A Retrospective Study of Anticholinergic Use and Later Mobilization as Risk Factors for Urinary Retention After Major Lower Extremity Joint Arthroplasty.

BACKGROUND: Postoperative urinary retention (POUR) is a common surgical complication of major joint arthroplasty and is associated with increased lengths of stay and urinary tract infections. Studies have found that certain anticholinergic medications and reduced mobility are associated with POUR. This study assessed the effect of anticholinergic burden and later postoperative ambulation on POUR. METHODS: In this retrospective cohort study, we included subjects who had undergone elective primary or revision hip or knee arthroplasty (total hip arthroplasty [THA] or total knee arthroplasty [TKA]) between March 2015 and December 2017 in a single health system. Anticholinergic burden was measured using the Anticholinergic Drug Scale (ADS). We performed bivariate and multivariable logistic regression with POUR as the dependent variable. Of the 1,397 study subjects, 622 (45%) underwent THA and 775 (55%) underwent TKA. Their mean age was 65 years (range, 21 to 98), and 841 (60%) were women. POUR developed in 183 (13%) subjects. RESULTS: In multivariable analyses, ADS was associated with POUR after THA (P < .05), but not TKA (P = .08), while later ambulation was not associated with POUR after either procedure (P > .3 for both). CONCLUSION: Anticholinergic burden after THA was independently associated with POUR. Strategies to reduce anticholinergic burden may help reduce POUR after THA.

Metabolic Rewiring by Loss of Sirt5 Promotes Kras-Induced Pancreatic Cancer Progression.

BACKGROUND & AIMS: SIRT5 plays pleiotropic roles via post-translational modifications, serving as a tumor suppressor, or an oncogene, in different tumors. However, the role SIRT5 plays in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: Published datasets and tissue arrays with SIRT5 staining were used to investigate the clinical relevance of SIRT5 in PDAC. Furthermore, to define the role of SIRT5 in the carcinogenesis of PDAC, we generated autochthonous mouse models with conditional Sirt5 knockout. Moreover, to examine the mechanistic role of SIRT5 in PDAC carcinogenesis, SIRT5 was knocked down in PDAC cell lines and organoids, followed by metabolomics and proteomics studies. A novel SIRT5 activator was used for therapeutic studies in organoids and patient-derived xenografts. RESULTS: SIRT5 expression negatively regulated tumor cell proliferation and correlated with a favorable prognosis in patients with PDAC. Genetic ablation of Sirt5 in PDAC mouse models promoted acinar-to-ductal metaplasia, precursor lesions, and pancreatic tumorigenesis, resulting in poor survival. Mechanistically, SIRT5 loss enhanced glutamine and glutathione metabolism via acetylation-mediated activation of GOT1. A selective SIRT5 activator, MC3138, phenocopied the effects of SIRT5 overexpression and exhibited antitumor effects on human PDAC cells. MC3138 also diminished nucleotide pools, sensitizing human PDAC cell lines, organoids, and patient-derived xenografts to gemcitabine. CONCLUSIONS: Collectively, we identify SIRT5 as a key tumor suppressor in PDAC, whose loss promotes tumorigenesis through increased noncanonic use of glutamine via GOT1, and that SIRT5 activation is a novel therapeutic strategy to target PDAC.

Effect of Near Work on Intraocular Pressure in Emmetropes.

OBJECTIVE: To determine whether accommodation induced by reading alters intraocular pressure (IOP) in healthy, young, emmetropic adults and to document the duration and magnitude of this effect. DESIGN: Cross-sectional study. Participants. Fifteen healthy, emmetropic young adults. METHODS: Subjects performed 20 minutes of near work (reading at 33 cm) followed by 20 minutes of far work (reading at 520 cm) while IOP was measured using an iCare tonometer at baseline and every 5 minutes thereafter. Statistical analysis was performed using repeated measures ANOVA. Main Outcome Measures. Intraocular pressure. RESULTS: IOP decreased significantly compared to baseline IOP after 10 minutes of near work (average change of -1.60 ± 2.2 (SD) mm Hg, p < 0.05). IOP remained lower than baseline IOP throughout all subsequent near and far work. The difference in IOP at the end of experimentation compared to baseline IOP was -1.87 ± 1.81 mm Hg (p < 0.05). IOP remained lower than baseline IOP throughout all subsequent near and far work. The difference in IOP at the end of experimentation compared to baseline IOP was -1.87 ± 1.81 mm Hg (. CONCLUSIONS: Near work decreases IOP in healthy emmetropes, and this effect is sustained for at least 20 minutes after discontinuing prolonged near work. Providers may need to consider this effect when measuring IOP in clinical practice.

Fluid administration rate for uncontrolled intraabdominal hemorrhage in swine.

BACKGROUND: We hypothesized that slow crystalloid resuscitation would result in less blood loss and a smaller hemoglobin decrease compared to a rapid resuscitation during uncontrolled hemorrhage. METHODS: Anesthetized, splenectomized domestic swine underwent hepatic lobar hemitransection. Lactated Ringers was given at 150 or 20 mL/min IV (rapid vs. slow, respectively, N = 12 per group; limit of 100 mL/kg). Primary endpoints were blood loss and serum hemoglobin; secondary endpoints included survival, vital signs, coagulation parameters, and blood gases. RESULTS: The slow group had a less blood loss (1.6 vs. 2.7 L, respectively) and a higher final hemoglobin concentration (6.0 vs. 3.4 g/dL). CONCLUSIONS: Using a fixed volume of crystalloid resuscitation in this porcine model of uncontrolled intraabdominal hemorrhage, a slow IV infusion rate produced less blood loss and a smaller hemoglobin decrease compared to rapid infusion.

Influence of suppression on restoration of spectral loudness summation in listeners with hearing loss.

Loudness depends on both the intensity and spectrum of a sound. Listeners with normal hearing perceive a broadband sound as being louder than an equal-level narrowband sound because loudness grows nonlinearly with level and is then summed across frequency bands. This difference in loudness as a function of bandwidth is reduced in listeners with sensorineural hearing loss (SNHL). Suppression, the reduction in the cochlear response to one sound by the simultaneous presentation of another sound, is also reduced in listeners with SNHL. Hearing-aid gain that is based on loudness measurements with pure tones may fail to restore normal loudness growth for broadband sounds. This study investigated whether hearing-aid amplification that mimics suppression can improve loudness summation for listeners with SNHL. Estimates of loudness summation were obtained using measurements of categorical loudness scaling (CLS). Stimuli were bandpass-filtered noises centered at 2 kHz with bandwidths in the range of 0.1-6.4 kHz. Gain was selected to restore normal loudness based on CLS measurements with pure tones. Gain that accounts for both compression and suppression resulted in better restoration of loudness summation, compared to compression alone. However, restoration was imperfect, suggesting that additional refinements to the signal processing and gain-prescription algorithms are needed.

Predictive Factors for Vestibular Loss in Children With Hearing Loss.

PURPOSE: The aim of this study was to determine if there are factors that can predict whether a child with hearing loss will also have vestibular loss. METHOD: A retrospective chart review was completed on 186 children with hearing loss seen at Boys Town National Research Hospital for vestibular testing from 1999 to 2015 through neurosensory genetics clinic or cochlear implant candidacy. Each child's medical chart was reviewed to obtain the following data: vestibular loss severity (classified as normal, bilateral, or mild to moderate), degree of hearing loss (bilateral pure-tone average [PTA]), imaging abnormalities (classified as "normal" or "abnormal"), parental concerns for gross motor delay (classified as "yes, there is concern" or "no, there is not a concern"), parent report of age when their child sat (months) and walked independently (months), comorbidities (classified as "yes" if there were 1 or more comorbidities or "no" if there were no comorbidities), and score on the Developmental Profile-3. RESULTS: Children were grouped according to vestibular loss severity; 115 children had normal vestibular function, 31 had bilateral vestibular loss, and 40 had mild-to-moderate vestibular loss. As severity of vestibular loss increased, children (a) sat and walked later, (b) scored more poorly on the Developmental Profile-3 physical subscale, (c) had more severe hearing loss, (d) had parents who more frequently reported concern for gross motor delay, and (e) were more likely to have other comorbidities. Of these factors, age-to-sit, age-to-walk, PTA, and parental concerns for gross motor developmental delay had the greatest ability to differentiate children with vestibular loss from children with normal vestibular function. For age-to-sit, using a cutoff value of 7.25 months yielded a sensitivity of 62% and a specificity of 81%. For age-to-walk, a cutoff value of 14.5 months yielded a sensitivity of 78% and a specificity of 77%. For PTA for the neurosensory genetics group, a cutoff value of 40 dB yielded a sensitivity of 80% and a specificity of 55%; however, a cutoff value of 66 dB yielded a sensitivity of 33% and an improved specificity of 91%. CONCLUSIONS: A referral for vestibular evaluation should be considered for children whose hearing loss is greater than 66 dB and particularly those who sit later than 7.25 months or walk later than 14.5 months or whose parents report concerns for gross motor development. Collectively, these factors appear to be more sensitive for identifying children with bilateral vestibular loss compared with children with mild-to-moderate vestibular loss. Because of the benefit of physical therapy, children identified with vestibular loss should then be referred to physical therapy for further evaluation and treatment.

Mobile Phone-Based Measures of Activity, Step Count, and Gait Speed: Results From a Study of Older Ambulatory Adults in a Naturalistic Setting.

BACKGROUND: Cellular mobile telephone technology shows much promise for delivering and evaluating healthcare interventions in cost-effective manners with minimal barriers to access. There is little data demonstrating that these devices can accurately measure clinically important aspects of individual functional status in naturalistic environments outside of the laboratory. OBJECTIVE: The objective of this study was to demonstrate that data derived from ubiquitous mobile phone technology, using algorithms developed and previously validated by our lab in a controlled setting, can be employed to continuously and noninvasively measure aspects of participant (subject) health status including step counts, gait speed, and activity level, in a naturalistic community setting. A second objective was to compare our mobile phone-based data against current standard survey-based gait instruments and clinical physical performance measures in order to determine whether they measured similar or independent constructs. METHODS: A total of 43 ambulatory, independently dwelling older adults were recruited from Nebraska Medicine, including 25 (58%, 25/43) healthy control individuals from our Engage Wellness Center and 18 (42%, 18/43) functionally impaired, cognitively intact individuals (who met at least 3 of 5 criteria for frailty) from our ambulatory Geriatrics Clinic. The following previously-validated surveys were obtained on study day 1: (1) Late Life Function and Disability Instrument (LLFDI); (2) Survey of Activities and Fear of Falling in the Elderly (SAFFE); (3) Patient Reported Outcomes Measurement Information System (PROMIS), short form version 1.0 Physical Function 10a (PROMIS-PF); and (4) PROMIS Global Health, short form version 1.1 (PROMIS-GH). In addition, clinical physical performance measurements of frailty (10 foot Get up and Go, 4 Meter walk, and Figure-of-8 Walk [F8W]) were also obtained. These metrics were compared to our mobile phone-based metrics collected from the participants in the community over a 24-hour period occurring within 1 week of the initial assessment. RESULTS: We identified statistically significant differences between functionally intact and frail participants in mobile phone-derived measures of percent activity (P=.002, t test), active versus inactive status (P=.02, t test), average step counts (P<.001, repeated measures analysis of variance [ANOVA]) and gait speed (P<.001, t test). In functionally intact individuals, the above mobile phone metrics assessed aspects of functional status independent (Bland-Altman and correlation analysis) of both survey- and/or performance battery-based functional measures. In contrast, in frail individuals, the above mobile phone metrics correlated with submeasures of both SAFFE and PROMIS-GH. CONCLUSIONS: Continuous mobile phone-based measures of participant community activity and mobility strongly differentiate between persons with intact functional status and persons with a frailty phenotype. These measures assess dimensions of functional status independent of those measured using current validated questionnaires and physical performance assessments to identify functional compromise. Mobile phone-based gait measures may provide a more readily accessible and less-time consuming measure of gait, while further providing clinicians with longitudinal gait measures that are currently difficult to obtain.

Changing Body Movement Patterns in 9-Year-Old Baseball Pitchers: A Pilot Study.

BACKGROUND: Arm injuries in throwing athletes continue to increase. Injuries may be due to multiple variables, including inefficient body movement patterns, especially in young baseball throwers. It is unclear whether these patterns can be efficiently altered in this population. PURPOSE/HYPOTHESIS: To investigate the effect of a novel 21-day throwing program on body movement patterns in youth baseball players using common practical tools. Our hypothesis was that this program would change body movement patterns over a relatively short period. STUDY DESIGN: Descriptive laboratory study. METHODS: Ten 9-year-old baseball athletes were asked to participate in a 21-consecutive day throwing program focused on decreasing inefficiencies. All participants underwent video evaluation from 2 vantage points as well as radar evaluation before and after the programs. Throwing arm humerothoracic and antecubital angles as well as pelvic angles in the frontal view were measured at the time of front (directional) leg heel/toe down (late cocking) for each of 3 pitches. Glove-side humerothoracic angles and back leg minimum popliteal angles were measured from behind for each of 3 additional pitches. Velocity was measured using a radar gun. All angular measurements were performed by a physical therapist blinded to the purposes of the program and study as well as to video chronology. RESULTS: Throwing arm antecubital angle (P = .01) and humerothoracic angle (P = .03) as well as back leg minimum popliteal angle (P = .03) all decreased, with mean decreases of 35°, 10°, and 8°, respectively. Velocity increased with decreased back leg popliteal angles (P = .019); mean velocity increased 2.6 mph (P = .016). CONCLUSION: Young baseball throwers can quickly retrain their bodies to accomplish different movement patterns. CLINICAL RELEVANCE: This novel throwing program may have implications for injury prevention and treatment as we identify better baseball-throwing movement patterns.

Impact of a Mobile Phone Intervention to Reduce Sedentary Behavior in a Community Sample of Adults: A Quasi-Experimental Evaluation.

BACKGROUND: Greater time spent sedentary is linked with increased risk of breast, colorectal, ovarian, endometrial, and prostate cancers. Given steadily increasing rates of mobile phone ownership, mobile phone interventions may have the potential to broadly influence sedentary behavior across settings. OBJECTIVE: The purpose of this study was to examine the short-term impact of a mobile phone intervention that targeted sedentary time in a diverse community sample. METHODS: Adults participated in a quasi-experimental evaluation of a mobile phone intervention designed to reduce sedentary time through prompts to interrupt periods of sitting. Participants carried mobile phones and wore accelerometers for 7 consecutive days. Intervention participants additionally received mobile phone prompts during self-reported sitting and information about the negative health impact of prolonged sedentariness. The study was conducted from December 2012 to November 2013 in Dallas, Texas. Linear mixed model regression analyses were conducted to evaluate the influence of the intervention on daily accelerometer-determined estimates of sedentary and active time. RESULTS: Participants (N=215) were predominantly female (67.9%, 146/215) and nonwhite (black: 50.7%, 109/215; Latino: 12.1%, 26/215; other: 5.6%, 12/215). Analyses revealed that participants who received the mobile phone intervention had significantly fewer daily minutes of sedentary time (B=-22.09, P=.045) and more daily active minutes (B=23.01, P=.04) than control participants. CONCLUSIONS: A simple mobile phone intervention was associated with engaging in less sedentary time and more physical activity. Findings underscore the potential impact of mobile phone interventions to positively influence sedentary behavior and physical activity.

Targeted Transthoracic Acoustic Activation of Systemically Administered Nanodroplets to Detect Myocardial Perfusion Abnormalities.

BACKGROUND: Liquid core nanodroplets containing condensed gaseous fluorocarbons can be vaporized at clinically relevant acoustic energies and have been hypothesized as an alternative ultrasound contrast agent instead of gas-core agents. The potential for targeted activation and imaging of these agents was tested with droplets formulated from liquid octafluoropropane (C3) and 1:1 mixtures of C3 with liquid decafluorobutane (C3C4). METHODS AND RESULTS: In 8 pigs with recent myocardial infarction and variable degrees of reperfusion, transthoracic acoustic activation was attempted using 1.3 to 1.7 MHz low (0.2 mechanical index [MI]) or high MI (1.2 MI) imaging in real time (32-64 Hertz) or triggered 1:1 at end systole during a 20% C3 or C3C4 droplet infusion. Any perfusion defects observed were measured and correlated with delayed enhancement magnetic resonance imaging and postmortem staining. No myocardial contrast was produced with any imaging setting when using C3C4 droplets or C3 droplets during low MI real-time imaging. However, myocardial contrast was observed in all 8 pigs with C3 droplets when using triggered high MI imaging and in 5 of 6 pigs that had 1.7 MHz real time-high MI imaging. Although quantitative myocardial contrast was lower with real-time high MI imaging than 1:1 triggering, the correlation between real-time resting defect size and infarct size was good (r=0.97; P<0.001), as was the correlation with number of transmural infarcted segments by delayed enhancement imaging. CONCLUSIONS: Targeted transthoracic acoustic activation of infused intravenous C3 nanodroplets is effective, resulting in echogenic and persistent microbubbles which provide real-time high MI visualization of perfusion defects.

The association of incomplete glenoid component seating and periprosthetic glenoid radiolucencies after total shoulder arthroplasty.

BACKGROUND: Radiolucent lines surrounding prosthetic glenoid components are commonly seen after unconstrained total shoulder arthroplasty and can be a harbinger of subsequent glenoid component failure. Whether less than 100% glenoid seating is associated with the development of radiolucent lines around glenoid prostheses is unknown. This study investigated the association between incomplete glenoid component seating and periprosthetic glenoid radiolucencies. METHODS: Thirty-six unconstrained total shoulder arthroplasties were performed in 29 patients for primary glenohumeral osteoarthritis with a minimum 2-year follow-up. All were implanted with a partially cemented all-polyethylene glenoid prosthesis. Patients were evaluated with standardized plain films preoperatively and postoperatively and with thin-cut computed tomography (CT) scans at the latest follow-up. The Lazarus and Yian classifications were used to assess radiolucency and seating on radiographs and CT scans. Ratings were calculated for intraobserver and interobserver reliability and given κ, the Kendall coefficient, and interclass correlation coefficient values. RESULTS: At a mean of 43 months (range 24-26 months) after surgery, neither Lazarus plain film radiolucency scores (P = .78) nor Yian CT radiolucency scores (P = .68) were associated with Lazarus plain film seating scores. Neither Lazarus plain film radiolucency scores (P = .25) nor Yian CT radiolucency scores (P = .91) were associated with modified Lazarus CT scan seating scores. CT allowed for better intraobserver and interobserver reliability in all categories. CONCLUSION: Radiolucencies around a partially cemented glenoid component were not associated with the degree of component seating. Complete seating of the glenoid component is not necessary to achieve radiographic implant stability at a mean follow-up of 43 months.

Pilot study of younger and older HIV-infected adults using traditional and novel functional assessments.

OBJECTIVES: Emerging data suggest that HIV disease and its treatment affect the aging process. Accurate and reliable measures of functional status are needed to investigate this further. DESIGN: A pilot study in groups of younger and older HIV-infected adults using objective measures of function. METHODS: Evaluations included neuropsychological testing, grip strength, balance assessed by the Wii Balance Board, and actigraphy. Surveys were used for depression, fatigue, loneliness, self-reported activity level, and sexual function. Two-samplet test or Wilcoxon rank sum tests were used for continuous variables and exact chi-square tests were used for comparison between groups. RESULTS: Twenty-one participants were 20 to 40 years old (younger; mean age, 31.5), and 20 were more than 50 years old (older; mean age, 56.5). There was no difference between groups for depression, fatigue, or loneliness. Overall, there was a trend to lower scores in the older age group for neuropsychologicalz score (P = .11) and for verbal learning (P = .09). Functioning in the memory domain was significantly lower in older subjects (P = .007). There was no difference in executive function, speed of processing, memory, motor skills, or total activity. Gender differences in sexual function were observed. Four older and 3 younger participants met the definition of frailty. Total activity by actigraphy did not correlate well with self-reported activity. CONCLUSIONS: Objective tests were well accepted and feasible to perform, although not all are suitable for widespread clinical or research use. Objective measurements of activity did not correlate well with patient self-report, which has implications for future studies in this area.

Adolescent and young adult exposure to physical activity and breast density.

PURPOSE: The objective of this study is to examine the role of early lifetime exposure to physical activity on magnetic resonance imaging-determined breast density measures. METHODS: Associations of adolescent (high school (ages 14-17 yr) and early adulthood, post-high school (ages 18-21 yr) and past year) leisure-time physical activity, as well as a principal component score including all three estimates, were examined with percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) in a cross-sectional analysis of 182 healthy women, ages 25-29 yr, enrolled in the Dietary Intervention Study in Children Follow-up Study (DISC06). Generalized linear mixed models were used to examine associations after adjustment for relevant covariates for the entire analytic sample. Analyses were repeated in nulliparous women and hormonal contraceptive nonusers. RESULTS: Physical activity during high school and post-high school were not statistically significantly related to %DBV or ADBV in multivariable models. Past year physical activity was positively related to %DBV in the unadjusted and partially adjusted models (P < 0.001 and P = 0.01, respectively), which did not adjust for body mass index (BMI). After additional adjustment for childhood and early adulthood BMI, this association became nonstatistically significant. The relation between past year physical activity and ADBV was not statistically significant. These findings were similar in nonusers of hormonal contraceptives. No statistically significant relations were found in nulliparous women or between the principal component score and %DBV or ADBV. CONCLUSION: Results from this study are consistent with previous research suggesting that physical activity during adolescence and early adulthood is unrelated to breast density.

Gene expression of vitamin D metabolic enzymes at baseline and in response to vitamin D treatment in thyroid cancer cell lines.

The association between vitamin D and thyroid cancer is unclear. It is unknown if CYP27A1 or CYP2R1 are present in normal thyroid or cancer cells and there is limited information regarding response to treatment with vitamin D. SV40 immortalized follicular cells (N-thy) and six thyroid cancer cell lines were treated with 10 µM vitamin D(3), 0.1 µM 1,25(OH)(2)D(3) or vehicle × 24 h. CYP27A1, CYP2R1, CYP27B1 and CYP24A1 mRNA were measured using quantitative real-time-PCR before and after treatment. Cell proliferation was also evaluated in TPC1 and C643 cells after treatment with D(3), 25(OH)D(3) and 1,25(OH)(2)D(3). Baseline CYP27A1 and CYP27B1 mRNA were present in all cells, CYP2R1 was higher and CYP24A1 mRNA was lower in cancer cell lines versus N-thy. TPC1 cells had increased CYP24A1 mRNA levels when treated with both D(3) (3.49, p < 0.001) and 1,25(OH)(2)D(3) (5.05, p < 0.001). C643 cells showed increased CYP24A1 mRNA expression when treated with 1,25(OH)(2)D(3) (5.36, p < 0.001). D(3), 25(OH)D(3) and 1,25(OH)(2)D(3) all significantly decreased cell proliferation in TPC1 and C643 cells. Overall, both cancerous and N-thy cell lines express CYP27A1 and CYP2R1 in addition to CYP27B1, establishing the potential to metabolize D(3) to 1,25(OH)(2)D(3). Additionally, vitamin D(3), 25(OH)D(3) and 1,25(OH)(2)D(3) all had an antiproliferative effect on two thyroid cancer cell lines.

Patterns of accelerometer-derived estimates of inactivity in middle-age women.

PURPOSE: The study's purpose was to characterize accelerometer-derived estimates of physical inactivity collected during five consecutive weeks in middle-age women. METHODS: Data were obtained from 63 participants (95.5%) enrolled in the Evaluation of Physical Activity Measures in Middle-Age Women Study. Inactive time (min · d(-1)) was estimated as the sum of activity counts <100, and inactive-to-active transitions were defined as an interruption in which a period of inactivity was immediately followed by a minute or more above 100 counts. A repeated-measures ANOVA using PROC MIXED (SAS/STAT software, v. 9.2) was used to describe hourly, daily, and weekly variation in estimates of physical inactivity. RESULTS: Participants were 52.7 ± 5.5 yr, 85.7% non-Hispanic white, and 63.5% postmenopausal, with a body mass index of 26.7 ± 5.1 kg · m(-2). Inactive time gradually increased as the day continued, particularly on weekend days. When compared with weekdays, average inactive time was lower on Saturday and Sunday (all P < 0.01 except for Saturday vs Monday, P < 0.10); Saturdays were not significantly different from Sundays. Breaks in inactive time were significantly lower on Sunday when compared with weekdays and Saturday (all P < 0.05), and fewer breaks were noted on Saturday when compared with Wednesday and Friday (both P < 0.01). After adjustment for total wear time or inactive time, most day-to-day differences were attenuated. Week-by-week differences in physical inactivity estimates were also not statistically significant. CONCLUSIONS: The results of this study suggest that inactive time increases as the day continues and that daily physical inactivity estimates are more stable after 1) adjustment for wear time or 2) when averaged over the week. Researchers should carefully consider the intended application of physical inactivity estimates before data collection and processing, analysis, and final data reporting.

The relationship between media use and psychological and physical assets among third- to fifth-grade girls.

BACKGROUND: Media use is associated with an increased risk of chronic disease and reduced quality of life among children. This study examined the relationship between media use during discretionary hours after school and psychological and physical assets among preadolescent girls. METHODS: A cross-sectional analysis was conducted using data from a larger quasi-experimental evaluation of a positive youth development program through sport for third- to fifth-grade girls. Indicators of media use were the number of hours per school day spent watching television and videos and using computers. Psychological assets included global self-esteem, body size satisfaction, and commitment to physical activity; physical assets included physical activity. Nested random effects analysis of variance (ANOVA) models were used to examine the relationship between media use and psychological and physical assets controlling for relevant confounding factors. RESULTS: The analytic sample included 1027 participants; most were ≥10 years old, non-White; 27% self-reported ≥4 hours of media use on school days. In adjusted results, media use was inversely associated with self-esteem (p = .008) and commitment to physical activity (p < .001). Time spent using media was not associated with body size satisfaction or physical activity in this age group. CONCLUSIONS: Media use was negatively associated with self-esteem and commitment to physical activity. It may be useful for school professionals to encourage after-school programs that offer opportunities for girls to reduce sedentary pursuits and improve important psychological and physical assets.

Rapid detection of coronary artery stenoses with real-time perfusion echocardiography during regadenoson stress.

BACKGROUND: Real-time myocardial contrast echocardiography permits the detection of myocardial perfusion abnormalities during stress echocardiography, which may improve the accuracy of the test in detecting coronary artery stenoses. We hypothesized that this technique could be used after a bolus injection of the selective A2A receptor agonist regadenoson to rapidly and safely detect coronary artery stenoses. METHODS AND RESULTS: In 100 patients referred for quantitative coronary angiography, real-time myocardial contrast echocardiography was performed during a continuous intravenous infusion of 3% Definity at baseline and at 2-minute intervals for up to 6 minutes after a regadenoson bolus injection (400 µg). Myocardial perfusion was assessed by examination of myocardial contrast replenishment after brief high mechanical index impulses. A perfusion defect was defined as a delay (>2 seconds) in myocardial contrast replenishment in 2 contiguous segments. Wall motion was also analyzed. The overall sensitivity/specificity/accuracy for myocardial perfusion analysis in detecting a >50% diameter stenosis was 80%/74%/78%, whereas for wall motion analysis it was 60%/72%/66% (P<0.001 for differences in sensitivity). Sensitivity for myocardial perfusion analysis was highest on images obtained during the first 2 minutes after regadenoson bolus (P<0.001 compared with wall motion), whereas wall motion sensitivity was highest at the 4-to-6-minute period after the bolus. No significant side effects occurred after regadenoson bolus injection. CONCLUSIONS: Regadenoson real-time myocardial contrast echocardiography appears to be a feasible, safe, and rapid noninvasive method for the detection of significant coronary artery stenoses.

Girls on the Run: a quasi-experimental evaluation of a developmentally focused youth sport program.

BACKGROUND: Evidence supporting the effectiveness of a developmental-focused youth sport (DYS) program designed exclusively for elementary school aged girls is mounting. The purpose of this study was to evaluate the impact of on the Girls on the Run program on psychological and physical assets among 3rd- to 5th-grade girls. METHODS: A longitudinal quasi-experimental study was conducted to evaluate intervention effects among 877 participants categorized into 1 of 3 groups (never, newly, and previously exposed). A 64-item self-report survey measured developmental assets at 3 time-points. Nested random effects ANOVA models were used to compare demographic factors and psychological and physical assets between exposure groups and to compare longitudinal differences in these assets. RESULTS: After adjustment for multiple comparisons, previous program participants had significantly higher physical activity commitment (P = .006) and physical activity levels (P = .047) at preintervention than never exposed. From pre- to postintervention body image improved in newly exposed participants (P = .03). Physical activity increased from preintervention to follow-up among never and newly exposed participants (all P < .05). CONCLUSIONS: Although we were unable to fully confirm the study hypotheses, the results of the current study provide new evidence to support future long-term studies examining the effectiveness of an innovative DYS program for 3rd- to 5th-grade girls.

Cyclin-dependent kinase 5 is amplified and overexpressed in pancreatic cancer and activated by mutant K-Ras.

PURPOSE: To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression. EXPERIMENTAL DESIGN: We used genetic, biochemical, and molecular biology methods to investigate the nature and function of overexpression of CDK5 and its activators p35 and p39 during the progression of pancreatic cancer. RESULTS: Amplification of the CDK5 gene or either of its main activators, p35 and p39, was observed in 67% of human pancreatic ductal adenocarcinoma (PDAC). CDK5, p35, and p39 were rarely expressed in pancreatic ducts whereas more than 90% of PDACs had increased levels of CDK5 and p35. Increased levels of CDK5, p35, and p39 protein were observed in several pancreatic cancer cell lines. Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. Increased CDK5 kinase activity was also observed in immortalized human pancreatic nestin-expressing (HPNE) cells expressing a mutant form of K-Ras (G12D) compared with HPNE cells expressing native K-Ras. G12D K-Ras increased cleavage of p35 to p25, a stable and greater activator of CDK5, thus implicating a role for CDK5 in early progression of PDAC. Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves mitogen-activated protein/extracellular signal-regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 protein levels. CONCLUSION: These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells.

The impact of weight and fat mass loss and increased physical activity on physical function in overweight, postmenopausal women: results from the Women on the Move Through Activity and Nutrition study.

OBJECTIVE: The aim of this study was to determine whether changes in leisure time physical activity (LTPA) and body composition reflect concomitant changes in 400-meter walk time. METHODS: Data were collected at the baseline and 48-month visits in the Women on the Move Through Activity and Nutrition study. At baseline, participants (n = 508) were randomized to the lifestyle intervention or health education group. The lifestyle intervention focused on weight (7%-10%) and waist circumference reduction through healthy lifestyle behavior change. Change in walk time over 48 months was the primary outcome. Secondary measures included change in LTPA and body composition measures including, body weight, body mass index, waist circumference, and dual-energy x-ray absorptiometry--derived fat and lean mass. RESULTS: Increased LTPA and reductions in body weight, body mass index, waist circumference, and fat mass were associated with decreased walk time from baseline to 48 months (P < 0.01). After stratification by group, LTPA was no longer significantly related to walk time in the health education group. CONCLUSIONS: Increased LTPA and weight loss resulted in improved physical function, as measured by the 400-meter walk, in a group of overweight, postmenopausal women. These findings support the use of the 400-meter walk to evaluate progress in physical activity or weight loss programs.