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1.
Artículo en Inglés | MEDLINE | ID: mdl-38869320

RESUMEN

RATIONALE: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. OBJECTIVES: To determine if the 1930's racist policy of redlining led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). METHODS: We categorized census tracts at birth of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into A, B, C, or D categories as defined by the Home Owners Loan Corporation (HOLC), with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract including the percentage of low-income households, the CDC's social vulnerability index (SVI), and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through census tract-level mediators adjusting for individual-level covariates. MEASUREMENTS AND MAIN RESULTS: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6% and 13.2% resided in census tracts with a HOLC grade of D. In mediation analyses, residing in grade D tracts (aOR = 1.03 [95%CI 1.01,1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for SVI and other tract-level variables. CONCLUSIONS: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.

2.
J Allergy Clin Immunol ; 152(1): 84-93, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36972767

RESUMEN

BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.


Asunto(s)
Asma , Masculino , Femenino , Adolescente , Humanos , Niño , Preescolar , Adulto Joven , Adulto , Incidencia , Asma/etiología , Etnicidad , Prevalencia , Evaluación de Resultado en la Atención de Salud
3.
Pediatr Allergy Immunol ; 33(1): e13704, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34811824

RESUMEN

BACKGROUND: Immunoglobulin E-mediated food allergy (IgE-FA) has emerged as a global public health concern. Immune dysregulation is an underlying mechanism for IgE-FA, caused by "dysbiosis" of the early intestinal microbiota. We investigated the association between infant gut bacterial composition and food-related atopy at age 3-5 years using a well-characterized birth cohort. METHODS: The study definition of IgE-FA to egg, milk, or peanut was based on physician panel retrospective review of clinical and questionnaire data collected from birth through age 3-5 years. Using 16S rRNA sequencing, we profiled the bacterial gut microbiota present in stool specimens collected at 1 and 6 months of age. RESULTS: Of 447 infants with data for analysis, 44 (9.8%) met physician panel review criteria for IgE-FA to ≥1 of the three allergens. Among children classified as IgE-FA at 3-5 years, infant stool samples showed significantly less diversity of the gut microbiota compared with the samples of children classified as no IgE-FA at age 3-5 years, especially for milk and peanut (all covariate-adjusted p's for alpha metrics <.007). Testing of individual operational taxonomic units (OTUs) revealed 6-month deficiencies in 31 OTUs for IgE-FA compared with no IgE-FA, mostly in the orders Lactobacillales, Bacteroidales, and Clostridiales. CONCLUSIONS: Variations in gut microbial composition in infant stool were associated with a study definition of IgE-FA at 3-5 years of age. This included evidence of a lack of bacterial diversity, deficiencies in specific OTUs, and delayed microbial maturation. Results support dysbiosis in IgE-FA pathogenesis.


Asunto(s)
Hipersensibilidad a los Alimentos , Microbioma Gastrointestinal , Alérgenos , Niño , Preescolar , Disbiosis , Humanos , Lactante , ARN Ribosómico 16S/genética
4.
Public Health Nutr ; 25(4): 954-963, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34325766

RESUMEN

OBJECTIVE: The objective of the current study was to determine if patients of a large health care system in Detroit who self-identify as food insecure live further away from healthy grocery stores compared with food secure patients. Second, we explored whether food insecurity and distance to healthy grocery stores are related to ecological measures of vehicle availability in the area of residence. DESIGN: A secondary data analysis that uses baseline data from a pilot intervention/feasibility study. SETTING: Detroit, Michigan, USA. PARTICIPANTS: Patients of Henry Ford Health System were screened for food insecurity to determine eligibility for a pilot intervention/feasibility study (i.e. Henry's Groceries for Health), conducted through a collaboration with Gleaners Community Foodbank of Southeastern Michigan. Only patients residing in Detroit city limits (including Highland Park and Hamtramck) were included in the secondary analysis. Of the 1,100 patients included in the analysis, 336 (31 %) were food insecure. RESULTS: After accounting for socio-demographic factors associated with food insecurity, we did not find evidence that food insecure patients lived further away from healthier grocery stores, nor was this modified by ecological measures of vehicle access. However, some neighbourhoods were identified as having a significantly higher risk of food insecurity. CONCLUSIONS: Food insecure patients in Detroit are perhaps limited by social and political determinants and not their immediate neighbourhood geography or physical access to healthy grocery stores. Future research should explore the complexity in linkages between household socio-economic factors, socio-cultural dynamics and the neighbourhood food environment.


Asunto(s)
Abastecimiento de Alimentos , Supermercados , Estudios Transversales , Inseguridad Alimentaria , Humanos , Medición de Resultados Informados por el Paciente
5.
J Allergy Clin Immunol ; 148(5): 1270-1280, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33964299

RESUMEN

BACKGROUND: Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective. OBJECTIVE: Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history. METHODS: Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated. RESULTS: The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females. CONCLUSIONS: US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.


Asunto(s)
Asma/epidemiología , Factores Sexuales , Factores Socioeconómicos , Adolescente , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Interacción Gen-Ambiente , Humanos , Incidencia , Masculino , Vigilancia en Salud Pública , Estados Unidos/epidemiología , Adulto Joven
6.
J Asthma ; 58(3): 370-377, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-31702415

RESUMEN

OBJECTIVE: The recruitment setting plays a key role in the evaluation of behavioral interventions. We evaluated a behavioral intervention for urban adolescents with asthma in three randomized trials conducted separately in three different settings over the course of 8 years. We hypothesized that characteristics of trial participants recruited from the ED and clinic settings would be significantly different from that of youth participating in the school-based trials. The intervention evaluated was Puff City, a web-based program that uses tailoring to improve asthma management behaviors. METHODS: The present analysis includes youth aged 13-19 years who reported a physician diagnosis of asthma and symptoms at trial baseline. In the three trials, all participants were randomized post-baseline to a web-based, tailored intervention (treatment) or generic web-based asthma education (control). RESULTS: Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (p < 0.001) and more caregiver depression (p < 0.001). Clinic-based participants were more likely to have computer/ internet access than participants from the school-based trial (p < 0.001). Both ED and clinic participants were more likely to report controller medication (p's < 0.001) and higher teen emotional support (p's < 0.01) when compared to the schools, but were less likely to report Medicaid (p's < 0.014) and exposure to environmental tobacco smoke (p < 0.001). CONCLUSION: Compared to participants in the school-based trials, participants recruited from ED and clinic settings differed significantly in terms of healthcare use, as well as psychosocial and sociodemographic factors. These factors can inform intervention content, and may impact external validity of behavioral interventions for asthma.


Asunto(s)
Asma/epidemiología , Asma/psicología , Selección de Paciente , Autocuidado/psicología , Adolescente , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Cuidadores/psicología , Depresión/epidemiología , Progresión de la Enfermedad , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Servicios de Salud/estadística & datos numéricos , Humanos , Masculino , Instituciones Académicas/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Apoyo Social , Factores Socioeconómicos , Contaminación por Humo de Tabaco/estadística & datos numéricos , Adulto Joven
7.
Ann Emerg Med ; 76(4): 515-526, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31959536

RESUMEN

STUDY OBJECTIVE: We explore reproductive-aged women's acceptance of contraception counseling in the emergency department (ED). METHODS: This study is phase 1 of an exploratory sequential mixed methods study. We purposively interviewed 31 participants with the following criteria: black, white, or Latina race/ethnicity; nonpregnant; aged 15 to 44 years; receiving nonemergency care; not using highly effective contraception; and did not intend to become pregnant. We conducted semistructured interviews with a piloted interview guide until reaching thematic saturation. We coded transcripts with an iteratively developed codebook, maintaining intercoder agreement greater than 80%. Qualitative acceptance of ED contraception counseling was grouped into 3 categories: acceptable, unacceptable, and equivocal. We conducted a thematic text analysis to assess themes expressing support and concern for ED contraception counseling. Qualitative findings were stratified by age, race, and frequency of ED use. Using components of grounded theory, we developed a conceptual model. RESULTS: Most participants (81%) accepted ED contraception counseling. Themes expressing support and concern for ED contraception counseling included opportunity to address women's unmet contraception needs, contraception is within the scope of ED practice, the ED is a convenient setting with competent providers, contraception is a sensitive topic, and the ED may be an inappropriate setting for some women. Latina participants had lower acceptance of ED contraception counseling. Dominant subthemes varied slightly by race, age, and frequency of ED use. CONCLUSION: Diverse women had high acceptance of contraception counseling in the ED. Perspectives expressing both support and concern in regard to ED contraception counseling were explored in detail.


Asunto(s)
Conducta Anticonceptiva/psicología , Anticonceptivos/uso terapéutico , Consejo/normas , Aceptación de la Atención de Salud/psicología , Adolescente , Adulto , Conducta Anticonceptiva/estadística & datos numéricos , Consejo/métodos , Consejo/estadística & datos numéricos , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Entrevistas como Asunto/métodos , Aceptación de la Atención de Salud/estadística & datos numéricos , Investigación Cualitativa , Grupos Raciales/estadística & datos numéricos , Encuestas y Cuestionarios
8.
Allergy Asthma Proc ; 41(3): 210-217, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32375966

RESUMEN

Background: Emotional disorders, including depression and anxiety, are more prevalent in individuals with asthma than in the general population and are associated with poor asthma outcomes. Identification of patients with increased levels of stress and anxiety may be helpful when treating asthma and during asthma counseling. Objective: To further characterize the relationship between asthma symptoms and perceived stress and trait anxiety in an adolescent population. Methods: Adolescents (N = 335) ages 14-17 years were recruited to examine the effect of stress on health measures. They were included in the present analysis if they reported current asthma, defined as self-reported clinician-diagnosed asthma plus one or more episodes of asthma in the past year. Asthma symptoms were assessed on a 7-point scale by using a standardized questionnaire that targets nocturnal awakening due to asthma, symptoms on awakening, activity limitation, shortness of breath, time spent wheezing, and short-acting bronchodilator use. Stress was measured by using the Perceived Stress Scale (PSS), and trait anxiety was measured by using the State-Trait Anxiety Inventory. Linear regression was used to associate asthma symptoms with PSS and trait anxiety. Results: Thirty-eight adolescents (11.3%), with mean ± standard deviation age 16.7 ± 0.9 years, reported current asthma. Four of the six asthma symptom assessments had significant associations with PSS: symptoms on awakening (ß = 4.82, p < 0.001), nocturnal awakening due to asthma (ß = 4.47, p < 0.001), activity limitation (ß = 2.78, p = 0.005), and shortness of breath (ß = 1.73, p = 0.014). These associations remained significant after adjusting for gender, race, and the body mass index percentile. Trait anxiety had significant associations with nocturnal awakening (ß = 9.28, p = 0.002) and symptoms on awakening (ß = 8.74, p = 0.002). Associations remained significant after adjusting for gender, race, and body mass index percentile. Conclusion: Asthma symptom severity is associated with increased perceived stress and trait anxiety. Adolescents with asthma may represent a population that is particularly vulnerable to perceived stress and anxiety, which highlights the importance of considering these factors in asthma counseling.


Asunto(s)
Ansiedad/psicología , Asma/fisiopatología , Disnea/fisiopatología , Personalidad , Ruidos Respiratorios/fisiopatología , Estrés Psicológico/psicología , Actividades Cotidianas , Adolescente , Asma/tratamiento farmacológico , Asma/psicología , Broncodilatadores/uso terapéutico , Femenino , Humanos , Modelos Lineales , Masculino , Vigilia
10.
Psychol Med ; 49(3): 491-500, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29792241

RESUMEN

BACKGROUND: Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups. METHODS: Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects. RESULTS: The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants. CONCLUSIONS: Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.


Asunto(s)
Terapia Cognitivo-Conductual/métodos , Depresión/terapia , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Telemedicina/métodos , Adulto , Anciano , Femenino , Humanos , Modelos Lineales , Masculino , Michigan , Persona de Mediana Edad , Resultado del Tratamiento
11.
Biochemistry ; 57(18): 2723-2732, 2018 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-29651842

RESUMEN

Despite its potent antibacterial activities against drug-resistant Gram-positive pathogens, oritavancin remains partially understood with respect to its primary mode of hydrogen bond interaction with a cell-wall peptide regarding the role of its lipophilic 4'-chlorobiphenyl moiety. Here we report a surface plasmon resonance (SPR) study performed in two cell-wall model surfaces, each prepared by immobilization with a vancomycin-susceptible Lys-d-Ala-d-Ala or vancomycin-resistant Lys-d-Ala-d-Lac peptide. Analysis of binding kinetics performed on the peptide surface showed that oritavancin bound ∼100-1000-fold more tightly than vancomycin on each model surface. Ligand competition experiments conducted by SPR and fluorescence spectroscopy provided evidence that such affinity enhancement can be attributed to its 4'-chlorobiphenyl moiety, possibly through a hydrophobic interaction that led to a gain of free energy with a contribution from enthalpy as suggested by a variable-temperature SPR experiment. On the basis of these findings, we propose a model for the bivalent motifs of interaction of oritavancin with cell-wall peptides, by which the drug molecule can retain a strong interaction even with the vancomycin-resistant peptide. In summary, this study advances our understanding of oritavancin and offers new insight into the significance of bivalent motifs in the design of glycopeptide antibiotics.


Asunto(s)
Pared Celular/química , Glicopéptidos/química , Péptidos/química , Vancomicina/química , Antibacterianos/química , Pared Celular/efectos de los fármacos , Bacterias Grampositivas/química , Bacterias Grampositivas/efectos de los fármacos , Humanos , Cinética , Ligandos , Lipoglucopéptidos , Estructura Molecular , Péptidos/uso terapéutico , Unión Proteica , Resonancia por Plasmón de Superficie , Vancomicina/uso terapéutico , Resistencia a la Vancomicina/efectos de los fármacos
12.
Langmuir ; 34(24): 7135-7146, 2018 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-29792710

RESUMEN

Multivalent ligand-receptor interaction provides the fundamental basis for the hypothetical notion that high binding avidity relates to the strong force of adhesion. Despite its increasing importance in the design of targeted nanoconjugates, an understanding of the physical forces underlying the multivalent interaction remains a subject of urgent investigation. In this study, we designed three vancomycin (Van)-conjugated dendrimers G5(Van) n ( n = mean valency = 0, 1, 4) for bacterial targeting with generation 5 (G5) poly(amidoamine) dendrimer as a multivalent scaffold and evaluated both their binding avidity and physical force of adhesion to a bacterial model surface by employing surface plasmon resonance (SPR) spectroscopy and atomic force microscopy. The SPR experiment for these conjugates was performed in a biosensor chip surface immobilized with a bacterial cell-wall peptide Lys-d-Ala-d-Ala. Of these, G5(Van)4 bound most tightly with a KD of 0.34 nM, which represents an increase in avidity by 2 or 3 orders of magnitude relative to a monovalent conjugate G5(Van)1 or free vancomycin, respectively. By single-molecule force spectroscopy, we measured the adhesion force between G5(Van) n and the same cell-wall peptide immobilized on the surface. The distribution of adhesion forces increased in proportion to vancomycin valency with the mean force of 134 pN at n = 4 greater than 96 pN at n = 1 at a loading rate of 5200 pN/s. In summary, our results are strongly supportive of the positive correlation between the avidity and adhesion force in the multivalent interaction of vancomycin nanoconjugates.


Asunto(s)
Bacterias/química , Pared Celular/química , Dendrímeros/química , Fenómenos Mecánicos , Péptidos/metabolismo , Vancomicina/química , Péptidos/química
14.
J Asthma ; 55(3): 266-274, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28562121

RESUMEN

OBJECTIVE: Among teens with asthma, challenges of disease management may be greater in those with a body mass index (BMI) >85th percentile compared to youth within the parameters for normal weight-for-age. This mixed-methods study assessed teens' awareness of the link between weight and asthma management, and perspectives on how medical providers might open a discussion about managing weight. METHOD: Teens aged 13-18, having BMI >85 percentile and chronic asthma, identified using health system databases and a staff email message board, were invited to complete a semi-structured, in-depth phone interview. Interviews were audio taped, transcribed, and qualitatively analyzed, using the Framework Method. Responses were summarized and themes identified. Descriptive summaries were generated for a 16-item survey of weight conversation starters. RESULTS: Of 35 teens interviewed, 24 (69%) were girls, 11 (31%) boys, 20 (63%) African-American. All teens reported having "the weight conversation" with their doctors, and preferred that parents be present. Half knew from their doctor about the link between being overweight and asthma, others knew from personal experience. Nearly all expressed the importance of providers initiating a weight management conversation. Most preferred conversation starters that recognized challenges and included parents' participation in weight management; least liked referred to "carrying around too much weight." CONCLUSIONS: Most teens responded favorably to initiating weight loss if it impacted asthma management, valued their provider addressing weight and family participation in weight management efforts. Adolescents' views enhance program development fostering more effective communication targeting weight improvement within the overall asthma management plan.


Asunto(s)
Asma/psicología , Motivación , Sobrepeso/psicología , Relaciones Médico-Paciente , Adolescente , Asma/terapia , Niño , Comunicación , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Sobrepeso/terapia , Padres , Pérdida de Peso
15.
Gastroenterology ; 150(4): 931-43, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26764183

RESUMEN

BACKGROUND & AIMS: A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. METHODS: We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn's disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. RESULTS: Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. CONCLUSIONS: Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Transformación Celular Neoplásica/genética , Colitis Ulcerosa/genética , Neoplasias Colorrectales/genética , Enfermedad de Crohn/genética , Análisis Mutacional de ADN , Exoma , Mutación , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Neoplasias Colorrectales/diagnóstico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Variaciones en el Número de Copia de ADN , Dosificación de Gen , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Fenotipo
17.
J Pediatr Gastroenterol Nutr ; 65(3): e60-e67, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28827481

RESUMEN

BACKGROUND AND OBJECTIVES: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota. METHODS: A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)ß1, TGFß2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. RESULTS: Individually, immunomodulators TGFß1 and TGFß2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFß1 and TGFß2, however, were not independent of one another, and the effect of TGFß2 was stronger than that of TGFß1. Higher levels of TGFß2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. CONCLUSIONS: Breast milk TGFß concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFß acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.


Asunto(s)
Lactancia Materna , Microbioma Gastrointestinal , Interleucina-10/inmunología , Leche Humana/inmunología , Factor de Crecimiento Transformador beta1/inmunología , Factor de Crecimiento Transformador beta2/inmunología , Adulto , Biomarcadores/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Recién Nacido , Interleucina-10/metabolismo , Masculino , Persona de Mediana Edad , Leche Humana/metabolismo , Estudios Prospectivos , Análisis de Regresión , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta2/metabolismo
18.
Ann Allergy Asthma Immunol ; 116(1): 43-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26596405

RESUMEN

BACKGROUND: The emergency department could represent a means of identifying patients with asthma who could benefit from asthma interventions. OBJECTIVE: To assess the initiation of a Web-based tailored asthma intervention in the emergency department of 2 urban tertiary care hospitals. METHODS: In addition to awareness strategies for emergency department staff (eg, attending nursing huddles, division meetings, etc), recruitment experiences are described for 2 strategies: (1) recruitment during an emergency department visit for acute asthma and (2) recruitment from patient listings (mail or telephone). Patient enrollment was defined as baseline completion, randomization, and completion of the first of 4 online sessions. RESULTS: Of 499 eligible patients 13 to 19 years old visiting the emergency department for asthma during the study period, 313 (63%) were contacted in the emergency department (n = 65) or by mail or telephone (n = 350). Of these, 121 (38.6%) were randomized. Mean age of the study sample was 15.4 years and 88.4% were African American. Refusal rates for emergency department recruitment and mail or telephone were 18.5% (12 of 65) and 16.6% (58 of 350), respectively. On average, emergency department enrollment took 44 to 67 minutes, including downtime. When surveyed, emergency department providers were more positive about awareness activities and emergency department recruitment than were research staff. CONCLUSION: Emergency department recruitment was feasible but labor intensive. Refusal rates were similar for the 2 strategies. Targeting patients with acute asthma in the emergency department is one way of connecting with youth at risk of future acute events.


Asunto(s)
Asma/tratamiento farmacológico , Servicio de Urgencia en Hospital , Selección de Personal , Adolescente , Adulto , Ciudades , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Michigan , Sistemas en Línea , Cooperación del Paciente , Encuestas y Cuestionarios , Centros de Atención Terciaria , Adulto Joven
19.
Ann Allergy Asthma Immunol ; 116(3): 219-224.e1, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26837607

RESUMEN

BACKGROUND: Suspected food allergies are the cause of more than 200,000 visits to the emergency department annually. Racial differences in the prevalence of food allergy have also been reported, but the evidence is less conclusive. Researchers continue to struggle with the identification of food allergy for epidemiologic studies. OBJECTIVE: To explore racial differences in IgE-mediated food allergy (IgE-FA) in a birth cohort. METHODS: We used a panel of board-certified allergists to systematically identify IgE-FA to egg, milk, or peanut in a multiethnic birth cohort in which patient medical history, patient symptoms, and clinical data were available through 36 months of age. RESULTS: Of the 590 infants analyzed, 52.9% were male and 65.8% African American. Sensitization (serum specific IgE >0.35 IU/mL) to the food allergens was significantly higher for African American children compared with non-African American children as has been previously reported. No statistically significant racial/ethnic differences in IgE-FA were observed; however, a higher proportion of African American children were designated as having peanut allergy, and the percentage of African American children with an IgE level greater than 95% predictive decision points for peanut was 1.7% vs 0.5% for non-African American children. With the use of logistic regression, race/ethnicity was not significantly associated with IgE-FA (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.17; P = .75) but was associated with sensitization to more than 1 of the food allergens (adjusted odds ratio, 1.80; 95% confidence interval, 1.22-2.65; P = .003). CONCLUSION: We did not observe an elevated risk of IgE-FA for African American children, although established differences in sensitization were observed. Racial/ethnic differences in sensitization must be taken into consideration when investigating disparities in asthma and allergy.


Asunto(s)
Etnicidad , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/inmunología , Alérgenos/clasificación , Alérgenos/inmunología , Animales , Preescolar , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulina E/sangre , Lactante , Recién Nacido , Masculino , Oportunidad Relativa , Prevalencia , Pruebas Cutáneas
20.
J Asthma ; 53(10): 1041-7, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27359106

RESUMEN

OBJECTIVE: This exploratory study assessed health literacy among urban African-American high school students to improve understanding of the association between adolescent health literacy and asthma. METHODS: We conducted a secondary data analysis of the control group (n = 181) of the Puff City randomized controlled trial (2006-2010), a web-based intervention to promote asthma management among students, grades 9 through 12. A validated self-report 3-item health literacy screening instrument was completed at final online follow-up survey. Logistic regression was used to explore the association between health literacy, demographic characteristics, quality of life, asthma management, and health care utilization. RESULTS: Multivariate analysis revealed that an overall inadequate health literacy score was associated with students who were more likely to be younger (OR 0.61; 95% CI 0.44-0.84), not on Medicaid (OR 0.36; 95% CI 0.17-0.76), have at least one hospitalization (OR 1.29; 95% CI 1.07-1.56); and a lower overall quality of life (OR 0.75; 95% CI 0.59-0.95). Those lacking confidence in filling out medical forms, needing help reading hospital materials, and having difficulty understanding written information were more likely to not have a rescue inhaler (OR 0.49; 95% CI 0.25-0.94), have one or more emergency visits (OR 1.21 95% CI 1.02-1.43), and one or more hospitalizations (OR 1.19; 95% CI 1.01-1.41), respectively. CONCLUSIONS: The findings indicate a significant association between inadequate health literary and suboptimal asthma management. It is important to advance understanding of adolescent health literacy, especially those at-risk, as they assume asthma self-management tasks and move toward independent adult self-care.


Asunto(s)
Asma/epidemiología , Negro o Afroamericano/estadística & datos numéricos , Alfabetización en Salud/estadística & datos numéricos , Adolescente , Adulto , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Medicaid , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Estados Unidos , Población Urbana/estadística & datos numéricos , Adulto Joven
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