIN. Parents reported that BEGIN is an important first step in treatment and offers a safe therapeutic environment. Feedback was then utilized to modify the intervention. CONCLUSIONS: BEGIN is desired by consumers and may lay the foundation for future engagement with treatment by facilitating agency. A feasibility trial is underway and future studies are needed to measure outcomes (e.g., treatment engagement) and evaluate BEGIN as an evidence-based PR psychoeducation model.
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Trastornos Psicóticos , Escolaridad , Humanos , Motivación , Padres , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/terapiaRESUMEN
OBJECTIVE: Qualitative research can shed light on the subjective experiences of individuals at clinical high risk (CHR) for psychosis, complement quantitative research, broaden our understanding of experiencing CHR, and inform intervention development. The aim of this study was to explore life experiences of individuals at CHR through qualitative research. METHOD: Participants were 37 individuals at CHR (20 male, 17 female) aged 16-34 (Mage = 23.32 ± 5.26), and 16 healthy controls (HCs; 7 male, 9 female) aged 18-34 (Mage = 25.37 ± 4.05). Qualitative data were obtained through open-ended interviews (30-45 min). No a priori hypotheses were made, and thematic analyses were used to develop themes. RESULTS: Four major themes and one subtheme related to identity were identified through the iterative thematic analysis: defining a self-concept (with a subtheme of creativity), identity development/formation, feeling different from others, and change from a former self. Over 80% of the CHR cohort spontaneously discussed topics related to their identity, compared to 38% of HCs. HCs only reported content within the defining a self-concept theme, while the CHR group reported content within all themes. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The present study demonstrates that identity formation is a major process for youth in general and that psychosis experiences can make this process more challenging. CHR participants spontaneously brought up multiple themes related to identity in open-ended interviews, suggesting the relevance of this topic in this population. Clinicians should continue to probe identity-related concerns on an individual basis and research should focus on integrating this framework into the conceptualization and treatment of CHR. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Trastornos Psicóticos , Autoimagen , Adolescente , Adulto , Emociones , Femenino , Humanos , Masculino , Trastornos Psicóticos/terapia , Investigación Cualitativa , Adulto JovenRESUMEN
BACKGROUND: Clubfoot, a congenital deformity that presents as a rigid, inward turning of the foot, affects approximately 1 in 1000 infants and occurs as an isolated birth defect in 80% of patients. Despite its high level of heritability, few causative genes have been identified, and mutations in known genes are only responsible for a small portion of clubfoot heritability. QUESTIONS/PURPOSES: (1) Are any rare gene variants enriched (that is, shared) in unrelated patients with isolated clubfoot? (2) Are there other rare variants in the identified gene (Filamin B) in these patients with clubfoot? METHODS: Whole-exome sequence data were generated from a discovery cohort of 183 unrelated probands with clubfoot and 2492 controls. Variants were filtered with minor allele frequency < 0.02 to identify rare variants as well as small insertions and deletions (indels) resulting in missense variants, nonsense or premature truncation, or in-frame deletions. A candidate deletion was then genotyped in another cohort of 974 unrelated patients with clubfoot (a replication cohort). Other rare variants in the candidate gene were also investigated. A segregation analysis was performed in multigenerational families of individuals with clubfoot to see if the genotypes segregate with phenotypes. Single-variant association analysis was performed using the Fisher two-tailed exact test (exact p values are presented to give an indication of the magnitude of the association). RESULTS: There were no recurrent variants in the known genes causing clubfoot in this study. A three-base pair in-frame codon deletion of Filamin B (FLNB) (p.E1792del, rs1470699812) was identified in 1.6% (3 of 183) of probands with clubfoot in the discovery cohort compared with 0% of controls (0 of 2492) (odds ratio infinity (inf) [95% CI 5.64 to inf]; p = 3.18 x 10-5) and 0.0016% of gnomAD controls (2 of 125,709) (OR 1.01 x 103 [95% CI 117.42 to 1.64 x 104]; p = 3.13 x 10-8). By screening a replication cohort (n = 974 patients), we found two probands with the identical FLNB deletion. In total, the deletion was identified in 0.43% (5 of 1157) of probands with clubfoot compared with 0% of controls and 0.0016% of gnomAD controls (OR 268.5 [95% CI 43.68 to 2.88 x 103]; p = 1.43 x 10-9). The recurrent FLNB p.E1792del variant segregated with clubfoot, with incomplete penetrance in two families. Affected individuals were more likely to be male and have bilateral clubfoot. Although most patients had isolated clubfoot, features consistent with Larsen syndrome, including upper extremity abnormalities such as elbow and thumb hypermobility and wide, flat thumbs, were noted in affected members of one family. We identified 19 additional rare FLNB missense variants located throughout the gene in patients with clubfoot. One of these missense variants, FLNB p.G2397D, exhibited incomplete penetrance in one family. CONCLUSION: A recurrent FLNB E1792 deletion was identified in 0.43% of 1157 isolated patients with clubfoot. Given the absence of any recurrent variants in our discovery phase (n = 183) for any of the known genes causing clubfoot, our findings support that novel and rare missense variants in FLNB in patients with clubfoot, although rare, may be among the most commonly known genetic causes of clubfoot. Patients with FLNB variants often have isolated clubfoot, but they and their family members may be at an increased risk of having additional clinical features consistent with Larsen syndrome. CLINICAL RELEVANCE: Identification of FLNB variants may be useful for determining clubfoot recurrence risk and comorbidities.
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Pie Equinovaro/genética , Secuenciación del Exoma , Filaminas/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Adulto JovenRESUMEN
Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development.