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OBJECTIVES: To identify the signs and symptoms that people living with acetabular hip dysplasia (AHD) describe and to provide an aid for translating the findings into practice. METHODS: A three-phased mixed methods study. Phase 1 employed an open-question online survey that enabled people with AHD (aged ≥16 years) to describe features associated with their condition. Responses were thematically analysed. A Phase 2 survey used these themes to establish how common those features were. Phase 3 created a mnemonic that prompts clinicians to suspect AHD. RESULTS: Ninety-eight respondents completed Phase 1 and sixty-two completed Phase 2. From the responses, five themes were identified: Demographic and Diagnostic Profile; Characteristics of Posture and Gait; Pain; Childhood Hip and Family History; and Hip Joint Characteristics. Within these themes, 19 common signs and symptoms were reported, represented by the ALPHA mnemonic. ALPHA describes a young age at onset of problems (Age), a limp (Limp), progressing pain (Pain), a history of childhood and family hip anomalies (History) as well as hip joint hypermobility and instability (Articulation). CONCLUSION: The findings extend current understanding of AHD indicators. ALPHA alerts clinicians to suspect a diagnosis of AHD. ALPHA may facilitate timelier referral of patients for diagnostic X-Ray and appropriate treatment. Future studies should evaluate its clinical utility.
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The rapidly growing body of research investigating media influence on body image in Latin America has not been previously comprehensively synthesised. We systematically reviewed studies of the relationships between media use/influence, body image, and sociocultural appearance ideals in Latin America (CRD42021254607). We searched PsycINFO/Medline, Pubmed, Web of Science, ERIC, Scopus, ProQuest Dissertations, SciElo, and LILACS for quantitative and qualitative peer-reviewed articles and doctoral theses in English, Spanish, and Portuguese. Research conducted in Latin America, published 1991-2023, measuring a) media use/influence, and b) body image or appearance ideals was included. 68 articles met inclusion criteria, and quality appraisal concluded that most were of medium/high quality. A narrative review found consistent quantitative relationships, stronger in women than men, between media use/internalisation of media ideals and both body dissatisfaction and thinner appearance ideals. In contrast, participants in qualitative studies acknowledged media influence on their body image, but perceived greater influence from family and peers. Limitations included a predominance of cross-sectional research from Brazil and Mexico with adolescents and young adults. Additional longitudinal, experimental, and interventional work from elsewhere in Latin America is needed, recruiting more diverse samples and assessing more culturally salient appearance aspects (e.g., skin tone and hair texture).
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BACKGROUND: Little is known about how use patterns of medications for opioid use disorder (MOUDs) evolve from pre-incarceration to post-incarceration among incarcerated individuals with opioid use disorder. This article describes pre- and post-incarceration MOUD receipt during a period when naltrexone was the only type of MOUD offered in a state prison system, the Massachusetts Department of Correction (MADOC). METHODS: A retrospective cohort study of individuals with opioid use disorder who had an incarceration episode in MADOC during January 2015 to March 2019. The data source was the Massachusetts Public Health Data Warehouse, a multi-sector data platform that links individual-level data from multiple statewide datasets. We described patterns of MOUD receipt during the four weeks prior to and after an incarceration episode. Multivariable logistic regression models characterized predictors of post-incarceration MOUD receipt. RESULTS: In the male sample (n=691 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (14.3 % to 18.3 %), naltrexone increased (5.0 % to 10.5 %), and methadone decreased (4.7 % to 1.7 %). Similarly, in the female sample (n=892 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (10.3 % to 12.3 %, naltrexone increased (4.5 % to 9.3 %), and methadone decreased (5.0 % to 2.9 %). Much of the post-release naltrexone receipt occurred among participants in MADOC's pre-release naltrexone program. CONCLUSIONS: MOUD receipt was low but increased slightly in the post-incarceration period. This change was driven by increases in buprenorphine and naltrexone and despite decreases in methadone.
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Encarceramento , Antagonistas de Entorpecentes , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Feminino , Humanos , Masculino , Buprenorfina/uso terapêutico , Estudos de Coortes , Encarceramento/estatística & dados numéricos , Massachusetts/epidemiologia , Metadona/uso terapêutico , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Prisioneiros , Estudos RetrospectivosRESUMO
BACKGROUND: Opioid-related overdose is the leading cause of death for people recently released from incarceration, however treatment with medications for opioid use disorder (MOUD) during incarceration can reduce the mortality risk. This study seeks to qualitatively analyze perceptions of post-release overdose risk from the perspectives of people who received MOUD while incarcerated in one of eight Massachusetts jails during 2021-2022 using the Risk Environment Framework to guide analyses. METHODS: N = 38 participants with lived experience of MOUD treatment during incarceration who are now living in the community were interviewed on factors that may contribute to or protect against post-release overdose risk. Themes were identified inductively and deductively using the Risk Environment Framework and its domains, which organizes themes along physical, social, economic, and policy environments on both the micro- and macro- scales. RESULTS: The physical risk environment included loss of opioid tolerance during incarceration, polysubstance use, and the toxicity of the regional drug supply as key producers of increased risk for post-release overdose. Social drivers of risk included peer group risk norms-including peer-driven harm reduction practices and interpersonal relationships between drug sellers and buyers-as well as macro-level social determinants of health such as housing insecurity and availability of mental health services. Economic drivers of post-release overdose risk included lack of income generation during incarceration and employment challenges. Participants discussed several aspects of policy that contribute to post-release overdose risk, including availability of harm reduction supplies, public health services, and broader policy around MOUD. CONCLUSIONS: The perspectives of people with lived experience are vital to understanding the disproportionate risks of overdose for those recently released from incarceration. Our results highlight the intersectional factors that produce and reproduce the post-release overdose risk environment, providing support for interventions across each domain of the Risk Environment Framework. By capturing perspectives from people with lived experience of OUD and incarceration during this critical period of risk, we can better identify interventions that target and mitigate overdose-related harm in this population.
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Transtornos Relacionados ao Uso de Opioides , Prisioneiros , Humanos , Masculino , Feminino , Adulto , Prisioneiros/psicologia , Massachusetts , Pessoa de Meia-Idade , Overdose de Drogas , Tratamento de Substituição de Opiáceos , Overdose de Opiáceos , Redução do Dano , Analgésicos Opioides , Adulto JovemRESUMO
Previous research on body appreciation across the lifespan has produced conflicting results that it increases with age, decreases with age, or is generally stable with an increase in women over 50-years-old. Furthermore, most of the research has been conducted in White, Western populations. Cross-cultural research suggests that both Chinese and African women experience similar sociocultural pressures as White Western women, and that appearance ideals are shifting to resemble a more Western ideal. We cross-sectionally and cross-culturally examined body appreciation across the lifespan, recruiting White Western women (UK, USA, Canada, and Australia), Black Nigerian women, and Chinese women. 1186 women aged 18-80 completed measures of body appreciation, internalisation of thin and athletic ideals, and perceived sociocultural pressure. Body appreciation did not vary with age in women from any country. Nigerian women reported the highest body appreciation, and Western women the lowest. Higher thin/athletic ideal internalisation, and higher perceived sociocultural pressure were significantly associated with lower body appreciation in all countries and age-groups. Overall, our findings indicate that although levels of body appreciation differ drastically between ethnicities and cultures, it is generally stable across age, and shows cross-culturally robust relationships between sociocultural internalisation and pressure.
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Imagem Corporal , Comparação Transcultural , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Canadá , Adulto Jovem , Imagem Corporal/psicologia , Idoso de 80 Anos ou mais , Estudos Transversais , Nigéria , Estados Unidos , Austrália , Fatores Etários , Reino Unido , População Branca/psicologiaRESUMO
BACKGROUND: Post-traumatic distal limb wounds cause discomfort and heal gradually by second intention. The topical application of Tri-Solfen (lidocaine hydrochloride, bupivacaine hydrochloride, adrenaline acid tartrate and cetrimide [LBAC]) produces effective postsurgical cutaneous analgesia in lambs, calves and piglets; however, its effect on wounds in horses is unknown. METHODS: The antinociceptive effect, measured by mechanical threshold (MT), and the wound healing impacts of LBAC compared with saline were investigated on surgically created 20 × 20 mm distal limb wounds in 10 horses. Treatment was applied once daily for 7 days following wounding on day 0. Mechanical thresholds were measured after treatment on days 1, 2 and 3. Healing was observed for 25 days. RESULTS: The topical application of LBAC immediately following wounding and its reapplication 24 hours later increased the average MT on the first post-traumatic day by 3 Newtons. However, no antinociceptive benefit was observed on days 2 or 3. Treatment with LBAC did not adversely affect wound healing when compared with saline. LIMITATIONS: Methodological differences preclude absolute MT comparisons between studies. The experimental design did not include a model of contaminated or naturally occurring wounds. CONCLUSION: LBAC may provide an early antinociceptive benefit when applied to uncontaminated surgically created wounds without compromising healing.
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Bupivacaína , Epinefrina , Lidocaína , Cicatrização , Animais , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Lidocaína/farmacologia , Cicatrização/efeitos dos fármacos , Cavalos , Epinefrina/administração & dosagem , Bupivacaína/administração & dosagem , Masculino , Cetrimônio , Administração Tópica , Feminino , Analgésicos/uso terapêutico , Analgésicos/administração & dosagem , Resultado do Tratamento , Ferimentos e Lesões/veterinária , Ferimentos e Lesões/tratamento farmacológico , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Anestésicos Locais/farmacologia , Pele/lesões , Pele/efeitos dos fármacos , Combinação de MedicamentosRESUMO
Background and Objectives: Patent foramen ovale (PFO) is present in approximately 25% of adult population. The prevalence of PFO is high in patients with cryptogenic stroke suggesting paradoxical embolism. PFO closure in carefully selected patients is an effective secondary preventive strategy in these patients. We report predictors of management recommendations by the multidisciplinary Board and their impact on outcomes. Methods: Brain-Heart Board comprises vascular and interventional neurology and cardiology subspecialties (structural, electrophysiology, and cardiac imaging). Adult patients referred to the Board for consideration of PFO closure between October 2017 to March 2021 were included in this retrospective cohort analysis. Demographics, comorbid conditions, risk of paradoxical embolism (RoPE) score, event frequencies (transient ischemic attack [TIA] or stroke, intracranial hemorrhage [ICH], post-PFO closure cardiac arrhythmias), and modified Rankin Scale (mRS) at 1 year were compared between the groups (PFO closure vs medical management). Multivariable logistic regression was used to identify factors associated with management recommendation and chi-square tests to test differences in outcomes for patients according to management. Results: Two hundred seventy patients (229 stroke; 41 TIA) were discussed by the Board for PFO closure. 119 (44.0%) patients were recommended for PFO closure of which 117 (98.3%) had evidence of ischemic infarct on imaging. In univariate analysis, age was similar (50 ± 11.9 vs 52 ± 12.8, p = 0.17), but RoPE score was higher in closure as compared with the medical management group (6 [IQR 5-7] vs 5 [IQR 4-7], p < 0.05). In multivariable analysis, TIA as the index event was an independent predictor of Board recommendation against PFO closure (OR 0.05, 95% CI 0.01-0.19, p < 0.05). Event frequency was low in both cohorts (5.9% vs 4.8%, p > 0.05) and comprised cardiac arrhythmias (6 cases of atrial fibrillation and 1 ICH in closure group; 1 TIA and 1 recurrent stroke in medical management group). Excellent functional outcome (mRS 0-1) was similar in both cohorts (66.3% vs 70.7%, p > 0.05) at 1 year. Discussion: Multidisciplinary Brain-Heart Board provides a clinical practice model of collaborative care to ensure proper patient selection for PFO closure. TIA as the index event is associated with recommendation of medical management by the multidisciplinary Brain-Heart Board.
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PURPOSE: The purpose of the study was to examine financial well-being among a diverse population of individuals with and without diabetes. METHODS: Data from the Understanding America Survey, a nationally representative, longitudinal panel, were utilized to identify adults with self-reported diabetes diagnoses between 2014 and 2020. We used longitudinal mixed effects regression models to assess the association between diabetes and financial well-being score (FWBS) among racial and ethnic population subgroups. Models included sex, age, marital status, household size, income, education, race/ethnicity, insurance, body mass index, employment, and health insurance, incorporating individual- and household-level fixed effects. Racial and ethnic differentials were captured using group-condition interactions. RESULTS: Black participants (17.06%) had the highest prevalence of diabetes, followed by White participants (12.2%), "other" racial groups (10.7%), and Hispanic participants (10.0%). In contrast, White participants (M = 67.66, SD = 22.63) and other racial groups (M = 67.99, SD = 18.45) had the highest FWBSs, followed by Hispanic participants (M = 59.31, SD = 22.78) and Black participants (M = 55.86, SD = 25.67). Compared to White participants, Black participants (ß = -5.49, SE = 0.71) and Hispanic participants (ß = -2.06, SE = 0.63) have significantly lower FWBSs. Compared to males, females (ß = -3.25, SE = 0.41) had lower FWBSs among individuals with diabetes. FWBSs of individuals with diabetes was 2.71 points lower (SE = 0.52), on average, than those without diabetes. Education, household size, age, marital status, and income were also significantly associated with FWBSs. CONCLUSIONS: Findings suggest potential disparities in the financial ramifications of diabetes among socially marginalized populations.
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Background: The ability to meet current and ongoing financial obligations, known as financial well-being (FWB), is not only associated with the likelihood of adverse health events but is also affected by unexpected health care expenditures. However, the relationship between FWB and common health outcomes is not well understood. Using data available in the Financial Well-Being Scale from the Consumer Financial Protection Bureau, we evaluated the impact of four vascular conditions-cardiovascular disease (CVD), stroke, high blood pressure (BP), and high cholesterol-on FWB and how these impacts varied between racial and ethnic groups. Methods: Using the Understanding America Survey-a nationally representative, longitudinal panel-we identified adults with self-reported diagnoses between 2014 and 2020 of high cholesterol, high BP, stroke, and CVD. We used stratified, longitudinal mixed regression models to assess the association between these diagnoses and FWB. Each condition was modeled separately and included sex, age, marital status, household size, income, education, race/ethnicity, insurance, body mass index, and an indicator of the condition. Racial and ethnic differentials were captured using group-condition interactions. Results: On average, Whites had the highest FWB Scale score (69.0, SD=21.8), followed by other races (66.7, SD=21.0), Hispanics (59.3, SD=21.6), and Blacks (56.2, SD=21.4). In general, FWB of individuals with vascular conditions was lower than that of those without, but the impact varied between racial and ethnic groups. Compared with Whites (the reference group), Blacks with CVD (-7.4, SD=1.0), stroke (-8.1, SD=1.5), high cholesterol (-5.7, SD=0.7), and high BP (6.1, SD=0.7) had lower FWB. Similarly, Hispanics with high BP (-3.0, SD=0.6) and CVD (-6.3, SD=1.3) had lower FWB. Income, education, insurance, and marital status were also correlated with FWB. Conclusions: These results indicated differences in the financial ramifications of vascular conditions among racial and ethnic groups. Findings suggest the need for interventions targeting FWB of individuals with vascular conditions, particularly those from minority groups.
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Hispânico ou Latino , Humanos , Feminino , Masculino , Hispânico ou Latino/estatística & dados numéricos , Hispânico ou Latino/psicologia , Pessoa de Meia-Idade , Estados Unidos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Negro ou Afro-Americano/psicologia , Estudos Longitudinais , Idoso , Doenças Cardiovasculares/etnologia , Doenças Vasculares/etnologia , Acidente Vascular Cerebral/etnologia , Hipertensão/etnologiaRESUMO
The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion and the coordination of movement across cells. Leader cells along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their coordinated direction of migration across multiple cells. Despite the observed importance of mechanical cues in leader cell formation and in controlling coordinated directionality of cell migration, the underlying biophysical mechanisms remain elusive. The mechanically-activated ion channel PIEZO1 was recently identified to play an inhibitory role during the reepithelialization of wounds. Here, through an integrative experimental and mathematical modeling approach, we elucidate PIEZO1's contributions to collective migration. Time-lapse microscopy reveals that PIEZO1 activity inhibits leader cell formation at the wound edge. To probe the relationship between PIEZO1 activity, leader cell formation and inhibition of reepithelialization, we developed an integrative 2D continuum model of wound closure that links observations at the single cell and collective cell migration scales. Through numerical simulations and subsequent experimental validation, we found that coordinated directionality plays a key role during wound closure and is inhibited by upregulated PIEZO1 activity. We propose that PIEZO1-mediated retraction suppresses leader cell formation which inhibits coordinated directionality between cells during collective migration.
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Canais Iônicos , Queratinócitos , Movimento Celular/fisiologiaRESUMO
INTRODUCTION: Traditionally, the study of aphasia focused on brain trauma, clinical biomarkers, and cognitive processes, rarely considering the social determinants of health. This study evaluates the relationship between aphasia impairment and demographic, socioeconomic, and contextual determinants among people with aphasia (PWA). METHODS: PWA indexed within AphasiaBank-a database populated by multiple clinical aphasiology centers with standardized protocols characterizing language, neuropsychological functioning, and demographic information-were matched with respondents in the Medical Expenditure Panel Survey based on response year, age, sex, race, ethnicity, time post stroke, and mental health status. Generalized log-linear regression models with bootstrapped standard errors evaluated the association between scores on the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R AQ) and demographic, economic, and contextual characteristics accounting for clustering of respondents and the stratification of data collection. Region, age, and income specific models tested the sensitivity of results. RESULTS: PWA over age 60 had 2.4% (SE = 0.020) lower WAB-R AQ scores compared with younger PWA. Compared to White PWA, Black and Hispanic PWA had 4.7% (SE = 0.03) and 0.81% (SE = 0.06) lower WAB-R AQ scores, respectively, as did those and living in the Southern US (-2.2%, SE = 0.03) even after controlling for age, family size, and aphasia type. Those living in larger families (ß = 0.005, SE = 0.008), with income over $30,000 (ß = 0.017, SE = 0.022), and a college degree (ß = 0.030, SE = 0.035) had higher WAB-R AQ relative to their counterparts. Region-specific models showed that racial differences were only significant in the South and Midwest, while ethnic differences are only significant in the West. Sex differences only appeared in age-specific models. Racial and ethnic differences were not significant in the high-income group regression. CONCLUSION: These findings support evidence that circumstances in which individuals live, work, and age are significantly associated with their health outcomes including aphasia impairment.
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Afasia , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Determinantes Sociais da Saúde , Afasia/complicações , Acidente Vascular Cerebral/complicações , IdiomaRESUMO
Importance: Agonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone. Objective: To evaluate postrelease outcomes after buprenorphine implementation. Design, Setting, and Participants: This cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024. Exposure: April 2019 implementation of buprenorphine during incarceration. Main Outcomes and Measures: Receipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation. Results: A total of 15â¯225 individuals were included. In the male sample there were 14â¯582 releases among 12â¯688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected. Conclusions and Relevance: In this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.
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Buprenorfina , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Feminino , Masculino , Humanos , Adulto , Prisões , Naltrexona , Estudos de Coortes , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Metadona/uso terapêutico , Buprenorfina/uso terapêuticoRESUMO
PURPOSE: Pepinemab, a humanized IgG4 monoclonal antibody, targets the SEMA4D (CD100) antigen to inhibit binding to its high-affinity receptors (plexin B1/PLXNB1, plexin B2/PLXNB2) and low-affinity receptor (CD72). SEMA4D blockade leads to increased cytotoxic T-cell infiltration, delayed tumor growth, and durable tumor rejection in murine tumor models. Pepinemab was well tolerated and improved T cell infiltration in clinical studies in adults with refractory tumors. SEMA4D was identified as a strong candidate proto-oncogene in a model of osteosarcoma. Based on these preclinical and clinical data, we conducted a phase 1/2 study to determine the recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics, and immunogenicity, of pepinemab in pediatric patients with recurrent/refractory solid tumors, and activity in osteosarcoma. EXPERIMENTAL DESIGN: Pepinemab was administered intravenously on Days 1 and 15 of a 28-day cycle at 20 mg/kg, the adult RP2D. Part A (phase 1) used a Rolling 6 design; Part B (phase 2) used a Simon 2-stage design in patients with osteosarcoma. Pharmacokinetics and target saturation were evaluated in peripheral blood. RESULTS: Pepinemab (20 mg/kg) was well tolerated and no dose-limiting toxicities were observed during Part A. There were no objective responses. Two patients with osteosarcoma achieved disease control and prolonged stable disease. Pepinemab pharmacokinetics were similar to adults. CONCLUSIONS: Pepinemab (20 mg/kg) is safe, well tolerated and resulted in adequate and sustained target saturation in pediatric patients. Encouraging disease control in two patients with osteosarcoma warrants further investigation with novel combination strategies to modulate the tumor microenvironment and antitumor immune response. CLINICAL TRIAL REGISTRY: This trial is registered as NCT03320330 at Clinicaltrials.gov. DISCLAIMER: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Recidiva Local de Neoplasia , Neoplasias , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Dose Máxima Tolerável , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologiaRESUMO
BACKGROUND: NULevel was a randomized control trial to evaluate a technology-assisted weight loss maintenance (WLM) program in the UK. The program included: (a) a face-to-face goal-setting session; (b) an internet platform, a pedometer, and wirelessly connected scales to monitor and report diet, physical activity, and weight, and; (c) regular automated feedback delivered by mobile phone, tailored to participants' progress. Components were designed to target psychological processes linked to weight-related behavior. Though intervention participants showed increased physical activity, there was no difference in WLM between the intervention and control groups after 12 months (Sniehotta FF, Evans EH, Sainsbury K, et al. Behavioural intervention for weight loss maintenance versus standard weight advice in adults with obesity: A randomized controlled trial in the UK (NULevel Trial). PLoS Med. 2019; 16(5):e1002793. doi:10.1371/journal.pmed.1002793). It is unclear whether the program failed to alter targeted psychological processes, or whether changes in these processes failed to influence WLM. PURPOSE: We evaluate whether the program influenced 16 prespecified psychological processes (e.g., self-efficacy and automaticity toward diet and physical activity), and whether these processes (at 6 months) were associated with successful WLM (at 12 months). METHODS: 288 adults who had previously lost weight were randomized to the intervention or control groups. The control group received wireless scales and standard advice via newsletters. Assessments occurred in person at 0, 6, and 12 months. RESULTS: The intervention significantly altered 10 of the 16 psychological processes, compared with the control group. However, few processes were associated with WLM, leading to no significant indirect effects of the intervention via the processes on WLM. CONCLUSIONS: Changes in targeted processes were insufficient to support WLM. Future efforts may more closely examine the sequence of effects between processes, behavior, and WLM.
Many tools exist to help people lose weight, but it is common for people to regain that weight over time. Thus, understanding how to support the maintenance of weight loss remains a priority. The NULevel program was a 12-month weight loss maintenance (WLM) intervention for individuals who had recently lost weight. It promoted psychological factors, shown to be tied to weight-related behaviors, using face-to-face and technology-based (e.g., mobile phone feedback) elements. For example, the program encouraged making plans to improve lifestyles (e.g., exercise, better diet) and promoted people's confidence in these behaviors. However, the program was not more successful than a control condition in maintaining weight loss. We sought to understand why this occurred. We found that the program was indeed successful in influencing most of the psychological factors it targeted. Instead, it was the psychological factors that failed to predict WLM. Were the psychological factors insufficient to impact behavior? Or did the promoted behaviors fail to aid WLM? Future research should focus on answering such questions. Doing so would inform whether interventions should target different psychological factors to change behaviors, or choose different sets of behaviors to support WLM.
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Obesidade , Programas de Redução de Peso , Adulto , Humanos , Obesidade/terapia , Obesidade/psicologia , Redução de Peso , Exercício Físico , DietaRESUMO
BACKGROUND: Implementation of medications for opioid use disorder (MOUD) in jails varies by facility and across states. Organizational climate, including staff attitudes toward change and exposure to education, can influence perceptions of innovations like MOUD in jails. Using a mixed methods design, we aimed to understand the association between organizational climate and jail staff perceptions of MOUD. METHODS: Jail staff (n = 111) who operate MOUD programs in 6 Massachusetts jails completed surveys that included the Organizational Readiness for Implementing Change (ORIC) survey. Random effects logistic regression models assessed associations between organizational climate and several outcomes of perceived MOUD efficacy, acceptability, and knowledge, while controlling for covariates. Jail staff (N = 61) participated in qualitative interviews and focus groups focused on organizational climate and knowledge diffusion, which we analyzed using inductive and deductive methods. RESULTS: The results indicate that organizational change readiness on the ORIC was associated with positive perceptions of MOUD, and educational resources facilitated MOUD implementation. Greater ORIC was associated with higher perception of methadone as highly acceptable for jail populations (Odds ratio [OR] 2.3, 95% Confidence Interval [CI] 1.2 to 4.4), and high knowledge of methadone (OR 2.3, 95% CI 1.1 to 4.9), with similar magnitude of effects for buprenorphine. High levels of training for jail staff on methadone and buprenorphine were also associated with higher knowledge of these medications (Methadone: OR 7.2, 95% CI 2.2 to 23.2; Buprenorphine: OR 3.4, 95% CI 1.2 to 9.5). Qualitative results point towards the importance of organizational climate and elucidate educational strategies to improve staff perceptions of MOUD. CONCLUSION: Results underscore the importance of organizational climate for successful implementation of jail MOUD programs and provide support for medication-specific educational resources as a facilitator of successful MOUD implementation in jail settings. Findings highlight implementation strategies that may improve jail staff perceptions of MOUD.
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Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Prisões Locais , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Metadona/uso terapêutico , Atitude do Pessoal de Saúde , Buprenorfina/uso terapêutico , Tratamento de Substituição de Opiáceos , Analgésicos OpioidesRESUMO
PIEZO1 channels play a critical role in numerous physiological processes by transducing diverse mechanical stimuli into electrical and chemical signals. Recent studies underscore the importance of endogenous PIEZO1 activity and localization in regulating mechanotransduction. To enable physiologically and clinically relevant human-based studies, we genetically engineered human induced pluripotent stem cells (hiPSCs) to express a HaloTag fused to endogenous PIEZO1. Combined with super-resolution imaging, our chemogenetic approach allows precise visualization of PIEZO1 in various cell types. Further, the PIEZO1-HaloTag hiPSC technology allows non-invasive monitoring of channel activity via Ca2+-sensitive HaloTag ligands, with temporal resolution approaching that of patch clamp electrophysiology. Using lightsheet imaging of hiPSC-derived neural organoids, we also achieve molecular scale PIEZO1 imaging in three-dimensional tissue samples. Our advances offer a novel platform for studying PIEZO1 mechanotransduction in human cells and tissues, with potential for elucidating disease mechanisms and development of targeted therapeutics.