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1.
J Arthroplasty ; 32(9): 2694-2700, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28456560

RESUMO

BACKGROUND: The purpose of this study was to analyze the nature of shared content of total joint arthroplasty patients on Instagram. Specifically, we evaluated social media posts for: (1) perspective and timing; (2) tone; (3) focus (activities of daily living [ADLs], rehabilitation, return-to-work); and (4) the comparison between hip and knee arthroplasties. METHODS: A search of the public Instagram domain was performed over a 6-month period. Total hip and knee arthroplasties (THA and TKA) were selected for the analysis using the following terms: "#totalhipreplacement," "#totalkneereplacement," and associated terms. 1287 individual public posts of human subjects were shared during the period. A categorical scoring system was utilized for media format (photo or video), time (preoperative, perioperative, or postoperative) period, tone (positive or negative), return-to-work, ADLs, rehabilitation, surgical site, radiograph image, satisfaction, and dissatisfaction. RESULTS: Ninety-one percent of the posts were shared during the postoperative period. Ninety-three percent of posts had a positive tone. Thirty-four percent of posts focused on both ADLs and 33.8% on rehabilitation. TKA patients shared more about their surgical site (14.5% vs 3.3%, P < .001) and rehabilitation (58.9% vs 8.8%, P < .001) than THA patients, whereas THA patients shared more about ADLs than TKA patients (60.5% vs 7.6%, P < .001). CONCLUSION: When sharing their experience on Instagram, arthroplasty patients did so with a positive tone, starting a week after surgery. TKA posts focused more on rehabilitation and wound healing than THA patients, whereas THA patients shared more posts on ADLs. The analysis of social media posts provides insight into what matters to patients after total joint arthroplasty.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Mídias Sociais/estatística & dados numéricos , Atividades Cotidianas , Artroplastia de Quadril/reabilitação , Artroplastia do Joelho/reabilitação , Humanos , Período Pós-Operatório , Retorno ao Trabalho
2.
J Early Adolesc ; 37(3): 414-432, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28824220

RESUMO

The present study examined whether emotional abuse and neglect differentially predicted decreases in emotional clarity, and whether emotional clarity, in turn, predicted increases in depressive symptoms. Participants included 204 early adolescents (52% African-American; 54% female; Mean age= 12.85 years) who completed four assessments with measures of depressive symptoms, emotional clarity, and emotional abuse and neglect. Hierarchical linear regressions indicated that emotional neglect significantly predicted decreases in emotional clarity, whereas emotional abuse did not. Further, mediational analyses revealed that decreases in emotional clarity mediated the relationship between emotional neglect and increases in depressive symptoms. The current study suggests that emotional neglect (more so than emotional abuse) may hinder an individual's ability to identify his or her own emotions, which may increase the risk of depressive symptoms during adolescence. These findings have significant implications for the development of intervention and prevention programs for depression.

3.
J Vasc Surg ; 64(6): 1835-1846.e1, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26781075

RESUMO

OBJECTIVE: Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. METHODS: A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. RESULTS: We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 µm2; P < .001) and distal graft (2800 µm2; P < .04), whereas the guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 µm2; P < .01). CONCLUSIONS: In this report, we summarize the literature on the aortic interposition graft model, present a detailed description of the anatomy and aortic interposition graft procedure in the rat and guinea pig, and describe a unique distribution of intimal formation that results in both species. This information will be helpful when designing studies to evaluate novel graft materials in the future.


Assuntos
Aorta/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Neointima , Animais , Aorta/patologia , Implante de Prótese Vascular/efeitos adversos , Cobaias , Hiperplasia , Teste de Materiais , Modelos Animais , Desenho de Prótese , Ratos Sprague-Dawley , Especificidade da Espécie , Fatores de Tempo
4.
J Surg Res ; 200(2): 722-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26490225

RESUMO

BACKGROUND: Little is known about how arterial injury, nitric oxide (NO), or the diabetic milieu impact microparticle (MP) levels in the vasculature. We hypothesized that MP levels would increase following local arterial injury, and that NO would modify MP levels differently based on the metabolic environment. MATERIALS AND METHODS: Type 1 diabetes was induced in male Lean Zucker (LZ) rats with streptozotocin, and type 2 diabetes was induced in male Zucker diabetic fatty rats through diet. Lean Zucker rats served as nondiabetic controls. The rat carotid balloon injury was performed ± NO (n > 4/group). Blood was obtained at intervals from baseline to 14 d after injury and analyzed for platelet MP (PMP), leukocyte MP (LMP), and endothelial MP (EMP) using fluorescence-activated cell sorting (FACS) analysis. RESULTS: At baseline, type 1 diabetic rats had the highest EMP levels (P < 0.05). After arterial injury, type 1 and type 2 diabetic rats had a transient increase in EMP levels (P < 0.05) before decreasing below baseline levels. Both LMP and PMP levels generally declined after injury in all three animal models but were the lowest in both type 1 and type 2 diabetic rats. NO therapy had little impact on MP levels in nondiabetic and type 1 diabetic rats after injury. Conversely, NO caused a dramatic increase in EMP, LMP, and PMP levels in type 2 diabetic animals at early time points after injury (P < 0.05). CONCLUSIONS: These data demonstrate that the diabetic milieu impacts MP levels at baseline, after arterial injury and with NO treatment.


Assuntos
Lesões das Artérias Carótidas/tratamento farmacológico , Micropartículas Derivadas de Células/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Sequestradores de Radicais Livres/uso terapêutico , Óxido Nítrico/uso terapêutico , Animais , Biomarcadores/sangue , Lesões das Artérias Carótidas/sangue , Lesões das Artérias Carótidas/complicações , Artéria Carótida Primitiva , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Citometria de Fluxo , Masculino , Ratos , Ratos Zucker , Estreptozocina , Resultado do Tratamento
5.
J Surg Res ; 202(2): 413-21, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27229117

RESUMO

BACKGROUND: Diabetic patients display aggressive restenosis after vascular interventions, likely because of proproliferative influences of hyperglycemia and hyperinsulinemia. We have shown that nitric oxide (NO) inhibits neointimal hyperplasia in type 2, but not in type 1, diabetic rats. Here, we examined proteasome activator 28 (PA28) after arterial injury in different diabetic environments, with or without NO. We hypothesize that NO differentially affects PA28 levels based on metabolic environment. MATERIALS AND METHODS: Vascular smooth muscle cell (VSMC) lysates from male, nondiabetic Lean Zucker (LZ) and Zucker Diabetic Fatty (ZDF) rats were assayed for 26S proteasome activity with or without PA28 and S-nitroso-N-acetylpenicillamine. LZ and ZDF VSMCs were treated with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate for 24 h. Balloon-injured carotid arteries from LZ, streptozotocin-injected LZ (STZ, type 1), and ZDF (type 2) rats treated with disodium 1-[2-(carboxylato)pyrrolidin-1-iyl]diazen-1-ium-1,2-diolate were harvested at 3 or 14 d. PA28α was assessed by Western blotting and immunofluorescent staining. RESULTS: S-nitroso-N-acetylpenicillamine reversed PA28-stimulated increases in 26S proteasome activity in LZ and ZDF VSMCs. Increased (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate lowered PA28α in LZ VSMCs but increased PA28α in ZDF VSMCs. At 3 d after injury, disodium 1-[2-(carboxylato)pyrrolidin-1-iyl]diazen-1-ium-1,2-diolate potentiated injury-induced PA28α decreases in LZ, STZ, and ZDF rats, suggesting VSMCs, depleted at this early time point, are major sources of PA28α. At 14 d after injury, total PA28α staining returned to baseline. However, although intimal and medial PA28α staining increased in injured STZ rats, adventitial PA28α staining increased in injured ZDF rats. CONCLUSIONS: PA28 dysregulation may explain the differential ability of NO to inhibit neointimal hyperplasia in type 1 versus type 2 diabetes.


Assuntos
Lesões das Artérias Carótidas/tratamento farmacológico , Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Neointima/prevenção & controle , Óxido Nítrico/uso terapêutico , Complexo de Endopeptidases do Proteassoma/metabolismo , Substâncias Protetoras/uso terapêutico , Animais , Biomarcadores/metabolismo , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/enzimologia , Artérias Carótidas/patologia , Lesões das Artérias Carótidas/complicações , Lesões das Artérias Carótidas/enzimologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Hiperplasia/etiologia , Hiperplasia/prevenção & controle , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/patologia , Neointima/enzimologia , Neointima/etiologia , Neointima/patologia , Óxido Nítrico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Zucker , Resultado do Tratamento
6.
J Youth Adolesc ; 45(1): 183-94, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25680559

RESUMO

Peer victimization is a significant risk factor for a range of negative outcomes during adolescence, including depression and anxiety. Recent research has evaluated individual characteristics that heighten the risk of experiencing peer victimization. However, the role of emotional clarity, or the ability to understand one's emotions, in being the target of peer victimization remains unclear. Thus, the present study evaluated whether deficits in emotional clarity increased the risk of experiencing peer victimization, particularly among adolescent girls, which, in turn, contributed to prospective levels of depressive and anxiety symptoms. In the present study, 355 early adolescents (ages 12-13; 53% female; 51% African American) who were part of the Adolescent Cognition and Emotion project completed measures of emotional clarity, depressive symptoms, and anxiety symptoms at baseline, and measures of peer victimization, depressive symptoms, and anxiety symptoms at follow-up. Moderation analyses indicated that deficits in emotional clarity predicted greater peer victimization among adolescent girls, but not adolescent boys. Moderated mediation analyses revealed that deficits in emotional clarity contributed to relational peer victimization, which, in turn, predicted prospective levels of depressive and anxiety symptoms among adolescent girls, but not boys. These findings indicate that deficits in emotional clarity represent a significant risk factor for adolescent girls to experience relational peer victimization, which, in turn, contributed to prospective levels of internalizing symptoms. Thus, prevention programs should target deficits in emotional clarity to prevent peer victimization and subsequent internalizing symptoms among adolescent girls.


Assuntos
Vítimas de Crime/psicologia , Emoções , Relações Interpessoais , Grupo Associado , Adolescente , Ansiedade/complicações , Criança , Mecanismos de Defesa , Depressão/complicações , Etnicidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários
7.
J Adolesc ; 42: 68-76, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25931160

RESUMO

Deficits in emotional clarity, the understanding and awareness of one's own emotions and the ability to label them appropriately, are associated with increased depressive symptoms. Surprisingly, few studies have examined factors associated with reduction in emotional clarity for adolescents, such as depressed mood and ruminative response styles. The present study examined rumination as a potential mediator of the relationship between depressive symptoms and changes in emotional clarity, focusing on sex differences. Participants included 223 adolescents (51.60% female, Mean age = 12.39). Controlling for baseline levels of emotional clarity, initial depressive symptoms predicted decreases in emotional clarity. Further, rumination prospectively mediated the relationship between baseline depressive symptoms and follow-up emotional clarity for girls, but not boys. Findings suggest that depressive symptoms may increase girls' tendencies to engage in repetitive, negative thinking, which may reduce the ability to understand and label emotions, a potentially cyclical process that confers vulnerability to future depression.


Assuntos
Adaptação Psicológica , Conscientização , Depressão/psicologia , Transtorno Depressivo/psicologia , Inteligência Emocional , Pensamento , Adolescente , Criança , Transtorno Depressivo/diagnóstico , Feminino , Identidade de Gênero , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Inquéritos e Questionários
8.
Am J Physiol Heart Circ Physiol ; 307(10): H1419-29, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25239800

RESUMO

Oral all-trans retinoic acid (atRA) has been shown to reduce the formation of neointimal hyperplasia; however, the dose required was 30 times the chemotherapeutic dose, which already has reported side effects. As neointimal formation is a localized process, new approaches to localized delivery are required. This study assessed whether atRA within a citrate-based polyester, poly(1,8 octanediolcitrate) (POC), perivascular membrane would prevent neointimal hyperplasia following arterial injury. atRA-POC membranes were prepared and characterized for atRA release via high-performance liquid chromatography with mass spectrometry detection. Rat adventitial fibroblasts (AF) and vascular smooth muscle cells (VSMC) were exposed to various concentrations of atRA; proliferation, apoptosis, and necrosis were assessed in vitro. The rat carotid artery balloon injury model was used to evaluate the impact of the atRA-POC membranes on neointimal formation, cell proliferation, apoptosis, macrophage infiltration, and vascular cell adhesion molecule 1 (VCAM-1) expression in vivo. atRA-POC membranes released 12 µg of atRA over 2 wk, with 92% of the release occurring in the first week. At 24 h, atRA (200 µmol/l) inhibited [(3)H]-thymidine incorporation into AF and VSMC by 78% and 72%, respectively (*P = 0.001), with negligible apoptosis or necrosis. Histomorphometry analysis showed that atRA-POC membranes inhibited neointimal formation after balloon injury, with a 56%, 57%, and 50% decrease in the intimal area, intima-to-media area ratio, and percent stenosis, respectively (P = 0.001). atRA-POC membranes had no appreciable effect on apoptosis or proliferation at 2 wk. Regarding biocompatibility, we found a 76% decrease in macrophage infiltration in the intima layer (P < 0.003) in animals treated with atRA-POC membranes, with a coinciding 53% reduction in VCAM-1 staining (P < 0.001). In conclusion, perivascular delivery of atRA inhibited neointimal formation and restenosis. These data suggest that atRA-POC membranes may be suitable as localized therapy to inhibit neointimal hyperplasia following open cardiovascular procedures.


Assuntos
Túnica Adventícia/efeitos dos fármacos , Lesões das Artérias Carótidas/terapia , Artéria Carótida Primitiva/efeitos dos fármacos , Estenose das Carótidas/terapia , Citratos/química , Portadores de Fármacos , Membranas Artificiais , Neointima , Polímeros/química , Tretinoína/administração & dosagem , Túnica Adventícia/metabolismo , Túnica Adventícia/patologia , Animais , Apoptose/efeitos dos fármacos , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Estenose das Carótidas/metabolismo , Estenose das Carótidas/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Hiperplasia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Ratos Sprague-Dawley , Recidiva , Fatores de Tempo , Molécula 1 de Adesão de Célula Vascular/metabolismo
9.
J Early Adolesc ; 34(7): 923-939, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-28936023

RESUMO

This study examined the proposal that difficulty understanding one's emotional experiences (i.e., deficits in emotional clarity) would interfere with the formulation of adaptive responses to interpersonal stress, which would then predict depressive symptoms. This process was examined across 3 years (fourth to sixth grade) during early adolescence. Participants included 636 youth (338 girls, 298 boys; X̅ age in fourth grade = 9.95, SD = .37) who completed measures assessing emotional clarity, stress responses, and depressive symptoms. Consistent with the hypothesized model, path analyses revealed that maladaptive interpersonal stress responses partially mediated the prospective contribution of deficits in emotional clarity to depressive symptoms. These findings implicate impairment in emotional understanding as a precursor to emerging interpersonal and psychological difficulties during a developmental stage of heightened vulnerability to depression, the transition to adolescence.

10.
J Clin Child Adolesc Psychol ; 42(4): 508-18, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23215673

RESUMO

Negative inferential style and deficits in emotional clarity have been identified as vulnerability factors for depression in adolescence, particularly when individuals experience high levels of life stress. However, previous research has not integrated these characteristics when evaluating vulnerability to depression. In the present study, a racially diverse community sample of 256 early adolescents (ages 12 and 13) completed a baseline visit and a follow-up visit 9 months later. Inferential style, emotional clarity, and depressive symptoms were assessed at baseline, and intervening life events and depressive symptoms were assessed at follow-up. Hierarchical linear regressions indicated that there was a significant three-way interaction between adolescents' weakest-link negative inferential style, emotional clarity, and intervening life stress predicting depressive symptoms at follow-up, controlling for initial depressive symptoms. Adolescents with low emotional clarity and high negative inferential styles experienced the greatest increases in depressive symptoms following life stress. Emotional clarity buffered against the impact of life stress on depressive symptoms among adolescents with negative inferential styles. Similarly, negative inferential styles exacerbated the impact of life stress on depressive symptoms among adolescents with low emotional clarity. These results provide evidence of the utility of integrating inferential style and emotional clarity as constructs of vulnerability in combination with life stress in the identification of adolescents at risk for depression. They also suggest the enhancement of emotional clarity as a potential intervention technique to protect against the effects of negative inferential styles and life stress on depression in early adolescence.


Assuntos
Cognição , Depressão/psicologia , Transtorno Depressivo/psicologia , Emoções , Estresse Psicológico/psicologia , Adolescente , Criança , Depressão/diagnóstico , Transtorno Depressivo/diagnóstico , Feminino , Seguimentos , Humanos , Acontecimentos que Mudam a Vida , Masculino , Fatores de Risco , Inquéritos e Questionários
11.
Cogn Emot ; 27(1): 63-84, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22775344

RESUMO

Recent work has identified behavioural approach system (BAS) sensitivity as a risk factor for the first onset and recurrence of mood episodes in bipolar disorder, but little work has evaluated risk factors for depression in individuals at risk for, but without a history of, bipolar disorder. The present study evaluated cognitive styles and the emotion-regulatory characteristics of emotional clarity and ruminative brooding as prospective predictors of depressive symptoms in individuals with high versus moderate BAS sensitivity. Three separate regressions indicated that the associations between dysfunctional attitudes, self-criticism, and neediness with prospective increases in depressive symptoms were moderated by emotional clarity and brooding. Whereas brooding interacted with these cognitive styles to exacerbate their impact on depressive symptoms, emotional clarity buffered against their negative impact. These interactions were specific to high-BAS individuals for dysfunctional attitudes, but were found across the full sample for self-criticism and neediness. These results indicate that emotion-regulatory characteristics and cognitive styles may work in conjunction to confer risk for and resilience against depression, and that some of these relationships may be specific to individuals at risk for bipolar disorder.


Assuntos
Transtorno Bipolar/diagnóstico , Depressão , Adolescente , Afeto , Atitude , Transtorno Bipolar/psicologia , Cognição , Emoções , Feminino , Humanos , Masculino , Modelos Psicológicos , Personalidade , Philadelphia , Análise de Regressão , Medição de Risco , Autoavaliação (Psicologia) , Adulto Jovem
12.
J Med Chem ; 66(18): 13116-13134, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37702400

RESUMO

Bromodomains are acetyl-lysine binding modules that are found in different classes of chromatin-interacting proteins. Among these are large chromatin remodeling complexes such as BAF and PBAF (variants of human SWI/SNF). Previous work has identified chemical probes targeting a subset of the bromodomains present in the BAF and PBAF complexes. Selective inhibitors of the individual bromodomains have proven challenging to discover, as the domains are highly similar. Here, elaboration of an aminopyridazine scaffold used previously to develop probes for the bromodomains of SMARCA2, SMARCA4, and the fifth bromodomain of PBRM1 yielded compounds with both potency and unusual selectivity for the second bromodomain of PBRM1. One of these, GNE-235, and its enantiomer control GNE-234 are suggested for initial cellular investigations of the function of the second bromodomain of PBRM1.


Assuntos
Proteínas que Contêm Bromodomínio , DNA Helicases , Proteínas Nucleares , Humanos , Proteínas de Ligação a DNA , Domínios Proteicos , Fatores de Transcrição , Proteínas que Contêm Bromodomínio/antagonistas & inibidores
13.
J Comp Eff Res ; 12(9): e230066, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37531245

RESUMO

Aim: Patients with polycythemia vera (PV), a rare and chronic blood cancer, are at a higher risk for thromboembolic events, progression to myelofibrosis, and leukemic transformation. In 2021, ropeginterferon alfa-2b-njft (BESREMi®) was approved in the US to treat adults with PV. The purpose of this study is to estimate the cost-effectiveness of ropeginterferon alfa-2b-njft, used as a first- or second-line treatment, for the treatment of patients with PV in the US. Materials & methods: A Markov cohort model was developed from the healthcare system perspective in the United States. Model inputs were informed by the PROUD-PV and CONTINUATION-PV studies and published literature. The model population included both low-risk and high-risk patients with PV. The model compared ropeginterferon alfa-2b-njft used either as first- or second-line versus an alternative treatment pathway of first-line hydroxyurea followed by ruxolitinib. Results: Over the modeled lifetime, ropeginterferon alfa-2b-njft provided an additional 0.4 higher quality-adjusted life years (QALYs) and 0.4 life-years with an added cost of USD60,175, resulting in a cost per QALY of USD141,783. The model was sensitive to treatment costs, the percentage of patients who discontinue hydroxyurea, the percentage of ropeginterferon alfa-2b-njft users who switch to monthly dosing, the percentage of ropeginterferon alfa-2b-njft users as 2nd line treatment, and the treatment response rates. A younger patient age at baseline and a higher percentage of patients with low-risk disease improved the cost-effectiveness of ropeginterferon alfa-2b-njft. Conclusion: Ropeginterferon alfa-2b-njft is a cost-effective treatment option for a broad range of patients with PV, including both low- and high-risk patients and patients with and without prior cytoreductive treatment with hydroxyurea.


Assuntos
Policitemia Vera , Adulto , Humanos , Policitemia Vera/tratamento farmacológico , Interferon-alfa/uso terapêutico , Hidroxiureia , Interferon alfa-2/uso terapêutico , Análise Custo-Benefício
14.
Arthrosc Sports Med Rehabil ; 4(2): e617-e622, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35494267

RESUMO

Purpose: To compare the repair strength, gap formation, and mode of failure between endoscopic and open double-row gluteus medius repairs in a cadaveric model. Methods: Six pairs of fresh-frozen human cadavers were used in this study. Gluteus medius tears were created in an open fashion and then repaired with either open or endoscopic techniques. Specimens were manually preloaded to 5 N, then cycled between 20-50 N for 150 cycles s. Then, a ramp to/s. Specimens were then returned to 10 N and ramped to failure at 1 mm/s. Gap formation and strengths of the construct were compared for the 2 techniques. Results: Biomechanical testing resulted in no significant differences in ultimate load (P = .86) or gap formation (P > .10) between groups. Ninety-two percent of specimens failed near the muscle origin on the ilium. Conclusions: This study shows that both open and endoscopic gluteus medius repairs are stronger than the muscle-bone interface in a cadaveric model and loaded biomechanically in tension between the ilium origin and femoral insertion. Further, endoscopic technique is able to replicate open, knotless gluteus medius repair technique in terms of gap formation in physiologic (i.e., subfailure) cyclic loading. Clinical Relevance: Gluteus medius tendinopathy is an increasingly common recognized etiology of lateral hip pain. When tears occur, debate exists over whether open or endoscopic repair procedures are optimal. Double-row endoscopic gluteus medius repair with knotless suture anchors may be an alternative to open repair.

15.
J Med Chem ; 65(16): 11177-11186, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35930799

RESUMO

Bromodomains are acetyllysine recognition domains present in a variety of human proteins. Bromodomains also bind small molecules that compete with acetyllysine, and therefore bromodomains have been targets for drug discovery efforts. Highly potent and selective ligands with good cellular permeability have been proposed as chemical probes for use in exploring the functions of many of the bromodomain proteins. We report here the discovery of a class of such inhibitors targeting the family VIII bromodomains of SMARCA2 (BRM) and SMARCA4 (BRG1), and PBRM1 (polybromo-1) bromodomain 5. We propose one example from this series, GNE-064, as a chemical probe for the bromodomains SMARCA2, SMARCA4, and PBRM1(5) with the potential for in vivo use.


Assuntos
DNA Helicases , Fatores de Transcrição , Proteínas de Ligação a DNA , Humanos , Proteínas Nucleares , Domínios Proteicos
16.
Child Dev ; 82(5): 1518-1530, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21765534

RESUMO

Little is known about individual differences in how children respond to peer aggression. This research explored the contribution of social goal orientation, specifically development goals (improving social skills and relationships), demonstration-approach goals (gaining positive judgments), and demonstration-avoidance goals (minimizing negative judgments). Children (M age = 7.97, SD = .34) were followed from 2(nd) to 3(rd) grade. Validity of the social goal orientation construct was established through correlations with situation-specific goals and social adjustment. Development goals predicted adaptive responses (more effortful engagement, problem solving, advice seeking; fewer involuntary responses); demonstration goals predicted maladaptive responses (less effortful engagement, problem solving; more disengagement, retaliation). This study contributes to theoretical understanding of the process of peer aggression and interventions to promote optimal social health.

17.
Child Dev ; 82(5): 1518-30, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21883154

RESUMO

This research explored the contribution of social goal orientation, specifically, development (improving social skills and relationships), demonstration-approach (gaining positive judgments), and demonstration-avoidance (minimizing negative judgments). Children (N = 373; M age = 7.97, SD = .34) were followed from 2nd to 3rd grades. Validity of the social goal orientation construct was established through correlations with situation-specific goals and social adjustment. Development goals predicted adaptive responses (more effortful engagement, problem solving, advice seeking; fewer involuntary responses); demonstration goals predicted maladaptive responses (less effortful engagement, problem solving; more disengagement, retaliation). This study contributes to theoretical understanding of the process of peer aggression and interventions to promote optimal social health.


Assuntos
Agressão/psicologia , Objetivos , Relações Interpessoais , Grupo Associado , Autoimagem , Identificação Social , Aprendizagem da Esquiva , Criança , Vítimas de Crime/psicologia , Feminino , Humanos , Julgamento , Estudos Longitudinais , Masculino , Determinação da Personalidade , Resolução de Problemas , Estudos Prospectivos , Comportamento Social , Percepção Social , Apoio Social , Socialização , Técnicas Sociométricas
18.
J Orthop Trauma ; 35(10): 512-516, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33512862

RESUMO

OBJECTIVES: To review a large, multicenter experience to identify the current salvage and amputation rates of these combined injuries and, where possible, the variables that predict amputation. DESIGN: Retrospective. SETTING: Nine trauma centers. PATIENTS: This study involved 199 patients presenting to 9 trauma centers with orthopaedic and vascular injuries resulting in ischemic limbs for whom the orthopaedic service was involved with the decision for salvage versus amputation. RESULTS: We reviewed 199 patients, 17-85 years of age. One hundred seventy-two of the injuries were open. Thirty-eight patients (19%) were treated with amputation upon admission as they were deemed to be unsalvageable. Of the remaining 161 patients who had attempted salvage, 36 (30%) required late amputation. Closed injuries were successfully salvaged in 25 of 27 cases (93%). The highest rate of amputation was in tibia fractures with a combined amputation rate of 62%. In those attempted to be salvaged, 21 of 48 (44%) required amputation. The ischemia time for successful salvage was significantly less, P = 0.03. One hundred twenty-four patients had their definitive vascular repair before the bony reconstruction. There were 15 vascular complications, of which 13 (86%) had the definitive vascular repair performed before the definitive osseous repair, although this was not statistically significant. CONCLUSIONS: In this series of combined orthopaedic and vascular injuries, we found a high rate of acute and late amputations. It is possible that other protocols, such as shunting and stabilizing the osseous injury, before vascular repair may benefit limb salvage, although this needs more study. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Ortopedia , Lesões do Sistema Vascular , Amputação Cirúrgica , Humanos , Isquemia/diagnóstico , Isquemia/epidemiologia , Isquemia/cirurgia , Salvamento de Membro , Estudos Retrospectivos , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/epidemiologia , Lesões do Sistema Vascular/cirurgia
19.
Cogn Emot ; 24(1): 94-110, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-26273121

RESUMO

This research examined neuropsychological and interpersonal factors that jointly confer vulnerability to youth depression. We proposed that (1) a reduced posterior right hemisphere bias during the processing of facial expressions contributes to subsequent depressive symptoms in youth, and (2) maladaptive responses to interpersonal stress account for this association. Drawing from theory and research indicating sex differences in rates of hemispheric development, we also investigated sex differences in the associations among a reduced posterior right hemisphere bias, maladaptive responses to interpersonal stress, and depressive symptoms. Hypotheses were examined in a longitudinal study of 95 4th - 8th graders (M age = 12.33, SD = 1.10). Results supported the notion that a reduced posterior right hemisphere bias confers vulnerability to depressive symptoms over time in a sex-specific fashion, and implicate maladaptive stress responses as an explanatory mechanism.

20.
J Appl Dev Psychol ; 31(4): 291-297, 2010 07.
Artigo em Inglês | MEDLINE | ID: mdl-22021945

RESUMO

This research investigated the contribution of deficits in emotional clarity to children's socioemotional adjustment. Specifically, this study examined the proposal that deficits in emotional clarity are associated with maladaptive interpersonal stress responses, and that maladaptive interpersonal stress responses act as a mechanism linking deficits in emotional clarity to childhood depressive symptoms. Participants included 345 3(rd) graders (M age = 8.89, SD = .34) assessed at two waves, approximately one year apart; youth completed self-report measures of emotional clarity, responses to interpersonal stress, and depressive symptoms. Results supported the hypothesized process model linking deficits in emotional clarity, maladaptive interpersonal stress responses, and depressive symptoms, adjusting for prior depressive symptoms. Findings have implications for theories of emotional competence and for depression-intervention efforts aimed at fostering emotional understanding and adaptive interpersonal stress responses.

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