Factors associated with urinary incontinence among Hispanic/Latina women in the United States: Findings from The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

PURPOSE: To identify factors associated with urinary incontinence (UI) in women of various Hispanic/Latina backgrounds. MATERIALS AND METHODS: We analyzed data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter, community-based cohort study which includes a health-related questionnaire assessing presence and type of UI. Complex survey logistic regression analysis was used to assess the cross-sectional association of Hispanic/Latina backgrounds and other factors of UI. All estimates accounted for HCHS/SOL survey design. RESULTS: Of 5027 women, 33.4% answered "yes" to UI. Rates of any UI ranged from approximately 21.9% to 40.3% in women of Dominican and Puerto-Rican background, respectively. Any UI and UI subtypes were associated with age older than 65 years, increasing body mass index, smoking status, any alcohol use, parity ≥3, and postmenopausal status. After controlling for covariates and when compared with women of Mexican background, women of Dominican background were less likely to have any UI (OR = 0.42, 95% CI 0.30-0.57), as were women of Cuban (OR = 0.48, 95% CI 0.37-0.62), Puerto-Rican (OR = 0.79, 95% CI 0.62-1.0), and mixed (OR = 0.62, 95% CI 0.39-0.99) background; and women of every other background except for South American were less likely to have stress UI. In addition, women of Cuban (OR = 0.53, 95% CI 0.32-0.86) and mixed (OR = 0.38, 95% CI 0.16-0.87) background were less likely to have urge UI than women of Mexican background. CONCLUSIONS: Our study demonstrates differences in UI by Hispanic/Latina background, suggesting collective designation of Hispanics/Latinas as a single ethnic group does not adequately describe UI among this diverse group.

Risk Factors for Cardiovascular Disease: Knowledge Gained from the Hispanic Community Health Study/Study of Latinos.

PURPOSE OF REVIEW: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) has made important contributions on the prevalence of and factors associated with cardiovascular disease (CVD) risk factors among diverse Hispanic/Latino adults in the US. This article summarizes the knowledge gained thus far on major CVD risk factors from this landmark study. RECENT FINDINGS: HCHS/SOL demonstrated the sizeable burdens of CVD risk in all major Hispanic/Latino groups in the US, as well as the marked variations in prevalence of hypertension, hypercholesterolemia, diabetes, obesity, and smoking by sex and background. It also identified sociodemographic, lifestyle, and sociocultural characteristics associated with risk factors. HCHS/SOL has yielded an expanding body of literature on characteristics associated with adverse CVD risk factors in this population. Long-term follow-up of this cohort will shed further light on the observed heterogeneity in CVD risk across Hispanic/Latino groups and identify specific risk/protective factors driving these variations.

Body image and disordered eating behaviors in Hispanic/Latino Youth: Findings from the Hispanic Community Health Study/Study of Latino Youth.

BACKGROUND: Prevalence of certain disordered eating behaviors is higher among Hispanic youth compared to non-Hispanics. Understanding the role of body image and social attitudes towards weight in disordered eating may inform treatment in Hispanic youth. METHODS: We analyzed data from the Hispanic Community Health Study/Study of Latino Youth (SOL Youth). Our sample included 1,463 children aged 8-16 years from four sites (Bronx, Chicago, Miami, San Diego) assessed in 2011-2014. Body image discrepancy score was calculated as the difference between perceived ideal body image and actual body image using two numbered visual graphs: adolescent (n = 728) or child (n = 735), each with slightly different scales. Questionnaires measured influences from social attitudes toward weight and disordered eating behaviors. Three disordered eating behaviors (dieting, overeating, and compensatory behaviors) were analyzed as the dependent variable. Logistic regression models adjusted for age, sex, acculturative stress, and field center to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: Mean body image discrepancy score was -0.79 for adolescents (SE = 0.08) and -0.50 for children (SE = 0.05), with a negative score signifying a perceived actual body image larger than their ideal. Body image discrepancy was strongly associated with dieting (dieting ≥5 times/year aOR = 0.64, 95% CI 0.53, 0.77) and compensatory behaviors (aOR = 0.65, 95% CI 0.50, 0.85) among adolescents, and was strongly associated with overeating among children (aOR = 0.74, 95% CI 0.61, 0.91). Significant associations were not observed with social attitudes towards weight. CONCLUSIONS: Associations observed with body image discrepancy and disordered eating behaviors can inform interventions in Hispanic/Latino youth, which should consider acculturative stress.

Maternal diabetes and hypertensive disorders in association with autism spectrum disorder.

Previous studies have shown complications of pregnancy, often examined in aggregate, to be associated with autism spectrum disorder (ASD). Results for specific complications, such as maternal diabetes and hypertension, have not been uniformly consistent and should be investigated independently in relation to ASD in a large community-based sample. The Study to Explore Early Development (SEED), a US multisite case-control study, enrolled children born in 2003-2006 at 2-5 years of age. Children were classified into three groups based on confirmation of ASD (n = 698), non-ASD developmental delay (DD; n = 887), or controls drawn from the general population (POP; n = 979). Diagnoses of any diabetes or hypertensive disorder during pregnancy were identified from prenatal medical records and maternal self-report. Logistic regression models estimated adjusted odds ratios (aOR) and confidence intervals (CI) adjusting for maternal age, race/ethnicity, education, smoking during pregnancy, and study site. Models for hypertension were additionally adjusted for parity and plurality. Among 2,564 mothers, we identified 246 (9.6%) with any diabetes and 386 (15.1%) with any hypertension in pregnancy. After adjustment for covariates, any diabetes during pregnancy was not associated with ASD (aOR = 1.10 [95% CI 0.77, 1.56]), but any hypertension was associated with ASD (aOR = 1.69 [95% CI 1.26, 2.26]). Results were similar for DD, and any diabetes (aOR = 1.29 [95% CI 0.94, 1.78]) or any hypertension (aOR = 1.71 [95% CI 1.30, 2.25]). Some pregnancy complications, such as hypertension, may play a role in autism etiology and can possibly serve as a prompt for more vigilant ASD screening efforts. Autism Res 2019, 12: 967-975. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied if common complications in pregnancy are associated with autism spectrum disorder (ASD) in a large sample of mothers and children. Our results show an association between conditions marked by high blood pressure and ASD, but no association with conditions marked by high blood sugar and ASD. Associations were similar for children who had a developmental disorder that was not ASD, suggesting that this relationship may not be specific to ASD.

Characterization of the enzymatic activity of the actin cross-linking domain from the Vibrio cholerae MARTX Vc toxin.

Vibrio cholerae is a Gram-negative bacterial pathogen that exports enterotoxins, which alter host cells through a number of mechanisms resulting in diarrheal disease. Among the secreted toxins is the multifunctional, autoprocessing RTX toxin (MARTX(Vc)), which disrupts actin cytoskeleton by covalently cross-linking actin monomers into oligomers. The region of the toxin responsible for cross-linking activity is the actin cross-linking domain (ACD). In this study, we demonstrate unambiguously that ACD utilizes G- and not F-actin as a substrate for the cross-linking reaction and hydrolyzes one molecule of ATP per cross-linking event. Furthermore, major actin-binding proteins that regulate actin cytoskeleton in vivo do not block the cross-linking reaction in vitro. Cofilin inhibits the cross-linking of G- and F-actin, at a high mole ratio to actin but accelerates F-actin cross-linking at low mole ratios. DNase I completely blocks the cross-linking of actin, likely due to steric hindrance with one of the cross-linking sites on actin. In the context of the holotoxin, the inhibition of Rho by the Rho-inactivating domain of MARTX(Vc) (Sheahan, K. L., and Satchell, K. J. F. (2007) Cell. Microbiol. 9, 1324-1335) would accelerate F-actin depolymerization and provide G-actin, alone or in complex with actin-binding proteins, for cross-linking by ACD, ultimately leading to the observed rapid cell rounding.

Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain.

Vibrio cholerae RTX is a large multifunctional bacterial toxin that causes actin crosslinking. Due to its size, it was predicted to undergo proteolytic cleavage during translocation into host cells to deliver activity domains to the cytosol. In this study, we identified a domain within the RTX toxin that is conserved in large clostridial glucosylating toxins TcdB, TcdA, TcnA, and TcsL; putative toxins from V. vulnificus, Yersinia sp., Photorhabdus sp., and Xenorhabdus sp.; and a filamentous/hemagglutinin-like protein FhaL from Bordetella sp. In vivo transfection studies and in vitro characterization of purified recombinant protein revealed that this domain from the V. cholerae RTX toxin is an autoprocessing cysteine protease whose activity is stimulated by the intracellular environment. A cysteine point mutation within the RTX holotoxin attenuated actin crosslinking activity suggesting that processing of the toxin is an important step in toxin translocation. Overall, we have uncovered a new mechanism by which large bacterial toxins and proteins deliver catalytic activities to the eukaryotic cell cytosol by autoprocessing after translocation.

The Actin cross-linking domain of the Vibrio cholerae RTX toxin directly catalyzes the covalent cross-linking of actin.

Vibrio cholerae is a Gram-negative bacterial pathogen that exports enterotoxins to alter host cells and to elicit diarrheal disease. Among the secreted toxins is the multifunctional RTX toxin, which causes cell rounding and actin depolymerization by covalently cross-linking actin monomers into dimers, trimers, and higher multimers. The region of the toxin responsible for cross-linking activity is the actin cross-linking domain (ACD). In this study, we further investigated the role of the ACD in the actin cross-linking reaction. We show that the RTX toxin cross-links actin independently of tissue transglutaminase, thus eliminating an indirect model of ACD activity. We demonstrate that a fusion protein of the ACD and the N-terminal portion of lethal factor from Bacillus anthracis (LF(N)ACD) has cross-linking activity in vivo and in crude cell extracts. Furthermore, we determined that LF(N)ACD directly catalyzes the formation of covalent linkages between actin molecules in vitro and that Mg(2+) and ATP are essential cofactors for the cross-linking reaction. In addition, G-actin is proposed as a cytoskeletal substrate of the RTX toxin in vivo. Future studies of the in vitro cross-linking reaction will facilitate characterization of the enzymatic properties of the ACD and contribute to our knowledge of the novel mechanism of covalent actin cross-linking.

Identification of a domain within the multifunctional Vibrio cholerae RTX toxin that covalently cross-links actin.

The Gram-negative pathogen Vibrio cholerae causes diarrheal disease through the export of enterotoxins. The V. cholerae RTX toxin was previously identified and characterized by its ability to round human laryngeal epithelial (HEp-2) cells. Further investigation determined that cell rounding is caused by the depolymerization of actin stress fibers, through the unique mechanism of covalent actin cross-linking. In this study, we identify a domain within the full-length RTX toxin that is capable of mediating the cross-linking reaction when transiently expressed within eukaryotic cells. A structure/function analysis of the actin cross-linking domain (ACD) reveals that a 412-aa, or a 47.8-kDa, region is essential for cross-linking activity. When this domain is deleted from the full-length toxin gene, actin cross-linking, but not cell rounding, is eliminated, indicating that this toxin carries multiple dissociable activities. The ACD shares 59% amino acid identity with a hypothetical protein from V. cholerae, VC1416, and transient expression of the C-terminal domain of VC1416 also results in actin cross-linking in eukaryotic cells. The presence of this second ACD linked to an Rhs-like element suggests that V. cholerae acquired the domain by horizontal gene transfer and the ACD was inserted into the RTX toxin by gene duplication through the evolution of V. cholerae.