Facilitators of peer leader retention within a Type 2 diabetes intervention trial for US Latinos/Hispanics of Mexican origin.

Peer support is effective in improving self-management behaviors and health outcomes among individuals with Type 2 diabetes. Volunteer peer support programs offer a cost-effective resource for diabetes self-management support; however, factors affecting the retention of volunteer peer leaders remain understudied. Herein, we examined factors associated with volunteer retention and satisfaction among 34 predominantly Mexican-origin peer leaders who assisted patients from a Federally Qualified Health Center located on the US/Mexico border with their diabetes management. Peer leaders completed surveys with open- and close-ended questions at baseline, 6 months and 12 months. Quantitative and qualitative data analyses were guided by the Volunteer Process Model. Using nonparametric Mann-Whitney U tests, self-efficacy as a peer leader at 6 months was most associated with interest to continue volunteering (P = 0.01), and satisfaction with support from the program at 12 months was most associated with interest to continue volunteering (P = 0.01). The qualitative data indicated that the relationship between the peer leaders and their patients was the primary factor for a satisfying volunteer experience. Future research should focus on increasing peer leaders' self-efficacy and satisfaction with program support and examine how organizations can support the development of the patient-peer relationship. Practitioners should consider appealing to volunteer peers' motivations to promote their retention.

A randomized controlled trial to prevent obesity among Latino paediatric patients.

BACKGROUND: Obesity disproportionately affects Latino youth. Community clinics are an important resource, yet there is little evidence for the efficacy of clinic-based approaches in this population. OBJECTIVE: The purpose of this study was to test the efficacy of a clinic-based intervention to lower body mass index (BMI) and improve body composition among overweight Latino children. METHODS: A randomized trial (2 group × 3 repeated measures) was conducted among 297 randomly sampled, overweight paediatric patients (5-10 years old) and their parents. The 12-month family-based culturally tailored behavioural intervention (Luces de Cambio) was based on the 'traffic light' concepts to address behaviour change and was delivered by clinic health educators and mid-level providers. The primary study outcome was child BMI (kg m-2 ) assessed at baseline, 6-month (n = 191) and 12-month (n = 201) post-baseline. A subsample of the children was examined for overall and site-specific adiposity using dual-energy X-ray absorptiometry (n = 79). RESULTS: There were no significant intervention effects on child BMI (p > 0.05); however, intervention children showed significantly (p < 0.05) lower total and trunk per cent fat compared with the usual care condition. CONCLUSIONS: The Luces intervention did not reduce child BMI, yet small but significant reductions were observed for child per cent body fat. Further research is needed to identify and reduce barriers to recruitment and participation among Latino families.

Childhood obesity prevention and control in city recreation centres and family homes: the MOVE/me Muevo Project.

BACKGROUND: Interventions to prevent and control childhood obesity have shown mixed results in terms of short- and long-term changes. OBJECTIVES: 'MOVE/me Muevo' was a 2-year family- and recreation centre-based randomized controlled trial to promote healthy eating and physical activity among 5- to 8-year-old children. It was hypothesized that children in the intervention group would demonstrate lower post-intervention body mass index (BMI) values and improved obesity-related behaviours compared with the control group children. METHODS: Thirty recreation centres in San Diego County, California, were randomized to an intervention or control condition. Five hundred forty-one families were enrolled and children's BMI, diet, physical activity and other health indicators were tracked from baseline to 2 years post-baseline. Analyses followed an intent-to-treat approach using mixed-effects models. RESULTS: No significant intervention effects were observed for the primary outcomes of child's or parent's BMI and child's waist circumference. Moderator analyses, however, showed that girls (but not boys) in the intervention condition reduced their BMI. At the 2-year follow-up, intervention condition parents reported that their children were consuming fewer high-fat foods and sugary beverages. CONCLUSIONS: Favourable implementation fidelity and high retention rates support the feasibility of this intervention in a large metropolitan area; however, interventions of greater intensity may be needed to achieve effects on child's BMI. Also, further research is needed to develop gender-specific intervention strategies so that both genders may benefit from such efforts.

The farnesyltransferase inhibitor, FTI-2153, inhibits bipolar spindle formation during mitosis independently of transformation and Ras and p53 mutation status.

Recently, we have shown that the farnesyltransferase inhibitor FTI-2153 induces accumulation of two human lung cancer cell lines in mitosis by inhibiting bipolar spindle formation during prometaphase. Here we investigate whether this mitotic arrest depends on transformation, Ras and/or p53 mutation status. Using DAPI staining (DNA) and immunocytochemistry (microtubules), we demonstrate that in normal primary foreskin fibroblasts (HFF), as well as in several cancer cell lines of different origins including human ovarian (OVCAR3), lung (A-549 and Calu-1) and fibrosarcoma (HT1080), FTI-2153 inhibits bipolar spindle formation and induces a rosette morphology with a monopolar spindle surrounded by chromosomes. In both malignant cancer cell lines and normal primary fibroblasts, the percentage of prometaphase cells with bipolar spindles decreases from 67-92% in control cells to 2-28% in FTI-2153 treated cells. This inhibition of bipolar spindle formation correlates with an accumulation of cells in prometaphase. The ability of FTI-2153 to inhibit bipolar spindle formation is not dependent on p53 mutation status since both wild-type (HFF, HT1080 and A-549) and mutant (Calu-1 and OVCAR3) p53 cells were equally affected. Similarly, both wild-type (HFF and OVCAR3) and mutant (HT1080, Calu-1 and A-549) Ras cells accumulate monopolar spindles following treatment with FTI-2153. However, two cell lines, NIH3T3 (WT Ras and WT p53) and the human bladder cancer cell line, T-24 (mutant H-Ras and mutant p53) are highly resistant to FTI-2153 inhibition of bipolar spindle formation. Finally, the ability of FTI-2153 to inhibit tumor cell proliferation does not correlate with inhibition of bipolar spindle formation. Taken together these results demonstrate that the ability of FTI-2153 to inhibit bipolar spindle formation and accumulate cells in mitosis is not dependent on transformation, Ras or p53 mutation status. Furthermore, in some cell lines, FTIs inhibit growth by mechanisms other than interfering with the prophase/metaphase traverse.

The farnesyltransferase inhibitor, FTI-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells.

Even though farnesyltransferase inhibitors (FTIs), a novel class of therapeutic agents presently in clinical trials, have preclinically outstanding anticancer activity and impressive lack of toxicity, their mechanism of action is not well understood. To enhance our understanding of how FTIs inhibit the growth of tumors, we have investigated their effects on cell cycle progression of two human lung cancer cell lines, A-549 and Calu-1. In this report, we show in synchronized A-549 and Calu-1 cells that FTI-2153 treatment resulted in a large accumulation of cells in the mitosis phase of the cell division cycle, with some cells in the G(0)/G(1) phase. Furthermore, microtubule immunostaining and 4,6-diamidino-2-phenylindole DNA staining demonstrated that the FTI-2153-induced accumulation in mitosis is due to the inability of these cells to progress from prophase to metaphase. FTI-2153 inhibited the ability of A-549 and Calu-1 cells to form bipolar spindles and caused formation of monoasteral spindles. Furthermore, FTI-2153 induced a ring-shaped chromosome morphology and inhibited chromosome alignment. Time-lapse videomicroscopy confirmed this result by showing that FTI-2153-treated cells are unable to align their chromosomes at the metaphase plate. FTI-2153 did not affect the localization to the kinetochores of two farnesylated centromeric proteins, CENP-E and CENP-F. Thus, a mechanism by which FTIs inhibit progression through mitosis and tumor growth is by blocking bipolar spindle formation and chromosome alignment.

The phosphoinositide 3-OH kinase/AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis.

Farnesyltransferase inhibitors (FTIs) represent a novel class of anticancer drugs that exhibit a remarkable ability to inhibit malignant transformation without toxicity to normal cells. However, the mechanism by which FTIs inhibit tumor growth is not well understood. Here, we demonstrate that FTI-277 inhibits phosphatidylinositol 3-OH kinase (PI 3-kinase)/AKT2-mediated growth factor- and adhesion-dependent survival pathways and induces apoptosis in human cancer cells that overexpress AKT2. Furthermore, overexpression of AKT2, but not oncogenic H-Ras, sensitizes NIH 3T3 cells to FTI-277, and a high serum level prevents FTI-277-induced apoptosis in H-Ras- but not AKT2-transformed NIH 3T3 cells. A constitutively active form of AKT2 rescues human cancer cells from FTI-277-induced apoptosis. FTI-277 inhibits insulin-like growth factor 1-induced PI 3-kinase and AKT2 activation and subsequent phosphorylation of the proapoptotic protein BAD. Integrin-dependent activation of AKT2 is also blocked by FTI-277. Thus, a mechanism for FTI inhibition of human tumor growth is by inducing apoptosis through inhibition of PI 3-kinase/AKT2-mediated cell survival and adhesion pathway.