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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.
JAMA Netw Open ; 7(2): e240535, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38416497

RESUMEN

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.


Asunto(s)
Contaminación del Aire , Asma , Niño , Embarazo , Femenino , Masculino , Humanos , Preescolar , Incidencia , Estudios de Cohortes , Dióxido de Nitrógeno , Asma/epidemiología , Asma/etiología , Contaminación del Aire/efectos adversos , Material Particulado/efectos adversos
3.
Indian J Psychiatry ; 64(4): 401-407, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36060713

RESUMEN

Background: The Indian population is suffering from a high prevalence of mental stress and the situation has been worsened by the COVID-19 pandemic. Mindfulness, which can also be conducted online, has been used as a stress-relieving therapy in the Western world. There is not much experience with mindfulness in the Indian population. The COVID-19 pandemic demands the development of alternative therapies which can reach out to the masses at a minimal cost, avoiding direct personal contact. The researchers wanted to explore the potential of mindfulness as a stress-relieving therapy. Aim: To note any improvement in perceived stress of the participants compared to the controls. Methods: Ninety apparently healthy adults were randomized into group M (all of whom participated in an online mindfulness program) and group C (all of whom attended placebo sessions), with 45 participants each. Final sample size was n = 42 (group M) and n = 38 (group C). The perceived stress was measured using the perceived stress scale before and after the program. Qualitative data was collected in the form of written responses to the question "Which aspect of mindfulness meditation appealed to you the most for stress relief?" and some themes were formed. Results: There was a significant decrease in perceived stress scale scores on completion of the program in group M. "Positive mental state" and "non-judgmental" were the most prominent emergent themes suggested by the participants, as per the qualitative data analysis. Conclusion: This preliminary study sees potential in an online mindfulness program as an alternative stress-relieving therapy. Further research is suggested to substantiate the results and optimize the implementation.

4.
JAMA Pediatr ; 176(8): 759-767, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35604671

RESUMEN

Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. Design, Setting, and Participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Main Outcomes and Measures: Prevalence of early and persistent childhood wheeze and asthma incidence. Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Conclusions and Relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.


Asunto(s)
Asma , Ruidos Respiratorios , Asma/etnología , Niño , Preescolar , Humanos , Incidencia , Ruidos Respiratorios/etiología , Factores Socioeconómicos , Estados Unidos/epidemiología , Población Blanca
5.
Proc Natl Acad Sci U S A ; 117(5): 2560-2569, 2020 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-31964835

RESUMEN

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains <1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability (h2), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.


Asunto(s)
Amish/genética , Genoma Humano , Adulto , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Genética de Población , Heterocigoto , Humanos , Masculino , Mutación , Linaje , Secuenciación Completa del Genoma , Adulto Joven
6.
J Allergy Clin Immunol ; 143(5): 1752-1759.e6, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30445065

RESUMEN

BACKGROUND: Few data exist on the predictors of asthma remission by early adulthood in North America. OBJECTIVE: The predictors of adult asthma remission were determined in a multiethnic population of patients with mild-to-moderate persistent childhood asthma. METHODS: Asthma remission in early adulthood was measured by using 2 definitions: a clinical and a strict definition. Both included normal lung function and the absence of symptoms, exacerbations, and medication use. The strict definition also included normal airways responsiveness. Predictors were identified from 23 baseline measures by using multivariate logistic regression. The probability of remission was modeled by using decision tree analysis. RESULTS: In 879 subjects the mean ± SD baseline age was 8.8 ± 2.1 years, 59.4% were male, and 68.7% were white. By adulthood, 229 (26.0%) of 879 participants were in clinical remission, and 111 (15.0%) of 741 participants were in strict remission. The degree of FEV1/forced vital capacity (FVC) ratio impairment was the largest predictor of asthma remission. More than half of boys and two thirds of girls with baseline FEV1/FVC ratios of 90% or greater were in remission at adulthood. Decreased airways responsiveness was also a predictor for both remission definitions (clinical remission odds ratio, 1.23 [95% CI, 1.09-1.39]; strict remission odds ratio, 1.52 [95% CI, 1.26-1.84]). The combination of normal FEV1/FVC ratio, airways responsiveness, and serum eosinophil count at baseline yielded greater than 80% probability of remission by adulthood. CONCLUSION: A considerable minority of patients with persistent childhood asthma will have disease remission by adulthood. Clinical prognostic indicators of asthma remission, including baseline lung function, can be seen from an early age.


Asunto(s)
Asma/diagnóstico , Eosinófilos/patología , Hipersensibilidad Respiratoria/diagnóstico , Adulto , Asma/epidemiología , Niño , Etnicidad , Femenino , Humanos , Recuento de Leucocitos , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Pruebas de Función Respiratoria , Hipersensibilidad Respiratoria/epidemiología , Resultado del Tratamiento , Estados Unidos/epidemiología
7.
PLoS One ; 13(4): e0194739, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29664908

RESUMEN

BACKGROUND: The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness. METHODS: We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC Wheezing Module items. Analyses included subgroups of children from three independent cohorts whose parents reported past wheezing: infants ages 0-2 in the INSPIRE birth cohort study (Cohort 1; n = 657), 6-7-year-old North American children from Phase One of the ISAAC study (Cohort 2; n = 2,765), and 5-6-year-old children in the EHAAS birth cohort study (Cohort 3; n = 102). Models were estimated using structural equation modeling. RESULTS: In all cohorts, covariance patterns implied by the latent variable model were consistent with the observed data, as indicated by non-significant χ2 goodness of fit tests (no evidence of model misspecification). Cohort 1 analyses showed that the latent factor structure was stable across time points and child sexes. In both cohorts 1 and 3, the latent wheezing severity variable was prospectively associated with wheeze-related clinical outcomes, including physician asthma diagnosis, acute corticosteroid use, and wheeze-related outpatient medical visits when adjusting for confounders. CONCLUSION: We developed an easily applicable continuous latent variable model of pediatric wheezing severity based on items from the well-validated ISAAC Wheezing Module. This model prospectively associates with asthma morbidity, as demonstrated in two ECHO birth cohort studies, and provides a more statistically powerful method of testing etiologic hypotheses of childhood wheezing illness and asthma.


Asunto(s)
Asma/patología , Ruidos Respiratorios/fisiopatología , Adolescente , Corticoesteroides/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Niño , Preescolar , Estudios de Cohortes , Ejercicio Físico , Femenino , Hospitalización , Humanos , Lactante , Recién Nacido , Modelos Lineales , Masculino , Ruidos Respiratorios/diagnóstico , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
8.
Sci Rep ; 8(1): 1696, 2018 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-29374192

RESUMEN

Collagenases are useful in enzymatic wound debridement. Clostridial collagenase, marketed as Collagenase Santyl Ointment (CSO), is FDA approved for such use. Building on the scientific premise that collagenases as well as collagen degradation products may regulate immune cell function, we sought to investigate the potential role of CSO in wound inflammation. We tested the hypothesis that in addition to enacting debridement, CSO contributes to the resolution of persistent wound inflammation. Wound macrophages were isolated from PVA sponges loaded with CSO or petrolatum and implanted in mice. Significant increase in pro-reparative and decrease in pro-inflammatory polarization was noted in macrophages of acute as well as diabetic wounds. Wound macrophages from CSO-treated group displayed increased production of anti-inflammatory cytokines IL-10 and TGF-ß, and decreased levels of pro-inflammatory cytokines TNF-α and IL-1ß. The active ingredient of CSO, CS-API, induced the expression of mϕheal /M(IL-4) polarization markers ex vivo. CS-API treatment attenuated transactivation of NF-κB and significantly induced STAT6 phosphorylation. A significant role of a novel PGE2-EP4 pathway in CS-API induced STAT6 activation and the mϕheal /M(IL-4) polarization was identified. Taken together, findings of this work reposition CSO as a potential agent that may be effective in resolving wound inflammation, including diabetic wounds.


Asunto(s)
Inflamación/tratamiento farmacológico , Inflamación/patología , Macrófagos/inmunología , Colagenasa Microbiana/administración & dosificación , Pomadas/administración & dosificación , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/patología , Animales , Citocinas/biosíntesis , Perfilación de la Expresión Génica , Ratones , Resultado del Tratamiento
9.
Ann Surg ; 266(2): 346-352, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-27501174

RESUMEN

OBJECTIVES: To document the existence of primary pancreatic secretinoma in patients with watery diarrhea syndrome (WDS) and achlorhydria and establish secretin as a diarrheogenic hormone. BACKGROUND: Vasoactive intestinal peptide (VIP) has been widely accepted as the main mediator of WDS. However, in 1968, Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors, WDS, and achlorhydria. During surgery on the first, a 24-year-old patient, they noticed distended duodenum filled with fluid and a dilated gallbladder containing dilute bile with high bicarbonate concentration. After excision of the tumor, WDS ceased and gastric acid secretion returned. The second, a 47-year-old, patient's metastatic tumor extract given intravenously in dogs, produced significantly increased pancreatic and biliary fluid rich in bicarbonate. They suggested a secretin-like hormone of islet cell origin explains WDS and achlorhydria. These observations, however, predated radioimmunoassay, immunohistochemical staining, and other molecular studies. METHODS: The first patient's tumor tissue was investigated for secretin and VIP. Using both immunohistochemistry and laser microdissection and pressure catapulting technique for RNA isolation and subsequent reverse transcription polymerase chain reaction, the expression levels of secretin, and VIP were measured. RESULTS: Immunoreactive secretin and its mRNA were predominantly found in the tumor tissue whereas VIP and its mRNA were scarce. CONCLUSIONS: The findings strongly support that the WDS and achlorhydria in this patient may have been caused by secretin as originally proposed in 1968 and that secretin may act as a diarrheogenic hormone.


Asunto(s)
Neoplasias Pancreáticas/metabolismo , Secretina/metabolismo , Vipoma/metabolismo , Adulto , Bicarbonatos/metabolismo , Agua Corporal/metabolismo , Femenino , Humanos , Inmunohistoquímica , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Captura por Microdisección con Láser , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Secretina/análisis
10.
Org Biomol Chem ; 14(39): 9294-9305, 2016 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-27714202

RESUMEN

A new class of tricyclic heterocycles 4H-benzo[g][1,2,3]triazolo[5,1-c][1,4]oxazocines was synthesized through a Knoevenagel condensation/azide-alkyne cycloaddition reaction cascade in one-pot operation. These eight membered ring containing heterocycles exhibited moderately high anticancer activity against four cancer cell lines; human cervix cancer cell line (HeLa), human prostate cancer cell line (DU145), human breast cancer cell line (MCF-7) and human breast adenocarcinoma epithelial cell line (MDA-MB-231). Our results indicate that these compounds have a weak cytotoxic effect on normal human mammary epithelial cell line (MCF-10A). Cell cycle and apoptosis assay indicate that they inhibit the cell cycle at the G2/M phase and induce apoptosis. Through the RED100 assay, it is evident that they have potential to inhibit pBR 322 plasmid DNA cleavage by BamH1. UV-visible, fluorescence titration and viscosity studies suggested that these compounds possess DNA binding affinity.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , ADN/metabolismo , Oxazocinas/química , Antineoplásicos/metabolismo , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales/métodos , Células HeLa , Humanos , Células MCF-7 , Oxazocinas/farmacología , Espectrofotometría Ultravioleta , Relación Estructura-Actividad , Viscosidad
11.
J Med Food ; 19(7): 701-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27414521

RESUMEN

UNLABELLED: The objective of the present study ( clinicaltrials.gov NCT02026414) was to observe the effects of oral supplementation of a purified and standardized Shilajit extract on skeletal muscle adaptation in adult overweight/class I obese human subjects from the U.S. POPULATION: Shilajit is a mineral pitch that oozes out of Himalayan rocks. The study design consisted of a baseline visit, followed by 8 weeks of 250 mg of oral Shilajit supplementation b.i.d., and additional 4 weeks of supplementation with exercise. At each visit, blood samples and muscle biopsies were collected for further analysis. Supplementation was well tolerated without any changes in blood glucose levels and lipid profile after 8 weeks of oral supplementation and the additional 4 weeks of oral supplementation with exercise. In addition, no changes were noted in creatine kinase and serum myoglobin levels after 8 weeks of oral supplementation and the additional 4 weeks of supplementation with exercise. Microarray analysis identified a cluster of 17 extracellular matrix (ECM)-related probe sets that were significantly upregulated in muscles following 8 weeks of oral supplementation compared with the expression at the baseline visit. This cluster included tenascin XB, decorin, myoferlin, collagen, elastin, fibrillin 1, and fibronectin 1. The differential expression of these genes was confirmed using quantitative real-time polymerase chain reaction (RT-PCR). The study provided maiden evidence that oral Shilajit supplementation in adult overweight/class I obese human subjects promoted skeletal muscle adaptation through upregulation of ECM-related genes that control muscle mechanotransduction properties, elasticity, repair, and regeneration.


Asunto(s)
Minerales/administración & dosificación , Músculo Esquelético/efectos de los fármacos , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Resinas de Plantas/administración & dosificación , Transcriptoma/efectos de los fármacos , Adaptación Fisiológica , Adulto , Suplementos Dietéticos , Ejercicio Físico , Proteínas de la Matriz Extracelular/genética , Femenino , Humanos , Masculino , Mecanotransducción Celular/efectos de los fármacos , Músculo Esquelético/fisiopatología , Regulación hacia Arriba/efectos de los fármacos
12.
Eur Respir J ; 48(1): 104-14, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27076579

RESUMEN

Methacholine bronchial provocation test provides the concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 s (FEV1) from baseline (PC20). The dose-response slope (DRS), and other continuous indices of responsiveness (CIR; the percentage decline from the post-diluent baseline FEV1 after the last dose of methacholine), and per cent recovery index (PRI; the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation) are alternative measures. The clinical relevance of these indices in predicting acute asthma exacerbations has not been fully evaluated.In two prospective cohorts of childhood and elderly asthmatics, baseline PC20, DRS, CIR and PRI were measured and evaluated as predictors of acute asthma exacerbations.We found that PRI was significantly related to the presence of asthma exacerbations during the first year of follow-up in both cohorts of childhood (p=0.025) and elderly asthmatics (p=0.003). In addition, PRI showed a significant association with the total number of steroid bursts during 4.3 years of follow-up in the cohort of childhood asthmatics (p=0.04).We demonstrated that PRI, an index of reversibility following methacholine-induced bronchoconstriction, was a good clinical predictor of acute exacerbations of asthma in both childhood and elderly asthmatics.


Asunto(s)
Asma/tratamiento farmacológico , Broncoconstricción/efectos de los fármacos , Broncoconstrictores/farmacología , Broncodilatadores/uso terapéutico , Progresión de la Enfermedad , Cloruro de Metacolina/farmacología , Administración por Inhalación , Anciano , Boston , Pruebas de Provocación Bronquial , Niño , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Modelos Logísticos , Masculino , Estudios Prospectivos , República de Corea
13.
Am J Pathol ; 185(10): 2596-606, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26118749

RESUMEN

Heterogeneity and high versatility are the characteristic features of the cells of monocyte-macrophage lineage. The mononuclear phagocyte system, derived from the bone marrow progenitor cells, is primarily composed of monocytes, macrophages, and dendritic cells. In regenerative tissues, a central role of monocyte-derived macrophages and paracrine factors secreted by these cells is indisputable. Macrophages are highly plastic cells. On the basis of environmental cues and molecular mediators, these cells differentiate to proinflammatory type I macrophage (M1) or anti-inflammatory or proreparative type II macrophage (M2) phenotypes and transdifferentiate into other cell types. Given a central role in tissue repair and regeneration, the review focuses on the heterogeneity of monocytes and macrophages with current known mechanisms of differentiation and plasticity, including microenvironmental cues and molecular mediators, such as noncoding RNAs.


Asunto(s)
Diferenciación Celular/fisiología , Plasticidad de la Célula/fisiología , Macrófagos/metabolismo , Monocitos/metabolismo , Regeneración/fisiología , Cicatrización de Heridas/fisiología , Animales , Humanos
14.
Histol Histopathol ; 30(11): 1255-69, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25892148

RESUMEN

Any tissue is made up of a heterogeneous mix of spatially distributed cell types. In response to any (patho) physiological cue, responses of each cell type in any given tissue may be unique and cannot be homogenized across cell-types and spatial co-ordinates. For example, in response to myocardial infarction, on one hand myocytes and fibroblasts of the heart tissue respond differently. On the other hand, myocytes in the infarct core respond differently compared to those in the peri-infarct zone. Therefore, isolation of pure targeted cells is an important and essential step for the molecular analysis of cells involved in the progression of disease. Laser capture microdissection (LCM) is powerful to obtain a pure targeted cell subgroup, or even a single cell, quickly and precisely under the microscope, successfully tackling the problem of tissue heterogeneity in molecular analysis. This review presents an overview of LCM technology, the principles, advantages and limitations and its down-stream applications in the fields of proteomics, genomics and transcriptomics. With powerful technologies and appropriate applications, this technique provides unprecedented insights into cell biology from cells grown in their natural tissue habitat as opposed to those cultured in artificial petri dish conditions.


Asunto(s)
Separación Celular , Perfilación de la Expresión Génica , Genómica , Captura por Microdisección con Láser , Animales , Biomarcadores/análisis , Separación Celular/métodos , Perfilación de la Expresión Génica/métodos , Marcadores Genéticos , Genómica/métodos , Humanos , Captura por Microdisección con Láser/métodos , Proteómica
15.
PLoS One ; 10(3): e0122327, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25799513

RESUMEN

This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue.


Asunto(s)
Ultrasonografía , Cicatrización de Heridas , Animales , Biomarcadores , Biopsia , Diagnóstico por Imagen/métodos , Diagnóstico por Imagen de Elasticidad , Modelos Animales , Flujo Sanguíneo Regional , Porcinos , Ultrasonografía/métodos
16.
Pediatr Pulmonol ; 50(10): 955-62, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25348842

RESUMEN

BACKGROUND AND OBJECTIVE: Cross-sectional gender differences in wheeze are well documented, but few studies have examined the gender-specific risk factors for wheeze longitudinally. This study aims to identify gender- and age-specific risk factors for wheeze from birth through adolescence. METHODS: The incidence of wheeze was ascertained every 6 months through age 14 years in a birth cohort consisting of 499 children with a parental history of atopy. Gender- and age-specific risk factors were identified through generalized estimating equations. RESULTS: A total of 454 (91.0%) and 351 (70.3%) children were followed past age 7 and 13 years, respectively. Maternal asthma was a risk factor for wheeze in girls (OR = 2.05, 95% CI 1.44-2.91, P < 0.0001) and boys (OR = 1.79, 1.29-2.48, P = 0.0004) and had a similar effect on wheeze throughout the ages. Paternal asthma (OR = 1.83, 1.38-2.57, P = 0.0005) and infant bronchiolitis (OR = 2.15, 1.47-3.14, P < 0.0001) were risk factors for boys only, with similar effects throughout the ages. CONCLUSION: Using a prospective cohort, we identified gender- and age-specific risk factors for wheeze. The identification of gender-specific early life risk factors may allow for timely interventions and a more personalized approach to the treatment of asthma.


Asunto(s)
Ruidos Respiratorios/etiología , Adolescente , Factores de Edad , Asma/complicaciones , Boston , Bronquiolitis/complicaciones , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Padres , Factores de Riesgo , Factores Sexuales
17.
J Cytol ; 30(2): 145-7, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23833408

RESUMEN

Spheno-occipital chordomas can rarely present as nasopharyngeal mass. Metastases occur only in advanced disease. They can pose a diagnostic dilemma when information about diagnosis of the primary tumor is not available. We present cytological findings in upper cervical lymph node of a case of nasopharyngeal chordoma and discuss possible differential in such a location.

18.
Int J Crit Illn Inj Sci ; 3(4): 229-34, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24459618

RESUMEN

BACKGROUND: Injury to the underlying structures of the hand carries the potential for serious handicap. To reduce this risk, even the smallest hand injuries require proper medical care. AIMS: To assess wound healing, mobility, and the ability to perform normal essential function post-operatively in open hand injuries associated with fracture. MATERIALS AND METHODS: Thirty patients with 45 metacarpal and phalangeal fractures of the hand were divided into three groups: Group 1 (n = 13) cases with single fractures of hand, excluding thumb; Group 2 (n = 9) cases with multiple fracture of hand, excluding thumb; Group 3 (n = 8) cases with fractures involving thumb and first metacarpal. Tendon injuries were repaired. For fractures, Kirschner wire fixation was done. In two cases with multiple fractures, Joshi's external support system (JESS) fixator was applied. Patients were followed up for 12 weeks. RESULTS: One patient with proximal phalangeal fracture developed extension lag. No stiffness was observed in any of the cases treated by intramedullary Kirschner wire fixation. No non-union or delayed union was observed following cross-wire fixation with two Kirschner wires. Two case of open fracture developed superficial infection. Two patients with multiple fractures developed angulation at fracture site after the Kirschner wires were removed 4 weeks postoperatively, and two cases of multiple fractures developed hypertrophic non-union. CONCLUSIONS: Delicate handling of tissues, preservation of gliding planes for tendons, prevention of infection, accurate reduction and fixation, and early and appropriate physiotherapy affect prognosis in case of hand injuries.

19.
PLoS One ; 7(7): e40383, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22815744

RESUMEN

OBJECTIVE: To examine the relation between mouse allergen exposure and asthma in Puerto Rican children. METHODS: Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV(1) and FEV(1)/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures. RESULTS: Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV(1) in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6-132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI =  -0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV(1) (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01). CONCLUSIONS: Mouse allergen is associated with a higher FEV(1) and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures.


Asunto(s)
Alérgenos/inmunología , Asma/inmunología , Asma/fisiopatología , Pulmón/inmunología , Pulmón/fisiopatología , Animales , Asma/epidemiología , Estudios de Casos y Controles , Niño , Ciudades/estadística & datos numéricos , Polvo/inmunología , Humanos , Pulmón/fisiología , Masculino , Ratones , Análisis Multivariante , Puerto Rico/epidemiología
20.
J Allergy Clin Immunol ; 129(6): 1484-90.e6, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22560959

RESUMEN

BACKGROUND: Puerto Rican and African American subjects share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults. OBJECTIVE: We sought to examine whether a greater proportion of African ancestry is associated with lower FEV(1) and forced vital capacity (FVC) in Puerto Rican children independently of socioeconomic status, health care access, or key environmental/lifestyle factors. METHODS: We performed a cross-sectional case-control study of 943 Puerto Rican children aged 6 to 14 years with (n= 520) and without (n= 423) asthma (defined as physician-diagnosed asthma and wheeze in the prior year) living in Hartford, Connecticut (n= 383), and San Juan, Puerto Rico (n= 560). We estimated the percentage of African racial ancestry in study participants using genome-wide genotypic data. We tested whether African ancestry is associated with FEV(1) and FVC using linear regression. Multivariate models were adjusted for indicators of socioeconomic status and health care and selected environmental/lifestyle exposures. RESULTS: After adjustment for household income and other covariates, each 20% increment in African ancestry was significantly associated with lower prebronchodilator FEV(1) (-105 mL; 95% CI, -159 to -51 mL; P< .001) and FVC (-133 mL; 95% CI, -197 to -69 mL; P< .001) and postbronchodilator FEV(1) (-152 mL; 95% CI, -210 to -94 mL; P< .001) and FVC (-145 mL; 95% CI, -211 to -79 mL; P< .001) in children with asthma. Similar but weaker associations were found for prebronchodilator and postbronchodilator FEV(1) (change for each 20% increment in African ancestry, -78 mL; 95% CI, -131 to -25 mL; P= .004) and for postbronchodilator FVC among children without asthma. CONCLUSIONS: Genetic factors, environmental/lifestyle factors, or both correlated with African ancestry might influence childhood lung function in Puerto Rican subjects.


Asunto(s)
Asma/etnología , Asma/fisiopatología , Población Negra , Adolescente , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Puerto Rico/epidemiología , Pruebas de Función Respiratoria , Capacidad Vital
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