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1.
Contemp Clin Trials ; 137: 107422, 2024 02.
Article in English | MEDLINE | ID: mdl-38145715

ABSTRACT

BACKGROUND: Limited English Proficiency (LEP) Latinxs experience a longer duration of untreated depression and anxiety. LEP Latinxs have difficulty accessing mental healthcare due to insufficient Spanish-speaking behavioral/mental health clinicians to meet demand. These under-resourced healthcare systems are less likely to be the site for the implementation of innovations. Digital interventions can provide an effective option for overcoming these barriers; yet, when digital evidence-based treatments are available, uptake and engagement is often low. This manuscript presents the protocol for the SUPERA (SUpport from PEeRs to expand Access) study which will evaluate the implementation of an evidence-based, Spanish language, digital cognitive-behavioral therapy (dCBT) intervention (i.e., SilverCloud) in safety-net primary care clinics for LEP Latinx patients with depression or anxiety. METHODS: We will conduct an effectiveness-implementation hybrid trial (Type 2) design comparing engagement and clinical outcomes in two modalities of dCBT delivery (peer-supported vs. unsupported). We will also compare provider-level outreach (using a clinic patient registry) versus inreach (traditional provider referral) to compare rates of initiation, completion, and cost. Participants will be 426 LEP Latinx adults ≥18 years of age, PHQ-9 ≥ 10 or GAD-7 ≥ 8, with access to the internet via smartphone, and not currently receiving individual psychotherapy. We will collect baseline, post-intervention (8 weeks), and follow up (3 months) data. CONCLUSION: The long-term goal of this research is to aid in the implementation of digital mental health interventions that can be sustainably implemented in low-resourced settings, while reducing the reliance on professionals, overcoming workforce deficits, and increasing relevance for diverse populations.


Subject(s)
Cognitive Behavioral Therapy , Depression , Adult , Humans , Depression/therapy , Anxiety Disorders/therapy , Anxiety/therapy , Cognitive Behavioral Therapy/methods , Language
2.
Int J Eat Disord ; 56(6): 1075-1086, 2023 06.
Article in English | MEDLINE | ID: mdl-36942361

ABSTRACT

OBJECTIVE: Acculturative stress, often experienced by members of minority groups, is related to problematic eating behaviors. What remains poorly understood is the function of perceived social support in this link. This study evaluated the moderating role of perceived support from family, the significant other, and friends in the association between acculturative stress and problematic eating behaviors, including emotional eating, uncontrolled eating, and cognitive restraint eating. METHOD: An online cross-sectional study was conducted with 497 Asian and Latinx college students using standardized questionnaires. Three hierarchical multivariable models were analyzed, with each eating behavior included as the outcome variable. Demographic variables (Step 1), general perceived stress (Step 2), and predictor variables (i.e., acculturative stress, perceived support; Step 3) were added using Method Enter. Interaction terms were entered using Method Stepwise (Step 4) to test for moderation effects. RESULTS: As perceived family support increased, the magnitude of the link between acculturative stress and higher uncontrolled eating increased (p = .002). When perceived significant other support was higher, the magnitude of the relationship between acculturative stress and higher emotional eating increased (p = .02). Higher perceived friend support was directly related to reduced uncontrolled eating (p = .002). DISCUSSION: This study highlights the heterogeneous effects of various sources of perceived support on the link between acculturative stress and problematic eating behaviors. Findings imply that problematic eating prevention and intervention programs might benefit from considering not only the acculturative stress experienced by racial/ethnic minority young adults but also the sources of support perceived. PUBLIC SIGNIFICANCE: Perceived support from family and the significant other increased the magnitude of the link between higher acculturative stress and increased problematic eating behaviors, whereas support from friends showed a direct relationship with reduced uncontrolled eating. The results highlight the nuanced functions of various sources of perceived social support and contribute to a deeper understanding of potential moderators in the relationship between acculturative stress and problematic eating behaviors among racial/ethnic minorities.


Subject(s)
Acculturation , Ethnicity , Feeding Behavior , Humans , Young Adult , Cross-Sectional Studies , Ethnicity/psychology , Friends , Hispanic or Latino/psychology , Minority Groups/psychology , Stress, Psychological/psychology , Asian/psychology
3.
Appetite ; 169: 105826, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34826527

ABSTRACT

Acculturative stress is associated with health behaviors that have downstream consequences for health outcomes. Eating disinhibition, a behavior characterized by eating emotionally and uncontrollably in the presence of disinhibiting stimuli, has been consistently associated with acculturative stress, but the underlying mechanism is not well-understood. The current study sought to test the role of depressive symptoms and gender on these associations. Asian undergraduate students (N = 477; 78% female) participated in an online cross-sectional study. Higher acculturative stress was associated with higher eating disinhibition (b = 3.45, 95% CI = [0.75, 6.15]), and depressive symptoms showed a partial indirect effect on this association (indirect effect = 0.57, 95% CIboot = [0.13, 1.34]). Among male young adults (b = 0.98, 95% CIboot = [0.24, 2.39]), the indirect correlation was stronger than among female young adults (b = 0.44, 95% CIboot = [0.05, 1.20]; non-significant trend), implying individual differences underlying the indirect effect of depressive symptoms in the acculturative stress and eating disinhibition correlation. The Intercultural Relations dimension of acculturative stress appeared to drive the observed associations. This study is among the first highlighting the role of acculturative stress, depressive symptoms, and gender in eating disinhibition and provides evidence that can inform health professionals to target at-risk Asian individuals with eating problems.


Subject(s)
Depression , Stress, Psychological , Acculturation , Cross-Sectional Studies , Depression/psychology , Female , Humans , Male , Stress, Psychological/psychology , Students/psychology , Young Adult
4.
Cells ; 10(4)2021 04 07.
Article in English | MEDLINE | ID: mdl-33917227

ABSTRACT

The T cell antigen receptor (TCR) is expressed on T cells, which orchestrate adaptive immune responses. It is composed of the ligand-binding clonotypic TCRαß heterodimer and the non-covalently bound invariant signal-transducing CD3 complex. Among the CD3 subunits, the CD3ε cytoplasmic tail contains binding motifs for the Src family kinase, Lck, and the adaptor protein, Nck. Lck binds to a receptor kinase (RK) motif and Nck binds to a proline-rich sequence (PRS). Both motifs only become accessible upon ligand binding to the TCR and facilitate the recruitment of Lck and Nck independently of phosphorylation of the TCR. Mutations in each of these motifs cause defects in TCR signaling and T cell activation. Here, we investigated the role of Nck in proximal TCR signaling by silencing both Nck isoforms, Nck1 and Nck2. In the absence of Nck, TCR phosphorylation, ZAP70 recruitment, and ZAP70 phosphorylation was impaired. Mechanistically, this is explained by loss of Lck recruitment to the stimulated TCR in cells lacking Nck. Hence, our data uncover a previously unknown cooperative interaction between Lck and Nck to promote optimal TCR signaling.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism , Oncogene Proteins/metabolism , Receptors, Antigen, T-Cell/metabolism , Signal Transduction , CD3 Complex/metabolism , Humans , Jurkat Cells , Phosphorylation , Protein Binding , ZAP-70 Protein-Tyrosine Kinase/metabolism
5.
Rev Med Inst Mex Seguro Soc ; 59(1): 65-72, 2021 02 02.
Article in Spanish | MEDLINE | ID: mdl-33667045

ABSTRACT

Background: Breast cancer is the main cause of death by cancer in Mexican women. High mammographic breast density is a well-established breast cancer risk factor that also increases the risk of death. However, there is limited data of breast density patterns among Mexican women and their association with breast cancer incidence and mortality. Objective: To determine the distribution of breast density patterns and BI-RADS (Breast Imaging Reporting and Data System) among women from Torreon, Coahuila. Method: Observational and retrospective study. Mammographic reports of women from Torreon, Mexico, were analyzed. Reports came from IMSS HGZ#16, Sanatorio Español and a private radiological office. Only mammographic records which described age, breast density and Bi-RADS reports were included. Differences on breast density distribution were analyzed with the Chi-Square test according to age, economic sectors and BI-RADS classification. Results: A total of 2,187 women were included, representing about 1% of the total adult women population of Torreon. The mean age was 54.4 years, and the mammographic density patterns distribution was: 19.15% fatty, 47.76% fibroglandular density, 27.10% heterogeneously dense, and 5.99% extremely dense. Conclusions: The main pattern in this Mexican population is the fibroglandular density, and extremely dense breast was only 6%. Our results suggest that non-dense breast tissue could increase breast cancer risk. Further studies on related risk factors, like body mass index are required.


Introducción: El cáncer de mama es la principal causa de muerte por cáncer en las mujeres mexicanas. La densidad mamaria alta es un factor de riesgo para desarrollar cáncer de mama, que también incrementa la mortalidad. Son escasos los estudios en México que describan la relación de los patrones de densidad mamaria con la incidencia y la mortalidad del cáncer de mama. Objetivo: Analizar la distribución de densidad mamaria y la proporción de BI-RADS (Breast Imaging Reporting and Data System) en mujeres de Torreón, Coahuila. Método: Estudio observacional y retrospectivo. Se recopilaron reportes de mastografía digital de diagnóstico o escrutinio del sector público (Instituto Mexicano del Seguro Social, Hospital General de Zona No. 16) y privado (Sanatorio Español y privados) en Torreón, Coahuila, de enero de 2013 a marzo de 2017. Solo se incluyeron reportes mamográficos que incluyeran edad, densidad mamaria y BI-RADS. Se analizó la distribución de densidad mamaria por edad, lugar de realización y BI-RADS mediante la prueba de ji al cuadrado. Resultados: Se incluyeron 2187 mujeres (cerca del 1% de la población de mujeres adultas de Torreón), con una edad media de 54.4 años. La distribución global de patrones mamográficos fue: 19.15% adiposo, 47.76% fibroglandular, 27.10% heterogéneamente denso y 5.99% denso. Conclusiones: El patrón predominante en las mujeres con cáncer de mama es el patrón fibroglandular; solo el 6% registraron mamas extremadamente densas. Los resultados sugieren que el tejido no denso podría aumentar el riesgo de cáncer de mama. Futuros estudios podrían analizar factores de riesgo como el índice de masa corporal.


Subject(s)
Breast Density , Breast Neoplasms , Mammography , Adult , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/epidemiology , Female , Humans , Mexico/epidemiology , Middle Aged , Retrospective Studies , Risk Factors
6.
J Interpers Violence ; 36(19-20): 9557-9579, 2021 10.
Article in English | MEDLINE | ID: mdl-31423868

ABSTRACT

Intimate partner violence (IPV) affects one in three women and can have long-lasting psychological effects, with abuse survivors typically exhibiting elevated stress and depressive symptoms. However, women with greater personal empowerment resources (i.e., self-care, agency, self-efficacy) and who practice relaxation techniques generally exhibit lower stress and depressive symptoms. The present study investigated the effectiveness of Personal Empowerment Programs (PEP) and practicing relaxation techniques in promoting empowerment and lowering stress and depressive symptoms. Ninety women were recruited from PEP classes conducted at domestic violence agencies in Orange County, California. Salivary cortisol and affect were assessed before and after one PEP class. Perceived stress, depressive symptoms, empowerment, and relaxation techniques were also assessed. Practicing relaxation techniques correlated with more empowerment. For women without sexual abuse experiences only, having completed more classes (>5 classes) in the program was associated with greater empowerment, less stress, and fewer depressive symptoms. Implications extend to future studies and interventions for IPV survivors.


Subject(s)
Domestic Violence , Intimate Partner Violence , Depression , Empowerment , Female , Humans , Survivors
8.
BMC Geriatr ; 20(1): 444, 2020 11 04.
Article in English | MEDLINE | ID: mdl-33148216

ABSTRACT

BACKGROUND: The Balance Evaluation Systems Test (BESTest) and its abbreviated version, the Mini-BESTest are clinical examination of balance impairment, but its psychometric properties have not yet been tested in European Spanish. We aimed to assess the psychometric properties of BESTest and Mini-BESTest in Spanish in community-dwelling elderly people. METHODS: We designed a cross-sectional transcultural adaptation and validation study. Convenience sample of thirty (N-30) adults aged 65 to 89 years old without balance problems were recruited. Two physiotherapists assessed participants at the same time. Internal consistency of Spanish BESTest and Mini-BESTest was carried out by obtaining the Cronbach Alpha. The reproducibility between raters was studied with the Intraclass Correlation Coefficient. The Pearson correlation coefficient was calculated by comparing the relationship between the BESTest, mini-BESTest, Berg Balance Scale (BBS) and Falls Efficacy Scale-International (FES-I). RESULTS: BESTest and Mini-BESTest showed good internal consistency. BESTest and Mini-BESTest total scores showed an excellent inter-rater agreement. There was a significant correlation between total score of the BESTest and the Mini-BESTest (r = 0.65; p < 0.001). BESTest had a moderate association with BBS and a strong association with FES-I. Mini-BESTest had a fair correlation with BBS and FES-I. Total scores obtained by women at BESTest and at Mini-BESTest were significantly lower than those reached by men. The differences observed in all the test when disaggregating data by sex require further research. CONCLUSIONS: Spanish versions of BESTest and Mini-BESTest are comprehensible for new raters. They are reliable tools to provide information on which particular balance systems show impairment in community dwelling older adults. Elderly women had a worse quality of balance and a greater perception of their risk of falling. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov with NCT03403218 on 2018/01/17.


Subject(s)
Independent Living , Postural Balance , Accidental Falls , Aged , Aged, 80 and over , Cross-Sectional Studies , Disability Evaluation , Female , Humans , Male , Psychometrics , Reproducibility of Results
9.
Nat Immunol ; 21(8): 902-913, 2020 08.
Article in English | MEDLINE | ID: mdl-32690949

ABSTRACT

Initiation of T cell antigen receptor (TCR) signaling involves phosphorylation of CD3 cytoplasmic tails by the tyrosine kinase Lck. How Lck is recruited to the TCR to initiate signaling is not well known. We report a previously unknown binding motif in the CD3ε cytoplasmic tail that interacts in a noncanonical mode with the Lck SH3 domain: the receptor kinase (RK) motif. The RK motif is accessible only upon TCR ligation, demonstrating how ligand binding leads to Lck recruitment. Binding of the Lck SH3 domain to the exposed RK motif resulted in local augmentation of Lck activity, CD3 phosphorylation, T cell activation and thymocyte development. Introducing the RK motif into a well-characterized 41BB-based chimeric antigen receptor enhanced its antitumor function in vitro and in vivo. Our findings underscore how a better understanding of the functioning of the TCR might promote rational improvement of chimeric antigen receptor design for the treatment of cancer.


Subject(s)
CD3 Complex/metabolism , Lymphocyte Activation/immunology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism , Receptors, Antigen, T-Cell/metabolism , Receptors, Chimeric Antigen/immunology , Amino Acid Motifs/immunology , Animals , CD3 Complex/immunology , Humans , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/immunology , Mice , Receptors, Antigen, T-Cell/immunology
10.
Psychoneuroendocrinology ; 107: 201-207, 2019 09.
Article in English | MEDLINE | ID: mdl-31150965

ABSTRACT

Migration experiences are inherently stressful and may negatively affect the health of immigrants. Bicultural identity integration (BII), individuals' views of their multiple cultures as compatible and complementary, and their ability to easily integrate these cultures into their daily lives, has been linked with health outcomes. The main goal of the present study was to determine whether perceived stress and cortisol, a hormone of the HPA axis implicated in the biopsychological pathway linking stress and disease, are associated with BII. The sample consisted of 127 male and female, primarily Latino (68.3%) university and community college students (M = 20.4 yrs, SD = 2.1) who were either foreign-born or had at least one foreign-born parent. Regression analyses indicate that individuals scoring low on the cultural harmony subscale of the BII reported more perceived stress, overall model, F(2,126) = 18.04, p < .001, and had higher salivary cortisol levels following a standardized laboratory stressor (Trier Social Stress Test), as indicated by a more pronounced cortisol mean increase, F(2,111) = 5.11, p = .01, and a larger cortisol area under the curve with respect to ground, F(2,108) = 5.85, p = .004, controlling for neuroticism. Our findings link perceived stress and cortisol reactivity with the BII cultural harmony subscale, above and beyond the known effects of neuroticism, suggesting that this construct is important to consider in biopsychosocical studies of immigrant stress and health.


Subject(s)
Emigrants and Immigrants/psychology , Stress, Psychological/metabolism , Acculturation , Ethnicity/psychology , Female , Hispanic or Latino/psychology , Humans , Hydrocortisone/analysis , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Male , Pituitary-Adrenal System/metabolism , Saliva/chemistry , Students/psychology , United States/ethnology , Young Adult
11.
BMC Pregnancy Childbirth ; 17(Suppl 2): 347, 2017 Nov 08.
Article in English | MEDLINE | ID: mdl-29143635

ABSTRACT

BACKGROUND: The perinatal period, which we here define as pregnancy and the first year postpartum, is a time in women's lives that involves significant physiological and psychosocial change and adjustment, including changes in their social status and decision-making power. Supporting women's empowerment at this particular time in their lives may be an attractive opportunity to create benefits for maternal and infant health outcomes such as reductions in perinatal depressive symptoms and premature birth rates. Thus, we here systematically review and critically discuss the literature that investigates the effects of empowerment, empowerment-related concepts and empowerment interventions on reductions in perinatal depressive symptoms, preterm birth (PTB), and low birthweight (LBW). METHODS: For this systematic review, we conducted a literature search in PsychInfo, PubMed, and CINAHL without setting limits for date of publication, language, study design, or maternal age. The search resulted in 27 articles reporting on 25 independent studies including a total of 17,795 women. RESULTS: The majority of studies found that, for the most part, measures of empowerment and interventions supporting empowerment are associated with reduced perinatal depressive symptoms and PTB/LBW rates. However, findings are equivocal and a small portion of studies found no significant association between empowerment-related concepts and perinatal depressive symptoms and PTB or LBW. CONCLUSION: This small body of work suggests, for the most part, that empowerment-related concepts may be protective for perinatal depressive symptoms and PTB/LBW. We recommend that future theory-driven and integrative work should include an assessment of different facets of empowerment, obtain direct measures of empowerment, and address the relevance of important confounders, including for example, ethnicity and socioeconomic status.


Subject(s)
Depression/psychology , Power, Psychological , Pregnancy Complications/psychology , Pregnant Women/psychology , Premature Birth/psychology , Adult , Female , Humans , Pregnancy , Young Adult
12.
Respiration ; 93(6): 424-429, 2017.
Article in English | MEDLINE | ID: mdl-28355600

ABSTRACT

BACKGROUND: There are few published studies about the usefulness of endobronchial ultrasound (EBUS) in patients infected with human immunodeficiency virus (HIV). The clinical spectrum of likely diseases in this population is varied and differs from patients not infected with HIV. OBJECTIVE: The aim of this study was to measure the usefulness of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) in HIV-infected patients with mediastinal lymphadenopathy. MATERIALS AND METHODS: We conducted an observational, cross-sectional, retrospective, descriptive study on patients with HIV infection and mediastinal lymphadenopathy who underwent EBUS-TBNA between September 2014 and April 2016. The patients' final diagnosis, regardless of the sample from which it was obtained, was considered the positive gold standard, and the absence of diagnosis was the negative. The study measured diagnostic accuracy of bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), and EBUS-TBNA. RESULTS: A total of 43 procedures were performed; 79.1% (34/43) of the patients were male, and the median age was 35 years (range, 22-66). The overall diagnostic yield including all types of samples was 90.7% (39/43); the yield of BAL was 50% (21), that of TBB 61.9% (26), and that of EBUS-TBNA was 60.5% (26). The combined yield of BAL with TBB was 69.8% (30); the yield of BAL with EBUS-TBNA was 86% (37) and that of TBB with EBUS-TBNA was 88.4% (38). The highest diagnostic accuracy was 97.7% for the combination of TBB and EBUS-TBNA. CONCLUSIONS: The most common infectious diagnoses were tuberculosis, with a higher diagnostic accuracy using EBUS-TBNA than BAL. With malignancies, both EBUS-TBNA and TBB were useful. EBUS-TBNA is a minimally invasive diagnostic tool that should be considered in these patients.


Subject(s)
Adenocarcinoma/diagnosis , HIV Infections/complications , Infections/diagnosis , Lung Neoplasms/diagnosis , Lymphadenopathy/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Mediastinal Diseases/diagnosis , Sarcoma, Kaposi/diagnosis , Adenocarcinoma/complications , Adenocarcinoma/pathology , Adult , Aged , Bacterial Infections/complications , Bacterial Infections/diagnosis , Bacterial Infections/pathology , Bronchoalveolar Lavage , Bronchoscopy , Cross-Sectional Studies , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Endosonography , Female , Humans , Infections/complications , Infections/pathology , Lung Neoplasms/complications , Lung Neoplasms/pathology , Lymphadenopathy/complications , Lymphadenopathy/pathology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Mediastinal Diseases/complications , Mediastinal Diseases/pathology , Mediastinum , Middle Aged , Mycoses/complications , Mycoses/diagnosis , Mycoses/pathology , Retrospective Studies , Sarcoma, Kaposi/complications , Sarcoma, Kaposi/pathology , Sensitivity and Specificity , Tuberculosis, Lymph Node/complications , Tuberculosis, Lymph Node/diagnosis , Tuberculosis, Lymph Node/pathology , Virus Diseases/complications , Virus Diseases/diagnosis , Virus Diseases/pathology , Young Adult
14.
Immunity ; 44(5): 1091-101, 2016 05 17.
Article in English | MEDLINE | ID: mdl-27192576

ABSTRACT

Signaling through the T cell receptor (TCR) controls adaptive immune responses. Antigen binding to TCRαß transmits signals through the plasma membrane to induce phosphorylation of the CD3 cytoplasmic tails by incompletely understood mechanisms. Here we show that cholesterol bound to the TCRß transmembrane region keeps the TCR in a resting, inactive conformation that cannot be phosphorylated by active kinases. Only TCRs that spontaneously detached from cholesterol could switch to the active conformation (termed primed TCRs) and then be phosphorylated. Indeed, by modulating cholesterol binding genetically or enzymatically, we could switch the TCR between the resting and primed states. The active conformation was stabilized by binding to peptide-MHC, which thus controlled TCR signaling. These data are explained by a model of reciprocal allosteric regulation of TCR phosphorylation by cholesterol and ligand binding. Our results provide both a molecular mechanism and a conceptual framework for how lipid-receptor interactions regulate signal transduction.


Subject(s)
Adaptive Immunity , Cholesterol/metabolism , Receptors, Antigen, T-Cell, alpha-beta/metabolism , T-Lymphocytes/immunology , Allosteric Regulation , Antigens/immunology , Antigens/metabolism , Histocompatibility Antigens/metabolism , Humans , Jurkat Cells , Lymphocyte Activation , Models, Immunological , Peptide Fragments/immunology , Peptide Fragments/metabolism , Phosphorylation , Protein Binding , Protein Conformation , Protein Stability , Signal Transduction
15.
Matern Child Health J ; 20(2): 422-33, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26728897

ABSTRACT

OBJECTIVE: Greater acculturation is associated with adverse perinatal outcomes in Mexican-American women, but the mechanisms by which acculturation influences perinatal outcomes are unclear. Pregnant acculturated Mexican-American women are more likely to engage in unhealthy prenatal behaviors relative to those less acculturated, including poor sleep. As sleep disruptions are associated with acculturation and negative perinatal outcomes, particularly maternal depression, alterations in sleep may adversely affect pregnant Mexican-American women. METHODS: Sixty pregnant women of Mexican descent completed surveys about sleep, acculturation, depressive symptoms and potential protective factor of social support. RESULTS: Acculturation, but not social support, significantly predicted increased sleep disruptions as well as overall feeling less refreshed upon waking across pregnancy. Moderation analysis indicated that more acculturated women who took longer to fall asleep reported increased depressive symptoms. Feeling refreshed upon waking also mediated the relationship between increased acculturation and elevated maternal depressive symptoms. CONCLUSIONS: Acculturation and altered sleep contribute to greater risk in Mexican-American women for maternal depressive symptoms in the perinatal period. These findings have implications for prevention and treatment of maternal mental health disorders, which may adversely affect perinatal outcomes in the vulnerable Mexican-American population.


Subject(s)
Acculturation , Depression/ethnology , Mexican Americans/psychology , Pregnancy Complications/psychology , Pregnant Women/ethnology , Sleep , Social Support , Adolescent , Adult , Cross-Sectional Studies , Depression/diagnosis , Depression/psychology , Family , Female , Humans , Longitudinal Studies , Mexican Americans/statistics & numerical data , Mexico/ethnology , Pregnancy , Pregnancy Complications/epidemiology , Pregnant Women/psychology , Risk Factors , Socioeconomic Factors , United States/epidemiology , Young Adult
16.
J Immunol ; 196(1): 448-58, 2016 Jan 01.
Article in English | MEDLINE | ID: mdl-26590318

ABSTRACT

Ligand binding to the TCR causes a conformational change at the CD3 subunits to expose the CD3ε cytoplasmic proline-rich sequence (PRS). It was suggested that the PRS is important for TCR signaling and T cell activation. It has been shown that the purified, recombinant SH3.1 domain of the adaptor molecule noncatalytic region of tyrosine kinase (Nck) can bind to the exposed PRS of CD3ε, but the molecular mechanism of how full-length Nck binds to the TCR in cells has not been investigated so far. Using the in situ proximity ligation assay and copurifications, we show that the binding of Nck to the TCR requires partial phosphorylation of CD3ε, as it is based on two cooperating interactions. First, the SH3.1(Nck) domain has to bind to the nonphosphorylated and exposed PRS, that is, the first ITAM tyrosine has to be in the unphosphorylated state. Second, the SH2(Nck) domain has to bind to the second ITAM tyrosine in the phosphorylated state. Likewise, mutations of the SH3.1 and SH2 domains in Nck1 resulted in the loss of Nck1 binding to the TCR. Furthermore, expression of an SH3.1-mutated Nck impaired TCR signaling and T cell activation. Our data suggest that the exact pattern of CD3ε phosphorylation is critical for TCR functioning.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Lymphocyte Activation/immunology , Oncogene Proteins/metabolism , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/immunology , Adaptor Proteins, Signal Transducing/genetics , Amino Acid Sequence , Binding Sites , CD3 Complex/metabolism , Cell Line, Tumor , Humans , Jurkat Cells , Oncogene Proteins/genetics , Phosphorylation , Proline-Rich Protein Domains , Protein Binding , Receptors, Antigen, T-Cell/immunology , Signal Transduction/immunology , src Homology Domains
17.
Biochim Biophys Acta ; 1853(4): 802-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25535948

ABSTRACT

In the last decade an increasing number of plasma membrane (PM) proteins have been shown to be non-randomly distributed but instead forming submicron-sized oligomers called nanoclusters. Nanoclusters exist independently of the ligand-bound state of the receptors and their existence implies a high degree of lateral organisation of the PM and its proteins. The mechanisms that drive receptor nanoclustering are largely unknown. One well-defined example of a transmembrane receptor that forms nanoclusters is the T cell antigen receptor (TCR), a multisubunit protein complex whose nanoclustering influences its activity. Membrane lipids, namely cholesterol and sphingomyelin, have been shown to contribute to TCR nanoclustering. However, the identity of the membrane microdomain in which the TCR resides remains controversial. Using a GFP-labeled TCR we show here that the resting TCR localized in the disordered domain of giant PM vesicles (GPMVs) and PM spheres (PMSs) and that single and nanoclustered TCRs are found in the high-density fractions in sucrose gradients. Both findings are indicative of non-raft localization. We discuss possible mechanisms of TCR nanoclustering in T cells. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.


Subject(s)
Membrane Microdomains/metabolism , Nanoparticles/chemistry , Receptors, Antigen, T-Cell/metabolism , Animals , Green Fluorescent Proteins/metabolism , Humans , Jurkat Cells , Lipids/chemistry , Mice , Protein Binding , Protein Structure, Tertiary , Protein Transport , Rats , Recombinant Fusion Proteins/metabolism , Unilamellar Liposomes/metabolism
18.
Cell Commun Signal ; 12: 21, 2014 Mar 26.
Article in English | MEDLINE | ID: mdl-24670066

ABSTRACT

BACKGROUND: Signalling by the T cell antigen receptor (TCR) results in the activation of T lymphocytes. Nck1 and Nck2 are two highly related adaptor proteins downstream of the TCR that each contains three SH3 and one SH2 domains. Their individual functions and the roles of their SH3 domains in human T cells remain mostly unknown. RESULTS: Using specific shRNA we down-regulated the expression of Nck1 or Nck2 to approximately 10% each in Jurkat T cells. We found that down-regulation of Nck1 impaired TCR-induced phosphorylation of the kinases Erk and MEK, activation of the AP-1 and NFAT transcription factors and subsequently, IL-2 and CD69 expression. In sharp contrast, down-regulation of Nck2 hardly impacts these activation read-outs. Thus, in contrast to Nck2, Nck1 is a positive regulator for TCR-induced stimulation of the Erk pathway. Mutation of the third SH3 domain of Nck1 showed that this domain was required for this activity. Further, TCR-induced NFAT activity was reduced in both Nck1 and Nck2 knock-down cells, showing that both isoforms are involved in NFAT activation. Lastly, we show that neither Nck isoform is upstream of p38 phosphorylation or Ca2+influx. CONCLUSIONS: In conclusion, Nck1 and Nck2 have non-redundant roles in human T cell activation in contrast to murine T cells.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Lymphocyte Activation , Oncogene Proteins/metabolism , Adaptor Proteins, Signal Transducing/chemistry , Adaptor Proteins, Signal Transducing/genetics , Antigens, CD/genetics , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/genetics , Antigens, Differentiation, T-Lymphocyte/metabolism , Humans , Interleukin-2/genetics , Interleukin-2/metabolism , Jurkat Cells , Lectins, C-Type/genetics , Lectins, C-Type/metabolism , MAP Kinase Signaling System , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Oncogene Proteins/chemistry , Oncogene Proteins/genetics , Protein Structure, Tertiary , Receptors, Antigen, T-Cell/metabolism , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism
19.
Exp Suppl ; 104: 9-23, 2014.
Article in English | MEDLINE | ID: mdl-24214615

ABSTRACT

Drug hypersensitivity reactions are immune mediated, with T lymphocytes being stimulated by the drugs via their T-cell antigen receptor (TCR). In the nonpathogenic state, the TCR is activated by foreign peptides presented by major histocompatibility complex molecules (pMHC). Foreign pMHC binds with sufficient affinity to TCRαß and thereby elicits phosphorylation of the cytoplasmic tails of the TCRαß-associated CD3 subunits. The process is called TCR triggering. In this review, we discuss the current models of TCR triggering and which drug properties are crucial for TCR stimulation. The underlying molecular mechanisms mostly include pMHC-induced exposure of the CD3 cytoplasmic tails or alterations of the kinase-phosphatase equilibrium in the vicinity of CD3. In this review, we also discuss triggering of the TCR by small chemical compounds in context of these general mechanisms.


Subject(s)
Histocompatibility Antigens/metabolism , Lymphocyte Activation , Receptor-CD3 Complex, Antigen, T-Cell/immunology , Superantigens/immunology , Animals , Histocompatibility Antigens Class II/immunology , Humans
20.
BMC Pediatr ; 12: 67, 2012 Jun 12.
Article in English | MEDLINE | ID: mdl-22691304

ABSTRACT

BACKGROUND: Tympanoplasty in children is a current and controversial theme. The success of tympanoplasty traditionally has been measured only by the post-operative integrity of the graft. Yet, there are other variables that may be used to determine success. The objectives of the present work were to analyze which factors are predictive of successful tympanoplasty in pediatric patients and to construct and validate a prognostic index that could be used as a tool to predict the success of tympanoplasty in children. SETTING: Department of Pediatric Otorhinolaryngology, tertiary-care hospital, Mexico City. PATIENTS: Forty-eight patients, who were older that five years of age, had persistent perforation of the tympanic membrane, and had undergone tympanoplasty (January 2005-June 2008), were followed for a year. MAIN OUTCOME MEASURES: The factors tested for their value as predictors were the following: age at time of surgery, state of contralateral ear, previous adenoidectomy, cause of perforation, size of perforation, infection at the time of surgery, state of mucosa, age at first occurrence of perforation, presence of craniofacial dysmorphia, and surgical technique. These factors were compared with the criterion, success, which was defined as attaining three positive outcomes: 1) integrity of the implant or membrane; 2) minimum of 10-dB gain in the auditory threshold or, in the case of normal hearing, conservation of same; and 3) air-filled space in the middle ear. The best model was obtained through logistic regression analysis; the model was validated. RESULTS: The most balanced prediction model was that in which the three success criteria were included, with age, surgical technique, and infection at surgery being excluded as variables. The additional 12 pediatric cases used in the validation had a probability of success >0.425 (best cut-off level); two patients (17%) had poor evolution. CONCLUSIONS: This is the first study that validated a predictive index of the result of tympanoplasty in children. This index predicted 81% of the successful outcomes.


Subject(s)
Decision Support Techniques , Tympanic Membrane Perforation/surgery , Tympanoplasty , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Health Status Indicators , Humans , Infant , Logistic Models , Male , Myringoplasty , Prospective Studies , Reproducibility of Results , Treatment Outcome
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