Citations

Abstract Rationale Disability guidelines are often based on pulmonary function testing, but factors other than lung function influence how an individual experiences physiologic impairment. Age may impact the perception of impairment in adults with chronic lung disease. Objectives To determine if self-report of physical functional impairment differs between older adults with chronic lung disease compared with younger adults with similar degrees of lung function impairment. Methods The Lung Tissue Research Consortium provided data on 981 participants with chronic obstructive pulmonary disease and interstitial lung disease who were well characterized with clinical, radiological, and pathological diagnoses. We used multiple logistic regression to determine if responses to health status questions (from the Short Form-12 and St. George’s Respiratory Questionnaire) related to perception of impairment differed in older adults (age ≥ 65 yr, n = 427) compared with younger adults (age < 65 yr, n = 393). Measurements and Main Results Pulmonary function was higher in older adults (median FEV1 %, 70) compared with younger adults (median FEV1 %, 62) (P < 0.001), whereas the median 6-minute-walk distance was similar between groups (372 m vs. 388 m, P = 0.21). After adjusting for potential confounders, older adults were less likely to report that their health limited them significantly in performing moderate activities (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.22–0.58) or climbing several flights of stairs (OR, 0.51; 95% CI, 0.34–0.77). The odds of reporting that their physical health limited the kinds of activities they performed were reduced by 63% in older adults (OR, 0.37; 95% CI, 0.24–0.58), and, similarly, the odds of reporting that their health caused them to accomplish less than they would like were also lower in older adults (OR, 0.39; 95% CI, 0.25–0.60). The OR for reporting that their breathing problem stops them from doing most things or everything was 0.35 (95% CI, 0.22–0.55) in older adults versus younger adults. Conclusions Older adults with chronic lung disease were less likely to report significant impairment in their activities compared with younger adults, suggesting they may perceive less limitation.

Abstract The cellular responses to two new temozolomide (TMZ) analogues, DP68 and DP86, acting against glioblastoma multiforme (GBM) cell lines and primary culture models are reported. Dose–response analysis of cultured GBM cells revealed that DP68 is more potent than DP86 and TMZ and that DP68 was effective even in cell lines resistant to TMZ. On the basis of a serial neurosphere assay, DP68 inhibits repopulation of these cultures at low concentrations. The efficacy of these compounds was independent of MGMT and MMR functions. DP68-induced interstrand DNA cross-links were demonstrated with H2O2-treated cells. Furthermore, DP68 induced a distinct cell–cycle arrest with accumulation of cells in S phase that is not observed for TMZ. Consistent with this biologic response, DP68 induces a strong DNA damage response, including phosphorylation of ATM, Chk1 and Chk2 kinases, KAP1, and histone variant H2AX. Suppression of FANCD2 expression or ATR expression/kinase activity enhanced antiglioblastoma effects of DP68. Initial pharmacokinetic analysis revealed rapid elimination of these drugs from serum. Collectively, these data demonstrate that DP68 is a novel and potent antiglioblastoma compound that circumvents TMZ resistance, likely as a result of its independence from MGMT and mismatch repair and its capacity to cross-link strands of DNA. Mol Cancer Ther; 14(1); 111–9. ©2014 AACR.

AbstractWith increasing numbers of people with Alzheimer's and other dementias across the globe, many countries have developed national plans to deal with the resulting challenges. In the United States, the National Alzheimer's Project Act, signed into law in 2011, required the creation of such a plan with annual updates thereafter. Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively treating Alzheimer's disease by 2025. To guide investments, activities, and the measurement of progress toward achieving this 2025 goal, in its first annual plan update (2013) HHS also incorporated into the plan a set of short, medium and long‐term milestones. HHS further committed to updating these milestones on an ongoing basis to account for progress and setbacks, and emerging opportunities and obstacles. To assist HHS as it updates these milestones, the Alzheimer's Association convened a National Plan Milestone Workgroup consisting of scientific experts representing all areas of Alzheimer's and dementia research. The workgroup evaluated each milestone and made recommendations to ensure that they collectively constitute an adequate work plan for reaching the goal of preventing and effectively treating Alzheimer's by 2025. This report presents these Workgroup recommendations.

ABSTRACTIntroduction: Numerous methods for motor unit number estimation (MUNE) have been developed. The objective of this article is to summarize and compare the major methods and the available data regarding their reproducibility, validity, application, refinement, and utility.Methods: Using specified search criteria, a systematic review of the literature was performed. Reproducibility, normative data, application to specific diseases and conditions, technical refinements, and practicality were compiled into a comprehensive database and analyzed.Results: The most commonly reported MUNE methods are the incremental, multiple‐point stimulation, spike‐triggered averaging, and statistical methods. All have established normative data sets and high reproducibility. MUNE provides quantitative assessments of motor neuron loss and has been applied successfully to the study of many clinical conditions, including amyotrophic lateral sclerosis and normal aging.Conclusions: MUNE is an important research technique in human subjects, providing important data regarding motor unit populations and motor unit loss over time.Muscle Nerve50: 884–893, 2014

BACKGROUND AND OBJECTIVE:There is ongoing concern that stimulant medications may adversely affect growth. In a sample of attention-deficit/hyperactivity disorder (ADHD) cases and controls from a population-based birth cohort, we assessed growth and the association between stimulant treatment and growth.METHODS:Subjects included childhood ADHD cases (N = 340) and controls (N = 680) from a 1976 to 1982 birth cohort (N = 5718). Height and stimulant treatment information were abstracted from medical records and obtained during a prospective, adult follow-up study. For each subject, a parametric penalized spline smoothing method modeled height over time, and the corresponding height velocity was calculated as the first derivative. Peak height velocity (PHV) age and magnitude were estimated from the velocity curves. Among stimulant-treated ADHD cases, we analyzed height Z scores at the beginning, at the end, and 24 months after the end of treatment.RESULTS:Neither ADHD itself nor treatment with stimulants was associated with differences in magnitude of PHV or final adult height. Among boys treated with stimulants, there was a positive correlation between duration of stimulant usage before PHV and age at PHV (r = 0.21, P = .01). There was no significant correlation between duration of treatment and change in height Z scores (r = −0.08 for beginning vs end change, r = 0.01 for end vs 24 months later change). Among the 59 ADHD cases treated for ≥3 years, there was a clinically insignificant decrease in mean Z score from beginning (0.48) to end (0.33) of treatment (P = .06).CONCLUSIONS:Our findings suggest that ADHD treatment with stimulant medication is not associated with differences in adult height or significant changes in growth.