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Clinical presentations of selective mutism (SM) vary widely across affected youth. Although studies have explored general externalizing problems in youth with SM, research has not specifically examined patterns of irritability. Relatedly, research has not considered how affected families differentially accommodate the anxiety of youth with SM as a function of the child's temper outbursts (i.e., phasic irritability) and general angry mood (i.e., tonic irritability). Data were drawn from a sample of treatment-seeking children and adolescents with a primary diagnosis of selective mutism (N = 152; Mean age = 6.12 years; 67.11% female), and their caregivers. Latent profile analysis (LPA) was used to identify distinct profiles in SM youth that were characterized by varying levels of phasic and/or tonic irritability. Analyses further examined whether these different profiles were associated with different levels of family accommodation and global impairment. LPA identified 5 profiles: SM with No irritability, SM with Low Phasic Irritability, SM with High Phasic Irritability, SM with High Phasic and Moderate Tonic Irritability, and SM with High Phasic and High Tonic Irritability. Patterns of family accommodation and global impairment were highest among youth belonging to profiles characterized by high phasic irritability. Findings highlight separable patterns of irritability across youth with SM, with phasic irritability (i.e., temper outbursts) appearing particularly linked with increased family accommodation and overall global impairment. Assessing phasic irritability is critical for optimizing treatment in youth with SM and can be useful for flagging possible patterns of family accommodation contributing to overall impairment.
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Humor Irritável , Humanos , Feminino , Humor Irritável/fisiologia , Masculino , Criança , Adolescente , Mutismo/psicologia , Família/psicologia , Ansiedade/psicologia , Análise de Classes Latentes , Pré-EscolarRESUMO
Selective mutism (SM) is a relatively rare, but highly interfering, child anxiety disorder characterized by a consistent failure to speak in certain situations, despite demonstrating fluent speech in other contexts. Exposure-based cognitive behavioral therapy and Parent-Child Interaction Therapy adapted for SM can be effective, but the broad availability and accessibility of such specialty care options remains limited. Stay-at-home guidelines to mitigate the spread of COVID-19 further limited the accessibility of office-based specialty care for SM. Building on separate lines of research supporting intensive treatments and telehealth service delivery models, this paper is the first to describe the development, preliminary feasibility, acceptability, and efficacy of a Remote Intensive Group Behavioral Treatment (IGBT) for families of young children with SM (N=9). Treatment leveraged videoconferencing technology to deliver caregiver training sessions, lead-in sessions, 5 consecutive daily IGBT sessions, and an individualized caregiver coaching session. Remote IGBT was found to be both feasible and acceptable. All families (100%) completed diagnostic assessments and caregiver-report questionnaires at four major study timepoints (i.e., intake, pre-treatment, post-treatment, 4-month follow-up) and participated in all treatment components. Caregivers reported high treatment satisfaction at post-treatment and 4-month follow-up and low levels of burden associated with treatment participation at post-treatment. Approximately half of participating children were classified as treatment responders by independent evaluators at post-treatment and 4-month follow-up. Although these pilot results should be interpreted with caution, the present work underscores the potential utility of using videoconferencing to remotely deliver IGBT to families in their natural environments.
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The unique needs of first-generation immigrants and their families have not been prioritized in mental healthcare. Cultural tailoring of child services requires valid, reliable, and efficient assessments of family cultural identity. The Abbreviated Multidimension Acculturation Scale (AMAS) is a self-report of acculturation and enculturation that has been evaluated in community, but not clinical, samples. We offer the first AMAS psychometric evaluation in a treatment-seeking sample of first-generation immigrant caregivers presenting for children's mental healthcare (N = 219). Analyses examined the internal consistency, concurrent validity, and factor structures of the long-form AMAS (42 items, six subscales), AMAS-10 (10 items, four subscales), and AMAS-14 (14 items, six subscales). Findings provide support for the AMAS-10 and AMAS-14, but not the full-length AMAS, in the present sample. Given urgent needs for culturally responsive care for first-generation populations, the AMAS-10 and AMAS-14 can be used in clinical settings to support cultural assessment, case conceptualization, and treatment planning.
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There is tremendous need for brief and supported, non-commercial youth- and caregiver-report questionnaires of youth anxiety. The pediatric and parent proxy short forms of the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale (8a v2.0) are free, brief, publicly accessible measures of youth- and caregiver-reported anxiety in children and adolescents. Despite increased use of the PROMIS, no study has evaluated performance of its anxiety scales in a sample of treatment-engaged anxious youth. Analyses were conducted on baseline data from the first 265 families (child MAge=11.14 years, 70% racial/ethnic minoritized youth) to enroll in the Kids FACE FEARS trial, a multisite comparative effectiveness trial of therapist-led vs. self-administered treatment for elevated youth anxiety. Confirmatory factor analysis (CFA) examined factor structure; omega coefficients and regression models examined internal consistency, convergent validity, and cross-informant reliability. CFA supported adjusted single-factor solutions across youth and caregiver reports, and internal consistency was high. Convergent validity was supported by medium-to-large associations with anxiety-related impairment and severity. Moderate cross-informant reliability between reports was found. Results showcase the first psychometric study of the PROMIS Anxiety scale short forms among treatment-engaged youth with elevated anxiety. Findings highlight the PROMIS Anxiety scale's utility in typical care settings for youth anxiety.
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Ansiedade , Qualidade de Vida , Adolescente , Humanos , Criança , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Medo , Pais , Medidas de Resultados Relatados pelo Paciente , Sistemas de InformaçãoRESUMO
Neurodegenerative diseases are a major cause of disability in the world, but their etiologies largely remain elusive. Genetic factors can only account for a minority of risk for most of these disorders, suggesting environmental factors play a significant role in the development of these diseases. Prolonged exposure to air pollution has recently been identified to increase the risk of Alzheimer's and Parkinson's diseases, but the molecular mechanisms by which it acts are not well understood. Zebrafish embryos exposed to diesel exhaust particle extract (DEPe) lead to dysfunctional autophagy and neuronal loss. Here, we exposed zebrafish embryos to DEPe and performed high throughput proteomic and transcriptomic expression analyses from their brains to identify pathogenic pathways induced by air pollution. DEPe treatment altered several biological processes and signaling pathways relevant to neurodegenerative processes, including xenobiotic metabolism, phagosome maturation, and amyloid processing. The biggest induction of gene expression in brains was in Cyp1A (over 30-fold). The relevance of this expression change was confirmed by blocking induction using CRISPR/Cas9, which resulted in a dramatic increase in sensitivity to DEPe toxicity, confirming that Cyp1A induction was a compensatory protective mechanism. These studies identified disrupted molecular pathways that may contribute to the pathogenesis of neurodegenerative disorders. Ultimately, determining the molecular basis of how air pollution increases the risk of neurodegeneration will help in the development of disease-modifying therapies.
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Poluentes Atmosféricos , Animais , Poluentes Atmosféricos/toxicidade , Emissões de Veículos/toxicidade , Peixe-Zebra , Proteômica , EncéfaloRESUMO
Caveolae, specialized plasma membrane invaginations present in most cell types, play important roles in multiple cellular processes including cell signaling, lipid uptake and metabolism, endocytosis and mechanotransduction. They are found in almost all cell types but most abundant in endothelial cells, adipocytes and fibroblasts. Caveolin-1 (Cav1), the signature structural protein of caveolae was the first protein associated with caveolae, and in association with Cavin1/PTRF is required for caveolae formation. Genetic ablation of either Cav1 or Cavin1/PTRF downregulates expression of the other resulting in loss of caveolae. Studies using Cav1-deficient mouse models have implicated caveolae with human diseases such as cardiomyopathies, lipodystrophies, diabetes and muscular dystrophies. While caveolins and caveolae are extensively studied in extra-ocular settings, their contributions to ocular function and disease pathogenesis are just beginning to be appreciated. Several putative caveolin/caveolae functions are relevant to the eye and Cav1 is highly expressed in retinal vascular and choroidal endothelium, Müller glia, the retinal pigment epithelium (RPE), and the Schlemm's canal endothelium and trabecular meshwork cells. Variants at the CAV1/2 gene locus are associated with risk of primary open angle glaucoma and the high risk HTRA1 variant for age-related macular degeneration is thought to exert its effect through regulation of Cav1 expression. Caveolins also play important roles in modulating retinal neuroinflammation and blood retinal barrier permeability. In this article, we describe the current state of caveolin/caveolae research in the context of ocular function and pathophysiology. Finally, we discuss new evidence showing that retinal Cav1 exists and functions outside caveolae.
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Cavéolas , Glaucoma de Ângulo Aberto , Camundongos , Animais , Humanos , Cavéolas/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Mecanotransdução Celular , Células Endoteliais/metabolismo , Homeostase , Serina Peptidase 1 de Requerimento de Alta Temperatura A/metabolismoRESUMO
Background Despite progress in youth anxiety assessment, there is need for a measure that is simultaneously (a) free, (b) brief, (c) focused broadly on anxiety and avoidance severity, frequency, and interference, and (d) concerned with the past week. The adult overall anxiety severity and impairment scale (OASIS) was adapted to yield a caregiver-report of past week youth anxiety and interference (OASIS-Y). Methods In a sample of diverse youth seeking anxiety services (N = 132; 67% racial/ethnic minority) and their caregivers, analyses examined the OASIS-Y factor structure, internal consistency, and convergent and divergent validity. Hierarchical linear modeling in a participant subset examined OASIS-Y sensitivity to treatment-related change. Results OASIS-Y internal consistency was high and confirmatory factor analysis supported a single-factor structure similar to that found in adults. OASIS-Y convergent validity was supported by a medium-sized association with an established, commercially available measure of youth anxiety, and divergent validity was supported by the absence of unique associations with measures of youth attention and externalizing problems. In a sample subset, session-by-session OASIS-Y scores significantly declined across treatment, and declined at a steeper rate among treatment "responders" versus "non-responders," providing evidence of OASIS-Y sensitivity to treatment-related change. Limitations This study focused on a clinical sample and cannot speak to OASIS-Y performance in community settings. Shared method-variance may have also influenced findings. Conclusions This study offers the first psychometric evaluation of the OASIS-Y, and underscores the promising clinical utility of the measure for assessing past week youth anxiety and impairment and for supporting routine outcome monitoring.
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Cuidadores , Etnicidade , Adolescente , Adulto , Ansiedade/diagnóstico , Humanos , Grupos Minoritários , Psicometria/métodos , Reprodutibilidade dos TestesRESUMO
Despite recent advances in the treatment of early child social anxiety, the broad accessibility of brick-and-mortar services has been limited by traditional barriers to care, and more recently by new obstacles related to efforts to slow the spread of COVID-19. The present waitlist-controlled trial examined the preliminary efficacy of a family-based behavioral parenting intervention (i.e., the iCALM Telehealth Program) that draws on Parent-Child Interaction Therapy and videoconferencing to remotely deliver clinician-led care for anxiety in early childhood. Young children (3-8â¯years) with a diagnosis of social anxiety disorder (Nâ¯=â¯40; 65% from ethnic/racial minority backgrounds) were randomly assigned to iCALM or waitlist. Intent-to-treat analyses found that at post, independent evaluators classified roughly half of the iCALM-treated children, but only 6% of waitlist children, as "Responders" (Wald testâ¯=â¯4.51; pâ¯=â¯.03). By Post, iCALM led to significantly greater reductions than waitlist in child anxiety symptoms, fear, discomfort, and anxiety-related social impairment, and also led to greater improvements in child soothability. By 6-month follow-up, the percentage of iCALM-treated children classified as "Responders" rose to roughly 60%. Exploratory moderation tests found iCALM was particularly effective in reducing life impairments and parental distress among families presenting with higher, relative to lower, levels of baseline parental accommodation. The present findings add to a growing body of research supporting the promise of technology-based strategies for broadening the portfolio of options for delivering clinician-led mental health services.
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COVID-19 , Telemedicina , Ansiedade/terapia , Pré-Escolar , Medo , Humanos , Internet , SARS-CoV-2RESUMO
Uncontrolled inflammation is associated with neurodegenerative conditions in central nervous system tissues, including the retina and brain. We previously found that the neural retina (NR) plays an important role in retinal immunity. Tumor necrosis factor Receptor-Associated Factor 3 (TRAF3) is a known immune regulator expressed in the retina; however, whether TRAF3 regulates retinal immunity is unknown. We have generated the first conditional NR-Traf3 knockout mouse model (Chx10-Cre/Traf3f/f) to enable studies of neuronal TRAF3 function. Here, we evaluated NR-Traf3 depletion effects on whole retinal TRAF3 protein expression, visual acuity, and retinal structure and function. Additionally, to determine if NR-Traf3 plays a role in retinal immune regulation, we used flow cytometry to assess immune cell infiltration following acute local lipopolysaccharide (LPS) administration. Our results show that TRAF3 protein is highly expressed in the NR and establish that NR-Traf3 depletion does not affect basal retinal structure or function. Importantly, NR-Traf3 promoted LPS-stimulated retinal immune infiltration. Thus, our findings propose NR-Traf3 as a positive regulator of retinal immunity. Further, the NR-Traf3 mouse provides a tool for investigations of neuronal TRAF3 as a novel potential target for therapeutic interventions aimed at suppressing retinal inflammatory disease and may also inform treatment approaches for inflammatory neurodegenerative brain conditions.
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Proteínas de Homeodomínio/genética , Neurônios/metabolismo , Retina/metabolismo , Fator 3 Associado a Receptor de TNF/genética , Fatores de Transcrição/genética , Animais , Modelos Animais de Doenças , Eletrorretinografia , Imunidade/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Neurônios/imunologia , Receptores CCR2/genética , Receptores CCR2/metabolismo , Retina/fisiologia , Fator 3 Associado a Receptor de TNF/deficiência , Fator 3 Associado a Receptor de TNF/metabolismo , Fatores de Transcrição/deficiência , Uveíte/etiologia , Uveíte/imunologia , Uveíte/metabolismo , Acuidade VisualRESUMO
Background:Video telehealth is an important tool for health care delivery during the COVID-19 pandemic. Given physical distancing recommendations, access to traditional in-person telehealth training for providers has been limited. Telesimulation is an alternative to in-person telehealth training. Telesimulation training with both remote participants and facilitators using telehealth software has not been described.Objective:We investigated the feasibility of a large group telesimulation provider training of telehealth software for remote team leadership skills with common neonatal cases and procedures.Methods:We conducted a 90-min telesimulation session with a combination of InTouch™ provider access software and Zoom™ teleconferencing software. Zoom facilitators activated InTouch software and devices and shared their screen with remote participants. Participants rotated through skill stations and case scenarios through Zoom and directed bedside facilitators to perform simulated tasks using the shared screen and audio connection. Participants engaged in a debrief and a pre- and postsurvey assessing participants' comfort and readiness to use telemedicine. Data were analyzed using descriptive statistics and paired t tests.Results:Twenty (n = 20) participants, five Zoom and eight bedside facilitators participated. Twenty-one (21) pre- and 16 postsurveys were completed. Most participants were attending neonatologists who rarely used telemedicine software. Postsession, participants reported increased comfort with some advanced InTouch features, including taking and sharing pictures with the patient (p < 0.01) and drawing on the shared image (p < 0.05), but less comfort with troubleshooting technical issues, including audio and stethoscope (p < 0.01). Frequently stated concerns were troubleshooting technical issues during a call (75%, n = 16) and personal discomfort with telemedicine applications and technology (56%, n = 16).Conclusion:Large group telesimulation is a feasible way to offer telehealth training for physicians and can increase provider comfort with telehealth software.
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COVID-19 , Telemedicina , Estudos de Viabilidade , Humanos , Recém-Nascido , Pandemias , SARS-CoV-2RESUMO
Research has examined suicide-related behaviors following exposure to suicide news articles, yet only a handful of studies utilized experimental designs. We aimed to address the limitations of these prior experimental studies by utilizing more realistic suicide articles and more empirically sound measures. 420 participants were randomly assigned to read a series of either suicide-related or neutral news articles, then complete a battery of questionnaires and the Death/Suicide Implicit Association Task. Overall, no significant differences between groups were observed, nor did we observe any moderation effect of individual vulnerabilities (e.g., lifetime suicidal ideation/behavior). We did not observe any immediate effects of exposure to suicide news articles. Further research examining potential mechanisms for imitative effects remains critically needed.
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Prevenção do Suicídio , Suscetibilidade a Doenças , Humanos , Ideação Suicida , Inquéritos e QuestionáriosRESUMO
Purpose: The immune-privileged environment and complex organization of retinal tissue support the retina's essential role in visual function, yet confound inquiries into cell-specific inflammatory effects that lead to dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in several retinal cell types and is implicated in immune regulation. However, whether Cav1 promotes or inhibits inflammatory processes in the retina (as well as in other tissues) remains unclear. Previously, we showed that global-Cav1 depletion resulted in reduced retinal inflammatory cytokine production but paradoxically elevated retinal immune cell infiltration. We hypothesized that these disparate responses are the result of differential cell-specific Cav1 functions in the retina. Methods: We used Cre/lox technology to deplete Cav1 specifically in the neural retinal (NR) compartment to clarify the role NR-specific Cav1 (NR-Cav1) in the retinal immune response to intravitreal inflammatory challenge induced by activation of Toll-like receptor-4 (TLR4). We used multiplex protein suspension array and flow cytometry to evaluate innate immune activation. Additionally, we used bioinformatics assessment of differentially expressed membrane-associated proteins to infer relationships between NR-Cav1 and immune response pathways. Results: NR-Cav1 depletion, which primarily affects Müller glia Cav1 expression, significantly altered immune response pathway regulators, decreased retinal inflammatory cytokine production, and reduced retinal immune cell infiltration in response to LPS-stimulated inflammatory induction. Conclusions: Cav1 expression in the NR compartment promotes the innate TLR4-mediated retinal tissue immune response. Additionally, we have identified novel potential immune modulators differentially expressed with NR-Cav1 depletion. This study further clarifies the role of NR-Cav1 in retinal inflammation.
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Caveolina 1/fisiologia , Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Retina/metabolismo , Retinite/induzido quimicamente , Animais , Western Blotting , Caveolina 1/deficiência , Citocinas/metabolismo , Sinergismo Farmacológico , Eletrorretinografia , Citometria de Fluxo , Imuno-Histoquímica , Inflamação/metabolismo , Inflamação/patologia , Injeções Intravítreas , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal , Nistagmo Optocinético/fisiologia , Proteômica , Retinite/metabolismo , Retinite/patologia , Salmonella typhimurium , Receptor 4 Toll-Like/metabolismoRESUMO
During the progression of ocular diseases such as retinopathy of prematurity and diabetic retinopathy, overgrowth of retinal blood vessels results in the formation of pathological neovascular tufts that impair vision. Current therapeutic options for treating these diseases include antiangiogenic strategies that can lead to the undesirable inhibition of normal vascular development. Therefore, strategies that eliminate pathological neovascular tufts while sparing normal blood vessels are needed. In this study we exploited the hyaloid vascular network in murine eyes, which naturally undergoes regression after birth, to gain mechanistic insights that could be therapeutically adapted for driving neovessel regression in ocular diseases. We found that endothelial cells of regressing hyaloid vessels underwent down-regulation of two structurally related E-26 transformation-specific (ETS) transcription factors, ETS-related gene (ERG) and Friend leukemia integration 1 (FLI1), prior to apoptosis. Moreover, the small molecule YK-4-279, which inhibits the transcriptional and biological activity of ETS factors, enhanced hyaloid regression in vivo and drove Human Umbilical Vein Endothelial Cells (HUVEC) tube regression and apoptosis in vitro. Importantly, exposure of HUVECs to sheer stress inhibited YK-4-279-induced apoptosis, indicating that low-flow vessels may be uniquely susceptible to YK-4-279-mediated regression. We tested this hypothesis by administering YK-4-279 to mice in an oxygen-induced retinopathy model that generates disorganized and poorly perfused neovascular tufts that mimic human ocular diseases. YK-4-279 treatment significantly reduced neovascular tufts while sparing healthy retinal vessels, thereby demonstrating the therapeutic potential of this inhibitor.
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Olho/irrigação sanguínea , Proteínas Oncogênicas/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , Regulador Transcricional ERG/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Vasos Sanguíneos/patologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Indóis/farmacologia , Camundongos , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-ets/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-ets/metabolismo , Vasos Retinianos/patologiaRESUMO
Purpose: Polymorphisms at the caveolin-1/2 locus are associated with glaucoma and IOP risk and deletion of caveolin-1 (Cav1) in mice elevates IOP and reduces outflow facility. However, the specific location/cell type responsible for Cav1-dependent regulation of IOP is unclear. We hypothesized that endothelial Cav1 in the conventional outflow (CO) pathway regulate IOP via endothelial nitric oxide synthase (eNOS) signaling. Methods: We created a mouse with targeted deletion of Cav1 in endothelial cells (Cav1ΔEC) and evaluated IOP, outflow facility, outflow pathway distal vascular morphology, eNOS phosphorylation, and tyrosine nitration of iridocorneal angle tissues by Western blotting. Results: Endothelial deletion of Cav1 resulted in significantly elevated IOP versus wild-type mice but not a concomitant decrease in outflow facility. Endothelial Cav1 deficiency did not alter the trabecular meshwork or Schlemm's canal morphology, suggesting that the effects observed were not due to developmental deformities. Endothelial Cav1 deletion resulted in eNOS hyperactivity, modestly increased protein nitration, and significant enlargement of the drainage vessels distal to Schlemm's canal. L-Nitro-arginine methyl ester treatment reduced outflow in Cav1ΔEC but not wild-type mice and had no effect on the size of drainage vessels. Endothelin-1 treatment decrease the outflow and drainage vessel size in both wild-type and Cav1ΔEC mice. Conclusions: Our results suggest that hyperactive eNOS signaling in the CO pathway of both Cav1ΔEC and global Cav1 knockout mice results in chronic dilation of distal CO vessels and protein nitration, but that Cav1 expression in the trabecular meshwork is sufficient to rescue CO defects reported in global Cav1 knockout mice.
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Humor Aquoso/metabolismo , Caveolina 1/genética , DNA/genética , Células Endoteliais/metabolismo , Glaucoma/genética , Pressão Intraocular/fisiologia , Polimorfismo Genético , Animais , Western Blotting , Caveolina 1/metabolismo , Modelos Animais de Doenças , Células Endoteliais/patologia , Glaucoma/metabolismo , Glaucoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de SinaisRESUMO
Recent efforts to improve access to evidence-based parent training programs using online delivery have largely neglected findings that young children with callous-unemotional (CU)-type conduct problems receive less benefit from parent training than children with conduct problems alone. The current study aimed to examine the moderating effect of child CU traits on efficacy and engagement outcomes associated with Internet-delivered Parent-Child Interaction Therapy (iPCIT) versus standard, clinic-based PCIT. Forty families (57.6% non-Hispanic Caucasian) with a 3-5 year-old (M = 3.95 years, SD = 0.9; 83.5% boys) child with a disruptive behavior disorder were randomized to either iPCIT or clinic-based PCIT. Families participated in four assessments across time; child conduct problems, global functioning and treatment responder status, and parent-rated treatment satisfaction were measured. Analyses revealed that the negative influence of CU traits on functional gains was not uniform across treatment formats. Specifically, the detrimental effect of CU traits on functional gains was significantly more pronounced among children treated with iPCIT than clinic-based PCIT. CU traits also predicted lower parental treatment satisfaction across delivery formats, but this effect was more pronounced among iPCIT parents. In contrast, CU traits did not moderate differential effects across iPCIT and clinic-based PCIT for conduct problem severity or treatment response status. Findings suggest that iPCIT is a promising treatment option for early conduct problems, particularly when access-to-care barriers exist, but that further research is needed to determine whether strategic adaptations to online programs can more optimally address the distinct needs of children with clinically significant CU traits.
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Terapia Comportamental/educação , Transtorno da Conduta/terapia , Emoções , Internet , Relações Pais-Filho , Pais/educação , Terapia Comportamental/métodos , Comportamento Infantil/psicologia , Pré-Escolar , Transtorno da Conduta/psicologia , Feminino , Humanos , Masculino , Pais/psicologia , Resultado do TratamentoRESUMO
We discuss quantum annealing of the two-dimensional transverse-field Ising model on a D-Wave device, encoded on L×L lattices with L≤32. Analyzing the residual energy and deviation from maximal magnetization in the final classical state, we find an optimal L dependent annealing rate v for which the two quantities are minimized. The results are well described by a phenomenological model with two powers of v and L-dependent prefactors to describe the competing effects of reduced quantum fluctuations (for which we see evidence of the Kibble-Zurek mechanism) and increasing noise impact when v is lowered. The same scaling form also describes results of numerical solutions of a transverse-field Ising model with the spins coupled to noise sources. We explain why the optimal annealing time is much longer than the coherence time of the individual qubits.
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Cancer is considered as the most lethal disease for human beings, and up to now many attempts were failed for prevention and treatment of this tremendous health problem. Consequently, this study purpose was to investigate novel therapeutic methods for cancer. The bacterial toxin can result in cell death throughout the induction of apoptosis in cancer cell lines. We evaluated apoptosis and the expression levels of long non-coding RNAs (lncRNAs) in PC3, ACHN and HDF cell lines that were transfected with pCDNA3.1(+)-seh and empty plasmid. pCDNA3.1(+)-seh treatment showed overexpression of GAS5 (p = 0.0033 and p = 0.0033) in PC3 and ACHN cells, down regulation of PCA3 and NEAT1 (p = 0.0092 and p = 0.0097) in the PC3 cells, and down regulation of PVT1 and MALAT1 (p = 0.0239 and p = 0.0133) in the ACHN cells in comparison with the empty plasmid, but there was no significant effect on HDF normal cells. Additionally, this study data demonstrated that the cell adhesion was down regulated. The flow cytometry data showed transfection by pCDNA3.1 (+)-seh could elevate PC3 and ACHN cell apoptosis levels in comparison with empty plasmid. This study findings propose that SEH toxin of S. aureus could be a useful candidate for therapeutic researches in cancer vaccine development.
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Although the retina resides within the immune-protected ocular environment, inflammatory processes mounted in the eye can lead to retinal damage. Unchecked chronic ocular inflammation leads to retinal damage. Thus, retinal degenerative diseases that result in chronic inflammation accelerate retinal tissue destruction and vision loss. Treatments for chronic retinal inflammation involve corticosteroid administration, which has been associated with glaucoma and cataract formation. Therefore, we must consider novel, alternative treatments. Here, we provide a brief review of our current understanding of chronic innate inflammatory processes in retinal degeneration and the complex role of a putative inflammatory regulator, Caveolin-1 (Cav1). Furthermore, we suggest that the complex role of Cav1 in retinal inflammatory modulation is likely dictated by cell type-specific subcellular localization.
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Caveolina 1/metabolismo , Inflamação/patologia , Retina/patologia , Humanos , Degeneração Retiniana/patologiaRESUMO
Drinking to cope is associated with suicide ideation and attempts. Event-based research shows drinking, particularly when alcohol is consumed in large quantities, increases the intensity of suicidal thoughts and immediate risk for attempt. Such findings suggest those who typically drink to cope may be especially likely to drink heavily in the hours preceding a suicide attempt. In the first examination of the association between regular use of alcohol as a coping strategy and acute alcohol consumption prior to a suicide attempt, participants included 130 patients hospitalized for a recent attempt. The number of drinks consumed in the acute period preceding the attempt, as well as past-year heavy drinking frequency, typical drinking motives, and depressive symptoms were assessed. The unique impacts of coping motives on odds of consuming any alcohol, and of using specific amounts of alcohol in the acute period, were determined through binary and multinomial logistic regressions. Results demonstrated that commonly drinking for coping motives increased the odds of heavy drinking - but not of using alcohol at low levels - during the acute period. Results held after adjusting for relevant covariates. Clinicians should assess drinking motives and prioritize prevention of drinking to cope to reduce risk of alcohol-related suicide attempts.
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Adaptação Psicológica , Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , Depressão/epidemiologia , Motivação , Tentativa de Suicídio/estatística & dados numéricos , Adaptação Psicológica/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação/fisiologia , Adulto JovemRESUMO
OBJECTIVE: Very few controlled trials have evaluated targeted treatment methods for childhood selective mutism (SM); the availability of evidence-based services remains limited. This study is the first controlled trial to evaluate an intensive group behavioral treatment (IGBT) for children with SM. METHOD: Twenty-nine children with SM (5-9 years; 76% female; 35% ethnic minority) were randomized to immediate SM 5-day IGBT or to a 4-week waitlist with psychoeducational resources (WLP), and were assessed at Week 4 and again 8 weeks into the following school year. RESULTS: IGBT was associated with high satisfaction and low perceived barriers to treatment participation. At Week 4, 50% of the immediate IGBT condition and 0% of the WLP condition were classified as "clinical responders." Further, Time × Condition interactions were significant for social anxiety severity, verbal behavior in social situations, and global functioning (but not for SM severity, verbal behavior in home settings, or overall anxiety). School-year follow-up assessments revealed significant improvements across all outcomes. Eight weeks into the following school year, 46% of IGBT-treated children were free of an SM diagnosis. In addition, teachers in the post-IGBT school year rated less school impairment and more classroom verbal behavior relative to teachers in the pre-IGBT school year. CONCLUSIONS: Findings provide the first empirical support for the efficacy and acceptability of IGBT for SM. Further study is needed to examine mechanisms of IGBT response, and other effective SM treatment methods, in order to clarify which treatment formats work best for which affected children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).