Walking activity in a large cohort of boys with Duchenne muscular dystrophy.

INTRODUCTION: In this study we explored walking activity in a large cohort of boys with Duchenne muscular dystrophy (DMD). METHODS: Step activity (monitored for 7 days), functional ability, and strength were quantified in ambulatory boys (5-12.9 years of age) with DMD and unaffected boys. Ambulatory status was determined 2 years later. RESULTS: Two to 5 days of activity monitoring predicted weekly step activity (adjusted R2 = 0.80-0.95). Age comparisons revealed significant declines for step activity with increasing age, and relationships were found between step activity with both function and strength (P < .01). Our regression model predicted 36.5% of the variance in step activity. Those who were still ambulatory after 2 years demonstrated baseline step activity nearly double that of those who were no longer walking 2 years later (P < .01). DISCUSSION: Step activity for DMD is related to and predictive of functional declines, which may be useful for clinical trials.

The Poly(ADP-ribose) Polymerase Enzyme Tankyrase Antagonizes Activity of the ß-Catenin Destruction Complex through ADP-ribosylation of Axin and APC2.

Most colon cancer cases are initiated by truncating mutations in the tumor suppressor, adenomatous polyposis coli (APC). APC is a critical negative regulator of the Wnt signaling pathway that participates in a multi-protein "destruction complex" to target the key effector protein ß-catenin for ubiquitin-mediated proteolysis. Prior work has established that the poly(ADP-ribose) polymerase (PARP) enzyme Tankyrase (TNKS) antagonizes destruction complex activity by promoting degradation of the scaffold protein Axin, and recent work suggests that TNKS inhibition is a promising cancer therapy. We performed a yeast two-hybrid (Y2H) screen and uncovered TNKS as a putative binding partner of Drosophila APC2, suggesting that TNKS may play multiple roles in destruction complex regulation. We find that TNKS binds a C-terminal RPQPSG motif in Drosophila APC2, and that this motif is conserved in human APC2, but not human APC1. In addition, we find that APC2 can recruit TNKS into the ß-catenin destruction complex, placing the APC2/TNKS interaction at the correct intracellular location to regulate ß-catenin proteolysis. We further show that TNKS directly PARylates both Drosophila Axin and APC2, but that PARylation does not globally regulate APC2 protein levels as it does for Axin. Moreover, TNKS inhibition in colon cancer cells decreases ß-catenin signaling, which we find cannot be explained solely through Axin stabilization. Instead, our findings suggest that TNKS regulates destruction complex activity at the level of both Axin and APC2, providing further mechanistic insight into TNKS inhibition as a potential Wnt pathway cancer therapy.

Perspectives on Sexual Health and Function of Recent Male Combat Veterans of Iraq and Afghanistan.

BACKGROUND: U.S. veterans of recent wars in Iraq and Afghanistan may be at greater risk for sexual dysfunction due to injuries, mental health conditions, medications used to treat those conditions, and psychosocial factors. OBJECTIVE: To explore the perceptions of recent Veterans about sexual health and dysfunction, contributing factors, its impact and solutions. DESIGN: Qualitative study. PARTICIPANTS: Eight men who screened positive for sexual dysfunction at initial presentation to a postdeployment clinic at a Veterans Affairs medical center. APPROACH: Patients who screened positive for sexual dysfunction and indicated an interest in participating were contacted and scheduled for an in-person private interview with a researcher. Interviews were semistructured, utilizing open-ended and follow-up probe questions to elicit the individual's perspective about sexual dysfunction and its cause, impact and solutions. Interviews were recorded, transcribed and analyzed for themes. KEY RESULTS: These heterosexual men discussed a range of sexual dysfunction in their activities including lack of desire, erectile dysfunction, delayed orgasm, premature ejaculation, and distraction. They also discussed the importance of setting or context and changes over time to their sexual health and function. The men shared their ideas about contributory factors, including normal aging, medication side effects, injury and a possible role for combat deployment more generally. Reported solutions for sexual dysfunction included medications, herbal remedies, and new positions and approaches to sexual activity. Participants reported discussing sexual dysfunction with their health-care providers and what was helpful. Finally, the men expressed in their own words the significant impact of sexual dysfunction on their self-perception, their partners, and their relationships. CONCLUSIONS: Sexual dysfunction in recent combat veterans can have important negative effects on their health and relationships. Our findings elucidate perceived contributory factors and preferred solutions, which can be applied by health-care providers to improve the management of sexual dysfunction in these patients.

Cardiovascular risk: gender differences in lifestyle behaviors and coping strategies.

BACKGROUND: Although cardiovascular disease (CVD) does not occur until mid to late life for most adults, the presence of risk factors, such as high blood pressure (BP) and cholesterol, has increased dramatically in young adults. PURPOSE: The present study examined the relationships between gender and coping strategies, lifestyle behaviors, and cardiovascular risks. METHOD: The sample consisted of 297 (71% female) university students. Participants completed a survey to assess demographics, lifestyle behaviors, and coping strategies, and a physiological assessment including lipid and blood pressure (BP) measurements. Data collection occurred from January 2007 to May 2008. RESULTS: Analyses revealed that age, ethnicity, greater body mass index (BMI), greater use of social support, and less frequent exercise were associated with higher cholesterol, while gender, age, greater BMI, and less frequent exercise were associated with higher systolic BP. There were two significant interactions: one between gender and avoidant coping and the other between gender and exercise on systolic BP, such that for men greater use of avoidant coping or exercise was associated with lower systolic BP. CONCLUSION: Understanding how young adults manage their demands and cope with stress sets the stage for understanding the developmental process of CVD. Both coping strategies and lifestyle behaviors must be considered in appraising gender-related cardiovascular risk at an early age before the disease process has begun.

Mindfulness and its Role in Physical and Psychological Health.

This study examined the relationships of mindfulness, a form of focused self-awareness, with physical and psychological health. Mindfulness was measured in terms of four stable forms of awareness: Observe, an awareness of internal and external stimuli; Describe, an ability to verbally express thoughts clearly and easily; Act with Awareness, the tendency to focus on present tasks with undivided attention; and Accept without Judgment, the tendency to take a nonjudgmental attitude toward one's own thoughts and emotions. These aspects of mindfulness were explored in relation to both physical health, which consisted of heart rate variability, a measure of overall cardiovascular health, and psychological health, which consisted of flourishing, existential well-being, negative affect, and social well-being in a sample of 506 undergraduate students. Individuals high in mindfulness showed better cardiovascular health and psychological health.

Tobacco education and counseling in obstetrics and gynecology clerkships: a survey of medical school program directors.

The 16,000 medical students completing OB/GYN clerkship programs each year provide a unique opportunity to motivate and mentor students in facilitating tobacco cessation. To determine the scope of current tobacco teaching in obstetrics/gynecology (OB/GYN) education at US medical schools and to assess opportunities for including new tobacco teaching, a 28-question survey was administered to directors and assistant directors at US medical school OB/GYN clerkship programs. Surveys were completed at 71% of schools. Only 9% reported having at least 15 min of dedicated teaching time for improving tobacco cessation skills. Nearly three-fourths of respondents reported teaching students how to intervene to reduce smoking during a work-up in the OB/GYN clinic, but only 43% reported that students would know where to refer someone wishing to quit. Only a third of respondents reported teaching students both to intervene with and refer OB/GYN patients who smoke. These findings suggest that although medical students see many OB and GYN patients who smoke, they have few opportunities to learn comprehensive cessation skills during their clerkships.

Cultural competency and tobacco control training in US medical schools: many but missed opportunities.

Tobacco-related morbidity and mortality disproportionately burdens America's most vulnerable populations, and many physicians in the USA are untrained in smoking cessation skills with patients of various literacy levels and races and ethnicities. An anonymous survey was administered to 860 second year and 827 fourth year students at 12 medical schools. A faculty representative at each of the schools completed an assessment of the curriculum and rated medical students' knowledge and skills for cultural competency. Report of experience in tobacco counseling for persons of various literacy levels and ethnicities rose from 42% (second year students) to 82% (fourth year students) and 48% (second year students) to 91% (fourth year students), respectively. However, only 37% of second year students and 40% of fourth year students reported that they had ever been taught to employ culturally competent strategies for tobacco cessation. This study found that almost two thirds of students in 12 medical schools reported no exposure to teaching about cultural competency and tobacco cessation, and approximately one third reported no practical experience with tobacco cessation counseling persons of various races and ethnicities. Effective cultural competency training for tobacco control should include teaching the social constructs of race, ethnicity, and socio-cultural concepts within a medical context. Additionally, students should receive supervised clinical opportunities to practice counseling, including opportunities to discuss and reflect on their experiences.

Ethnicity and Type D personality as predictors of heart rate variability.

This study examined the relationship between Type D personality and heart rate variability (HRV) during three guided imagery experiences (baseline, stressful, and uplifting) in a non-medical sample. The interaction between African-American ethnicity and Type D personality was predictive of both low and high frequency HRV during stressful imagery experiences. The importance of identifying group influences when assessing psychological and cardiovascular health was discussed.

Phanerozoic trends in the global diversity of marine invertebrates.

It has previously been thought that there was a steep Cretaceous and Cenozoic radiation of marine invertebrates. This pattern can be replicated with a new data set of fossil occurrences representing 3.5 million specimens, but only when older analytical protocols are used. Moreover, analyses that employ sampling standardization and more robust counting methods show a modest rise in diversity with no clear trend after the mid-Cretaceous. Globally, locally, and at both high and low latitudes, diversity was less than twice as high in the Neogene as in the mid-Paleozoic. The ratio of global to local richness has changed little, and a latitudinal diversity gradient was present in the early Paleozoic.

Tobacco cessation and prevention practices reported by second and fourth year students at US medical schools.

BACKGROUND: Tobacco dependence counseling is recommended to be included as core curriculum for US medical students. To date, there has been little information on students' self-reported skills and practice opportunities to provide 5A's (Ask, Advise, Assess, Assist, and Arrange) counseling for tobacco cessation. METHODS: We conducted anonymous surveys of second year and fourth year students at multiple US medical schools between February 2004 and March 2005 (overall response rate 70%). We report on the tobacco control practices of the 860 second year and 827 fourth year students completing the survey. MEASUREMENTS AND MAIN RESULTS: Fourth year students reported multiple opportunities to learn tobacco counseling in case-based discussions, simulated patient encounters, and clinical skills courses. They reported more instruction in family medicine (79%) and Internal Medicine (70%) than Pediatrics (54%), Obstetrics/Gynecology (41%), and Surgery clerkships (16%). Compared with asking patients about smoking, advising smokers to quit, and assessing patient willingness to quit, fourth year students were less likely to have multiple practice opportunities to assist the patient with a quit plan and arrange follow-up contact. More than half of second year students reported multiple opportunities for asking patients about smoking but far fewer opportunities for practicing the other 4 As. CONCLUSIONS: By the beginning of their fourth year, most students in this group of medical schools reported multiple opportunities for training and practicing basic 5A counseling, although clear deficits for assisting patients with a quit plan and arranging follow-up care exist. Addressing these deficits and integrating tobacco teaching through tailored specific instruction across all clerkships, particularly in Surgery, Pediatrics, and Obstetrics/Gynecology is a challenge for medical school education.

Smoking Sleuths: a pilot tobacco prevention elective for medical school students.

BACKGROUND: Smoking Sleuths is an experiential learning curriculum that was developed and taught to elementary through high school aged children by medical students. METHODS: A total of 14 first- and 4th-year medical students from 2 medical schools participated in the tobacco service learning elective. RESULTS: Medical students trained Adolescent Tobacco Education Leaders who provided tobacco education to peers and members of the public. CONCLUSIONS: Smoking Sleuths provides opportunities for medical students to learn counseling and health education skills across many disciplines. The elective may have a broader audience in schools of allied health, nursing, dentistry, education, and public health.

Basic skills for working with smokers: a pilot test of an online course for medical students.

BACKGROUND: Online learning can be an excellent method for presenting clinical skills to address health behaviors. METHODS: Medical students pilot tested a skills-building course consisting of an online component and a practical application. RESULTS: A total of 38 students were registered, 25 (66%) completed the online component, and 22 (58%) completed both course components. Students reported they were adequately trained to administer the brief 5A intervention to patients who smoke and they intended to deliver the intervention routinely. CONCLUSIONS: Online skills-building courses can have a positive effect on students' knowledge and skills and can be used across health behaviors promote healthy lifestyles.

A randomized trial to improve early detection and prevention practices among siblings of melanoma patients.

BACKGROUND: Identifying high-risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first-degree relatives of melanoma patients represent a risk group who may experience a 'teachable moment' for enhanced education and risk reduction. METHODS: We report a randomized trial testing an intervention that provided personalized telephone counseling and individually tailored materials to siblings of recently-diagnosed melanoma patients. The purpose of this study was to test whether an intervention could lead to improvements in siblings' skin cancer risk reduction practices. Intervention condition participants received the following: (1) an initial motivational and goal-setting telephone intervention session delivered by the health educator; (2) three sets of computer-generated materials specifically tailored to individual responses from the baseline survey; (3) three telephone counseling sessions with the health educator, timed to follow receipt of the mailed materials; and (4) linkages to free screening programs. Families in the usual care arm received the suggestion from the physician that patients diagnosed with melanoma notify the family members about their diagnosis and encourage the family members to be screened. RESULTS: 494 siblings were recruited to the study and 403 siblings remained in the study through at least 6 months. At 12 months, intervention siblings were more likely to examine all moles, including those on the back (OR, 1.76; 95% CI, 1.06-2.91). Compared with baseline, the number of participants in both groups that had received a skin cancer examination more than doubled, with no differences between groups. At 12 months, two-thirds of siblings in both groups reported routine use of sunscreen, but there were no differences in change over baseline between the two groups. CONCLUSIONS: This study is the one of the first, to our knowledge, to address skin cancer risk-reduction strategies in a sample of individuals who have a recent family diagnosis of melanoma. Diagnosis of melanoma in a family member provides an important opportunity to intervene with others in that family. The components of the intervention may provide a useful foundation for future efforts to target the more than half million siblings at risk for melanoma, a lethal but preventable disease.

Bioavailability and safety of a high dose of docosahexaenoic acid triacylglycerol of algal origin in cystic fibrosis patients: a randomized, controlled study.

OBJECTIVE: Several studies have reported omega-3 and omega-6 fatty acid imbalances in patients with cystic fibrosis (CF). Whether these imbalances contribute to or are manifestations of the pathophysiology of CF is unknown. The study objective was to determine bioavailability, tissue accretion, and safety of a large dose of an algal source of docosahexaenoic acid (DHA) triacylglycerol and to observe effects on lung function in patients with CF. METHODS: Twenty subjects with CF (8 to 20 y of age) were randomly assigned to receive algal oil providing 50 mg of DHA per kilogram per day (1 to 4.2 g of DHA per subject per day) or placebo for 6 mo. Fatty acids, liver enzymes, and lipid soluble antioxidants were measured in blood at baseline and at 1, 3, and 6 mo. Rectal biopsy specimens were collected at baseline and at 3 mo for fatty acid analysis. Lung function, anthropometrics, and adverse experiences were monitored throughout the study. RESULTS: Compared with placebo, DHA supplementation increased plasma, erythrocyte, and rectal DHA levels four- to five-fold (P < 0.001) with concomitant decreases in blood arachidonic acid levels and the ratio of arachidonic acid to DHA. Supplementation was well tolerated, with no treatment-related changes in liver enzymes, growth, or antioxidant status. DHA supplementation had no detectable effect on lung function during the course of this study. CONCLUSIONS: Algal DHA triacylglycerol oil is readily absorbed, well tolerated, and increases blood and tissue DHA levels in patients with CF. No adverse developments were associated with this large dose of DHA oil. Larger studies of longer duration are needed to determine whether DHA supplementation results in any clinically significant benefits in patients with CF.

Tobacco control competencies for US medical students.

The 2004 National Action Plan for Tobacco Cessation recommended that the US Department of Health and Human Services convene a diverse group of experts to ensure that competency in tobacco dependence interventions be a core graduation requirement for all new physicians and other key health care professionals. Core competencies would guide the design of new modules and explicitly outline the learning objectives for all graduating medical students. In 2002, the National Cancer Institute funded a consortium to develop, test, and integrate tobacco curricula at 12 US medical schools. Because there was neither an explicit set of tobacco competencies for medical schools nor a process to develop them, one of the consortium's tasks was to articulate competencies and learning objectives.

Type III secretion phenotypes of Pseudomonas aeruginosa strains change during infection of individuals with cystic fibrosis.

Pseudomonas aeruginosa is a frequent cause of respiratory exacerbations in individuals with cystic fibrosis. An important virulence determinant of this pathogen is its type III protein secretion system. In this study, the type III secretion properties of 435 P. aeruginosa respiratory isolates from 56 chronically infected individuals with cystic fibrosis were investigated. Although it had been previously reported that 75 to 90% of P. aeruginosa isolates from patients with hospital-acquired pneumonia secreted type III proteins, only 12% of isolates from cystic fibrosis patients did so, with nearly all of these isolates secreting ExoS and ExoT but not ExoU. Despite the low overall prevalence of type III protein-secreting isolates, at least one secreting isolate was cultured from one-third of cystic fibrosis patients. Interestingly, the fraction of cystic fibrosis patient isolates capable of secreting type III proteins decreased with duration of infection. Although 90% of isolates from the environment, the presumed reservoir for the majority of P. aeruginosa strains that infect patients with cystic fibrosis, secreted type III proteins, only 49% of isolates from newly infected children, 18% of isolates from chronically infected children, and 4% of isolates from chronically infected adults with cystic fibrosis secreted these proteins. Within individual patients, isolates of clonal origin differed in their secretion phenotypes, indicating that as strains persisted in cystic fibrosis patient airways, their type III protein secretion properties changed. Together, these findings indicate that following infection of cystic fibrosis patient airways, P. aeruginosa strains gradually change from a type III protein secretion-positive phenotype to a secretion-negative phenotype.

Changing patterns of sun protection between the first and second summers for very young children.

OBJECTIVES: To determine if an intensive intervention directed to mothers of newborns would increase levels of sun protection practice and lower rates of sunburning for their children; and to examine changes in sun protection practices and burning rates experienced between the first and second summers of life. DESIGN: Randomized study. SETTING AND PARTICIPANTS: Mothers of infants residing in the coastal town of Falmouth, Mass. INTERVENTION: Mothers were randomly selected to receive hospital education alone or hospital education plus tailored materials and telephone counseling. MAIN OUTCOME MEASURES: Child's sun protection practices and degree of skin damage at mean ages 6 and 18 months, as reported by the mother. RESULTS: Baseline surveys were completed by 108 mothers; 92 (85%) of the mothers completed posttests. There were few differences between intervention and control groups in use of sun protection for infants from the first summer (mean age, 6 months) to the second summer (mean age, 18 months). The child's routine use of hats, shirts, and shade dropped substantially from the first to the second summer. Conversely, sunscreen use rose from 34% to 93% (P<.001) for both groups during the same period. During the first summer, 22% of children received a sunburn or tan compared with 54% during the second summer (P<.001). CONCLUSIONS: Comprehensive sun protection begins to decline at a much earlier age than previously reported. Future studies should focus on parents' beliefs about the need for, and practice of, vigilant sun protection as their children grow from infancy to toddlerhood.

Evaluation of current tobacco curriculum at 12 US medical schools.

BACKGROUND: Training medical students in tobacco prevention and treatment skills is critical if we are to have competent physicians prepared to address the grave levels of morbidity and mortality associated with tobacco use. Tobacco Prevention and Cessation Education at US Medical Schools (PACE), a National Cancer Institute funded project, was launched to assess and improve curriculum content and teaching at 12 US medical schools. METHODS: The 2003 survey was completed by faculty and administrators. The survey was divided into four main sections: tobacco content and skills, curricular evaluation, faculty perceptions of barriers and promoters, and educational vision. RESULTS: Thirty-six percent of all medical school courses had some tobacco-related content. Five schools provided a total of between 4 and 8 hours of teaching, 5 schools provided 10-13 hours, and 2 schools provided 17 and 18 hours of teaching. Of the 12 schools, 8 had fewer hours devoted to tobacco teaching in the clerkships than during the 1st-year courses. Only 2 schools noted any tobacco content for Obstetrics/Gynecology clerkships, and only 4 schools provided teaching in the pediatric setting (range 5-201 minutes). CONCLUSION: In comparison to earlier studies, it appears that more tobacco content is now integrated into medical school courses. More improvement is necessary, however, particularly in tobacco use prevention. Institutions need to examine the role of faculty in prioritizing tobacco information and promoting a culture that builds competency in tobacco control and treatment.

Skin cancer prevention and detection practices among siblings of patients with melanoma.

BACKGROUND: Family members of patients with melanoma have an increased risk of the disease, and families with multiple affected members account for about 10% of melanoma cases. These statistics suggest that first-degree relatives of patients with melanoma, who are at particularly high risk, warrant targeted public health action. OBJECTIVE: We sought to document rates for dermatologist examinations for cutaneous lesions, the practice of skin self-examination, and sunscreen use in this at-risk group. METHODS: Before participation in a randomized trial, 404 siblings of recently diagnosed patients with melanoma completed a survey on beliefs and practices regarding skin cancer prevention and detection. RESULTS: Sixty-two percent of participants had carefully examined their skin, 54% routinely used sunscreen, and 27% had received a skin cancer examination by a dermatologist during the past year; 47% had never received a dermatologist examination. Multivariate analysis found modifiable positive predictors for skin self-examination and dermatologist examinations, including having a clinician with whom to talk about melanoma and believing in the importance of regular skin examinations by a physician. Significant modifiable negative predictors included enjoyment of being tanned, not being sure what to look for when examining moles, and feeling uncomfortable having others look at their skin. CONCLUSIONS: Skin self-examination rates among these high-risk siblings are markedly higher than in population-based studies. However, many siblings were not screened for skin cancer by a dermatologist despite having strong risk profiles, being nearly fully insured, and being under care of primary care physicians. Improvements in communication between physicians and high-risk families and changes in office systems to assess family history of melanoma could increase screening rates for the estimated 1 million siblings of patients with melanoma.