The Physical Activity and Alzheimer's Disease (PAAD) Study: Cognitive outcomes.

Background: Alzheimer's disease is a progressive disease that degrades cognitive functioning and ultimately results in death. Currently, there is no cure for Alzheimer's disease and, hence, the identification of preventative strategies is important. Physical activity (PA) is a behavioral intervention that holds promise with respect to delaying the onset of Alzheimer's disease. Purpose: The purpose of this study was to explore the differential cognitive benefits achieved in response to PA as a function of a person's genetic risk for AD. Methods: Older cognitively normal adults (50-65 years) with a family history of AD (FHxAD) participated in an 8-month PA program. Cognitive performance was measured at baseline, pretest, midtest, and posttest and changes over time were assessed as a function of apolipoprotein E (APOE) status (carriers: 1-2 copies of the ɛ4 allele; noncarriers: 0 copies of the ɛ4 allele). Results: Improvements in memory were associated with PA participation irrespective of APOE ɛ4 carrier status. Conclusions: Future experimental studies are needed to confirm that PA causes improvements to cognitive performance in older cognitively normal adults with a FHxAD and that these improvements are equivalent for cognitively normal APOE ɛ4 carriers and noncarriers.

Further evidence of the limited role of candidate genes in relation to infant-mother attachment outcomes.

In this paper, we examine the associations between specific candidate genes (DRD2, DRD4, COMT, biallelic and tri-allelic 5HTTLPR, and OXTR) and infant attachment outcomes as main effects and in conjunction with maternal sensitivity. The sample included 200 infants (97 European American, 94 African-American, and 9 biracial) and their mothers. Maternal sensitivity and overtly negative maternal behavior were observed when infants were 6 months and 1 year old in distress-eliciting contexts, attachment was assessed via the Strange Situation at age 1, and DNA samples were collected when children were 2 years old. Consistent with recent research in large samples, there was little evidence that these genes are associated with attachment security, disorganization, or distress as main effects (in additive, dominant, and homozygous models) or in conjunction with maternal sensitivity or overtly negative behavior (primarily dominance models). Furthermore, there was little evidence that associations vary as a function of race.

Nano-SPRi Aptasensor for the Detection of Progesterone in Buffer.

Progesterone is a steroid hormone that plays a central role in the female reproductive processes such as ovulation and pregnancy with possible effects on other organs as well. The measurement of progesterone levels in bodily fluids can assist in early pregnancy diagnosis and can provide insight for other reproductive functions. In this work, the detection of progesterone was examined by integrating novel aptamer development with a nanoEnhanced surface plasmon resonance imaging sensor. First, we developed X-aptamers and selected them for binding to progesterone. Then, we took advantage of the multi-array feature of SPRi to develop an optimized biosensor capable of simultaneously screening the 9 X-aptamers developed to determine the binding capabilities of each aptamer. The sensor surface design conditions were further optimized for the sandwich assay, which employed nanoEnhancers (NIR-streptavidin coated quantum dots) for ultrasensitive detection of progesterone molecules. The assay designed was examined over a concentration range of 1.575 ng/mL to 126 µg/mL resulting in a limit of detection (LOD) of 1.575 ng/mL (5 nM) in phosphate buffer.

Clinical utility of a Web-enabled risk-assessment and clinical decision support program.

PURPOSE: Risk-stratified guidelines can improve quality of care and cost-effectiveness, but their uptake in primary care has been limited. MeTree, a Web-based, patient-facing risk-assessment and clinical decision support tool, is designed to facilitate uptake of risk-stratified guidelines. METHODS: A hybrid implementation-effectiveness trial of three clinics (two intervention, one control). PARTICIPANTS: consentable nonadopted adults with upcoming appointments. PRIMARY OUTCOME: agreement between patient risk level and risk management for those meeting evidence-based criteria for increased-risk risk-management strategies (increased risk) and those who do not (average risk) before MeTree and after. MEASURES: chart abstraction was used to identify risk management related to colon, breast, and ovarian cancer, hereditary cancer, and thrombosis. RESULTS: Participants = 488, female = 284 (58.2%), white = 411 (85.7%), mean age = 58.7 (SD = 12.3). Agreement between risk management and risk level for all conditions for each participant, except for colon cancer, which was limited to those <50 years of age, was (i) 1.1% (N = 2/174) for the increased-risk group before MeTree and 16.1% (N = 28/174) after and (ii) 99.2% (N = 2,125/2,142) for the average-risk group before MeTree and 99.5% (N = 2,131/2,142) after. Of those receiving increased-risk risk-management strategies at baseline, 10.5% (N = 2/19) met criteria for increased risk. After MeTree, 80.7% (N = 46/57) met criteria. CONCLUSION: MeTree integration into primary care can improve uptake of risk-stratified guidelines and potentially reduce "overuse" and "underuse" of increased-risk services.Genet Med 18 10, 1020-1028.

Comparative Analysis of Human Growth Hormone in Serum Using SPRi, Nano-SPRi and ELISA Assays.

Sensitive and selective methods for the detection of human growth hormone (hGH) over a wide range of concentrations (high levels of 50-100 ng ml(-) (1) and minimum levels of 0.03 ng ml(-) (1)) in circulating blood are essential as variable levels may indicate altered physiology. For example, growth disorders occurring in childhood can be diagnosed by measuring levels of hGH in blood. Also, the misuse of recombinant hGH in sports not only poses an ethical issue it also presents serious health threats to the abuser. One popular strategy for measuring hGH misuse, relies on the detection of the ratio of 22 kDa hGH to total hGH, as non-22 kDa endogenous levels drop after exogenous recombinant hGH (rhGH) administration. Surface plasmon resonance imaging (SPRi) is an analytical tool that allows direct (label-free) monitoring and visualization of biomolecular interactions by recording changes of the refractive index adjacent to the sensor surface in real time. In contrast, the most frequently used colorimetric method, enzyme-linked immunosorbent assay (ELISA) uses enzyme labeled detection antibodies to indirectly measure analyte concentration after the addition of a substrate that induces a color change. To increase detection sensitivity, amplified SPRi uses a sandwich assay format and near infrared quantum dots (QDs) to increase signal strength. After direct SPRi detection of recombinant rhGH in spiked human serum, the SPRi signal is amplified by the sequential injection of detection antibody coated with near-infrared QDs (Nano-SPRi). In this study, the diagnostic potential of direct and amplified SPRi was assessed for measuring rhGH spiked in human serum and compared directly with the capabilities of a commercially available ELISA kit.

Family health history: an essential starting point for personalized risk assessment and disease prevention.

Family health history (FHH) information is well established as a basis for assessing a patient's personal disease risk, but is underutilized for diagnosis and making medical recommendations. Epidemiological and genetic information have heightened the value of FHH to an individual's health. This has motivated the development of new FHH collection tools and strategies for family members, but will require greater awareness and knowledge by both patients and practitioners. FHH will be increasingly important as genomic data become a mainstay of medical diagnostics, since in many cases, a medically important FHH results from lineage-specific genetic variants. The impact of complementary FHH and genomic information will drive the pursuit of personalized and precise targeting of treatments and interventions aimed at maintaining patient health.

Feasibility of a bilateral 4000-6000 Hz notch as a phenotype for genetic association analysis.

OBJECTIVE: Noise-induced hearing loss (NIHL) is a worldwide health problem and a growing concern among young people. Although some people appear to be more susceptible to NIHL, genetic association studies lack a specific phenotype. We tested the feasibility of a bilateral 4000-6000 Hz audiometric notch as a phenotype for identifying genetic contributions to hearing loss in young adults. DESIGN: A case-control-control study was conducted to examine selected SNPs in 52 genes previously associated with hearing loss and/or expressed in the cochlea. A notch was defined as a minimum of a 15-dB drop at 4000-6000 Hz from the previous best threshold with a 5-dB 'recovery' at 8000 Hz. STUDY SAMPLE: Participants were 252 individuals of European descent taken from a population of 640 young adults who are students of classical music. Participants were grouped as No-notch (NN), Unilateral Notch (UN), or Bilateral Notch (BN). RESULTS: The strongest evidence of a genetic association with the 4000-6000 Hz notch was a nonsynonymous SNP variant in the ESRR- gene (rs61742642:C> T, P386S). Carriers of the minor allele accounted for 26% of all bilateral losses. CONCLUSION: This study indicates that the 4000-6000 Hz bilateral notch is a feasible phenotype for identifying genetic susceptibility to hearing loss.

Nanopore Analysis of Single-Stranded Binding Protein Interactions with DNA.

We study the binding of E. coli single-stranded binding protein (SSB) to single-stranded DNA (ssDNA) using a solid-state nanopore assay. We find that saturated nucleoprotein complexes can be distinguished easily from free SSB, ssDNA, or double-stranded DNA individually and demonstrate that the high affinity of SSB for ssDNA can be exploited to achieve high-fidelity differentiation from duplex molecules in a mixture. We then study nucleoprotein filament formation by systematically varying the amount of SSB relative to ssDNA. We observe a concomitant shift in the mean amplitude of electrical events that is consistent with weakly cooperative binding. Finally, we compare circular and linearized ssDNA saturated with SSB and use the results to infer structural details of the nucleoprotein complex.

Innovative Research Design Exploring the Effects of Physical Activity and Genetics on Cognitive Performance in Community-Based Older Adults.

Physical activity is predictive of better cognitive performance and lower risk of Alzheimer's disease (AD). The apolipoprotein E gene (APOE) is a susceptibility gene for AD with the e4 allele being associated with a greater risk of AD. Cross-sectional and prospective research shows that physical activity is predictive of better cognitive performance for those at greater genetic risk for AD. However, the moderating role of APOE on the effects of a physical activity intervention on cognitive performance has not been examined. The purpose of this manuscript is to justify the need for such research and to describe the design, methods, and recruitment tactics used in the conductance of a study designed to provide insight as to the extent to which cognitive benefits resulting from an 8-month physical activity program are differentiated by APOE e4 status. The effectiveness of the recruitment strategies and the feasibility of recruiting APOE e4 carriers are discussed.

Use of a patient-entered family health history tool with decision support in primary care: impact of identification of increased risk patients on genetic counseling attendance.

Several barriers inhibit collection and use of detailed family health history (FHH) in primary care. MeTree, a computer-based FHH intake and risk assessment tool with clinical decision support, was developed to overcome these barriers. Here, we describe the impact of MeTree on genetic counseling (GC) referrals and attendance. Non-adopted, English speaking adults scheduled for a well-visit in two community-based primary-care clinics were invited to participate in an Implementation-Effectiveness study of MeTree. Participants' demographic characteristics and beliefs were assessed at baseline. Immediately after an appointment with a patient for whom GC was recommended, clinicians indicated whether they referred the patient and, if not, why. The study genetic counselor kept a database of patients with a GC recommendation and contacted those with a referral. Of 542 patients completing MeTree, 156 (29 %) received a GC recommendation. Of these, 46 % (n = 72) were referred and 21 % (n = 33) underwent counseling. Patient preferences, additional clinical information unavailable to MeTree, and an incomplete clinician evaluation of the FHH accounted for the 85 patients clinicians chose not to refer. Although MeTree identified a significant proportion of patients for whom GC was recommended, persistent barriers indicate the need for improved referral processes and patient and physician education about the benefits of GC.

Implementing family health history risk stratification in primary care: impact of guideline criteria on populations and resource demand.

UNLABELLED: The Genomic Medicine Model aims to facilitate patient engagement, patient/provider education of genomics/personalized medicine, and uptake of risk-stratified evidence-based prevention guidelines using MeTree, a patient-facing family health history (FHH) collection and clinical decision support (CDS) program. Here we report the number of increased risk (above population-level risk) patients identified for breast/ovarian cancer, colon cancer, hereditary syndrome risk, and thrombosis; the prevalence of FHH elements triggering increased-risk status; and the resources needed to manage their risk. STUDY DESIGN: hybrid implementation-effectiveness study of adults with upcoming well-visits in 2 primary care practices in Greensboro, NC. PARTICIPANTS: 1,184, mean age = 58.8, female = 58% (N = 694), non-white = 20% (N = 215). Increased Risk: 44% (N = 523). RECOMMENDATIONS: genetic counseling = 26% (N = 308), breast MRI = 0.8% (N = 10), breast chemoprophylaxis = 5% (N = 58), early/frequent colonoscopies = 19% (N = 221), ovarian cancer screening referral = 1% (N = 14), thrombosis testing/counseling = 2.4% (N = 71). FHH elements: 8 FHH elements lead to 37.3% of the increased risk categorizations (by frequency): first-degree-relative (FDR) with polyps age ≥60 (7.1%, N = 85), three relatives with Lynch-related cancers (5.4%, N = 65), FDR with polyps age <60 (5.1%, N = 61), three relatives on same side of family with same cancer (4.9%, N = 59), Gail score ≥1.66% (4.9%, N = 58), two relatives with breast cancer (one ≤age 50) (4.1%, N = 49), one relative with breast cancer ≤age 40 (4.1%, N = 48), FDR with colon cancer age ≥60 (1.7%, N = 20). MeTree identifies a high percentage of individuals in the general primary care population needing non-routine risk management/prevention for the selected conditions. Implementing risk-stratification in primary care will likely increase demand for related-resources, particularly colon screening and GC. Understanding the prevalence of FHH elements helps predict resource needs and may aid in guideline development.

Providing patient education: impact on quantity and quality of family health history collection.

BACKGROUND: Family health history (FHH) is an underutilized tool in primary care to identify and risk-stratify individuals with increased cancer risk. OBJECTIVE: Evaluate the influence of patient education on quantity and quality of FHH entered into a primary care-based software program, and impact on the program's cancer risk management recommendations. DESIGN: Two primary care practices within a larger type II hybrid implementation-effectiveness controlled clinical trial. PARTICIPANTS: English speaking non-adopted patients with a well visit appointment December 2012-March 2013. INTERVENTIONS: One to two weeks prior to their well visit appointment, participants entered their FHH into the program. PARTICIPANTS were then provided educational materials describing key FHH components. They were instructed to use the interval to collect additional FHH information. Patients then returned for their scheduled appointment, and updated their FHH with any new information. MAIN MEASURES: Percentage per pedigree of relatives meeting individual quality criteria. Changes made after patient education and changes to recommendations for surveillance, chemoprevention or genetic counseling referral. KEY RESULTS: Post patient education, pedigrees exhibited a greater percentage (per pedigree) of: deceased relatives with age at death (84 vs. 81 % p = 0.02), deceased relatives with cause of death (91 vs. 87 % p = 0.02), relatives with a named health condition (45 vs. 42 % p = 0.002), and a greater percentage of relatives with high quality records (91 vs. 89 % p = 0.02). Of 43 participants with pedigree changes that could trigger changes in risk stratified prevention recommendations, 12 participants (28 %) received such changes. CONCLUSIONS: Patient education improves FHH collection and subsequent risk stratification utilized in providing actionable evidence-based care recommendations for cancer risk management.

Quality of family history collection with use of a patient facing family history assessment tool.

BACKGROUND: Studies have shown that the quality of family health history (FHH) collection in primary care is inadequate to assess disease risk. To use FHH for risk assessment, collected data must have adequate detail. To address this issue, we developed a patient facing FHH assessment tool, MeTree. In this paper we report the content and quality of the FHH collected using MeTree. DESIGN: A hybrid implementation-effectiveness study. Patients were recruited from 2009 to 2012. SETTING: Two community primary care clinics in Greensboro, NC. PARTICIPANTS: All non-adopted adult English speaking patients with upcoming appointments were invited to participate. INTERVENTION: Education about and collection of FHH with entry into MeTree. MEASURES: We report the proportion of pedigrees that were high-quality. High-quality pedigrees are defined as having all the following criteria: (1) three generations of relatives, (2) relatives' lineage, (3) relatives' gender, (4) an up-to-date FHH, (5) pertinent negatives noted, (6) age of disease onset in affected relatives, and for deceased relatives, (7) the age and (8) cause of death (Prim Care31:479-495, 2004.). RESULTS: Enrollment: 1,184. Participant demographics: age range 18-92 (mean 58.8, SD 11.79), 56% male, and 75% white. The median pedigree size was 21 (range 8-71) and the FHH entered into MeTree resulted in a database of 27,406 individuals. FHHs collected by MeTree were found to be high quality in 99.8% (N = 1,182/1,184) as compared to <4% at baseline. An average of 1.9 relatives per pedigree (range 0-50, SD 4.14) had no data reported. For pedigrees where at least one relative has no data (N = 497/1,184), 4.97 relatives per pedigree (range 1-50, SD 5.44) had no data. Talking with family members before using MeTree significantly decreased the proportion of relatives with no data reported (4.98% if you talked to your relative vs. 10.85% if you did not, p-value < 0.001.). CONCLUSION: Using MeTree improves the quantity and quality of the FHH data that is collected and talking with relatives prior to the collection of FHH significantly improves the quantity and quality of the data provided. This allows more patients to be accurately risk stratified and offered appropriate preventive care guided by their risk level. TRIAL NUMBER: NCT01372553.

Collection of family health history for assessment of chronic disease risk in primary care.

BACKGROUND: Family health history can predict a patient's risk for common complex diseases. This project assessed the completeness of family health history data in medical charts and evaluated the utility of these data for performing risk assessments in primary care. METHODS: Family health history data were collected and analyzed to determine the presence of quality indicators that are necessary for effective and accurate assessment of disease risk. RESULTS: More than 99% of the 390 paper charts analyzed contained information about family health history, which was usually scattered throughout the chart. Information on the health of the patient's parents was collected more often than information on the health of other relatives. Key information that was often not collected included age of disease onset, affected side of the family, and second-degree relatives affected. Less than 4% of patient charts included family health histories that were informative enough to accurately assess risk for common complex diseases. LIMITATIONS: Limitations of this study include the small number of charts reviewed per provider, the fact that the sample consisted of primary care providers in a single geographic location, and the inability to assess ethnicity, consanguinity, and other indicators of the informativeness of family health history. CONCLUSIONS: The family health histories collected in primary care are usually not complete enough to assess the patient's risk for common complex diseases. This situation could be improved with use of tools that analyze the family health history information collected and provide risk-stratified decision support recommendations for primary care.

Development and validation of a primary care-based family health history and decision support program (MeTree).

INTRODUCTION: Family health history is a strong predictor of disease risk. To reduce the morbidity and mortality of many chronic diseases, risk-stratified evidence-based guidelines strongly encourage the collection and synthesis of family health history to guide selection of primary prevention strategies. However, the collection and synthesis of such information is not well integrated into clinical practice. To address barriers to collection and use of family health histories, the Genomedical Connection developed and validated MeTree, a Web-based, patient-facing family health history collection and clinical decision support tool. MeTree is designed for integration into primary care practices as part of the genomic medicine model for primary care. METHODS: We describe the guiding principles, operational characteristics, algorithm development, and coding used to develop MeTree. Validation was performed through stakeholder cognitive interviewing, a genetic counseling pilot program, and clinical practice pilot programs in 2 community-based primary care clinics. RESULTS: Stakeholder feedback resulted in changes to MeTree's interface and changes to the phrasing of clinical decision support documents. The pilot studies resulted in the identification and correction of coding errors and the reformatting of clinical decision support documents. MeTree's strengths in comparison with other tools are its seamless integration into clinical practice and its provision of action-oriented recommendations guided by providers' needs. LIMITATIONS: The tool was validated in a small cohort. CONCLUSION: MeTree can be integrated into primary care practices to help providers collect and synthesize family health history information from patients with the goal of improving adherence to risk-stratified evidence-based guidelines.

Patient and primary care provider experience using a family health history collection, risk stratification, and clinical decision support tool: a type 2 hybrid controlled implementation-effectiveness trial.

BACKGROUND: Family health history (FHH) is the single strongest predictor of disease risk and yet is significantly underutilized in primary care. We developed a patient facing FHH collection tool, MeTree, that uses risk stratification to generate clinical decision support for breast cancer, colorectal cancer, ovarian cancer, hereditary cancer syndromes, and thrombosis. Here we present data on the experience of patients and providers after integration of MeTree into 2 primary care practices. METHODS: This was a Type 2 hybrid controlled implementation-effectiveness study in 3 community-based primary care clinics in Greensboro, NC. All non-adopted adult English speaking patients with upcoming routine appointments were invited. Patients were recruited from December 2009 to the present and followed for one year. Ease of integration of MeTree into clinical practice at the two intervention clinics was evaluated through patient surveys after their appointment and at 3 months post-visit, and physician surveys 3 months after tool integration. RESULTS: Total enrollment =1,184. Average time to complete MeTree = 27 minutes. Patients found MeTree: easy to use (93%), easy to understand (97%), useful (98%), raised awareness of disease risk (85%), and changed how they think about their health (86%). Of the 26% (N = 311) asking for assistance to complete the tool, age (65 sd 9.4 vs. 57 sd 11.8, p-value < 0.00) and large pedigree size (24.4 sd 9.81 vs. 22.2 sd 8.30, p-value < 0.00) were the only significant factors; 77% of those requiring assistance were over the age of 60. Providers (N = 14) found MeTree: improved their practice (86%), improved their understanding of FHH (64%), made practice easier (79%), and worthy of recommending to their peers (93%). CONCLUSIONS: Our study shows that MeTree has broad acceptance and support from both patients and providers and can be implemented without disruption to workflow.

Ligand binding pocket function of Drosophila USP is necessary for metamorphosis.

The widely accepted paradigm that epoxidized methyl farnesoates ("juvenile hormones," JHs) are the principal sesquiterpenoid hormones regulating insect metamorphosis was assessed in Drosophila melanogaster. GC-MS analysis of circulating methyl farnesoids during the mid to late 3rd instar showed that methyl farnesoate is predominant over methyl epoxyfarnesoate (=JH III). The circulating concentration of methyl farnesoate (reaching nearly 500 nM), was easily high enough on a kinetic basis to load the Drosophila ortholog of the nuclear hormone receptor RXR (also known as "ultraspiracle," USP), whereas the circulating concentrations of JH III and methyl bisepoxyfarnesoate (bisepoxyJH III) were not. The hypothesis that the ligand pocket of USP necessarily binds an endogenous ligand for differentiation of the immature to the adult was tested with USP mutated at residue that normally extends a side chain into the ligand binding pocket. An equilibrium binding assay confirmed that the mutation (Q288A) strongly altered methyl farnesoate interaction with USP, while a heterologous cell-line transfection assay confirmed that the mutation did not allosterically alter the transcriptional response of the ultraspiracle/ecdysone receptor heterodimer to ecdysteroid signaling. Transgenic wildtype USP driven by the cognate natural promoter rescued null animals to develop to the adult inside a normally formed puparium, while in contrast animals transgenically expressing instead the ligand pocket mutant exhibited developmental derangement at the larval to pupal transition, including failure to form a properly shaped or sclerotized puparium. Other point mutations to the pocket strongly reducing affinity for methyl farnesoate similarly disrupted the larval to pupal metamorphosis. These results suggest that normal larval to pupal maturation in this mecopteran model insect requires the involvement of a distinct endocrine axis of USP binding to its own endogenous terpenoid ligand.

The genomic medicine model: an integrated approach to implementation of family health history in primary care.

As an essential tool for risk stratification, family health history (FHH) is a central component of personalized medicine; yet, despite its widespread acceptance among professional societies and its established place in the medical interview, its widespread adoption is hindered by three major barriers: quality of FHH collection, risk stratification capabilities and interpretation of risk stratification for clinical care. To overcome these barriers and bring FHH to the forefront of the personalized medicine effort, we developed the genomic medicine model (GMM) for primary care. The GMM, founded upon the principles of the Health Belief Model, Adult Learning Theory and the implementation sciences, shifts responsibility for FHH onto the patient, uses information technology (MeTree©) for risk stratification and interpretation, and provides education across multiple levels for each stakeholder, freeing up the clinical encounter for discussion around personalized preventive healthcare plans. The GMM has been implemented and optimized as part of an implementation-effectiveness hybrid pilot study for breast/ovarian cancer, colon cancer and thrombosis, and risk for hereditary cancer syndromes in two primary care clinics in NC, USA. This paper describes the conceptual development of the model and key findings relevant for broader uptake and sustainability in the primary care community.

Collagen gene variants previously associated with anterior cruciate ligament injury risk are also associated with joint laxity.

BACKGROUND: Genetic association studies demonstrate a relationship between several collagen gene variants and anterior cruciate ligament (ACL) injury, yet the mechanism of these relationships is still unclear. Joint laxity is a heritable trait; increased magnitudes of anterior knee laxity (AKL), genu recurvatum (GR), and general joint laxity (GJL) have been consistently associated with a greater risk of ACL injury. Joint laxity may constitute an important intermediate phenotype for the genetic association with ACL injury that can be measured clinically. HYPOTHESIS: To determine if genetic variants within the COL1A1, COL5A1, and COL12A1 genes, previously associated with ACL injury, were also associated with greater magnitudes of AKL, GR, and GJL. STUDY DESIGN: Descriptive laboratory study. METHODS: Blood samples and measures of AKL, GR, and GJL were obtained from 124 (50 male, 74 female) healthy, recreationally active subjects. Genomic DNA was extracted from the blood samples and genotyped for single-nucleotide polymorphisms previously examined relative to ACL injury. Univariate analyses of variance compared the magnitude of each laxity variable across the 3 genotypes for each single-nucleotide polymorphism in both sex-combined and sex-specific models. RESULTS: Specific genotypes were associated with greater GR in all subjects. Some genotypes were associated with greater magnitudes of GR, AKL, and GJL in females only. CONCLUSIONS: Gene variants previously associated with ACL injury risk were in large part also associated with joint laxity. Sex-specific genetic associations with joint laxity were consistent with those previously reported for ACL injury. CLINICAL RELEVANCE: These data provide insight into potential pathways through which genotypic variants in collagen genes have the potential to alter ligament structure and behavior and, thus, ACL injury risk.

The use of a family history risk assessment tool within a community health care system: views of primary care providers.

Primary care providers (PCPs) offered input regarding the incorporation of a family health history (FHH) risk assessment tool into a community health care system (CHCS). Sixteen PCPs participated in one of three focus groups. Perceived impediments included the lack of standard screening guidelines, effective screening tests, genetic counseling resources, and services for high-risk patients. The PCPs were concerned about their level of expertise, the cost of preventive health care, and genetic discrimination. They also were concerned about the use of a FHH tool by oncologists within the CHCS because of communication gaps between oncologists and PCPs, lack of clarity regarding follow-up and legal liability, and reimbursement issues. To integrate a FHH tool into a CHCS, PCPs will need consultation and referral services, evidence-based recommendations, and "just-in-time" educational resources. Oncologists who use the tool will need to develop a streamlined communication system with PCPs, establish clearly defined roles, and ensure patient follow-up.