Thermal sensitisation by lonidamine of human melanoma cells grown at low extracellular pH

Purpose: This study tested the ability of lonidamine (LND), a clinically applicable inhibitor of monocarboxylate transporters (MCT), to thermally sensitise human melanoma cells cultured at a tumour-like extracellular pH (pH_e) 6.7.

Materials and methods: Human melanoma DB-1 cells cultured at pH_e 6.7 and pH_e 7.3 were exposed to 150?µM LND for 3?h, beginning 1?h prior to heating at 42?°C (2?h). Intracellular pH (pH_i) was determined using 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) and whole spectrum analysis. Levels of heat shock proteins (HSPs) were determined by immunoblot analysis. Cell survival was determined by colony formation.

Results: Treatment with LND at pH_e 6.7 reduced pH_i to 6.30?±?0.21, reduced thermal induction of HSPs, and sensitised cells growing at pH_e 6.7 to 42?°C. When LND was combined with an acute acidification from pH_e 6.7 to pH_e 6.5, pH_i was reduced to 6.09?±?0.26, and additional sensitisation was observed. LND had negligible effects on cells cultured at pH 7.3.

Conclusions: The results show that LND can reduce pH_i in human melanoma cells cultured at a tumour-like low pH_e so that the 42?°C induction of HSPs are abrogated and the cells are sensitised to thermal therapy. Cells cultured at a normal tissue-like pH_e 7.3 were not sensitised to 42?°C by LND. These findings support the strategy that human melanoma cells growing in an acidic environment can be sensitised to thermal therapy in vivo by exposure to an MCT inhibitor such as LND.     

The Activity Support Scale for Multiple Groups (ACTS-MG): Child-reported Physical Activity Parenting in African American and Non-Hispanic White Families

This study aimed to assess the psychometric properties of a child-report, multidimensional measure of physical activity (PA) parenting, the Activity Support Scale for Multiple Groups (ACTS-MG), in African American and non-Hispanic white families. The ACTS-MG was administered to children aged 5 to 12 years. A three factor model of PA parenting (Modeling of PA, Logistic Support, and Restricting Access to Screen-based Activities) was tested separately for mother's and fathers' PA parenting. The proposed three-factor structure was supported in both racial groups for mothers’ PA parenting and in the African American sample for fathers’ PA parenting. Factorial invariance between racial groups was demonstrated for mother's PA parenting. Building on a previous study examining the ACTS-MG parent-report, this study supports the use of the ACTS-MG child-report for mothers’ PA parenting. However, further research is required to investigate the measurement of fathers’ PA parenting across racial groups.     

Longitudinal Associations Between HIV Risk Reduction and Out-of-School Time Program Participation

PurposeThe study aimed to determine the longitudinal associations between several variables assessing positive youth development and HIV risk-reduction practices.MethodsParticipants were 329 youth enrolled in out-of-school time programs in New York City. Longitudinal data were collected in three waves during 2008-2009 (baseline, 6-month follow-up, and 12-month follow-up). Because of the nested nature of the data, multivariate analyses were performed using multilevel models.ResultsAt baseline, HIV risk reduction was associated with female gender, greater individual-level program participation, and greater school connectedness. Over time, HIV risk reduction was associated with program-level participation: Individuals in groups with program-level participation scores 1 standard deviation below the average showed significant declines in risk reduction practices over the 1-year study period compared with individuals in more participatory programs.ConclusionsThis study provides support for the out-of-school environment as an important context for sustaining HIV risk reduction and positive health promotion practices.     

Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels

This work investigated the effects of cellular encapsulation density and differentiation stage on the osteogenic capacity of injectable, dual physically and chemically gelling hydrogels comprised of thermogelling macromers and polyamidoamine crosslinkers. Undifferentiated and osteogenically predifferentiated mesenchymal stem cells (MSCs) were encapsulated within 20 wt% composite hydrogels with gelatin microparticles at densities of six or 15 million cells/mL. We hypothesized that a high encapsulation density and predifferentiation would promote increased cellular interaction and accelerate osteogenesis, leading to enhanced osteogenic potential in vitro. Hydrogels were able to maintain the viability of the encapsulated cells over a period of 28 days, with the high encapsulation density and predifferentiation group possessing the highest DNA content at all time points. Early alkaline phosphatase activity and mineralization were promoted by encapsulation density, whereas this effect by predifferentiation was only observed in the low seeding density groups. Both parameters only demonstrated short-lived effects when examined independently, but jointly led to greater levels of alkaline phosphatase activity and mineralization. The combined effects suggest that there may be optimal encapsulation densities and differentiation periods that need to be investigated to improve MSCs for biomaterial-based therapeutics in bone tissue engineering.     

Evaluating the Impact of a School-based Prevention Program on Self-esteem,Body Image,and Risky Dieting Attitudes and Behaviors Among Kaua‘i Youth

Eating disorders and obesity (EDO) are increasing among youth, having serious long-term physical and psychological consequences. The purpose of this study was to determine if significant differences exist in EDO risk factors following participation of 4–6th grade students in a school-based EDO prevention curriculum. This community-based research project assessed students at baseline and one week following EDO intervention. Primary outcome variables measured self-esteem, body dissatisfaction, and high risk eating attitudes and behaviors. Pre and post-test differences were calculated using mixed models, correcting for clustering within schools and teachers. This study found mean changes in all scores in healthy directions, as well as movement of students into lower risk groups post-intervention. This program demonstrated that a classroom curriculum is associated with decreased risks of EDO in boys and girls, supporting prevention programs at an early age for both sexes. Studies to determine long term benefit and guide booster interventions are warranted.