Systemic DNA Damage and Repair Activity Vary by Race in Breast Cancer Survivors.

Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the target tissue (e.g., breast). We investigated race-based differences in DNA damage and repair, using a novel CometChip assay, in circulating leukocytes from breast cancer survivors who had completed primary cancer therapy and were cancer free. We observed novel race-based differences in systemic DNA damage and repair activity in cancer survivors, but not in cells from healthy volunteers. Basal DNA damage in leukocytes was higher in White survivors, but Black survivors showed a much higher induction after bleomycin treatment. Double-strand break repair activity was also significantly different between the races, with cells from White survivors showing more sustained repair activity compared to Black leukocytes. These results suggest that cancer and cancer therapy might have long-lasting effects on systemic DNA damage and repair mechanisms that differ in White survivors and Black survivors. Findings from our preliminary study in non-cancer cells (circulating leukocytes) suggest systemic effects beyond the target site, with implications for accelerated aging-related cancer survivorship disparities.

A scoping review of portable sensing for out-of-lab anterior cruciate ligament injury prevention and rehabilitation.

Anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) surgery are common. Laboratory-based biomechanical assessment can evaluate ACL injury risk and rehabilitation progress after ACLR; however, lab-based measurements are expensive and inaccessible to most people. Portable sensors such as wearables and cameras can be deployed during sporting activities, in clinics, and in patient homes. Although many portable sensing approaches have demonstrated promising results during various assessments related to ACL injury, they have not yet been widely adopted as tools for out-of-lab assessment. The purpose of this review is to summarize research on out-of-lab portable sensing applied to ACL and ACLR and offer our perspectives on new opportunities for future research and development. We identified 49 original research articles on out-of-lab ACL-related assessment; the most common sensing modalities were inertial measurement units, depth cameras, and RGB cameras. The studies combined portable sensors with direct feature extraction, physics-based modeling, or machine learning to estimate a range of biomechanical parameters (e.g., knee kinematics and kinetics) during jump-landing tasks, cutting, squats, and gait. Many of the reviewed studies depict proof-of-concept methods for potential future clinical applications including ACL injury risk screening, injury prevention training, and rehabilitation assessment. By synthesizing these results, we describe important opportunities that exist for clinical validation of existing approaches, using sophisticated modeling techniques, standardization of data collection, and creation of large benchmark datasets. If successful, these advances will enable widespread use of portable-sensing approaches to identify ACL injury risk factors, mitigate high-risk movements prior to injury, and optimize rehabilitation paradigms.

An 8-week exercise study to improve cancer treatment related fatigue and QOL among African American breast cancer patients undergoing radiation treatment: A pilot randomized clinical trial.

BACKGROUND: Cancer treatment related fatigue (CTRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors. The primary objective of the PEDLAR study is to test the feasibility of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CTRF and improving health-related QOL among African-American breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in African-American women with breast cancer. METHODS: It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group. RESULTS: Participants in intervention group reported high satisfaction with exercise and adherence was >75% for exercise sessions. CONCLUSIONS: African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).

Dietary fiber intake and metabolic syndrome in postmenopausal African American women with obesity.

Fiber intake may be associated with lower risk of metabolic syndrome (MetS) but data from metabolically unhealthy African American women is sparse. We examined the association of dietary fiber intake and MetS among postmenopausal African American women with obesity. Baseline cross-sectional data from the Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial of 213 women (mean age 58.3 years) were used. Dietary intake was assessed by Food Frequency Questionnaires (FFQs). Multivariate linear and logistic regressions were performed to estimate associations of MetS with fiber intake and adherence to dietary fiber intake guidelines, respectively. Mean daily fiber intake was (10.33 g/1000kcal) in women with impaired metabolic health. We observed an inverse association of total fiber intake with MetS. One unit increase in energy-adjusted fiber intake was associated with a 0.10 unit decrease in the MetS z-score (p = 0.02). Similar results were obtained for both soluble and insoluble fiber. In multivariate-adjusted analyses, participants not adherent to fiber intake recommendations were more likely to have MetS as compared to those reporting intakes in the recommended range (adjusted odds ratio 4.24, 95% CI: 1.75, 10.30). Of the MetS components, high fasting glucose and high triglycerides were all associated with lower intake of fiber. Study participants who consumed a higher amount of fiber had a better overall metabolic profile and were less likely to have MetS in our cross-sectional analysis of postmenopausal African American women with obesity and unhealthy metabolic profiles.

The Effect of a 6-Month Exercise Intervention Trial on Allostatic Load in Black Women at Increased Risk for Breast Cancer: the FIERCE Study.

BACKGROUND: Allostatic load comprises cardiovascular, metabolic, and inflammatory markers, which is characterized by abdominal obesity, high blood glucose levels, impaired glucose tolerance, dyslipidemia, and hypertension and associated with an increased risk in breast cancer. METHODS: The study was a 6-month, 3-arm randomized controlled trial of two moderate-intensity exercise interventions (compared with a control group) among obese, physically inactive, postmenopausal Black women aged 45 to 65 years, who were at increased risk for breast cancer based on the CARE model. Two hundred thirteen participants were randomly assigned to (1) supervised, facility-based aerobic exercise intervention (n = 73), (2) home-based exercise intervention (n = 69), or (3) a wait-listed control group (n = 71). The intervention effects of exercise on allostatic load were examined with intent-to-treat analyses using generalized linear models. RESULTS: It was revealed that statistically significant decreases in allostatic load over the 6-month period for both exercise intervention groups (i.e., home-based and supervised arms) compared to the controls were observed among the total population, pc-h = 0.023 and pc-s = 0.035, as well as among women with a family history of breast cancer, pc-h = 0.006 and pc-s = 0.012. CONCLUSIONS: Short-term aerobic activity improved allostatic load scores in metabolically unhealthy postmenopausal Black women at increased risk for cancer. TRIAL REGISTRATION: Clinical trial registration number NCT02103140.

A Feasibility Study of Smoking Cessation Utilizing an Exercise Intervention among Black Women: 'Quit and Fit'.

BACKGROUND: Women who engage in higher levels of exercise while trying to quit smoking have been shown to be less likely to relapse and to sustain their smoking abstinence longer. This study sought to examine the benefits of exercise for improving smoking cessation among Black women. METHODS: We evaluated the feasibility of a 12-week smoking and exercise intervention, Quit and Fit, tailored for Black women. All participants (intervention and control) received 12 weeks of smoking cessation counseling via telephone and 9 weeks of nicotine lozenges. Participants who were randomly assigned to the intervention condition were also assigned to a 12-week exercise group. RESULTS: Thirty-eight women were enrolled and 27 completed a 12-week follow-up assessment. Women from the intervention group were more likely to complete the 12-week follow-up assessment compared to participants in the control group (80% vs. 61%). Overall, 7 of the 38 participants (18%) were abstinent at 12 weeks (biochemically verified by expired carbon monoxide). Among the 25 women who completed the 12-week follow-up, abstinence was reported in 33% of the intervention group and 20% of the control group. Using an intent-to-treat approach, 25% of women in the intervention group were abstinent at 12 weeks (n = 5), compared to 11.1% for the control group (n = 2). These differences were not statistically significant. CONCLUSIONS: The overall retention rate was 71% (27/38) at 12 weeks with higher among the intervention group (16/20; 80%) compared to the control group (11/18; 61%). The study demonstrates that it is feasible to retain African-American women in a short-term study of smoking cessation and exercise.

Can you hear me now?: Improving palliative care access through telehealth.

Telehealth has been increasingly used to expand healthcare access over the last two decades. However, this had not been the case for palliative care (PC), because telehealth was considered nontraditional and impractical due to the sensitive nature of conversations and a "high touch" philosophy. Motivated by limited PC access to rural and underserved populations and positive PC telehealth studies, clinical PC telehealth models have been developing. However, nearly overnight, the COVID-19 pandemic accelerated the use and uptake of telehealth across health care and especially in PC. As a result, clinicians, administrators, and others agree that telehealth is "here to stay," and will likely maintain widespread use and refinement beyond rural areas. The purpose of this review is to describe exemplar PC telehealth programs in research and clinical practice, including pros and cons, lessons learned, and future directions for the ongoing development and expansion of PC via telehealth across diseases and the lifespan.

Implementing a Clinic-Based Telehealth Support Service (FamilyStrong) for Family Caregivers of Individuals with Grade IV Brain Tumors.

Background: Nearly 3 million U.S. family caregivers support someone with cancer. However, oncology clinic-based service lines that proactively screen, assess, and support cancer caregivers are nearly nonexistent. Objective: To examine first-year experiences of a nurse-led clinic-based telehealth support service (FamilyStrong) for family caregivers of patients with recently diagnosed grade IV brain tumors. Methods: This is a retrospective evaluation of operational outcomes from initial implementation of the FamilyStrong Service, developed in partnership with Caregiver and Bereavement Support Services at the University of Alabama at Birmingham (UAB) and the UAB Center for Palliative and Supportive Care. From August 2018 to December 2019, 53 family caregivers were proactively identified and enrolled by a palliative care nurse, working approximately one day/week, who performed monthly caregiver distress thermometer screenings by phone and provided emotional, educational, problem-solving, and referral support. Results: Enrolled family caregivers were a mean age of 53.5 years and mostly female (62.3%), full- or part-time employed (67.9%), and the patient's spouse/partner (79.3%). Caregivers provided support 6.7 days/week for 11.2 hours/day. The palliative care nurse performed 235 distress screenings and provided support that included 68 documented instances of emotional, problem-solving, and educational support, 41 nurse-facilitated communications with the neuro-oncology team about patient issues, and 24 referrals to UAB and community services (e.g., counseling). The most common problems caregivers wanted assistance with included: managing their relative's health condition and symptoms (51%), coordinating care/services (21%), and planning for the future/advance care planning (17%). Discussion: The FamilyStrong Program is among the first "real world" oncology clinic-based formal support services for advance cancer family caregivers.

Pre-operative gastrocnemius lengths in gait predict outcomes following gastrocnemius lengthening surgery in children with cerebral palsy.

Equinus deformity is one of the most common gait deformities in children with cerebral palsy. We examined whether estimates of gastrocnemius length in gait could identify limbs likely to have short-term and long-term improvements in ankle kinematics following gastrocnemius lengthening surgery to correct equinus. We retrospectively analyzed data of 891 limbs that underwent a single-event multi-level surgery (SEMLS), and categorized outcomes based on the normalcy of ankle kinematics. Limbs with short gastrocnemius lengths that received a gastrocnemius lengthening surgery as part of a SEMLS (case limbs) were 2.2 times more likely than overtreated limbs (i.e., limbs who did not have short lengths, but still received a lengthening surgery) to have a good surgical outcome at the follow-up gait visit (good outcome rate of 71% vs. 33%). Case limbs were 1.2 times more likely than control limbs (i.e., limbs that had short gastrocnemius lengths but no lengthening surgery) to have a good outcome (71% vs. 59%). Three-fourths of the case limbs with a good outcome at the follow-up gait visit maintained this outcome over time, compared to only one-half of the overtreated limbs. Our results caution against over-prescription of gastrocnemius lengthening surgery and suggest gastrocnemius lengths can be used to identify good surgical candidates.

Enrichment of ovine gonadotropes via adenovirus gene targeting enhances assessment of transcriptional changes in response to estradiol-17 beta†.

Gonadotropes represent approximately 5-15% of the total endocrine cell population in the mammalian anterior pituitary. Therefore, assessing the effects of experimental manipulation on virtually any parameter of gonadotrope biology is difficult to detect and parse from background noise. In non-rodent species, applying techniques such as high-throughput ribonucleic acid (RNA) sequencing is problematic due to difficulty in isolating and analyzing individual endocrine cell populations. Herein, we exploited cell-specific properties inherent to the proximal promoter of the human glycoprotein hormone alpha subunit gene (CGA) to genetically target the expression of a fluorescent reporter (green fluorescent protein [GFP]) selectively to ovine gonadotropes. Dissociated ovine pituitary cells were cultured and infected with an adenoviral reporter vector (Ad-hαCGA-eGFP). We established efficient gene targeting by successfully enriching dispersed GFP-positive cells with flow cytometry. Confirming enrichment of gonadotropes specifically, we detected elevated levels of luteinizing hormone (LH) but not thyrotropin-stimulating hormone (TSH) in GFP-positive cell populations compared to GFP-negative populations. Subsequently, we used next-generation sequencing to obtain the transcriptional profile of GFP-positive ovine gonadotropes in the presence or absence of estradiol 17-beta (E2), a key modulator of gonadotrope function. Compared to non-sorted cells, enriched GFP-positive cells revealed a distinct transcriptional profile consistent with established patterns of gonadotrope gene expression. Importantly, we also detected nearly 200 E2-responsive genes in enriched gonadotropes, which were not apparent in parallel experiments on non-enriched cell populations. From these data, we conclude that CGA-targeted adenoviral gene transfer is an effective means for selectively labeling and enriching ovine gonadotropes suitable for investigation by numerous experimental approaches.

Circulating microRNAs and endothelial cell migration rate are associated with metabolic syndrome and fitness level in postmenopausal African American women.

Postmenopausal African American women are at elevated risk for metabolic syndrome (MetS), which predisposes them to cardiovascular disease and other chronic diseases. Circulating microRNAs (ci-miR) are potential mediators of cardiometabolic diseases also impacted by cardiorespiratory fitness (CRF) level. Using real-time quantitative PCR, we compared the expression of vascular-related ci-miRs (miR-21-5p, miR-92a-3p, miR-126-5p, miR-146a-5p, miR-150-5p, miR-221-3p) in sedentary, overweight/obese, postmenopausal African American women based on 1) presence (n = 31) or absence (n = 42) of MetS and 2) CRF level (VO2peak ) (Very Low < 18.0 mL·kg-1 ·min-1 [n = 31], Low = 18.0-22.0 mL·kg-1 ·min-1 [n = 24], or Moderate >22.0 mL·kg-1 ·min-1 [n = 18]). Endothelial migration rate in response to subjects' serum was assessed to determine the effect of circulating blood-borne factors on endothelial repair. Ci-miR-21-5p was the only ci-miR that differed between women with MetS compared to those without MetS (0.93 ± 0.43 vs. 1.28 ± 0.71, P = 0.03). There were borderline significant differences (P = 0.06-0.09) in ci-miR-21-5p, 126-5p, and 221-3p levels between the CRF groups, and these three ci-miRs correlated with VO2peak (r = -0.25 to -0.28, P < 0.05). Endothelial migration rate was impaired in response to serum from women with MetS compared to those without after 16-24 h. Serum from women with Moderate CRF induced greater endothelial migration than the Very Low and Low CRF groups after 4 and 16-24 h, that was also not different from a young, healthy reference group. Ci-miR-21-5p is lower in postmenopausal African American women with MetS, while ci-miRs-21-5p, 126-5p, and 221-3p are associated with CRF. Factors which impair endothelial cell migration rate are present in serum of women with MetS, though having Moderate CRF may be protective.

Looking Back, Moving Forward: A Retrospective Review of Care Trends in an Academic Palliative and Supportive Care Program from 2004 to 2016.

Objective: To examine a rural-serving HBPC program's 12-year experience and historical trends to inform future program direction and expansion. Background: There is limited information about longitudinal trends in mature hospital-based palliative care (HBPC) programs serving racially diverse rural populations. Methods: This is a retrospective cross-sectional study of operational and patient-reported outcomes from the University of Alabama at Birmingham (UAB) Center for Palliative and Supportive Care (CPSC) inpatient (n=11,786) and outpatient (n=315) databases from October 2004 to March 2016. Results: Inpatients were a mean age of 63.7 years, male (50.1%), white (62.3%), general medicine referred (19.5%), primarily for goals of care (84.4%); 47.1% had "do not resuscitate/do not intubate" status and 46.9% were transferred to the Palliative Care and Comfort Unit (PCCU) after consultation. Median time from admission to consultation was three days, median PCCU length of stay (LOS) was four days, and median hospital LOS was nine days. Increased emergency department and cardiology referrals were notable in later years. Outpatients' mean age was 53.02 years, 63.5% were female, 76.8% were white, and 75.6% had a cancer diagnosis. Fatigue, pain, and disturbed sleep were the most common symptoms at the time of the visit; 34.6% reported mild-to-moderate depressive symptoms. Of patients reporting pain (64.8%), one-third had 50% or less relief from pain treatment. Discussion: The CPSC, which serves a racially diverse rural population, has demonstrated robust growth. We are poised to scale and spread our lessons learned to underserved communities.

Estimating the effect size of surgery to improve walking in children with cerebral palsy from retrospective observational clinical data.

Single-event multilevel surgery (SEMLS) is a standard treatment approach aimed at improving gait for patients with cerebral palsy, but the effect of this approach compared to natural progression without surgical intervention is unclear. In this study, we used retrospective patient history, physical exam, and three-dimensional gait analysis data from 2,333 limbs to build regression models estimating the effect of SEMLS on gait, while controlling for expected natural progression. Post-hoc classifications using the regression model results identified which limbs would exhibit gait within two standard deviations of typical gait at the follow-up visit with or without a SEMLS with 73% and 77% accuracy, respectively. Using these models, we found that, while surgery was expected to have a positive effect on 93% of limbs compared to natural progression, in only 37% of limbs was this expected effect a clinically meaningful improvement. We identified 26% of the non-surgically treated limbs that may have shown a clinically meaningful improvement in gait had they received surgery. Our models suggest that pre-operative physical therapy focused on improving biomechanical characteristics, such as walking speed and strength, may improve likelihood of positive surgical outcomes. These models are shared with the community to use as an evaluation tool when considering whether or not a patient should undergo a SEMLS.

OpenSim: Simulating musculoskeletal dynamics and neuromuscular control to study human and animal movement.

Movement is fundamental to human and animal life, emerging through interaction of complex neural, muscular, and skeletal systems. Study of movement draws from and contributes to diverse fields, including biology, neuroscience, mechanics, and robotics. OpenSim unites methods from these fields to create fast and accurate simulations of movement, enabling two fundamental tasks. First, the software can calculate variables that are difficult to measure experimentally, such as the forces generated by muscles and the stretch and recoil of tendons during movement. Second, OpenSim can predict novel movements from models of motor control, such as kinematic adaptations of human gait during loaded or inclined walking. Changes in musculoskeletal dynamics following surgery or due to human-device interaction can also be simulated; these simulations have played a vital role in several applications, including the design of implantable mechanical devices to improve human grasping in individuals with paralysis. OpenSim is an extensible and user-friendly software package built on decades of knowledge about computational modeling and simulation of biomechanical systems. OpenSim's design enables computational scientists to create new state-of-the-art software tools and empowers others to use these tools in research and clinical applications. OpenSim supports a large and growing community of biomechanics and rehabilitation researchers, facilitating exchange of models and simulations for reproducing and extending discoveries. Examples, tutorials, documentation, and an active user forum support this community. The OpenSim software is covered by the Apache License 2.0, which permits its use for any purpose including both nonprofit and commercial applications. The source code is freely and anonymously accessible on GitHub, where the community is welcomed to make contributions. Platform-specific installers of OpenSim include a GUI and are available on simtk.org.

Effect of exercise on metabolic syndrome in black women by family history and predicted risk of breast cancer: The FIERCE Study.

BACKGROUND: This study examined the effects of supervised and home-based exercise interventions on changes in metabolic syndrome (MetS) according to breast cancer risk (high vs low) in black women enrolled in the Focused Intervention on Exercise to Reduce Cancer (FIERCE) trial. METHODS: Postmenopausal, obese, metabolically unhealthy black women, 45 to 65 years old, were randomized to supervised aerobic exercise (73 women), home-based walking-based exercise (69 women), or a control arm (71 women). Participants in the exercise arms underwent a 6-month intervention with study assessments conducted at the baseline and 6 months. The primary outcome measure was MetS (fasting glucose, waist circumference, blood pressure, serum triglycerides, and high-density lipoprotein [HDL]). The intervention effects on MetS, stratified by breast cancer risk as measured by the family history of breast cancer and model-based projected breast cancer risk, were examined with intent-to-treat analyses using generalized estimating equation models. RESULTS: Among women with a family history of breast cancer, the exercise arms had lower mean MetS z scores, which suggested an improvement in the metabolic profile, than controls at 6 months (controls, + 0.55; home-based arm, -0.97, P < .01; supervised arm, -0.89, P < .01). Stratified analyses by projected breast cancer risk suggested similar but statistically nonsignificant findings, with those at high risk having more favorable changes in the MetS z score in the exercise arms versus the control arm. These changes were primarily attributable to changes in blood pressure, triglycerides, and HDL. CONCLUSIONS: Short-term aerobic activity regimens may improve the metabolic profile and thereby reduce breast cancer risk in obese, metabolically unhealthy black women at high risk for cancer. © 2018 American Cancer Society.

Impact of preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria on the incidence of sepsis following transrectal ultrasound guided prostate biopsy.

With the universal adoption of antibiotic prophylaxis prior to prostate biopsy, the current risk of post-biopsy infection (including sepsis) is <2%. Preoperative prophylactic antibiotic regimens can vary, and although fluoroquinolones have emerged as the standard of care, there is no universally agreed upon preoperative antibiotic regimen. Recently, an increase in the proportion of postoperative infections caused by fluoroquinolone-resistant Escherichia coli (as well as other Enterobacteriaceae) has led to the exploration of simple, practical, and cost-effective methods to minimize this postoperative infection risk. We performed a prospective, nonrandomized, controlled study of preoperative rectal cultures to screen for rectal colonization with fluoroquinolone-resistant bacteria using ciprofloxacin-supplemented MacConkey agar culture media. To evaluate the feasibility and practicality of this test, one provider used the results of rectal swab cultures collected during the preoperative outpatient evaluation to adjust each patient's preoperative antibiotic prophylaxis when fluoroquinolone-resistant enteric bacteria were detected, whereas two other providers continued usual preoperative care and empiric antimicrobial prophylaxis. Rectal colonization with fluoroquinolone-resistant bacteria was detected in 19/152 (12.5%) of patients. In our intention-to-treat analysis (N=268), the rate of post-biopsy sepsis was 3.6% lower in the group that was screened for rectal colonization with fluoroquinolone-resistant bacteria prior to transrectal prostate biopsy. The observed risk reduction in the rectal screening group trended toward, but did not achieve, statistical significance. We suggest that preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria may be a useful step toward mitigating post-prostate biopsy sepsis.

The feasibility and acceptability of a diet and exercise trial in overweight and obese black breast cancer survivors: The Stepping STONE study.

PURPOSE: Black breast cancer survivors have high rates of obesity and low physical activity levels. Little is known about the acceptability and feasibility of interventions in this population. OBJECTIVE: A two-arm RCT was launched to assess the efficacy of a culturally targeted 12-week multimodal lifestyle intervention in overweight and obese black survivors. METHODS: Intervention components included nutrition education, exercise groups, and survivor-led motivational interviewing phone sessions. The analytic sample included women who completed the trial (intervention n=10; control n=12). Anthropometric measures, physical activity, and VO2max were assessed at baseline and follow-up. Change scores (intervention vs. control) were assessed with Wilcoxon rank-sum tests. A process evaluation assessed intervention acceptability. RESULTS: Overall adherence was 70% and overall satisfaction was high (86%). Despite the 5% weight loss target, the intervention group lost 0.8% but BMI improved. Total physical activity levels increased in the intervention vs. control arm (+3501METmin/week vs. +965METmin/week, respectively). VO2max improved in the intervention group (+0.10±1.03kg/L/min). Intervention participants reduced energy intake (-207.3±31.5kcals) and showed improvements in fat intake (-15.5±3.8g), fiber (+3.2±1.2g) and % energy from fat (-4.8±3.1%). Survivors suggested providing diet/exercise information within a cancer context. CONCLUSIONS: Group and individualized intervention strategies are acceptable to black survivors. Observed differences between self-report and objective outcomes may suggest reporting bias or changes in body composition. Increasing supervised intervention components and assessment of body composition will be important for future trials.

An exercise trial targeting African-American women with metabolic syndrome and at high risk for breast cancer: Rationale, design, and methods.

BACKGROUND: Metabolic syndrome and obesity are known risk factors for breast cancers. Exercise interventions can potentially modify circulating biomarkers of breast cancer risk but evidence in African-Americans and women with metabolic syndrome is lacking. METHODS/DESIGN: The Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial is a prospective, 6-month, 3-arm, randomized controlled trial to examine the effect of exercise on obesity, metabolic syndrome components, and breast cancer biomarkers among African-American women at high risk of breast cancer. Two hundred-forty inactive women with metabolic syndrome and absolute risk of breast cancer ≥ 1.40 will be randomized to one of the three trial arms: 1) a supervised, facility-based exercise arm; 2) a home-based exercise arm; and 3) a control group that maintains physical activity levels through the course of the trial. Assessments will be conducted at baseline, 3 months, and 6 months. The primary outcome variables are anthropometric indicators of obesity, metabolic syndrome components, and inflammatory, insulin-pathway, and hormonal biomarkers of breast cancer risk. DISCUSSION: The FIERCE trial will provide evidence on whether a short-term exercise intervention might be effective in reducing breast cancer risk among African-American women with comorbidities and high breast cancer risk--a group traditionally under-represented in non-therapeutic breast cancer trials. CLINICAL TRIAL REGISTRATION NUMBER: NCT02103140.

Shift work in nurses: contribution of phenotypes and genotypes to adaptation.

BACKGROUND: Daily cycles of sleep/wake, hormones, and physiological processes are often misaligned with behavioral patterns during shift work, leading to an increased risk of developing cardiovascular/metabolic/gastrointestinal disorders, some types of cancer, and mental disorders including depression and anxiety. It is unclear how sleep timing, chronotype, and circadian clock gene variation contribute to adaptation to shift work. METHODS: Newly defined sleep strategies, chronotype, and genotype for polymorphisms in circadian clock genes were assessed in 388 hospital day- and night-shift nurses. RESULTS: Night-shift nurses who used sleep deprivation as a means to switch to and from diurnal sleep on work days (∼25%) were the most poorly adapted to their work schedule. Chronotype also influenced efficacy of adaptation. In addition, polymorphisms in CLOCK, NPAS2, PER2, and PER3 were significantly associated with outcomes such as alcohol/caffeine consumption and sleepiness, as well as sleep phase, inertia and duration in both single- and multi-locus models. Many of these results were specific to shift type suggesting an interaction between genotype and environment (in this case, shift work). CONCLUSIONS: Sleep strategy, chronotype, and genotype contribute to the adaptation of the circadian system to an environment that switches frequently and/or irregularly between different schedules of the light-dark cycle and social/workplace time. This study of shift work nurses illustrates how an environmental "stress" to the temporal organization of physiology and metabolism can have behavioral and health-related consequences. Because nurses are a key component of health care, these findings could have important implications for health-care policy.

Can biomechanical variables predict improvement in crouch gait?

Many patients respond positively to treatments for crouch gait, yet surgical outcomes are inconsistent and unpredictable. In this study, we developed a multivariable regression model to determine if biomechanical variables and other subject characteristics measured during a physical exam and gait analysis can predict which subjects with crouch gait will demonstrate improved knee kinematics on a follow-up gait analysis. We formulated the model and tested its performance by retrospectively analyzing 353 limbs of subjects who walked with crouch gait. The regression model was able to predict which subjects would demonstrate 'Improved' and 'Unimproved' knee kinematics with over 70% accuracy, and was able to explain approximately 49% of the variance in subjects' change in knee flexion between gait analyses. We found that improvement in stance phase knee flexion was positively associated with three variables that were drawn from knowledge about the biomechanical contributors to crouch gait: (i) adequate hamstrings lengths and velocities, possibly achieved via hamstrings lengthening surgery, (ii) normal tibial torsion, possibly achieved via tibial derotation osteotomy, and (iii) sufficient muscle strength.