Cellular heterogeneity plays a pivotal role in a variety of functional processes in vivo including carcinogenesis. However, our knowledge about cell-to-cell diversity and how differences in individual cells manifest in alterations at the population level remains very limited mainly due to the lack of appropriate tools enabling studies at the single-cell level. We present a study on changes in cellular heterogeneity in the context of pre-malignant progression in response to hypoxic stress. Utilizing pre-malignant progression of Barrett’s esophagus (BE) as a disease model system we studied molecular mechanisms underlying the progression from metaplastic to dysplastic (pre-cancerous) stage. We used newly developed methods enabling measurements of cell-to-cell differences in copy numbers of mitochondrial DNA, expression levels of a set of mitochondrial and nuclear genes involved in hypoxia response pathways, and mitochondrial membrane potential. In contrast to bulk cell studies reported earlier, our study shows significant differences between metaplastic and dysplastic BE cells in both average values and single-cell parameter distributions of mtDNA copy numbers, mitochondrial function, and mRNA expression levels of studied genes. Based on single-cell data analysis, we propose that mitochondria may be one of the key factors in pre-malignant progression in BE.

Objective: To assess the informational, educational and instrumental environments among Mexican healthcare settings for their potential to promote physical activity (PA).

Materials and Methods: The Environmental Physical Activity Assessment Tool for Healthcare Settings (EPATHS) was developed to assess the PA environments of 40 clinics/hospitals representing the three Mexican healthcare systems in Guadalajara. The EPATHS assessed the presence and quality of PA enhancing features in the informational (e.g. signage),educational (e.g. pamphlets), and instrumental (e.g. stairs)environments of included clinics/hospitals.

Results: 28 (70%) clinics/hospitals had more than one floor with stairs; 60% of these had elevators. Nearly 90% of stairs were visible, accessible and clean compared to fewer than 30% of elevators. Outdoor spaces were observed in just over half (55%) of clinics/hospitals, and most (70%) were of good quality. Only 25% clinics/hospitals had educational PA materials.

Conclusions: The PA instrumental environment of Mexican healthcare settings is encouraging. The informational and educational environments could improve.

Objective: This cross sectional study aims to determine the effects of gender and parental perception of safety at school on children’s physical activity (PA) levels.

Materials and Methods: Parents of school aged Mexican children residing in Guadalajara, Mexico City, and Puerto Vallarta, completed surveys about their children’s PA measures. The physical activity indicators were evaluated using linear and logistical regression models.

Results: Analysis did not indicate that gender moderated the relationship between parental perception of safety and PA measures, but significant gender issues exist with girls participating less than boys in the three measures of PA in this study (p<0.001).

Conclusion: Results suggest the need for additional interventions promoting physical activity in girls in Mexico.

Quantitative three-dimensional (3D) computed tomography (CT) imaging of living single cells enables orientation-independent morphometric analysis of the intricacies of cellular physiology. Since its invention, x-ray CT has become indispensable in the clinic for diagnostic and prognostic purposes due to its quantitative absorption-based imaging in true 3D that allows objects of interest to be viewed and measured from any orientation. However, x-ray CT has not been useful at the level of single cells because there is insufficient contrast to form an image. Recently, optical CT has been developed successfully for fixed cells, but this technology called Cell-CT is incompatible with live-cell imaging due to the use of stains, such as hematoxylin, that are not compatible with cell viability. We present a novel development of optical CT for quantitative, multispectral functional 4D (three spatial + one spectral dimension) imaging of living single cells. The method applied to immune system cells offers truly isotropic 3D spatial resolution and enables time-resolved imaging studies of cells suspended in aqueous medium. Using live-cell optical CT, we found a heterogeneous response to mitochondrial fission inhibition in mouse macrophages and differential basal remodeling of small (0.1 to 1 fl) and large (1 to 20 fl) nuclear and mitochondrial structures on a 20- to 30-s time scale in human myelogenous leukemia cells. Because of its robust 3D measurement capabilities, live-cell optical CT represents a powerful new tool in the biomedical research field.

Background: Low physical activity (PA) and fruit and vegetable (F&V) consumption in early childhood are continued public health challenges. This manuscript describes outcomes from two pilot studies for Sustainability via Active Garden Education (SAGE), a program designed to increase PA and F&V consumption among 3 to 5 year old children.

Methods: SAGE was developed using community-based participatory research (CBPR) and delivered to children (N = 89) in early care and education centers (ECEC, N = 6) in two US cities. Children participated in 12 one-hour sessions that included songs, games, and interactive learning activities involving garden maintenance and taste tests. We evaluated reach, efficacy, adoption, implementation, and potential for maintenance of SAGE following the RE-AIM framework. Reach was evaluated by comparing demographic characteristics among SAGE participants and residents of target geographic areas. Efficacy was evaluated with accelerometer-measured PA, F&V consumption, and eating in the absence of hunger among children, parenting practices regarding PA, and home availability of F&V. Adoption was evaluated by the number of ECEC that participated relative to the number of ECEC that were recruited. Implementation was evaluated by completion rates of planned SAGE lessons and activities, and potential for maintenance was evaluated with a parent satisfaction survey.

Results: SAGE reached ECEC in neighborhoods representing a wide range of socioeconomic status, with participants’ sociodemographic characteristics representing those of the intervention areas. Children significantly increased PA during SAGE lessons compared to usual lessons, but they also consumed more calories in the absence of hunger in post- vs. pre-intervention tests (both p < .05). Parent reports did not suggest changes in F&V consumption, parenting PA practices, or home F&V availability, possibly due to low parent engagement. ECEC had moderate-to-high implementation of SAGE lessons and curriculum. Potential for maintenance was strong, with parents rating SAGE favorably and reporting increases in knowledge about PA and nutrition guidelines for young children.

Conclusions: SAGE successfully translated national PA guidelines to practice for young children but was less successful with nutrition guidelines. High adoption and implementation and favorable parent reports suggest high potential for program sustainability. Further work to engage parents and families of young children in ECEC-based PA and nutrition programming is needed.

Driven by an increasing number of studies demonstrating its relevance to a broad variety of disease states, the bioenergy production phenotype has been widely characterized at the bulk sample level. Its cell-to-cell variability, a key player associated with cancer cell survival and recurrence, however, remains poorly understood due to ensemble averaging of the current approaches. We present a technology platform for performing oxygen consumption and extracellular acidification measurements of several hundreds to 1,000 individual cells per assay, while offering simultaneous analysis of cellular communication effects on the energy production phenotype. The platform comprises two major components: a tandem optical sensor for combined oxygen and pH detection, and a microwell device for isolation and analysis of single and few cells in hermetically sealed sub-nanoliter chambers. Our approach revealed subpopulations of cells with aberrant energy production profiles and enables determination of cellular response variability to electron transfer chain inhibitors and ion uncouplers.

The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an ‘epigenetic’ drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat’s differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.

Background: Continuous monitoring technologies such as accelerometers and pedometers are the gold standard for physical activity (PA) measurement. However, inconsistencies in use, analysis, and reporting limit the understanding of dose–response relationships involving PA and the ability to make comparisons across studies and population subgroups. These issues are particularly detrimental to the study of PA across different ethnicities with different PA habits. This systematic review examined the inclusion of published guidelines involving data collection, processing, and reporting among articles using accelerometers or pedometers in Hispanic or Latino populations.

Methods: English (PubMed; EbscoHost) and Spanish (SCIELO; Biblioteca Virtual en Salud) articles published between 2000 and 2013 using accelerometers or pedometers to measure PA among Hispanics or Latinos were identified through systematic literature searches. Of the 253 abstracts which were initially reviewed, 57 met eligibility criteria (44 accelerometer, 13 pedometer). Articles were coded and reviewed to evaluate compliance with recommended guidelines (N = 20), and the percentage of accelerometer and pedometer articles following each guideline were computed and reported.

Results: On average, 57.1 % of accelerometer and 62.2 % of pedometer articles reported each recommended guideline for data collection. Device manufacturer and model were reported most frequently, and provision of instructions for device wear in Spanish was reported least frequently. On average, 29.6 % of accelerometer articles reported each guideline for data processing. Definitions of an acceptable day for inclusion in analyses were reported most frequently, and definitions of an acceptable hour for inclusion in analyses were reported least frequently. On average, 18.8 % of accelerometer and 85.7 % of pedometer articles included each guideline for data reporting. Accelerometer articles most frequently included average number of valid days and least frequently included percentage of wear time.

Discussion: Inclusion of standard collection and reporting procedures in studies using continuous monitoring devices in Hispanic or Latino population is generally low.

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

Hydrophobic platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (PtTFPP) was physically incorporated into micelles formed from poly(ε-caprolactone)-block-poly(ethylene glycol) to enable the application of PtTFPP in aqueous solution. Micelles were characterized using dynamic light scattering (DLS) and atomic force microscopy (AFM) to show an average diameter of about 140 nm. PtTFPP showed higher quantum efficiency in micellar solution than in tetrahydrofuran (THF) and dichloromethane (CH₂Cl₂). PtTFPP in micelles also exhibited higher photostability than that of PtTFPP suspended in water. PtTFPP in micelles exhibited good oxygen sensitivity and response time. This study provided an efficient approach to enable the application of hydrophobic oxygen sensors in a biological environment.