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1.
Immunity ; 50(3): 655-667.e4, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893588

RESUMO

Restoration of barrier-tissue integrity after injury is dependent on the function of immune cells and stem cells (SCs) residing in the tissue. In response to skin injury, hair-follicle stem cells (HFSCs), normally poised for hair generation, are recruited to the site of injury and differentiate into cells that repair damaged epithelium. We used a SC fate-mapping approach to examine the contribution of regulatory T (Treg) cells to epidermal-barrier repair after injury. Depletion of Treg cells impaired skin-barrier regeneration and was associated with a Th17 inflammatory response and failed HFSC differentiation. In this setting, damaged epithelial cells preferentially expressed the neutrophil chemoattractant CXCL5, and blockade of CXCL5 or neutrophil depletion restored barrier function and SC differentiation after epidermal injury. Thus, Treg-cell regulation of localized inflammation enables HFSC differentiation and, thereby, skin-barrier regeneration, with implications for the maintenance and repair of other barrier tissues.


Assuntos
Diferenciação Celular/fisiologia , Quimiocina CXCL5/metabolismo , Epiderme/metabolismo , Folículo Piloso/metabolismo , Interleucina-17/metabolismo , Regeneração/fisiologia , Linfócitos T Reguladores/metabolismo , Animais , Células Epidérmicas/metabolismo , Células Epiteliais/metabolismo , Cabelo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-38615728

RESUMO

BACKGROUND & AIMS: Celiac disease (CD) mass screening remains controversial in part because of a paucity of data to support its benefit. The Autoimmunity Screening for Kids study is a mass screening study for pediatric CD and type 1 diabetes in Colorado. METHODS: This study prospectively follows up children ages 1 to 17 years who screened positive for tissue transglutaminase IgA autoantibodies in the Autoimmunity Screening for Kids study subsequently referred for diagnostic evaluation. Children diagnosed with CD by biopsy or serologic criteria were included in this study. Evaluation at baseline and 12 month follow-up evaluation included demographics, laboratory studies, symptoms, health-related quality of life, anxiety/depression, and gluten-free diet adherence. Paired Student t test, chi-square, and Wilcoxon sign rank tests compared baseline and follow-up data. For symptom scores, odds of improvement were assessed. RESULTS: Of the 52 children with CD enrolled, 42 children completed 12-month follow-up evaluation. On the symptom questionnaire completed at diagnostic evaluation, 38 of 42 children reported 1 or more symptoms. CD mean symptom severity and frequency scores improved from baseline to follow-up evaluation (P < .001). Reported health-related quality of life scores improved among caregivers (P = .002). There was no significant change in reported anxiety or depression. Iron deficiency without anemia was common at baseline (21 of 24 children; 87.5%) and normalized at follow-up evaluation (11 of 21 children; 52.3%). Twenty-six of 28 families reported good or excellent gluten-free diet adherence. CONCLUSIONS: This novel study of children with CD identified through a mass screening program demonstrated improvement in symptoms, quality of life, and iron deficiency after 1 year follow-up evaluation. This demonstrates that there may be benefit to CD mass screening.

3.
Am J Gastroenterol ; 119(2): 374-377, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37787442

RESUMO

INTRODUCTION: We evaluated the associations between celiac disease (CD) prevalence and regional sociodemographic variables in the United States. METHODS: The outcome was CD relative prevalence, defined as number of patients with CD among those in a Medicare registry per 3-digit ZIP code. Linear regression models assessed associations between relative prevalence of CD and sociodemographic variables. RESULTS: CD relative prevalence was positively correlated with median income, urban area, and proximity to a CD specialty center and negatively correlated with Black race, Latino/Hispanic ethnicity, and median social deprivation index score ( P < 0.01, all). DISCUSSION: CD relative prevalence is associated with indicators of economic advantage.


Assuntos
Doença Celíaca , Fatores Sociodemográficos , Humanos , Negro ou Afro-Americano , Doença Celíaca/epidemiologia , Medicare , Prevalência , Estados Unidos/epidemiologia , Hispânico ou Latino , Privação Social
4.
Am J Gastroenterol ; 118(3): 539-545, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219178

RESUMO

INTRODUCTION: The Environmental Determinants of Diabetes in the Young study follows an HLA risk selected birth cohort for celiac disease (CD) development using a uniform protocol. Children under investigation come from 6 different regions within Europe and the United States. Our aim was to identify regional differences in CD autoimmunity and CD cumulative incidence for children born between 2004 and 2010. METHODS: Children (n = 6,628) with DQ2.5 and/or DQ8.1 were enrolled prospectively from birth in Georgia, Washington, Colorado, Finland, Germany, and Sweden. Children underwent periodic study screening for tissue transglutaminase antibodies and then CD evaluation per clinical care. Population-specific estimates were calculated by weighting the study-specific cumulative incidence with the population-specific haplogenotype frequencies obtained from large stem cell registries from each site. RESULTS: Individual haplogenotype risks for CD autoimmunity and CD varied by region and affected the cumulative incidence within that region. The CD incidence by age 10 years was highest in Swedish children at 3%. Within the United States, the incidence by age 10 years in Colorado was 2.4%. In the model adjusted for HLA, sex, and family history, Colorado children had a 2.5-fold higher risk of CD compared to Washington. Likewise, Swedish children had a 1.4-fold and 1.8-fold higher risk of CD compared with those in Finland and Germany, respectively. DISCUSSION: There is high regional variability in cumulative incidence of CD, which suggests differential environmental, genetic, and epigenetic influences even within the United States. The overall high incidence warrants a low threshold for screening and further research on region-specific CD triggers.


Assuntos
Doença Celíaca , Criança , Humanos , Incidência , Doença Celíaca/epidemiologia , Doença Celíaca/genética , Doença Celíaca/diagnóstico , Predisposição Genética para Doença , Autoanticorpos , Autoimunidade
5.
J Immunol ; 207(7): 1763-1775, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470859

RESUMO

Regulatory T cells (Tregs) reside in nonlymphoid tissues where they carry out unique functions. The molecular mechanisms responsible for Treg accumulation and maintenance in these tissues are relatively unknown. Using an unbiased discovery approach, we identified LAYN (layilin), a C-type lectin-like receptor, to be preferentially and highly expressed on a subset of activated Tregs in healthy and diseased human skin. Expression of layilin on Tregs was induced by TCR-mediated activation in the presence of IL-2 or TGF-ß. Mice with a conditional deletion of layilin in Tregs had reduced accumulation of these cells in tumors. However, these animals somewhat paradoxically had enhanced immune regulation in the tumor microenvironment, resulting in increased tumor growth. Mechanistically, layilin expression on Tregs had a minimal effect on their activation and suppressive capacity in vitro. However, expression of this molecule resulted in a cumulative anchoring effect on Treg dynamic motility in vivo. Taken together, our results suggest a model whereby layilin facilitates Treg adhesion in skin and, in doing so, limits their suppressive capacity. These findings uncover a unique mechanism whereby reduced Treg motility acts to limit immune regulation in nonlymphoid organs and may help guide strategies to exploit this phenomenon for therapeutic benefit.


Assuntos
Proteínas de Transporte/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores de Retorno de Linfócitos/metabolismo , Pele/imunologia , Linfócitos T Reguladores/imunologia , Animais , Proteínas de Transporte/genética , Movimento Celular , Células Cultivadas , Humanos , Tolerância Imunológica , Ativação Linfocitária , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Imunológicos , Especificidade de Órgãos , Receptores de Retorno de Linfócitos/genética , Fator de Crescimento Transformador beta/metabolismo
6.
J Pediatr Gastroenterol Nutr ; 77(4): 532-535, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37438889

RESUMO

Although swallowed topical steroids are effective in inducing histological remission in eosinophilic esophagitis (EoE), their efficacy is limited by treatment nonadherence. In this study, we objectively measured adherence rates to swallowed topical steroids in adolescents with EoE over the course of 8 weeks and analyzed the association between adherence rate, disease and demographic features, symptom severity, and medication-taking habit strength. We found that approximately 20% of adolescents with EoE were over-dosing on their medications. After excluding these patients, mean adherence rate was 67.0% (±19.4%) and median adherence rate was 63% (interquartile range 53%-88%). Adherence was not associated with demographic features, disease history, symptom severity, or quality of life but was associated with habit strength (Pearson r = 0.48, P = 0.04). These findings suggest that habit strength may serve as a potential target for interventions aimed at improving adherence in adolescents with EoE.


Assuntos
Esofagite Eosinofílica , Humanos , Adolescente , Esofagite Eosinofílica/diagnóstico , Fluticasona/uso terapêutico , Qualidade de Vida , Esteroides/uso terapêutico , Administração Oral
7.
J Pediatr Gastroenterol Nutr ; 77(4): 536-539, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37491718

RESUMO

In 2022, the US Food and Drug Administration approved dupilumab for treatment of eosinophilic esophagitis (EoE). The aims of this study were to report physician and patient perspectives on initiating dupilumab. A 2-pronged approach was used: (1) data on physician prescribing practices was gathered via retrospective chart review of EoE patients prescribed dupilumab and (2) pediatric patients on dupilumab were approached to complete a questionnaire regarding reasons for initiation. During this time, 42 patients were prescribed dupilumab. From the physician's perspective, the primary reasons for dupilumab included nonresponse to topical corticosteroids (TCS) (52%), nonadherence (28%), adverse effects (10%), or to treat multiple atopic diseases (5%). The median dupilumab initiation time, from day prescribed to first injection, was 37 days [interquartile range (IQR) 37]. Almost all required prior authorization (PA) (98%), while 17% required letter of appeal and 2% required peer-to-peer. Fifteen patients (36%) completed the questionnaire portion of the study. From the patient's perspective, the primary reasons for dupilumab initiation included nonresponse to TCS (27%), nonadherence to TCS (27%), concern about adverse effects of TCS (7%), and treatment of multiple atopic diseases (33%). In conclusion, physicians are prescribing dupilumab primarily for nonresponse to TCS and almost all required PA with a long delay to starting dupilumab.


Assuntos
Fármacos Dermatológicos , Esofagite Eosinofílica , Humanos , Criança , Esofagite Eosinofílica/tratamento farmacológico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Glucocorticoides/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Avaliação de Resultados da Assistência ao Paciente , Resultado do Tratamento
8.
Environ Monit Assess ; 195(7): 827, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37294356

RESUMO

The Chir-Pine (Pinus roxburghii) and Banj-Oak (Quercus leucotrichophora)-dominated ecosystems of central Himalaya provide significant green services. However, responses of these ecosystems, with respect to ecosystem carbon flux variability, to changing microclimate are not yet studied. Since quantification of ecosystem responses to fluctuation in the microclimate, particularly rainfall, is expected to be beneficial for management of these ecosystems, this study aims (i) to quantify and compare amplitude of rainfall-induced change in the carbon fluxes of Chir-Pine and Banj-Oak-dominated ecosystems using wavelet methods, and (ii) to quantify and compare dissimilarities in the ecosystem exchanges due to varying rainfall spell and amount. Eddy covariance-based continuous daily micrometeorological and flux data, during the 2016-2017 monsoon seasons (total 244 days, 122 days of June-September), from two sites in Uttarakhand, India, are used for this purpose. We find that both Chir-Pine and Banj-Oak-dominated ecosystems are the sinks of carbon, and Chir-Pine-dominated ecosystem sequesters around 1.8 times higher carbon than the Banj-Oak. A systematic enhancement in the carbon assimilation of the Chir-Pine-dominated ecosystem is noted with increasing rainfall spell following a statistically significant power-law relationship. We have also identified a rainfall amount threshold for Chir-Pine and Banj-Oak-dominated ecosystems (10 ± 0.7 and 17 ± 1.2 mm, respectively) that resulted in highest ecosystem carbon assimilation in monsoon. The general inference of this study accentuates that Banj-Oak-dominated ecosystem is more sensitive to maximum rain within a spell whereas the Chir-Pine-dominated ecosystem is more responsive to increasing rainfall spell duration.


Assuntos
Pinus , Quercus , Ecossistema , Quercus/fisiologia , Estações do Ano , Carbono , Árvores/fisiologia , Monitoramento Ambiental , Florestas
9.
J Pediatr Gastroenterol Nutr ; 75(2): 181-185, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35641896

RESUMO

Mental health is a growing concern in pediatric celiac disease (CD). This study utilized the Revised Children's Anxiety and Depression Scale (RCADS) to investigate anxiety and depression symptom rates. Participants were children ages 8 to 17 years (M = 11.7, SD = 2.7; N = 175) with biopsy-proven CD (Median = 1.1 years post-diagnosis, IQR = 0-4) categorized into groups based on the child's age, caregiver or child respondent, presence or absence of comorbidities, and gluten-free diet duration. Self-reported RCADS scores showed 39% of children having clinically significant concerns for anxiety or depression ( P < 0.0001) but only 7% of caregiver-proxy RCADS scores indicated significant concerns for the child's anxiety and 14% for the child's depression. Rates of child-reported anxiety and depression symptoms were significantly higher for those without medical comorbidities than those with ( P = 0.04). Therefore, screening for mental health concerns, particularly anxiety and depression, should be routinely performed in pediatric patients with CD.


Assuntos
Doença Celíaca , Depressão , Adolescente , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Doença Celíaca/complicações , Doença Celíaca/psicologia , Criança , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Humanos , Escalas de Graduação Psiquiátrica
10.
Qual Life Res ; 31(7): 2107-2118, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34984588

RESUMO

PURPOSE: To evaluate the impact of celiac disease (CD) and the gluten-free diet (GFD) on the health-related quality of life (HRQoL) in children with CD in the United States using validated measures. We hypothesize that CD negatively impacts the child and caregivers' HRQoL. METHODS: Participants included children with a confirmed diagnosis of CD and their caregivers (n = 246) seen in a CD multidisciplinary clinic. Caregivers completed the Pediatric Quality of Life (PedsQL) parent-proxy scale to report on their child's HRQoL and the Family Impact Module (FIM), which assesses the impact of caring for a child with a chronic illness. Their children completed the age-appropriate PedsQL. PedsQL and FIM results were compared to published data for children with gastroenterological conditions and a healthy cohort using non-parametric tests. RESULTS: Children with CD reported significantly lower HRQoL than reports from healthy controls across all PedsQL domains (P < 0.001, Cohen d = 0.8), and lower compared to children with other organic gastrointestinal conditions in Social Functioning (P < 0.001, Cohen d = 0.5) and overall Psychosocial Functioning (P < 0.001, Cohen d = 0.3) domains. Results from the caregiver's report on their own HRQoL were significantly worse than that reported by historical controls in the domains of Communication (P < 0.001, Cohen d = 0.3) and Worry (P < 0.001, Cohen d = 0.8), yet similar on all other domains. CONCLUSIONS: In our population, CD is associated with low HRQoL scores for both children and their caregivers. Screening children and families for HRQoL can identify patients and families in need of additional support in this higher-risk population.


Assuntos
Cuidadores , Doença Celíaca , Cuidadores/psicologia , Criança , Dieta Livre de Glúten , Humanos , Pais/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários
11.
Anal Chem ; 93(22): 8054-8061, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34038078

RESUMO

Multicellular spheroids are superior to other culture geometries in reproducing critical physiological conditions of tumors, such as the diffusion of oxygen, nutrients, waste, and drugs, leading to a more precise model of in vivo drug sensitivity and resistance. Previously reported spheroid culture platforms are often difficult to use, expensive, single-use, or mechanically unstable. Here, we report a facile, mechanically stable, high-throughput spheroid culture platform based on hierarchically textured omniphobic surfaces. The developed omniphobic surfaces display very high contact angles with a range of different liquids, including the cell-laden culture media, thereby minimizing the cell surface contact area. Additionally, these surfaces maintain these high contact angles for extended periods of time to ensure cell aggregation. Using this novel platform, we demonstrate the generation and maintenance of robust multicellular spheroids, as well as heterogeneous, multicell-type spheroids. The platform is extremely robust, resistant to mechanical shock, allows for on-plate imaging, and is also the first-ever spheroid generation platform that can be reused repeatedly. Finally, the platform is suitable for on-plate drug screening and enables the first-ever, on-plate immunofluorescence staining and imaging of spheroids.


Assuntos
Neoplasias , Esferoides Celulares , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos
12.
J Pediatr ; 235: 246-252.e1, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33811869

RESUMO

OBJECTIVE: To measure adherence rates to swallowed topical steroids in children with eosinophilic esophagitis (EoE), describe factors related to adherence, and determine the association between adherence, symptoms, perceived disease severity, and quality of life in children with EoE. STUDY DESIGN: Subjects in this cross-sectional study of 117 children between 5 and 18 years old with EoE completed the Pediatric Eosinophilic Esophagitis Symptoms Score V2.0 (PEESS), Pediatric Quality of Life Inventory Eosinophilic Esophagitis Module (PedsQL EoE), a Medication-Taking Checklist (MTC), and a demographics questionnaire. Adherence rate was calculated based on reported number of missed doses/prescribed doses in the last week. Parent-reported measures were used for children aged 5-12 years and self-report was used for children aged 13-18 years. RESULTS: Adolescents had lower adherence rates than younger children (76.2 ± 24.5% vs 88.6 ± 16.7%, P = .002). Adherence rates were not associated with disease history, PEESS, or PedsQL EoE scores but instead correlated with MTC scores (Pearson r of 0.65, P < .001 for child-report and Pearson r of 0.74, P < .001 for parent-report). Symptomatology was associated with worse quality of life (PEESS Frequency: r = -0.7, P < .001; PEESS Severity: r = -0.71, P < .001 for children 5-12 years old; PEESS Frequency: r = -0.61, P < .001; PEESS Severity: r = -.5, P < .001 for adolescents). CONCLUSIONS: Unrelated to their clinical history, demographic factors, symptoms, and quality of life, adolescents with EoE have lower medication adherence rates. The MTC may serve as a clinical tool to discuss adherence and provide targeted educational counseling regarding adherence interventions.


Assuntos
Esofagite Eosinofílica/psicologia , Adesão à Medicação/estatística & dados numéricos , Qualidade de Vida , Índice de Gravidade de Doença , Administração Oral , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Esofagite Eosinofílica/tratamento farmacológico , Humanos , Esteroides/administração & dosagem , Inquéritos e Questionários
13.
Clin Obstet Gynecol ; 64(2): 398-406, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33904845

RESUMO

Mobile applications and telehealth services are being used to unprecedented degrees in maternal and child care, with uncertain impact on population health outcomes. In this article, we will review the role of the COVID-19 pandemic in accelerating large scale implementation of telehealth services, known and anticipated impacts on maternal and child health and related inequities, and potential strategies to optimize outcomes at the population level.


Assuntos
Serviços de Saúde da Criança , Saúde da Criança , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Serviços de Saúde Materna , Telemedicina/métodos , COVID-19/prevenção & controle , Centers for Medicare and Medicaid Services, U.S. , Criança , Serviços de Saúde da Criança/organização & administração , Pré-Escolar , Etnicidade , Feminino , Política de Saúde , Humanos , Lactente , Recém-Nascido , Serviços de Saúde Materna/organização & administração , Grupos Minoritários , Aplicativos Móveis , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Determinantes Sociais da Saúde , Telemedicina/organização & administração , Estados Unidos
14.
J Pediatr Gastroenterol Nutr ; 71(6): 744-748, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32910623

RESUMO

OBJECTIVES: Exclusive enteral nutrition (EEN) is infrequently used in the United States but is an effective treatment for pediatric Crohn disease (CD). Limited data exists regarding patient and parent perspectives on this treatment modality. The aim of this study was to determine parent and provider perspectives regarding EEN and understand parent-cited barriers to its use. METHODS: We surveyed the parents/guardians of children ages 1 through 17 with CD in our institution regarding EEN. Healthcare provider perspectives regarding reason for stopping EEN and those cited by survey respondents were compared using retrospective chart review. RESULTS: One hundred fifteen (62.5%) out of 184 recipients responded to the survey. Ninety percentage of respondents had heard of EEN but of these, 26% had not discussed it with their gastroenterologist. Thirty-eight patients (33%) were treated in the past and 15 (13%) were currently on EEN. Common barriers cited by current EEN users were cost/finances and difficult social situations. Of the children who stopped EEN, most did so as parents felt it was not working (n = 14, 37%). In these cases, their primary gastroenterologist cited treatment failure for 4 cases and nonadherence for 6. CONCLUSIONS: Despite the efficacy of EEN and interest in dietary treatments by patients with CD, there are many barriers surrounding effective communication and successful implementation of dietary therapies. Future research is needed regarding patient-physician communication, cost mitigation, and coping with the social limitations of dietary therapies.


Assuntos
Doença de Crohn , Nutrição Enteral , Atitude Frente a Saúde , Criança , Doença de Crohn/terapia , Humanos , Lactente , Pais , Indução de Remissão , Estudos Retrospectivos
15.
BMC Ophthalmol ; 20(1): 90, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143668

RESUMO

BACKGROUND: To compare vision-related quality of life (VRQOL) between acute and chronic Central serous chorioretinopathy (CSC) and correlate this with Cohen's Perceived Stress Scale (PSS) questionnaire. METHODS: Patients who were diagnosed with both acute and chronic CSC were recruited in this study. Vision-related quality of life (VRQOL) was assessed with Rasch revised National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ25) and perceived stress with Cohen's PSS questionnaire in 118 subjects with either acute or chronic CSC. The quality of life score was compared between patients with acute and chronic CSC. Correlations between the functional score and visual acuity (VA), stage of CSC, and stress were studied. RESULTS: There was no significant difference in VRQOL between Acute and Chronic CSC. In Acute CSC, affected eye VA correlated significantly with near vision question of the visual function subscale. Better eye VA correlated significantly with distance vision, social function, role limitation and dependency of the socioeconomic subscale. In chronic CSC, affected eye VA correlated with social function question of the socioemotional subscale and the better eye VA correlated with driving and distance vision of the visual function subscale. No other significant correlations with VA were noted. No correlations were observed between outcome of Cohen's PSS questionnaire and NEI-VFQ25 scores of acute and chronic CSC. CONCLUSION: The VRQOL is similar between acute and chronic CSC. Perceived stress was not found to influence the VRQOL in CSC.


Assuntos
Coriorretinopatia Serosa Central/psicologia , Qualidade de Vida , Estresse Psicológico/etiologia , Acuidade Visual , Doença Aguda , Adulto , Coriorretinopatia Serosa Central/complicações , Coriorretinopatia Serosa Central/fisiopatologia , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estresse Psicológico/psicologia
16.
J Immunol ; 196(5): 2010-4, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26826250

RESUMO

Foxp3-expressing regulatory T cells (Tregs) reside in tissues where they control inflammation and mediate tissue-specific functions. The skin of mice and humans contain a large number of Tregs; however, the mechanisms of how these cells function in skin remain largely unknown. In this article, we show that Tregs facilitate cutaneous wound healing. Highly activated Tregs accumulated in skin early after wounding, and specific ablation of these cells resulted in delayed wound re-epithelialization and kinetics of wound closure. Tregs in wounded skin attenuated IFN-γ production and proinflammatory macrophage accumulation. Upon wounding, Tregs induce expression of the epidermal growth factor receptor (EGFR). Lineage-specific deletion of EGFR in Tregs resulted in reduced Treg accumulation and activation in wounded skin, delayed wound closure, and increased proinflammatory macrophage accumulation. Taken together, our results reveal a novel role for Tregs in facilitating skin wound repair and suggest that they use the EGFR pathway to mediate these effects.


Assuntos
Receptores ErbB/imunologia , Linfócitos T Reguladores/imunologia , Cicatrização/imunologia , Animais , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Subpopulações de Linfócitos T/imunologia
17.
J Pediatr Gastroenterol Nutr ; 66(3): e67-e70, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28806297

RESUMO

We aimed to determine whether tissue transglutaminase (tTG) autoantibody positivity was associated with dietitian-assessed adherence to a gluten-free diet in pediatric patients with celiac disease and identify areas where adherence falters. We reviewed the records of children with celiac disease who had a standardized evaluation of adherence by a registered dietitian. A negative tTG value was not associated with good adherence (P = NS). Adherent and nonadherent children differed with respect to purposeful and accidental gluten exposure (P < 0.0001), knowledge (P = 0.003), cross-contact (P = 0.003), potential exposure via medications and cosmetics (P = 0.004), and potential exposure while at restaurants (P < 0.0001), but not with respect to potential exposure at school (P = NS). Based on our findings, we suggest that negative tTG levels are not necessarily indicative of good adherence to a gluten-free diet in pediatric patients with celiac disease. A separate assessment of adherence is needed focusing on knowledge, behavior while dining out, and intent to adhere.


Assuntos
Autoanticorpos/sangue , Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Proteínas de Ligação ao GTP/imunologia , Cooperação do Paciente , Transglutaminases/imunologia , Adolescente , Biomarcadores/sangue , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Doença Celíaca/psicologia , Criança , Pré-Escolar , Dieta Livre de Glúten/psicologia , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Nutricionistas , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Proteína 2 Glutamina gama-Glutamiltransferase , Adulto Jovem
18.
J Pediatr Gastroenterol Nutr ; 66(4): 603-608, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28906318

RESUMO

OBJECTIVE: As both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) are associated with malnutrition and feeding dysfunction, this study compares growth, nutrition, and feeding behaviors in children with GERD and EoE. METHODS: Subjects ages 1 to 7 years with GERD or EoE were enrolled in a prospective study. Assessments included length/height, weight, 3-day food diary, serum biomarkers of nutrition, and the Behavioral Pediatric Feeding Assessment Scale. RESULTS: Mean weight-for-length z scores in GERD and EoE children were -0.93 and -1.14 (p = NS) and mean body mass index z scores were 0.29 and -0.13 (P = NS). Vitamin D intake was below the daily recommended intake in GERD subjects. EoE subjects' intake was below daily recommended intake of Vitamin D and calcium. GERD and EoE groups both had normal intake of calories, carbohydrates, proteins, fats, and iron, and normal serum ferritin (25 vs 34 ng/mL), prealbumin (21 vs 20 mg/dL), parathyroid hormone (42 vs 37 pg/mL), and Vitamin D (both 30 ng/mL). Behavioral Pediatric Feeding Assessment Scale problem and frequency scores were similar in GERD and EoE subjects but were higher than those of a historical cohort of healthy controls (Hedges' g of 0.95 and 1.1, respectively). EoE subjects on food allergen restriction diets had significantly less feeding dysfunction than those on regular diets. CONCLUSIONS: As a selected group of children with uncomplicated GERD or EoE were without nutritional deficiencies but had maladaptive feeding, providing anticipatory guidance to minimize mealtime challenges, monitoring for improvement, or referring to a feeding therapist, may be beneficial. A trial of food allergen restriction may provide additional benefit for those with EoE.


Assuntos
Esofagite Eosinofílica/complicações , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Refluxo Gastroesofágico/complicações , Estado Nutricional , Antropometria , Biomarcadores/sangue , Criança , Transtornos da Nutrição Infantil/epidemiologia , Transtornos da Nutrição Infantil/etiologia , Pré-Escolar , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
19.
J Natl Med Assoc ; 110(3): 297-302, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29778134

RESUMO

OBJECTIVE: To evaluate the frequency of central serous chorioretinopathy (CSC) in African Americans/blacks within an academic center in a predominantly African American city, as the current belief is that CSC is rare in this population. METHODS: A retrospective review of all patients' charts diagnosed with CSC at Wilmer Eye Institute/Johns Hopkins University from August 2009-August 2015 was conducted via an electronic health record search (EPIC). The charts were categorized by self-reported race and gender. The diagnosis was confirmed by multiple physician consensus through chart and imaging review. Fluorescein angiograms were classified as single versus multiple point leakage. OCTs were evaluated for subfoveal thickness, location of fluid, presence or absence of pigment epithelial detachment. Color photos were categorized as to the extent of retinal pigment epithelial changes. RESULTS: Of the 590 charts identified via EPIC as CSC patients, 407 were confirmed as CSC through chart and imaging review. 45 patients (11.1%) were African Americans and 298 patients (73.2%) were Caucasians. Of all patients seen during the study period, 0.09% of African Americans at Wilmer had CSC and 0.18% of Caucasians had CSC. While three fold more Caucasians were seen during the study period as compared to African Americans, this study's prevalence rate in African Americans/blacks at Wilmer Eye Institute was half of that in Caucasian/whites. CONCLUSIONS: CSC has been reported as exceedingly rare in African Americans, but our study suggests that CSC may be underestimated in this population. A large nationally representative population based study is needed to determine true racial prevalence to ensure that the diagnosis of CSC is not overlooked in African Americans.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Coriorretinopatia Serosa Central , Fundo de Olho , Epitélio Pigmentado da Retina , Acuidade Visual , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/epidemiologia , Coriorretinopatia Serosa Central/etnologia , Estudos Transversais , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/métodos , Epitélio Pigmentado da Retina/diagnóstico por imagem , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica/métodos , Estados Unidos/epidemiologia
20.
Med Care ; 55(12): 985-990, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29135769

RESUMO

BACKGROUND: Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. OBJECTIVE: To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. RESEARCH DESIGN: Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). SUBJECTS: Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). MEASURES: The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. RESULTS: A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). CONCLUSIONS: Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.


Assuntos
Medicaid , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/terapia , Complicações na Gravidez/terapia , Adulto , Estudos Transversais , Definição da Elegibilidade , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Metadona/economia , Tratamento de Substituição de Opiáceos/economia , Transtornos Relacionados ao Uso de Opioides/economia , Gravidez , Complicações na Gravidez/economia , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
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