Sexual Dysfunction among Latino men and women with poorly controlled diabetes

Latinos are the largest minority population in the United States and are diagnosed with diabetes at nearly twice the rate of non-Hispanic whites. Latinos not only suffer disproportionately from diabetes but also from diabetes related complications, including sexual dysfunction. Much of the existing literature on sexual dysfunction among Latinos with diabetes has focused on erectile dysfunction (ED). There is a dearth of information on sexual functioning among Latina women with diabetes or information on both genders in other sexual domains. Our study examined the prevalence of sexual dysfunction among a cohort of 106 poorly controlled Latino diabetics in South Florida who participated in the Miami Healthy Heart Initiative, an NIH/NLBI sponsored clinical trial addressing diabetes management among Latinos. We explored gender differences in various domains of sexual health and examined the role of poor glycemic control and depression on sexual dysfunction. A large proportion of both genders in our sample met the criteria for sexual dysfunction though females exhibited a greater prevalence than males. Depression affected more than one third of our sample, but we did not find any significant associations between sexual dysfunction and depression. We also did not find a linear correlation between glycemic control and sexual dysfunction. We concluded that interventions are needed to address high rates of sexual dysfunction among Latinos with diabetes with particular emphasis on Latina women, who were much more likely than men to report problems with desire and other areas of sexual functioning. Until effective pharmacologic agents to improve desire among women with diabetes become available, clinicians caring for this population should consider behavioral approaches that may limit the impact of sexual dysfunction

A Community Needs Assessment of the Physical Activity and Food Environment in a Predominantly Hispanic U.S. City

Introduction: Hispanics suffer disproportionately compared with non-Hispanic Whites from health conditions that are affected by physical inactivity and poor dietary habits. Method: A needs assessment was conducted in Hialeah, Florida, the largest enclave of Cubans in the United States, to assess the perspectives of community stakeholders and members regarding the roles of physical activity and nutrition environments. Interviews were performed with community stakeholders (n = 21), and responses were grouped into major themes. Surveys were conducted with community members (n = 85). Descriptive analyses were used to categorize responses and potential differences across responses were explored. Results: Both community members and stakeholders reported that the local park system was a major asset to healthy living in Hialeah and agreed that traffic issues and a lack of walkability were major barriers to being physically active; however, there was variability in the response to the quality of the food environment. Conclusion: The perspectives of the community members and stakeholders will be valuable in highlighting pathways to enhancing the health and wellness of the residents of Hialeah

Neurofilament Heavy Polypeptide Regulates the Akt-β-Catenin Pathway in Human Esophageal Squamous Cell Carcinoma

Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth. We observed promoter methylation and loss of expression in neurofilament heavy polypeptide (NEFH) in a significant proportion of primary esophageal squamous cell carcinoma (ESCC) samples that were of a high tumor grade and advanced stage. RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo, whereas forced expression of NEFH significantly inhibited cell growth and colony formation. Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase, via activation of the Akt/β-catenin pathway, resulting in enhanced aerobic glycolysis and mitochondrial dysfunction. The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of β-catenin expression, and was decreased by the treatment of 2-Deoxyglucose, a glycolytic inhibitor, or API-2, an Akt inhibitor. Loss of NEFH activates the Akt/β-catenin pathway and increases glycolysis and mitochondrial dysfunction. Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways

Cluster randomized trial of the impact of an obesity prevention intervention on child care center nutrition and physical activity environment over two years

Objective: The prevalence of obesity among preschool-aged children in the United States remains unacceptably high. Here we examine the impact of Healthy Caregivers-Healthy Children (HC2) Phase 2, a child care center (CCC)-based obesity prevention intervention on changes in the CCC nutrition and physical activity environment over two school years. Design: This was a cluster randomized trial with 12 CCC receiving the HC2 intervention arm and 12 in the control arm. The primary outcome was change in the Environment and Policy Assessment and Observation (EPAO) tool over two school years (Fall-2015, Spring-2016 and Spring-2017). Changes in EPAO physical activity and nutrition score were analyzed via a (1) random effects mixed models and (2) mixed models to determine the effect of HC2 versus control. Setting: The study was conducted in 24 CCCs serving low-income, ethnically diverse families in Miami-Dade County. Participants: Intervention CCCs received (1) teachers/parents/children curriculum; (2) snack, beverage, physical activity, and screen time policies; and (3) menu modifications. Results: Two-year EPAO nutrition score changes in intervention CCCs were almost twice that of control CCCs. The EPAO physical activity environment scores only slightly improved in intervention CCCs versus control CCCs. Intervention CCCs showed higher combined EPAO physical activity and nutrition scores compared to control CCCs over the 2-year study period (β=0.09, P=0.05). Conclusions: Obesity prevention programs can have a positive impact on the CCC nutrition environment and can promote healthy weight in early childhood. CCCs may need consistent support to improve the physical activity environment to ensure the policies remain intact

Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3

The MDM2 homolog MDMX is an important regulator of p53 during mouse embryonic development. DNA damage promotes MDMX phosphorylation, nuclear translocation, and degradation by MDM2. Here we show that MDMX copurifies with 14-3-3, and DNA damage stimulates MDMX binding to 14-3-3. Chk2-mediated phosphorylation of MDMX on S367 is important for stimulating 14-3-3 binding, MDMX nuclear import by a cryptic NLS, and degradation by MDM2. Mutation of MDMX S367 inhibits ubiquitination and degradation by MDM2, and prevents MDMX nuclear import. Expression of 14-3-3 stimulates the degradation of phosphorylated MDMX. Chk2 and 14-3-3 cooperatively stimulate MDMX ubiquitination and overcome the inhibition of p53 by MDMX. These results suggest that MDMX-14-3-3 interaction plays a role in p53 response to DNA damage by regulating MDMX localization and stability. We also show the identification of a cryptic nuclear localization sequence within the C-terminus RING finger domain MDMX. Mutation of MDMX on one lysine residue at position 468 to glutamic acid completely abrogates the nuclear import after DNA damage. This mutation had no effect on MDM2-mediated nuclear import of MDMX in cotransfection assays, suggesting that it is specifically required for the MDM2-independent nuclear import. Interestingly, the MDMX- K468E mutant induces the expression of p21 more efficiently than the wild-type MDMX after ionizing radiation (IR). Furthermore, the K468E mutant induction of p21 is associated with enhanced G1 arrest after DNA damage. These results indicate an important function of MDMX nuclear import in regulating p53 activity after DNA damage

Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3

The MDM2 homolog MDMX is an important regulator of p53 during mouse embryonic development. DNA damage promotes MDMX phosphorylation, nuclear translocation, and degradation by MDM2. Here we show that MDMX copurifies with 14-3-3, and DNA damage stimulates MDMX binding to 14-3-3. Chk2-mediated phosphorylation of MDMX on S367 is important for stimulating 14-3-3 binding, MDMX nuclear import by a cryptic NLS, and degradation by MDM2. Mutation of MDMX S367 inhibits ubiquitination and degradation by MDM2, and prevents MDMX nuclear import. Expression of 14-3-3 stimulates the degradation of phosphorylated MDMX. Chk2 and 14-3-3 cooperatively stimulate MDMX ubiquitination and overcome the inhibition of p53 by MDMX. These results suggest that MDMX-14-3-3 interaction plays a role in p53 response to DNA damage by regulating MDMX localization and stability. We also show the identification of a cryptic nuclear localization sequence within the C-terminus RING finger domain MDMX. Mutation of MDMX on one lysine residue at position 468 to glutamic acid completely abrogates the nuclear import after DNA damage. This mutation had no effect on MDM2-mediated nuclear import of MDMX in cotransfection assays, suggesting that it is specifically required for the MDM2-independent nuclear import. Interestingly, the MDMX- K468E mutant induces the expression of p21 more efficiently than the wild-type MDMX after ionizing radiation (IR). Furthermore, the K468E mutant induction of p21 is associated with enhanced G1 arrest after DNA damage. These results indicate an important function of MDMX nuclear import in regulating p53 activity after DNA damage

A Machine Learning Approach for Predicting Early Childhood Obesity among Ethnically Diverse Families

Early childhood obesity continues to be a clinical and public health challenge in the United States; almost a third of children ages 2-to-5 years old are either overweight or obese. Non-Hispanic Blacks (NHB) have double and Hispanics have triple the rates of obesity by age 5 compared to non-Hispanic Whites (NHW) and Asians (10.4%, 15.6%, 5.2%, and 5.0%, respectively). Current evidence suggests that pregnancy, infancy, and early childhood are critical periods in the development of overweight/obesity throughout the lifespan. However, the majority of studies included non-Hispanic White, high-income study samples, presenting serious doubts as to the generalizability of their conclusions. To better understand how early life factors impact the onset of childhood obesity by age 2, this study utilized data from the UHealth Electronic Medical Records (EMR) database. First, multivariate linear regression models were conducted on a series of prenatal and perinatal risk and protective variables and the outcome of zBMI at age 2 years. Next, race/ethnicity was analyzed as a moderator of the relationship between each of those risk/protective variables and zBMI at age 2 years. Finally, age- and sex-specific BMI percentiles were dichotomized into overweight versus lean and a series of data mining techniques were conducted to investigate predictors including 10-fold cross validation of logistic regression, Classification and Regression Trees (CART) methodology, and naïve Bayes estimation. Obesity complicating pregnancy and Medicaid use were consistent risk factors, and breastfeeding initiation was a consistent protective factor. Results from this dissertation inform clinical decision support recommendations as well as the development of obesity prevention interventions targeting pregnancy, prenatal, and early childhood developmental periods

Medication administration by caregiving youth: An inside look at how adolescents manage medications for family members

Children take on the role of family caregiver throughout the world. No prior published research exists surrounding the particular circumstances of the task of medication administration and management by these youth, which was explored in this study. A series of focus groups were conducted using semi-structured interviews of 28 previously identified caregiving youth ages 12–19 years old who live in the United States. Data analysis followed guidelines of conventional content analysis. The following categories emerged about youth caregivers handling medications: 1) tasks involve organizational and administrative responsibilities; 2) youth have varying degrees of knowledge pertaining to these medications; 3) most share responsibility with other family members; 4) they lack formal education about their responsibilities; 5) multiple challenges exist relating to this task; 6) managing medications is associated with emotional responses; and 7) possible safety issues exist. These responsibilities represent a unique hardship and merit support and research from the medical, healthcare, legislative, and public health communities, among others

Glucometer Use and Glycemic Control Among Hispanic Patients With Diabetes in Southern Florida

Self-monitoring of blood glucose (SMBG) has been deemed a critical component of diabetes care in the United States. To be effective, patients must have some diabetes knowledge, glucometer proficiency, and an ability to take appropriate actions when certain readings are obtained. However, most patients take no action in response to out-of-range glucometer readings, and in many populations, SMBG practices are not associated with improved glycemic control. Thus, SMBG utilization is being reconsidered in other countries. Nonetheless, SMBG behaviors are increasingly recommended in the United States, where the Hispanic population represents the fastest-growing minority group and is disproportionately affected by suboptimal diabetes outcomes. Because a growing number of interventions aim to reduce diabetes disparities by improving glycemic control among minorities, it is essential to determine whether efforts should focus on SMBG practices. We present data on SMBG behaviors and glycemic control among participants from the Miami Healthy Heart Initiative (MHHI), a National Institutes of Health/National Heart, Lung, and Blood Institute–sponsored trial assessing a community health worker (CHW) intervention among Hispanic patients with poorly controlled diabetes. This study examined the effects of a CHW intervention on SMBG practices, glycosylated hemoglobin (HbA1c), and knowledge of appropriate responses to glucometer readings among Hispanic patients with diabetes. This study was an ancillary investigation within MHHI, a randomized, controlled trial in 300 Hispanic patients. Participants were intervention-group members who received 12 months of CHW support. Assessments were administered at baseline and poststudy to determine potential barriers to optimal health. Items from validated instruments were used to determine knowledge of appropriate responses to different glucose readings. These data were linked to HbA1c values. Means and frequencies were used to describe population characteristics and glucometer proficiency. Paired-sample t tests examined potential differences in HbA1c outcomes and SMBG practices. Qualitative data were collected from the CHWs who worked with study participants. Our population was diverse, representing several countries. Mean HbA1c improved significantly, from 10% to 8.8% (P ≤ 0.001). SMBG practices did not change. At baseline, 96% of patients reported owning a glucometer and 94% reported knowing how to use it. However, quantitative assessments and qualitative data suggested that participants had suboptimal knowledge regarding actions that could cause an out-of-range reading or how to respond to certain readings. SMBG behaviors were not associated with glycemic control in our sample. We conclude that a CHW intervention may improve glycemic control without improving SMBG practices. Future interventions may reconsider whether efforts should be directed toward improving SMBG behaviors