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OBJECTIVE: To describe the safety and effectiveness of treating pediatric patients who have pulmonary arterial hypertension (PAH) with selexipag in a real-world, multi-center cohort, given that data supporting its use in pediatric PAH are sparse. STUDY DESIGN: We report a multi-center, retrospective, cohort study of children with PAH treated with selexipag. Demographic and clinical variables were extracted from the medical records. Clinical parameters were analyzed at 3 timepoints: pre-selexipag, 3-12 months post-selexipag, and >12 months follow-up. RESULTS: Eighty-seven patients were included, 32 received selexipag as add-on to background therapy, and 55 transitioned from another prostanoid. Median starting and final doses were 4.7 and 28.5 µg/kg/dose BID, respectively. Add-on patients demonstrated improved indexed pulmonary to systemic vascular resistance ratio after selexipag initiation (PVRi/SVRi, 0.62v0.53, p=0.034) with a lower average mean pulmonary artery pressure (MPAP, 46v39 mmHg, p=NS), and oxygen consumption (VO2 max 27.8v30.9 mL/kg/min, p=NS). Transition patients demonstrated stable MPAP (47v45 mmHg, p=NS) and a lower mean PVRi (10.9v8.2 Wood units*m2, p=NS) but late functional worsening in some with VO2 max decreased at follow-up (26.0v19.5 ml/kg/min). Side effects were noted in 40% of the cohort but prompted discontinuation in only 2%. CONCLUSIONS: In a large, multi-center cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring.
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Disturbed balance between matrix metalloproteinases (MMPs) and their respective tissue inhibitors (TIMPs) is a well-recognized pathophysiological component of pulmonary arterial hypertension (PAH). Both classes of proteinases have been associated with clinical outcomes as well as with specific pathological features of ventricular dysfunction and pulmonary arterial remodeling. The purpose of this study was to evaluate the circulating levels of MMPs and TIMPs in children with PAH undergoing the same-day cardiac magnetic resonance imaging (MRI) and right heart catheterization. Children with PAH (n = 21) underwent a same-day catheterization, comprehensive cardiac MRI evaluation, and blood sample collection for proteomic analysis. Correlative analysis was performed between protein levels and 1) standard PAH indices from catheterization, 2) cardiac MRI hemodynamics, and 3) pulmonary arterial stiffness. MMP-8 was significantly associated with the right ventricular end-diastolic volume (R = 0.45, P = 0.04). MMP-9 levels were significantly associated with stroke volume (R = -0.49, P = 0.03) and pulmonary vascular resistance (R = 0.49, P = 0.03). MMP-9 was further associated with main pulmonary arterial stiffness evaluated by relative area change (R = -0.79, P < 0.01).TIMP-2 and TIMP-4 levels were further associated with the right pulmonary artery pulse wave velocity (R = 0.51, P = 0.03) and backward compression wave (R = 0.52, P = 0.02), respectively. MMPs and TIMPs warrant further clinically prognostic evaluation in conjunction with the conventional cardiac MRI hemodynamic indices.NEW & NOTEWORTHY Metalloproteinases have been associated with clinical outcomes in pulmonary hypertension and with specific pathological features of ventricular dysfunction and pulmonary arterial remodeling. In this study, we demonstrated that plasma circulating levels of metalloproteinases and their inhibitors are associated with standard cardiac MRI hemodynamic indices and with the markers of proximal pulmonary arterial stiffness. Particularly, MMP-9 and TIMP-2 were associated with several different markers of pulmonary arterial stiffness. These findings suggest the interplay between the extracellular matrix (ECM) remodeling and overall hemodynamic status in children with PAH might be assessed using the peripheral circulating MMP and TIMP levels.
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Hipertensão Pulmonar/fisiopatologia , Metaloproteinases da Matriz/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Rigidez Vascular/fisiologia , Função Ventricular/fisiologia , Adolescente , Pressão Arterial/fisiologia , Criança , Feminino , Hemodinâmica/fisiologia , Humanos , Hipertensão Pulmonar/sangue , Masculino , Artéria Pulmonar/fisiopatologiaRESUMO
Individuals diagnosed with borderline personality disorder (BPD) experience significant and pervasive impairment in interpersonal, social, and vocational functioning, and accumulating evidence suggests that impairments in functioning often persist despite significant decreases in symptom severity. Previous research indicates that shame-proneness and guilt-proneness are associated with symptoms of BPD that can affect functioning (such as aggression toward others), but very few studies have examined the impact of shame-proneness and guilt-proneness on validated measures of psychosocial functioning. Forty women with BPD completed measures of shame-proneness and guilt-proneness, psychosocial functioning, and BPD symptom severity. Results from multiple regression analyses indicate that women with BPD who tend to experience higher levels of shame-proneness and lower levels of guilt-proneness report poor performance in school and work settings and in interpersonal relationships. Strengths of the study include the use of a validated measure of functioning as the primary outcome. Limitations and future directions are discussed.
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Transtorno da Personalidade Borderline/psicologia , Culpa , Relações Interpessoais , Funcionamento Psicossocial , Vergonha , Adulto , Feminino , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Despite the high prevalence and significant health consequences of substance use disorders, rates of treatment seeking are low. Identifying as an "addict" caries a mainstream connotation that the individual is blameworthy, which contributes to unique stressors and stigma that shape how they are viewed and treated. While substantial literature demonstrates this stigmatizing perspective may serve as a barrier to treatment-seeking, other studies present discrepant findings. The current study seeks to examine the role of fear of stigma and anticipation of being stigmatized in the relationship between internalized stigma and help-seeking for substance use disorders. OBJECTIVE: We examined substance use-related stigma, fear of stigma, and treatment-seeking behaviors in a national sample of young adults with a history of problematic substance use. METHODS: Participants (N = 171) completed an online, anonymous survey. RESULTS: When controlling for enacted stigma and severity of alcohol and other drug use problems, more fear of stigma significantly mediated the relationship between higher internalized stigma and more help-seeking intentions. The sequentially mediated paths between internalized stigma and both help-seeking intentions and previous behaviors through fear of stigma and anticipated stigma were not significant. CONCLUSIONS: Findings highlight the importance of fear of substance-related stigma as one mechanism by which internalized stigma may motivate individuals to seek treatment for substance use problems.
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Estigma Social , Transtornos Relacionados ao Uso de Substâncias , Medo , Humanos , Intenção , Aceitação pelo Paciente de Cuidados de Saúde , Transtornos Relacionados ao Uso de Substâncias/terapia , Inquéritos e Questionários , Adulto JovemRESUMO
This study evaluated the pharmacokinetics of intravenous (IV) and subcutaneous (SC) treprostinil in pediatric patients with pulmonary vascular disease, and compared them with existing adult data from a similar cohort. Blood samples were collected from pediatric patients receiving steady-state IV or SC treprostinil and were assessed for plasma treprostinil concentration using liquid chromatography and tandem mass spectrometry. Forty participants, 15 receiving IV and 25 receiving SC treprostinil, were included in the analysis. Age ranged from 0.1 to 15.6 years. The median dose of treprostinil was 45.5 ng·kg·min with a range of 8-146 ng·kg·min. There was a linear relationship between treprostinil dose and plasma concentration with an R of 0.57. On average, there were higher blood concentrations per given dose of IV treprostinil compared with those per given dose of SC, but the difference was not significant. Compared with adult data, the slope of the pediatric data was similar, but the y-intercept was significantly lower. Additionally, the concentration per dose ratio was significantly higher in adults compared with children. Pediatric patients have significantly lower average blood concentrations of treprostinil per given dose compared with adults, and higher, but not significantly so, blood concentrations when treprostinil is administered IV as compared with SC administration.
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Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacocinética , Epoprostenol/análogos & derivados , Hipertensão Arterial Pulmonar/tratamento farmacológico , Adolescente , Fatores Etários , Anti-Hipertensivos/sangue , Criança , Pré-Escolar , Cromatografia Líquida , Estudos Transversais , Monitoramento de Medicamentos , Epoprostenol/administração & dosagem , Epoprostenol/sangue , Epoprostenol/farmacocinética , Feminino , Humanos , Lactente , Infusões Intravenosas , Infusões Subcutâneas , Masculino , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/fisiopatologia , Espectrometria de Massas em Tandem , Estados UnidosRESUMO
Although sexual assault (SA) prevention programs on college campuses are increasingly prevalent, no studies explore the influence of program components on outcomes. Empathy exercises are frequently included in such programs, with the intent of changing participant emotions and attitudes in order to change subsequent behavior. This study evaluated whether the inclusion of an empathy exercise within a SA prevention program impacted participants' emotions and attitudes, and subsequent helping behaviors in SA bystander situations. Three-hundred and seventy students (63% women) participated in an evaluation of a mandatory bystander intervention program; half the students received the program containing an empathy exercise and half received the program that did not. For women only, participation in the program with the empathy exercise led to more negative emotions and fewer attitudes condoning SA, the latter of which influenced greater prosocial bystander behaviors 6 months later.
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Atitude , Vítimas de Crime/psicologia , Empatia , Delitos Sexuais/prevenção & controle , Delitos Sexuais/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , New England , Avaliação de Programas e Projetos de Saúde , Distribuição por Sexo , Estudantes , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
While the majority of research on dating violence (DV) and sexual assault (SA) in college students has focused on heterosexual students, victimization rates among sexual minority students are the same or higher than that of their heterosexual counterparts. The current study sought to explore sexual minority college students' perceptions of the prevalence of DV and SA, risk and protective factors, and barriers to seeking help, using focus groups. A total of 14 sexual minority students ranging in age from 18 to 24 participated across 2 focus groups. Findings suggest the majority of the students perceived DV and SA among sexual minority individuals to be less common compared to their heterosexual counterparts and to be less common on their campus compared to other colleges and universities. Students' reflections about risk and protective factors overlapped with those previously established among heterosexuals as well as factors unique to the sexual minority community. Students identified societal, community, and psychological-level barriers related to help-seeking. We provide recommendations for practice based on the current findings (e.g., colleges could expand current educational material about DV and SA to include more recognition of these issues for sexual minority students). (PsycINFO Database Record
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Violência por Parceiro Íntimo/psicologia , Violência por Parceiro Íntimo/estatística & dados numéricos , Estupro/psicologia , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Percepção Social , Estudantes/psicologia , Adolescente , Vítimas de Crime/psicologia , Vítimas de Crime/estatística & dados numéricos , Cultura , Feminino , Grupos Focais , Humanos , Masculino , Prevalência , Adulto JovemRESUMO
BACKGROUND: In patients with melanoma, ipilimumab (an antibody against cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]) prolongs overall survival, and nivolumab (an antibody against the programmed death 1 [PD-1] receptor) produced durable tumor regression in a phase 1 trial. On the basis of their distinct immunologic mechanisms of action and supportive preclinical data, we conducted a phase 1 trial of nivolumab combined with ipilimumab in patients with advanced melanoma. METHODS: We administered intravenous doses of nivolumab and ipilimumab in patients every 3 weeks for 4 doses, followed by nivolumab alone every 3 weeks for 4 doses (concurrent regimen). The combined treatment was subsequently administered every 12 weeks for up to 8 doses. In a sequenced regimen, patients previously treated with ipilimumab received nivolumab every 2 weeks for up to 48 doses. RESULTS: A total of 53 patients received concurrent therapy with nivolumab and ipilimumab, and 33 received sequenced treatment. The objective-response rate (according to modified World Health Organization criteria) for all patients in the concurrent-regimen group was 40%. Evidence of clinical activity (conventional, unconfirmed, or immune-related response or stable disease for ≥24 weeks) was observed in 65% of patients. At the maximum doses that were associated with an acceptable level of adverse events (nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram), 53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrent-regimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible. Among patients in the sequenced-regimen group, 18% had grade 3 or 4 adverse events related to therapy and the objective-response rate was 20%. CONCLUSIONS: Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; ClinicalTrials.gov number, NCT01024231.).
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Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno CTLA-4/imunologia , Feminino , Humanos , Infusões Intravenosas , Ipilimumab , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nivolumabe , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
Although evidence suggests that bystander prevention programs are promising interventions for decreasing sexual violence and dating violence on college campuses, there have been no studies to date evaluating moderators of bystander program effectiveness. The current study evaluates whether different demographic characteristics, attitudes, knowledge, and behaviors at pretest predict change over a 6-month follow-up for students who participated in a bystander prevention program. Participants in the three assessments (pretest, posttest, 6-month follow-up) included 296 college students who were mandated to attend a bystander program during their first year orientation. Analyses showed that with few exceptions, the bystander program worked best for students who were most at risk given their pretest demographics and levels of attitudes condoning dating violence and sexual violence, bystander efficacy, and bystander behaviors. Results are discussed in terms of suggestions for future research.
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Conhecimentos, Atitudes e Prática em Saúde , Violência por Parceiro Íntimo/psicologia , Delitos Sexuais/psicologia , Estudantes/psicologia , Adolescente , Adulto , Feminino , Promoção da Saúde/métodos , Humanos , Relações Interpessoais , Violência por Parceiro Íntimo/prevenção & controle , Masculino , Análise Multinível , New England , Distribuição por Sexo , Delitos Sexuais/prevenção & controle , Sexualidade , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
INTRODUCTION: An inability to tolerate distress is a significant predictor of early smoking lapse following a cessation attempt. We conducted a preliminary randomized controlled trial to compare a distress tolerance (DT) treatment that incorporated elements of exposure-based therapies and Acceptance and Commitment Therapy to standard smoking cessation treatment (ST). METHODS: Smokers with a history of early lapse in prior quit attempts received either DT (N = 27; 9 2-hr group and 6 50-min individual sessions) or ST (N = 22; 6 90-min group and 1 20-min individual session), plus 8 weeks of transdermal nicotine patch. RESULTS: At the end of behavioral treatment, odds of abstinence among participants receiving DT were 6.46 times greater than among participants receiving ST (66.7% vs. 31.8%), equivalent to a medium- to large-effect size. Odds of abstinence for DT were still 1.73 times greater at 8 weeks, corresponding to a small- to medium-effect size, although neither this difference nor those at 13 and 26 weeks were statistically significant. Furthermore, of those who lapsed to smoking during the first week postquit, DT participants had more than 4 times greater odds of abstinence than ST participants at the end of treatment. Relative to ST, DT participants also reported a larger decrease in experiential avoidance, a hypothesized DT treatment mediator, prior to quit day. The trajectory of negative mood and withdrawal symptoms in DT differed from ST and was largely consistent with hypotheses. CONCLUSIONS: Reasons for the decrease in abstinence in DT after treatment discontinuation and suggestions for future research are discussed.
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Nicotina/administração & dosagem , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Tabagismo/terapia , Adolescente , Adulto , Afeto , Idoso , Terapia Comportamental , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Síndrome de Abstinência a Substâncias/psicologia , Síndrome de Abstinência a Substâncias/terapia , Fatores de Tempo , Dispositivos para o Abandono do Uso de Tabaco , Tabagismo/psicologia , Resultado do Tratamento , Adulto JovemRESUMO
Adventive populations of Trissolcus japonicus (Ashmead), an egg parasitoid of the invasive agricultural pest, brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), have been detected in the United States since 2014. Given its importance as an H. halys biocontrol agent, efforts to redistribute T. japonicus began within some US states. Our surveillance for T. japonicus in northwestern Virginia in 2016-2017 yielded annual detections only in 1 county. Thus, to promote its broader establishment, releases of H. halys egg masses parasitized by T. japonicus from Virginia occurred in 2018 (2 releases) and 2020 (1 release) at 9 sites throughout Virginia's tree fruit production regions. Monitoring of T. japonicus and H. halys, using yellow sticky cards deployed in H. halys host trees and pheromone-baited sticky traps, respectively, was conducted from 2018 to 2022. Annual captures of H. halys adults and nymphs appeared to reflect adequate populations to support T. japonicus establishment across most or all sites. Prerelease monitoring yielded a single T. japonicus at 1 site. By 2022, T. japonicus was detected at or near 7 of the remaining 8 release sites, with first detections varying between 1 and 2 yr from the releases in 2018 and 2020. Captures at most sites were very low, but establishment at several locations was indicated by detections in 2-4 seasons. In 2022, T. japonicus surveillance at 11 additional sites in northwestern Virginia yielded detections at all locations, including those at which it had not been detected in 2016-2017, providing evidence for its range expansion.
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Heterópteros , Himenópteros , Animais , Virginia , Estações do Ano , ÁrvoresRESUMO
Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure.
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College students are at particular risk for sexual assault victimization, yet research tends to focus on women as victims and men as perpetrators. The purpose of this study was to investigate gender differences in the prevalence, context, and predictors of sexual assault victimization among college students. Results showed that women were significantly more likely to have been sexually assaulted in a 2-month time period, but the context of victimization varied little by gender. Victimization was predicted by sexual orientation, time spent socializing and partying, and severe dating violence victimization for men and by year in school, time spent on the Internet, drinking and using drugs, and being a stalking and dating violence victim for women. Results are discussed in the context of routine activities theory and implications for prevention and future research.
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Vítimas de Crime/estatística & dados numéricos , Relações Interpessoais , Parceiros Sexuais , Maus-Tratos Conjugais/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Adulto , Vítimas de Crime/psicologia , Feminino , Humanos , Masculino , Prevalência , Medição de Risco , Autoimagem , Distribuição por Sexo , Meio Social , Maus-Tratos Conjugais/psicologia , Estudantes/psicologia , Estados Unidos/epidemiologia , Universidades , Saúde da Mulher , Adulto JovemRESUMO
Prior research has assumed that individuals with PTSD find positive emotions enjoyable and rewarding. While intuitive, this assumption is problematic for a number of reasons. A growing body of literature suggests that positive emotions can be unwanted and uncomfortable experiences for many people, particularly individuals with PTSD. Yet our empirical and theoretical models of PTSD do not adequately account for this complexity. Throughout the following pages, we argue that the same behavioral processes that have been heavily researched and associated with fear and avoidance of negative emotions and PTSD can be extended to positive emotions as well. We propose the integrated constructionist approach to emotions, which integrates learning theory principles with a constructionist approach and suggest that trauma experiences lead to a shift in the evaluation, interpretation, and labeling of an individual's internal experiences. This evaluative shift results in generalized patterns of emotional responding characterized by efforts to downregulate internal stimuli that were previously defined as positive and may have been appetitive pre-trauma. We subsequently highlight the theoretical, empirical, and clinical importance of taking an idiographic approach to understanding and working with emotions among individuals with PTSD.
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Transtornos de Estresse Pós-Traumáticos , Emoções , Medo , Humanos , Modelos Teóricos , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
Sexual minority individuals, due to additional chronic stress they experience from living with a marginalized identity, may be perceived as vulnerable targets by motivated perpetrators of stalking. Using campus climate data collected over 11 years, researchers explore stalking victimization with a particular focus on the experiences of sexual minority college students. To get a better understanding of stalking as experienced by this population, this study investigated descriptive qualities and prevalence of stalking victimization among college students to compare experiences of sexual minority and heterosexual individuals. Additionally, using a routine activities theory framework, this study explored multiple sexual minority identities as unique predictors of stalking victimization. Results showed that bisexual and pansexual women were significantly more likely to experience stalking than heterosexual women, and gay men were significantly more likely to experience stalking than heterosexual men. In samples that included heterosexual, gay, lesbian, bisexual, and pansexual students, having a sexual minority identity predicted stalking victimization for men, and having a non-monosexual (bisexual or pansexual) identity predicted stalking victimization for women. When looking across all sexual orientations, sexual minority identity significantly predicted stalking victimization for both men and women. Results are discussed in the context of routine activities theory and future directions for exploring stalking in sexual minority populations are identified.
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Bullying , Vítimas de Crime , Minorias Sexuais e de Gênero , Feminino , Humanos , Masculino , Comportamento Sexual , EstudantesRESUMO
Intimate partner aggression (IPA) victimization and substance use have been well established as risk factors for IPA perpetration (Leonard, 2005; Sprunger et al., 2015). Recent research has identified a negative association between distress tolerance and physical and psychological IPA perpetration, specifically in males in substance use treatment (Shorey et al., 2017). Research examining the interplay of problem substance use, distress tolerance, and other forms of IPA (i.e., sexual coercion, controlling behaviors) in non-clinical samples is limited. The present analysis aimed to examine the potential moderating effect of distress tolerance on problem alcohol use and four types of IPA perpetration (physical assault, psychological aggression, sexual coercion, and controlling behaviors) in a diverse, national sample (N = 323; 44.3% female; 52.9% sexual minority; age M = 33.61 years, SD = 8.71). Results showed that alcohol use and distress tolerance had differing influences on each IPA perpetration type. In line with hypotheses, distress tolerance significantly moderated the relationship between problem alcohol use and two forms of IPA (physical assault and controlling behaviors); this relationship was stronger for individuals with low levels of distress tolerance. Significant interaction effects did not emerge for psychological aggression or sexual coercion. Findings suggest that treatment strategies that focus specifically on increasing distress tolerance may be effective in reducing alcohol-facilitated IPA perpetration involving physical assault and controlling behaviors.
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Alcoolismo , Violência por Parceiro Íntimo , Transtornos Relacionados ao Uso de Substâncias , Adulto , Agressão/psicologia , Feminino , Humanos , Violência por Parceiro Íntimo/psicologia , Masculino , Comportamento Sexual , Parceiros Sexuais/psicologiaRESUMO
To infer potential causal relationships between 3D chromatin structure, enhancers, and gene transcription, we mapped each feature in a genome-wide fashion across eight narrowly spaced time points of macrophage activation. Enhancers and genes connected by loops exhibit stronger correlations between histone H3K27 acetylation and expression than can be explained by genomic distance or physical proximity alone. At these looped enhancer-promoter pairs, changes in acetylation at distal enhancers precede changes in gene expression. Changes in gene expression exhibit a directional bias at differential loop anchors; gained loops are associated with increased expression of genes oriented away from the center of the loop, and lost loops are often accompanied by high levels of transcription within the loop boundaries themselves. These results are consistent with a reciprocal relationship where loops can facilitate increased transcription by connecting promoters to distal enhancers, whereas high levels of transcription can impede loop formation.
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Cromatina , Genômica , Regiões Promotoras Genéticas/genética , Acetilação , Elementos Facilitadores Genéticos/genéticaRESUMO
Group IVA cytosolic phospholipase A(2) (cPLA(2)α) catalyzes the first step in the arachidonic acid cascade leading to the synthesis of important lipid mediators, the prostaglandins and leukotrienes. We previously described a patient deficient in cPLA(2)α activity, which was associated with mutations in both alleles encoding the enzyme. In this paper, we describe the biochemical characterization of each of these mutations. Using saturating concentrations of calcium, we showed that the R485H mutant was nearly devoid of any catalytic activity, that the S111P mutation did not affect the enzyme activity, and that the known K651R polymorphism was associated with activity slightly higher than that of the wild type. Using MDCK cells, we showed that translocation to the Golgi in response to serum activation was impaired for the S111P mutant but not for the other mutants. Using immortalized mouse lung fibroblasts lacking endogenous cPLA(2)α activity, we showed that both mutations S111P and R485H/K651R caused a profound defect in the enzyme catalytic activity in response to cell stimulation with serum. Taken together, our results show that the S111P mutation hampers calcium binding and membrane translocation without affecting the catalytic activity, and that the mutation R485H does not affect membrane translocation but blocks catalytic activity that leads to inactivation of the enzyme. Interestingly, our results show that the common K651R polymorphism confers slightly higher activity to the enzyme, suggesting a role of this residue in favoring a catalytically active conformation of cPLA(2)α. Our results define how the mutations negatively influence cPLA(2)α function and explain the inability of the proband to release arachidonic acid for eicosanoid production.
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Fosfolipases A2 do Grupo IV/metabolismo , Mutação , Animais , Biocatálise , Linhagem Celular , Cães , Fosfolipases A2 do Grupo IV/deficiência , Fosfolipases A2 do Grupo IV/genética , Humanos , Camundongos , Camundongos Knockout , Transporte ProteicoRESUMO
OBJECTIVE: Betrayal Trauma Theory posits that interpersonal traumas are particularly injurious when the perpetrator is a person that the victim previously trusted and was close to. A relevant protective factor to examine is social support, which may influence PTSD symptomology through its influence on emotion regulation. The aim of the current study was to examine differences in the associations between social support, emotion regulation, and PTSD symptom severity for survivors of betrayal trauma and nonbetrayal trauma. METHOD: Two hundred and 73 trauma survivors (age: M = 25.96 years, SD = 9.42 years; 80.2% female; 63.7% White) completed the anonymous, online survey. RESULTS: Across both groups, emotion regulation mediated the relationship between social support and PTSD symptom severity. A multiple-samples SEM analysis showed that the betrayal group evidenced a weaker relationship between social support and emotion regulation. CONCLUSIONS: Findings suggest that survivors of high betrayal trauma may not engage with their social support in ways that foster emotion regulation skills. Therefore, for high betrayal trauma survivors specifically, group interventions that involve the survivor and close contact(s), may be particularly beneficial in enhancing emotion regulation and decreasing PTSD symptomology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Regulação Emocional , Transtornos de Estresse Pós-Traumáticos , Adulto , Traição , Feminino , Humanos , Masculino , Apoio Social , SobreviventesRESUMO
High rates of relapse and overdose during early recovery from opioid use disorder (OUD) highlight the importance of providing effective treatment during this crucial phase. While early treatment often focuses on managing urges and withdrawal symptoms, eliciting personally salient motivators may help to target predictors of treatment outcomes such as motivation and self-efficacy. This experimental study examined the effect of a brief values clarification exercise on motivation and self-efficacy for abstinence in a sample of n = 93 individuals in brief residential treatment for OUD. Participants were randomly assigned to values clarification or a time management control condition exercise. Self-efficacy for abstinence as measured by a validated single-item measure was higher for participants in the values condition (M = 8.7) compared to control (M = 7.8, p = .013), while motivation for abstinence as measured by the commitment to sobriety scale was similarly high for both the values clarification (M = 28.0) and control (M = 27.8, p = .642) groups. There were no group differences in delay discounting, the theorized mediator of these relationships. Taken together, these results suggest that even a brief values clarification exercise may increase self-efficacy for abstinence when added to early residential treatment for OUD.