Health, education and community: Assets and needs of a small urban community in north east Tamaulipas, Mexico: A community based participatory research assessment

This study explored the health, education, social assets, needs, attitudes, and behaviors of residents of Ferrocarril #4, a small urban community in Tamaulipas, Mexico. A collaborative Participatory Action Research approach was used to emphasize community involvement. Using Triangulation to ensure validity, qualitative methods included key informant in depth interviews, participant observation and participatory discussion groups with women and men. A personal interview with a probability sample of women was done. The median age of interviewees was 37 years. The majority was married or had a partner. Over half of respondents completed grades 6-9. Employed women (25%) earned a median weekly salary equivalent to ∼56 USD. Women with health insurance (67.7%) were covered mainly through Social Security and Seguro Popular. One in 5 reported bad health. Barriers to care were primarily money and transportation. To improve health care, women wanted a full service clinic in or close to the community and affordable health care. Socially, 28% of respondents had no close friends in the community and most did not participate in beneficial community activities. Many women did not socialize with others and help from neighbors was situational. Primary school teachers lacked parental support and it interfered with classroom efforts. Healthy community discussion groups focused on personal and environmental hygiene and safety. Valuable assets exist in the community. To date, collaborative efforts resulted in a school First Aid station, a school nurse visit weekly, posting of emergency contact phone numbers in the school and community center, and development of a student health information form. ^

Antibodies targeting hepatoma-derived growth factor as a novel strategy in treating lung cancer.

Hepatoma-derived growth factor (HDGF) is overexpressed in lung cancer and the overexpression correlates with aggressive biological behaviors and poor clinical outcomes. We developed anti-HDGF monoclonal antibodies and tested their antitumor activity in lung cancer xenograft models. We also determined biological effects in tumors treated with the antibody alone or in combination with bevacizumab/avastin (an anti-vascular endothelial growth factor antibody) and/or gemcitabine (a chemotherapeutic agent). We found the anti-HDGF was effective to inhibit tumor growth in non-small cell lung cancer xenograft models. In the A549 model, compared with control IgG, tumor growth was substantially inhibited in animals treated with anti-HDGF antibodies, particularly HDGF-C1 (P = 0.002) and HDGF-H3 (P = 0.005). When HDGF-H3 was combined with either bevacizumab or gemcitabine, we observed enhanced tumor growth inhibition, particularly when the three agents were used together. HDGF-H3-treated tumors exhibited significant reduction of microvessel density with a pattern distinctive from the microvessel reduction pattern observed in bevacizumab-treated tumors. HDGF-H3-treated but not bevacizumab-treated tumors also showed a significant increase of apoptosis. Interestingly, many of the apoptotic cells in HDGF-H3-treated tumors are stroma cells, suggesting that the mechanism of the antitumor activity is, at least in part, through disrupting formation of tumor-stroma structures. Our results show that HDGF is a novel therapeutic target for lung cancer and can be effectively targeted by an antibody-based approach.

Positional cloning and characterization of the human aniridia and murine small eye genes

Aniridia (AN) is a congenital, panocular disorder of the eye characterized by the complete or partial absence of the iris. The disease can occur in both the sporadic and familial forms which, in the latter case, is inherited as an autosomal dominant trait with high penetrance. The objective of this study was to isolate and characterize the genes involved in AN and Sey, and thereby to gain a better understanding of the molecular basis of the two disorders.^ Using a positional cloning strategy, I have approached and cloned from the AN locus in human chromosomal band 11p13 a cDNA that is deleted in two patients with AN. The deletions in these patients overlap by about 70 kb and encompass the 3$\sp\prime$ end of the cDNA. This cDNA detects a 2.7 kb mRNA encoded by a transcription unit estimated to span approximately 50 kb of genomic DNA. The message is specifically expressed in all tissues affected in all forms of AN, namely within the presumptive iris, lens, neuroretina, the superficial layers of the cornea, the olfactory bulbs, and the cerebellum. Sequence analysis of the AN cDNA revealed a number of motifs characteristic of certain transcription factors. Chief among these are the presence of the paired domain, the homeodomain, and a carboxy-terminal domain rich in serine, threonine and proline residues. The overall structure shows high homology to the Drosophila segmentation gene paired and members of the murine Pax family of developmental control genes.^ Utilizing a conserved human genomic DNA sequence as probe, I was able to isolate an embryonic murine cDNA which is over 92% homologous in nucleotide sequence and virtually identical at the amino acid level to the human AN cDNA. The expression pattern of the murine gene is the same as that in man, supporting the conclusion that it probably corresponds to the Sey gene. Its specific expression in the neuroectodermal component of the eye, in glioblastomas, but not in the neural crest-derived PC12 pheochromocytoma cell line, suggests that a defect in neuroectodermal rather mesodermal development might be the common etiological factor underlying AN and Sey. ^

A process evaluation of a health literacy intervention targeting pediatric providers' communication skills at the Texas Children's Health Plan

Background. Health literacy is an important determinant for quality health care, and affects communication between patients and physicians. Poor communication may result in negative effects in health. Improved communication between patients and physicians could positively affect health outcomes. Communication skills are teachable.^ Objectives. (1) to evaluate the process involved in the design and implementation of a health literacy intervention targeting pediatric providers’ communication skills at the Texas Children’s Health Plan in Houston, Texas; and (2) to describe lessons learned from this process that may be used in future attempts to address the issue of health literacy and health communication. ^ Design/methods. The process evaluation of the implementation of a health literacy strategy at the Texas Children’s Health Plan (TCHP) consisted of a critical analysis of all documents and minutes from meetings of the team of investigators. It also involved a secondary analysis of data collected between December 2006 and June 2007. Descriptive statistics, paired t-test and Wilcoxon-signed-rank test were employed in analyzing the data. This information was complemented with a limited review of existing literature on communication skills training programs. ^ Results. The design of the educational intervention followed recommendations from experts in the field of health literacy. The delivery of the intervention was possible and benefited from existing resources and logistics within the TCHP. Very few targeted providers participated in two offerings of the workshop (6.6% and 1.7% respectively). After the educational intervention, providers showed increased knowledge of health literacy facts and its effects in health (p=0.001); increased awareness of the low health literacy problem (p=0.003); increased expectations for change in practice (p=0.002), and intent to use health literacy strategies for communication immediately following the intervention (p=0.001). Low participation indicated the need for further investigation of barriers to, and means for successful implementation of programs aimed to improving health communication. ^ Conclusions. A short, focused intervention utilizing health literacy strategies for communication appeared effective in increasing knowledge and intentions for change in a small group of pediatric providers. ^

Induction of synthetic lethality in mutant KRAS cells for non-small cell lung cancers chemoprevention and therapy

Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. Despite improvement in treatment strategies, the 5-year survival rate of lung cancer patients remains low. Thus, effective chemoprevention and treatment approaches are sorely needed. Mutations and activation of KRAS occur frequently in tobacco users and the early stage of development of non-small cell lung cancers (NSCLC). So they are thought to be the primary driver for lung carcinogenesis. My work showed that KRAS mutations and activations modulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors by up-regulating death receptors and down-regulating decoy receptors. In addition, we showed that KRAS suppresses cellular FADD-like IL-1β-converting enzyme (FLICE)-like inhibitory protein (c-FLIP) expression through activation of ERK/MAPK-mediated activation of c-MYC which means the mutant KRAS cells could be specifically targeted via TRAIL induced apoptosis. The expression level of Inhibitors of Apoptosis Proteins (IAPs) in mutant KRAS cells is usually high which could be overcome by the second mitochondria-derived activator of caspases (Smac) mimetic. So the combination of TRAIL and Smac mimetic induced the synthetic lethal reaction specifically in the mutant-KRAS cells but not in normal lung cells and wild-type KRAS lung cancer cells. Therefore, a synthetic lethal interaction among TRAIL, Smac mimetic and KRAS mutations could be used as an approach for chemoprevention and treatment of NSCLC with KRAS mutations. Further data in animal experiments showed that short-term, intermittent treatment with TRAIL and Smac mimetic induced apoptosis in mutant KRAS cells and reduced tumor burden in a KRAS-induced pre-malignancy model and mutant KRAS NSCLC xenograft models. These results show the great potential benefit of a selective therapeutic approach for the chemoprevention and treatment of NSCLC with KRAS mutations.