Results from the dissemination of an evidence-based telephone-delivered intervention for healthy lifestyle and weight loss: the Optimal Health Program

Despite proven efficacy, there are few published evaluations of telephone-delivered interventions targeting physical activity, healthy eating, and weight loss in community dissemination contexts. This study aims to evaluate participant and program outcomes from the Optimal Health Program, a telephone-delivered healthy lifestyle and weight loss program provided by a primary health care organization. Dissemination study used a single-group, repeated measures design; outcomes were assessed at 6-month (mid-program; n = 166) and 12-month (end of program; n = 88) using paired analyses. The program reached a representative sample of at-risk, primary care patients, with 56 % withdrawing before program completion. Among completers, a statistically significant improvement between baseline and end of program was observed for weight [mean change (SE) −5.4 (7.0) kg] and waist circumference [−4.8 (9.7) cm], underpinned by significant physical activity and dietary change. Findings suggest that telephone-delivered weight loss and healthy lifestyle programs can provide an effective model for use in primary care settings, but participant retention remains a challenge

Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study

<p>Abstract</p> <p>Background</p> <p>Low dietary intake of the essential nutrient choline and its metabolite betaine may increase atherogenesis both through effects on homocysteine methylation pathways as well as through choline's antioxidants properties. Nutrient values for many common foods for choline and betaine have recently become available in the U.S. nutrient composition database. Our objective was to assess the association of dietary intake of choline and betaine with incident coronary heart disease (CHD), adjusting for dietary intake measurement error.</p> <p>Methods</p> <p>We conducted a prospective investigation of the relation between usual intake of choline and betaine with the risk of CHD in 14,430 middle-aged men and women of the biethnic Atherosclerosis Risk in Communities study. A semi-quantitative food frequency questionnaire was used to assess nutrient intake. Proportional hazard regression models were used to calculate the risk of incident CHD. A regression calibration method was used to adjust for measurement error.</p> <p>Results</p> <p>During an average 14 years of follow-up (1987–2002), 1,072 incident CHD events were documented. Compared with the lowest quartile of intake, incident CHD risk was slightly and non-significantly higher in the highest quartile of choline and choline plus betaine, HR = 1.22 (0.91, 1.64) and HR = 1.14 (0.85, 1.53), controlling for age, sex, education, total energy intake, dietary intakes of folate, methionine and vitamin B₆. No association was found between dietary choline intake and incident CHD when correcting for measurement error.</p> <p>Conclusion</p> <p>Higher intakes of choline and betaine were not protective for incident CHD. Similar investigations in other populations are of interest.</p

Negative Regulation of Interferon-β Gene Expression during Acute and Persistent Virus Infections

The production of type I interferons (IFNs) in response to viral infections is critical for antiviral immunity. However, IFN production is transient, and continued expression can lead to inflammatory or autoimmune diseases. Thus, understanding the mechanisms underlying the negative regulation of IFN expression could lead to the development of novel therapeutic approaches to the treatment of these diseases. We report that the transcription factor IRF3 plays a central role in the negative regulation of interferon-β (IFNβ) expression during both acute and persistent (chronic) virus infections. We show that the degradation of IRF3 during acute infections, rather than the activation of transcriptional repressors, leads to the down regulation of IFNβ expression. We also show that the block to IFNβ expression in mouse embryonic fibroblasts that are persistently infected with Sendai virus (SeV) correlates with the absence of transcriptionally active IRF3. Remarkably, ongoing protein synthesis and viral replication are required to maintain repression of the IFNβ gene in persistently infected cells, as the gene can be activated by the protein synthesis inhibitor cycloheximide, or by the antiviral drug ribavirin. Finally, we show that the SeV V protein inhibits IRF3 activity in persistently infected cells. Thus, in conjunction with the known interference with STAT1 by the SeV C protein, both IFN activation and its signaling pathways are blocked in persistently infected cells. We conclude that the transcription factor IRF3 is targeted for turnover and inactivation through distinct mechanisms from both the host cells and virus, leading to the inhibition of IFNβ gene expression during acute and persistent viral infections. These observations show that IRF3 plays a critical role, not only in the activation of the IFNβ gene, but also in the controlling the duration of its expression. (284 words

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two-to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.212.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Conclusion: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Peer reviewe

Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”

We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus

Misunderstandings Concerning Genetics Among Patients Confronting Genetic Disease

Critical questions arise about misunderstandings of genetics. We interviewed for 2 h each, 64 individuals who had or were at risk for Huntington's disease (HD), breast cancer or Alpha‐1 antitrypsin deficiency. These individuals revealed various misunderstandings that can affect coping, and testing, treatment and reproductive decisions. A therapeutic misconception about testing appeared: that testing would be helpful in and of itself. Many believed they could control genetic disorders (even HD), yet these beliefs were often incorrect, and could impede coping, testing, and treatment. Misunderstandings about statistics and genetics often fueled each other, and reflected denial, and desires for hope and control. Emotional needs can thus outweigh understandings of genetics and statistics, and providers’ input. Individuals often maintained non‐scientific beliefs, though embarrassed by these. These data have implications for care, and public and professional education. Misunderstandings’ persistence, despite realization of their inaccuracy, suggests that providers need to address not just cognitive facts, but underlying emotional issues

Repeated long-distance dispersal and convergent evolution in hazel

Closely related species with a worldwide distribution provide an opportunity to understand evolutionary and biogeographic processes at a global scale. Hazel (Corylus) is an economically important genus of tree and shrub species found in temperate regions of Asia, North America and Europe. Here we use multiple nuclear and chloroplast loci to estimate a time-calibrated phylogenetic tree of the genus Corylus. We model the biogeographic history of this group and the evolutionary history of tree and shrub form. We estimate that multiple Corylus lineages dispersed long distances between Europe and Asia and colonised North America from Asia in multiple independent events. The geographic distribution of tree versus shrub form of species appears to be the result of 4–5 instances of convergent evolution in the past 25 million years. We find extensive discordance between our nuclear and chloroplast trees and potential evidence for chloroplast capture in species with overlapping ranges, suggestive of past introgression. The important crop species C. avellana is estimated to be closely related to C. maxima, C. heterophylla var. thunbergii and the Colurnae subsection. Our study provides a new phylogenetic hypothesis or Corylus and reveals how long-distance dispersal can shape the distribution of biodiversity in temperate plants

The History of Preconception Care: Evolving Guidelines and Standards

This article explores the history of the preconception movement in the United States and the current status of professional practice guidelines and standards. Professionals with varying backgrounds (nurses, nurse practitioners, family practice physicians, pediatricians, nurse midwives, obstetricians/gynecologists) are in a position to provide preconception health services; standards and guidelines for numerous professional organizations, therefore, are explored. The professional nursing organization with the most highly developed preconception health standards is the American Academy of Nurse Midwives (ACNM); for physicians, it is the American College of Obstetricians and Gynecologists (ACOG). These guidelines and standards are discussed in detail