Limited Genomics Training Among Physicians Remains a Barrier to Genomics-Based Implementation of Precision Medicine.

The field of precision medicine has undergone significant growth over the past 10 years. Despite increasing applications of clinical genetic and genomic testing, studies consistently report limited knowledge of genetics and genomics among healthcare providers. This study explored barriers to the implementation of precision medicine by surveying physicians working in a large academic medical center.

The Development of a Novel, Standards-Based Core Curriculum for Community Facing, Clinic-Based Community Health Workers.

Historically, CHW trainings have been developed to support community-based CHWs. When CHWs have been trained to engage with patients, typically such trainings have been for short term grant funded projects, focusing on a specific health intervention and not for long term, ongoing engagement of CHWs employed in clinical settings. To the best of our knowledge, this is the first such effort to describe the development of a standards-based training curriculum for clinic-based CHWs using a novel conceptual framework.

Argentina's National Program for Control of Breast Cancer: Time 1, Patient Navigation, and Patient Cancer Education Experience.

Argentina has the second highest mortality rate for breast cancer (BC) in South America. The age-standardized incidence of BC in Argentina is 73 per 100,000. Despite the availability of early detection services, 30% of BCs are diagnosed at advanced disease stages.

Serum levels of L1-ORF1p and airflow limitation.

http://bit.ly/2ZEIjNv.

Driving the precision medicine highway: community health workers and patient navigators.

The general public is currently bombarded with direct-to-consumer advertising, real time "medical" guidance through the internet, access to digital devices that capture health information, and science-based adds that promote foods, cosmetics, and dietary supplements. Unfortunately, much of this information relies on terminology and concepts not well-understood by consumers, particularly those with lower levels of health and genomic literacy. Such constraints align with the limitations of the American public to obtain and process the basic medical information needed to make appropriate healthcare decisions.

Precision prevention: A focused response to shifting paradigms in healthcare.

The study of LINE-1 retroelements and their role in the pathogenesis of diseases of the lung such as COPD and lung cancer may provide valuable diagnostic and therapeutic tools to identify pre-emptively individuals at risk of pulmonary disease progression. Limited information is presently available on the role of LINE-1 in the regulation of disease phenotypes and the development of novel therapeutics designed to curtail LINE-1-mediated pathogenesis. Successful implementation of precision prevention strategies may help to spare those impacted by obstructive pulmonary disease from continued deterioration, while realizing significant cost savings and improved quality of healthcare.

Genetics and epigenetics of pediatric leukemia in the era of precision medicine.

Pediatric leukemia represents a heterogeneous group of diseases characterized by germline and somatic mutations that manifest within the context of disturbances in the epigenetic machinery and genetic regulation. Advances in genomic medicine have allowed finer resolution of genetic and epigenetic strategies that can be effectively used to risk-stratify patients and identify novel targets for therapy. This review discusses the genetic and epigenetic mechanisms of leukemogenesis, particularly as it relates to acute lymphocytic leukemias, the mechanisms of epigenetic control of leukemogenesis, namely DNA methylation, histone modifications, microRNAs, and LINE-1 retroelements, and highlights opportunities for precision medicine therapeutics in further guiding disease management.

LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells.

Although several lines of evidence have established the central role of epithelial-to-mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE-1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis .

Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases.

The aryl hydrocarbon receptor agonist benzo(a)pyrene reactivates LINE-1 in HepG2 cells through canonical TGF-β1 signaling: implications in hepatocellular carcinogenesis.

Long interspersed nuclear element-1 (L1) is a genetic element that mobilizes throughout the mammalian genome via retrotransposition and damages host DNA via mutational insertions, chromosomal rearrangements, and reprogramming of gene expression. The cellular mechanisms responsible for aberrant L1 expression during cancer pathogenesis are unclear. Previously, we have shown that L1 reactivation in several human cell lines is dependent upon the activation of aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor member of the PAS superfamily of proteins.

LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex.

Background: Long Interspersed Nuclear Element-1 (L1) is an oncogenic mammalian retroelement silenced early in development via tightly controlled epigenetic mechanisms. We have previously shown that the regulatory region of human and murine L1s interact with retinoblastoma (RB) proteins to effect retroelement silencing. The present studies were conducted to identify the corepressor complex responsible for RB-mediated silencing of L1.

Culturally-Tailored Education Programs to Address Health Literacy Deficits and Pervasive Health Disparities among Hispanics in Rural Shelbyville, Kentucky.

Objectives: This investigation was conducted to evaluate the impact of culturally-tailored education on health knowledge among Hispanic residents of rural, Shelbyville, KY.

Design: The program identified specific pathways to address health literacy deficits and disparities identified through a community-wide health assessment completed in 2010.

Results: A total of 43 Hispanic males who shared deficiencies in community-wide health infrastructure were enrolled in the program.

Health status, perceptions and needs of Hispanics in rural Shelbyville, Kentucky.

This cross-sectional study was completed to characterize the health status, perceptions and needs of Hispanics in Shelbyville, KY, USA. Community Health Workers interviewed 668 Hispanic residents in Shelbyville, KY, USA. Data were collected from 2009 to 2010 and analyzed from 2011 until present.

In vivo expression of Helicobacter pylori virulence genes in patients with gastritis, ulcer, and gastric cancer.

The best-studied Helicobacter pylori virulence factor associated with development of peptic ulcer disease or gastric cancer (GC) rather than asymptomatic nonatrophic gastritis (NAG) is the cag pathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into host epithelial cells. Here we used real-time reverse transcription-PCR (RT-PCR) to measure the in vivo expression of genes on the cagPAI and of other virulence genes in patients with NAG, duodenal ulcer (DU), or GC. In vivo expression of H.

Helicobacter pylori genotyping from American indigenous groups shows novel Amerindian vacA and cagA alleles and Asian, African and European admixture.

It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups.

A mutant Ahr allele protects the embryonic kidney from hydrocarbon-induced deficits in fetal programming.

Background: The use of experimental model systems has expedited the elucidation of pathogenetic mechanisms of renal developmental disease in humans and the identification of genes that orchestrate developmental programming during nephrogenesis.

Objectives: We conducted studies to evaluate the role of AHR polymorphisms in the disruption of renal developmental programming by benzo(a)pyrene (BaP).

Methods: We used metanephric cultures of C57BL/6J (C57) mice expressing the Ahr(b-1) allele and B6.

Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru.

Operational research using a mixed method, cross-sectional, case-study approach assessed the feasibility and health system impact of large-scale implementation of human papillomavirus (HPV) vaccination into routine vaccine delivery by the Ministry of Health in Peru. The strategy was school-based vaccination of fifth grade girls in 527 primary schools in Piura region. Our evaluation showed that school-based HPV vaccination is feasible without major changes in existing health systems.

A primary Helicobacter pylori infection does not protect against reinfection in children after eradication therapy.

Background: Helicobacter pylori infection is one of the most common chronic infections in the world, and is acquired mainly during childhood. It is not clear to which extent a primary infection protects the child from reinfection. Our aim was to determine the possible protection conferred by a primary infection against H.

Environmental risk factors of disease in the Cameron Park Colonia, a Hispanic community along the Texas-Mexico border.

Objectives: This report summarizes the results of a cross-sectional study in Cameron Park in 2000-2001 to identify disease prevalence and health concerns among colonia residents and to identify environmental exposures to potentially adverse environmental conditions.

Results: Asthma and allergies were among the most prevalent respiratory diseases reported in both adults and children of Cameron Park. Other diseases affecting the community in higher numbers included diabetes and heart disease/high blood pressure.

Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.

In this descriptive study we investigated the genetic structure of 513 Mexican indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi, Purépecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua-Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua-Coyolillo) based on mtDNA haplogroups. These communities are geographically and culturally isolated; parents and grandparents were born in the community. Our data show that 98.

Extracorporeal membrane oxygenation: successful bridge to pediatric heart transplantation.

Since the year 2000, extracorporeal membrane oxygenation (ECMO) support for cardiac failure has been employed in the post operative care of children at the Centro Cardiovascular de Puerto Rico y el Caribe. Our experience with the application of ECMO had been limited to circulatory support after repair of congenital cardiac lesions. We report the first case in Puerto Rico where ECMO was used successfully as bridge to pediatric heart transplantation.

High rates of recurrence and of transient reinfections of Helicobacter pylori in a population with high prevalence of infection.

Objectives: Little is known concerning the magnitude of reinfection versus recrudescence of Helicobacter pylori (H. pylori) infection after eradication treatment. The aims of this study were to determine the magnitude of H.

Embracing the local: enriching scientific research, education, and outreach on the Texas-Mexico border through a participatory action research partnership.

Cameron Park, Texas, is a colonia (an isolated, unincorporated rural settlement without municipal improvements) on the Texas-Mexico border in the Lower Rio Grande Valley, in Cameron County near Brownsville, Texas. Cameron Park has a population of 5,961 residents, 99.3% of whom are Hispanic.