Host perspectives on international fieldwork placements for U.S.-based genetic counseling students.

Genetic counseling students from the United States are often interested in international summer fieldwork placements, but little is known about the hosts' perspectives when considering such requests. We sent out surveys to 132 international genetics providers (genetics clinics and genetics programs), to identify advantages, barriers and expectations for U.S.-based genetic counseling students seeking a fieldwork placement. Twenty-seven (20.4% response rate) participants from 14 different countries shared their experiences and views. Providers placed higher emphasis on teaching and benefits to students (95.2%) rather than intrinsic benefits to their programs (90.4%). Lack of American Board of Genetic Counseling's (ABGC) reciprocal recognition (30%) and cost of training (25%), were rated as the strongest barriers to hosting U.S.-based students. Surprisingly, 'Language Barrier' (20%), although mentioned in open-ended comments, was not ranked highly as a barrier. When asked about expectations of students, active participation in student-led counseling sessions under supervision was encouraged by a majority of participants (55.6%). Where most genetic counseling literature is U.S.-centric, this study reports on insights gathered from international genetics providers. Our study encourages U.S.-based programs to consider these findings when designing exchange programs and international fieldwork placements.

Influence of Obesity on the Relationship of Cardiometabolic Risks Factors With Cardiovascular Disease in Older African and European Americans.

PURPOSE: This study evaluated the impact of obesity on cardiometabolic risk factors (CRF) interrelationships and predictive efficiency of CVD development in older African (AA) and European Americans (EA). DESIGN: A comparative research design evaluated CRF risk profile differences between participant groups. SETTING: Seven neighborhoods in a southern US city. SUBJECTS: A sample of 179 older AA (n = 128) and EA (n = 51) adults. MEASURES: Non-fasting blood samples were evaluated for lipids and lipoproteins, glycosylated hemoglobin, systolic -(SBP) and diastolic blood pressure (DBP), body mass index (BMI), body fat percentage (BF%) and physical function. ANALYSIS: Data were analysis with descriptive statistics, t-tests, and correlations. RESULTS: AA were heavier than EA although all had above average age-appropriate fitness. Means and relationships between CRF and other variables were different (P < .05) based on race. Both AA (41.3 + 5.8) and EA (38.6 + 6.4) BF% were CRF risks. Holding BMI constant, CRF were generally not related, and the relationships were different for AA and EA. AA had a range of 13.0 to 27.2% more favorable values for cholesterol, HDL-C, and triglyceride. EA had favorable A1c (EA 5.8 vs AA 6.2%) values. CONCLUSIONS: A limitation of this report is the small sample size. Although further research is warranted, these findings suggest population specific CRF selections would improve CVD prediction in AA.

Cardiometabolic risk factors and cardiovascular disease predictions in older African and European Americans.

Cardiometabolic (CMO) risks factors do not provide similar cardiovascular disease (CVD) predictions in young African (AA) and European Americans (EA) adults. Whether CMO risk predictions contribute to this disparity in older adults is unclear. We hypothesize that older AA CMO clustering pattern will be different from EA clustering patterns when determine with non-fasting lipid and lipoproteins. The participants were 106 older adults (66 AA and 40 EA) from a working/middle class neighborhood (income $46,364 - $80,904) in an urban North Carolina community. The participants were evaluated for CMO risk factors (total cholesterol, high- (HDL) and low-density lipoproteins (LDL), triglyceride (TG), glycosylated hemoglobin (HbA1c), systolic -SBP- and diastolic blood pressures -DBP), body mass index (BMI), body fat % (BF%) and timed up and go test (assessed falls risk and physical function). The AA participants were heavier, had higher BMI, BF%, and timed up and go values (p < 0.01). The data were evaluated for differences (t-test) and Pearson correlations for relationships. If data differ by p < 0.05 the data were significantly different. The AA had a 17.6 % higher HDL (64.7 vs 55.1 mg/dL - p < 0.05) and 7.6 % higher HbA1c (5.8 vs 5.4 % - p < 0.01) than EA. Higher HDL values in EA indicate lower CVD risks. The HDL paradox for AA (AA had higher HDL values, but greater CVD risks) was observed and the HbA1c difference may be misleading, as similar glucose values in AA tend to have higher HbA1c values. Lipid, lipoprotein, and blood pressure was not different between the races. AA had higher body composition and HDL values. Although future research on this topic with larger samples, dietary data and detailed descriptions of participations medications is warranted to validate findings from this study. These data suggest older AA and EA adults with similar environmental conditions have similar CMO risks when measures with none fasting blood samples. Since AA have a greater prevalence of CVD, these finding suggests that population specific CMO risk factor clustering may be more effective predictors of CVD for AA.

Sleep and Risk for Metabolic Syndrome, Hypertension, Diabetes and Obesity Among Community-Dwelling Older Adults.

Older adults often face a variety of health problems that are found less frequently in younger populations. Metabolic syndrome and other related diseases are common due to a variety of age and lifestyle factors. Sleep, often operationalized only as duration, quality, or apnea diagnosis, is associated with worse health outcomes across the lifespan. However, sleep is multi-faceted and may require a collection of measures in order to reflect this. This study examined a suite of self-reported sleep habits (risk for sleep apnea, night time duration, nap duration, quality, timing, and consistency of duration and timing) and physiological data in a sample of 144 older adults. Sleep-related variables as a group predicted risk for metabolic syndrome, hypertension, and diabetes but was not a clear predictor of obesity. Of the individual measures, risk for apnea and consistency of sleep duration throughout the week predicted risk for metabolic syndrome (apnea b = .64, p < .05; duration inconsistencies b = .22, p < .05). The findings of the study suggest that greater consistency in sleep schedules may benefit the health of older adult populations' risk for these disorders.

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder.

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.

Sub-lethal effects of Roundup™ on tadpole anti-predator responses.

Roundup™ is a commonly used pesticide applied to agriculture and forest habitats. These areas are generally ideal for amphibians due to the presence of small, ephemeral water bodies. While Roundup™ has been shown to have lethal effects on many species of amphibians, effects on behaviour and sensory perception have yet to be considered. Here, we exposed wood frog tadpoles to a sub-lethal concentration of Roundup™ and showed that the ability of tadpoles to respond to injured conspecific cues, an important source of information regarding local predation risk, was impaired. Subsequent experiments revealed that impaired responses likely result from a chemical reaction between the Roundup™ and the cues and that tadpoles chronically exposed to Roundup™ had reduced basal movement rates compared with unexposed tadpoles. Our data demonstrate that environmentally-relevant concentrations of Roundup™ can drastically alter movement and anti-predator responses of tadpoles, with potential negative consequences for the population.

Differential gene expression in high- and low-active inbred mice.

Numerous candidate genes have been suggested in the recent literature with proposed roles in regulation of voluntary physical activity, with little evidence of these genes' functional roles. This study compared the haplotype structure and expression profile in skeletal muscle and brain of inherently high- (C57L/J) and low- (C3H/HeJ) active mice. Expression of nine candidate genes [Actn2, Actn3, Casq1, Drd2, Lepr, Mc4r, Mstn, Papss2, and Glut4 (a.k.a. Slc2a4)] was evaluated via RT-qPCR. SNPs were observed in regions of Actn2, Casq1, Drd2, Lepr, and Papss2; however, no SNPs were located in coding sequences or associated with any known regulatory sequences. In mice exposed to a running wheel, Casq1 (P = 0.0003) and Mstn (P = 0.002) transcript levels in the soleus were higher in the low-active mice. However, when these genes were evaluated in naïve animals, differential expression was not observed, demonstrating a training effect. Among naïve mice, no genes in either tissue exhibited differential expression between strains. Considering that no obvious SNP mechanisms were determined or differential expression was observed, our results indicate that genomic structural variation or gene expression data alone is not adequate to establish any of these genes' candidacy or causality in relation to regulation of physical activity.

Comparison of low and intermediate source strengths for (125)I prostate brachytherapy implants.

PURPOSE: To compare the implant quality and clinical outcomes for patients treated with low and intermediate strength (125)I seeds in prostate brachytherapy implants. METHODS AND MATERIALS: This retrospective review included 390 consecutive patients treated with prostate brachytherapy from 1999 to 2006. The first 142 patients were implanted with source strengths lower than 0.415U (0.327mCi), with the subsequent 248 patients implanted with source strengths higher than 0.493U (0.388mCi). Clinical, dosimetric, toxicity, and outcome data were compared between these two cohorts of patients. RESULTS: Despite having similar prostate volumes, fewer sources (median, 95 vs. 113; p<0.0001) and fewer needles (median, 23 vs. 29; p<0.0001) were implanted in the intermediate strength cohort. The postimplant dosimetry demonstrated better quality implants in patients treated with intermediate strength sources (median D90, 160.0Gy vs. 139.6Gy; p<0.0001), with greater dose inhomogeneity identified in the intermediate strength cohort of patients. A higher incidence of late rectal toxicity was identified in patients treated with intermediate strength sources despite lower rectal doses in this cohort. The biochemical relapse-free survival, prostate cancer survival, and overall survival were not significantly different between the two cohorts. CONCLUSIONS: The transition from low to intermediate strength sources has led to fewer resources being used and improved postoperative dosimetry. Although there were more rectal complications identified in the intermediate strength cohort of patients in this analysis, there were no other significantly worse clinical or biochemical outcomes for patients implanted with intermediate strength sources.

Regional treatment margins for prostate brachytherapy.

PURPOSE: This study quantified the treatment margin (TM) around the prostate that received 100% of the prescribed dose and analyzed postimplant dosimetry in different regions of the prostate for (125)I seed implants. METHODS AND MATERIALS: An average target volume (ATV) was created from postoperative MRI scan contours drawn independently by five radiation oncologists in 40 patients. The MRI was fused with the postoperative CT for dosimetry purposes. The TM, defined as the radial distance between the ATV and the 100% isodose line, was measured at 16 points at the base, midgland, and apex. The ATV was divided into four quadrants: anterior-superior, posterior-superior, anterior-inferior, and posterior-inferior quadrants. The values of the dose that covers 90% of the ATV (D90) and the percentage of the ATV receiving the prescribed dose (V100) received by the whole prostate and its four quadrants were documented. RESULTS: The range of the mean TM, in millimeter, was -8.88 to 3.68, 1.12 to 10.42, and 6.27 to 18.25 at the base, midgland, and apex, respectively. The mean D90 was 135.8, 162.8, 191.0, and 194.6 Gy for the anterior-superior, posterior-superior, anterior-inferior, and posterior-inferior quadrants, respectively. CONCLUSIONS: Despite having a relatively uniform preoperative planning target volume, this study identified variable TMs postoperatively in different regions of the prostate. In particular, the anterior base is most underdosed, whereas the lateral regions of the midgland and apex have generous TMs. Postimplant dosimetric parameters were lowest in the anterior-inferior quadrant.

Physical activity preferences for low-income sedentary urban African American older adults.

The objective of this study was to determine (a) activity preferences for low-income sedentary urban African American older adults and (b) information needed to deliver a lay physical activity intervention in the community for this population. This descriptive qualitative study used six focus groups. Participants were African American, 55 and older, had low incomes, and had sedentary behavior. Physical activity themes included excitement/emotion for physical activity, group physical activity, and location of physical activity. Themes regarding aspects of being a lay community health worker included beneficial service, uncertainty, logistics concerns, and delivery method preferences. The findings from this study will provide the basis for an intervention for low-income sedentary African American older adults. Preferences for physical activity, concerns about and supports needed for individuals to serve as lay community health workers, various types of training materials, and preferred technology for physical activity participation are identified and discussed.

Effects of Supraphysiological Doses of Sex Steroids on Wheel Running Activity in Mice.

The regulatory mechanisms of physical activity are postulated to include environmental and biological/genetic factors. In particular, the sex steroids appear to have profound effects on wheel running in rodents. The purpose of this project was to investigate the effects of 17ß-estradiol and testosterone on wheel running distance, duration, and speed in male and female C57BL/6J mice. The mice (N=46) were provided free access to running wheels interfaced with computers to track daily running distance, duration, and speed. Activity was assessed at baseline in intact mice, after surgical gonadectomy, and after replacement with either 17ß-estradiol or testosterone. Upon removal of the gonads, physical activity levels were significantly reduced in both males and females. Distance (10-30% of baseline) and duration (20-47% of baseline) measures were most affected by the loss of endogenous steroids, while running speed (60-77% of baseline) though significantly reduced-decreased by a much lower magnitude. Testosterone replacement fully recovered running distance, duration, and speed to pre-surgical levels in both sexes (100% of baseline). Distance (30-42% of baseline) and duration (43-47% of baseline) were partially recovered by 17ß-estradiol, but not to baseline levels. Speed (100% of baseline) was fully recovered by 17ß-estradiol replacement in males and females. This study suggests that physical activity in mice is affected by endogenous steroids and can be altered by exogenous steroid replacement. The differences in the recovery abilities of 17ß-estradiol and testosterone suggest that both estrogenic and androgenic pathways may be involved to variable degrees in activity regulation.

Driven to be inactive? The genetics of physical activity.

The health implications of physical inactivity, including its integral role in promoting obesity, are well known and have been well documented. Physical activity is a multifactorial behavior with various factors playing a role in determining individual physical activity levels. Research using both human and animal models in the past several years has clearly indicated that genetics is associated with physical activity. Furthermore, researchers have identified several significant and suggestive genomic quantitative trait loci associated with physical activity. To date, the identities of the causal genes underlying physical activity regulation are unclear, with few strong candidate genes. The current research provides a foundation from which future confirmatory research can be launched as well as determination of the mechanisms through which the genetic factors act. The application of this knowledge could significantly augment the information available for physical activity behavior change interventions resulting in more efficient programs for those predisposed to be inactive.

Strain screen and haplotype association mapping of wheel running in inbred mouse strains.

Previous genetic association studies of physical activity, in both animal and human models, have been limited in number of subjects and genetically homozygous strains used as well as number of genomic markers available for analysis. Expansion of the available mouse physical activity strain screens and the recently published dense single-nucleotide polymorphism (SNP) map of the mouse genome (approximately 8.3 million SNPs) and associated statistical methods allowed us to construct a more generalizable map of the quantitative trait loci (QTL) associated with physical activity. Specifically, we measured wheel running activity in male and female mice (average age 9 wk) in 41 inbred strains and used activity data from 38 of these strains in a haplotype association mapping analysis to determine QTL associated with activity. As seen previously, there was a large range of activity patterns among the strains, with the highest and lowest strains differing significantly in daily distance run (27.4-fold), duration of activity (23.6-fold), and speed (2.9-fold). On a daily basis, female mice ran further (24%), longer (13%), and faster (11%). Twelve QTL were identified, with three (on Chr. 12, 18, and 19) in both male and female mice, five specific to males, and four specific to females. Eight of the 12 QTL, including the 3 general QTL found for both sexes, fell into intergenic areas. The results of this study further support the findings of a moderate to high heritability of physical activity and add general genomic areas applicable to a large number of mouse strains that can be further mined for candidate genes associated with regulation of physical activity. Additionally, results suggest that potential genetic mechanisms arising from traditional noncoding regions of the genome may be involved in regulation of physical activity.

Repeatability of exercise behaviors in mice.

PURPOSE: Measurements of exercise behaviors in rodents such as maximal treadmill endurance and physical activity are often used in the literature; however, minimal data are available regarding the repeatability of measurements used for these exercise behaviors. This study assessed the repeatability of a commonly used maximal exercise endurance treadmill test as well as voluntary physical activity measured by wheel running in mice. METHODS: Repeatability of treadmill tests were analyzed for both inbred and outbred mice in addition to a 10 week repeatability analysis using Balb/cJ mice (n=20). Voluntary daily physical activity was assessed by distance, duration, and speed of wheel running (WR). Physical activity measurements on days 5 and 6 of WR in a large cohort (n=739) of both inbred and outbred mice were compared. RESULTS: No significant differences (p>0.05) in exercise endurance were found between different cohorts of Balb/cJ and DBA/2J mice indicating strains overall generally test the same; however, significant differences between tests were seen within BaD2F(2) animals (p<0.001). Bland-Altman analysis revealed a lack of agreement between weekly endurance tests within mouse, and correlation analysis showed lack of consistent correlations between weekly endurance tests within mouse. No significant differences were found for WR measurements within mouse between days (p=0.99). High correlations between days within mouse for WR were found (r=0.74-0.85). CONCLUSIONS: High intra-mouse variability between repeated endurance tests suggests that treadmill testing in an enclosed chamber with shock grid for motivation to run in mice is not repeatable. Conversely, high correlation and agreement between days of wheel-running measurements suggest that voluntary activity (WR) is repeatable and stable within individual mice.

An evidence-based exercise program implemented in congregate-meal sites.

BACKGROUND: This study examined the feasibility of implementing the EnhanceFitness Program (formerly Lifetime Fitness Program), an evidence-based exercise program, at congregate-meal sites that generally serve low-income older adults. METHODS: A 12-week aerobic and strength training exercise program was held at senior centers 3 times a week. RESULTS: The mean age of the 31 participants was 73.5 years+/-6.7 years (60-86). Participants' compliance with attending the exercise class was 74%. Paired t tests were used to evaluate change after the intervention. Three out of six components of the Senior Fitness Test increased significantly after the exercise intervention (P<.003). Three out of the eight self-reported health concepts of the SF-36 demonstrated significant improvement after the exercise intervention (P<.003). CONCLUSION: These data indicate that an evidence-based exercise program can be successfully implemented in this population.

The effects of aerobic training and nutrition education on functional performance in low socioeconomic older adults.

PURPOSE: To describe the population in terms of risk for disability and compare the effects of a walking intervention and nutrition education intervention on risk modification and functional performance in lower socioeconomic older adults using a randomized controlled study. METHODS: Twenty-six community-dwelling older adults aged 60 and older were randomly assigned to a 16-week walking exercise group or a nutrition education control group. Peak aerobic capacity and physical function were measured at baseline and post intervention. Physical function was measured using the Medical Outcomes Study Short Form Health Survey Physical Function subscale, Short Physical Performance Battery, Physical Performance Test, and Continuous Scale Physical Functional Performance 10 item test (CS-PFP10). RESULTS: Eighty-five percent of the participants were at risk for preclinical disability of which 50% were at risk for moderate disability. The walking exercise group significantly improved in peak aerobic capacity (18.9%), physical function (25%) using the CS-PFP10 compared to the control group. CONCLUSION: These findings highlight the importance of physical activity and indicate that walking, a simple exercise that can be done without specialized exercise leader or equipment can significantly increase peak aerobic capacity and physical function in just 4 months.