Increased Sensitivity to Physical Activity in Healthy Older Adults Predicts Worse Pain and Functional Outcomes

poster abstractPrior research indicates older adults with knee osteoarthritis (OA) have increased sensitivity to physical activity (SPA) and respond to physical activities of stable intensity with increases in pain. SPA predicted self-reported pain and function in older adults with knee OA. It is unknown whether SPA is present in healthy older adults without chronic pain and predicts functional outcomes. The purpose of this study was to determine if SPA in response to a standardized 6-minute Walk Test cross-sectionally predicted selfreported pain, physical function, and physical activity behaviors in healthy older adults. Forty-two older adults (age=67.5±5 years) completed the Pain subscale of the Quality of Well Being scale (QWB–measures the frequency and severity of pain during common daily activities), the Short Form Health Survey (SF-36–measure of physical function), the 6-Minute Walk Test (6MWT), and wore an accelerometer on the hip for 7 days. Subjects rated overall bodily discomfort (0-100 scale) prior to and during each minute of the 6MWT. RPE was recorded at the end of the walk. An SPA index was created by subtracting the initial bodily discomfort ratings from the peak ratings. Average moderate to vigorous physical activity/day (MVPA) and steps/day were recorded from the accelerometer. Dependent variables were analyzed with hierarchical linear regressions with SPA as the final predictor. Sixty percent of older adults experienced SPA (SPA=9.5±15.6). After accounting for age, sex, BMI, and meters walked on the 6MWT, SPA significantly predicted steps and MVPA per day, RPE on the 6MWT, and severity and frequency of activity related pain on the QWB scale. These results revealed that increased SPA in healthy older adults was associated with fewer steps and MVPA per day, greater exertion on 6MWT, and greater self-reported activity-related pain. This study was funded by the IUPUI School of PETM Faculty Research Opportunity Grant

Cigarette Smoking and Parkinson's Disease

This is a review on cigarette smoking and Parkinson's disease (PD). The relationship between cigarette smoking and Parkinson's disease is very controversial. Cigarette smoking is an established risk factor for various diseases such as lung cancer, COPD and heart disease. However, beneficial effects have been debated over the years. It was in the late 1950 s that studies reported a negative association between smoking and Parkinson's disease. More recently, several epidemiological studies have found a significant negative association between cigarette smoking and PD. That is, patients who smoke are 50% less likely to have PD when compared to their non-smoker counterparts. This suggests that cigarette smoking may have a "neuroprotective" effect on PD

Disordered eating and eating disorders among women seeking fertility treatment: A systematic review

The purpose of this systematic review is to evaluate the prevalence of disordered eating and eating disorders among women seeking fertility treatment. Observational studies were searched in Ovid MEDLINE, Web of Science, Embase, and PsycInfo. Studies published prior to September 2020 when the search was conducted were considered. Inclusion criteria included (1) original and empirical research, (2) published in a peer-reviewed journal, and (3) reported on disordered eating among women seeking fertility treatment in the sample or reported on prevalence of eating disorders among women seeking fertility treatment in the sample. Independent screening of abstracts was conducted by two authors (LH and AH). Ten studies met the inclusion criteria. Sample size, study location, measures, and results for each study in this review were reported. Among women pursuing fertility treatment, rates of current eating disorders ranged from 0.5 to 16.7%, while past eating disorder prevalence rates ranged from 1.4 to 27.5%. Current anorexia nervosa or bulimia nervosa was reported by up to 2% and 10.3% of women, respectively, while history of anorexia nervosa or bulimia nervosa was reported by up to 8.5% and 3.3% of women, respectively. Binge eating disorder or other eating disorders were reported by up to 18.5% and 9.1% of women, respectively. Disordered eating pathology was endorsed by 1.6 to 48% of women seeking fertility treatment. Endorsement of pathological eating attitudes was generally higher among women seeking fertility treatment with current or past eating disorders as compared to community samples, with the exception of dietary restraint. Rates of current and past eating disorders are higher among women seeking fertility treatment than in the general population. Providers treating women with infertility should be cognizant of these prevalence rates and consider screening for eating pathology in their patients as this may contribute to their likelihood of successful conception and/or subsequent pregnancy outcomes

Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts. METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured. RESULTS: In participants with heterozygous SOD1 INTERPRETATION: These results highlight the ability of stable isotope labeling approaches and peptide deamidation to discern the influence of disease mutations on protein kinetics and stability and support implementation of this method to optimize clinical trial design of gene and molecular therapies for neurological disorders. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03449212

Weighing the Association Between BMI Change and Suicide Mortality

OBJECTIVE: Suicide rates continue to rise, necessitating the identification of risk factors. Obesity and suicide mortality rates have been examined, but associations among weight change, death by suicide, and depression among adults in the United States remain unclear. METHODS: Data from 387 people who died by suicide in 2000-2015 with a recorded body mass index (BMI) in the first and second 6 months preceding their death ( index date ) were extracted from the Mental Health Research Network. Each person was matched with five people in a control group (comprising individuals who did not die by suicide) by age, sex, index year, and health care site (N=1,935). RESULTS: People who died by suicide were predominantly male (71%), White (69%), and middle aged (mean age=57 years) and had a depression diagnosis (55%) and chronic health issues (57%) (corresponding results for the control group: 71% male, 66% White, 14% with depression diagnosis, and 43% with chronic health issues; mean age=56 years). Change in BMI within the year before the index date statistically significantly differed between those who died by suicide (mean change=-0.72±2.42 kg/m(2)) and the control group (mean change=0.06±4.99 kg/m(2)) (p\u3c0.001, Cohen\u27s d=0.17). A one-unit BMI decrease was associated with increased risk for suicide after adjustment for demographic characteristics, mental disorders, and Charlson comorbidity score (adjusted odds ratio=1.11, 95% confidence interval=1.05-1.18, p\u3c0.001). For those without depression, a BMI change was significantly associated with suicide (p\u3c0.001). CONCLUSIONS: An increased suicide mortality rate was associated with weight loss in the year before a suicide after analyses accounted for general and mental health indicators

The above L-band and P-band airborne synthetic aperture radar surveys

Permafrost-affected ecosystems of the Arctic-boreal zone in northwestern North America are undergoing profound transformation due to rapid climate change. NASA\u27s Arctic Boreal Vulnerability Experiment (ABoVE) is investigating characteristics that make these ecosystems vulnerable or resilient to this change. ABoVE employs airborne synthetic aperture radar (SAR) as a powerful tool to characterize tundra, taiga, peatlands, and fens. Here, we present an annotated guide to the L-band and P-band airborne SAR data acquired during the 2017, 2018, 2019, and 2022 ABoVE airborne campaigns. We summarize the g 1/480 SAR flight lines and how they fit into the ABoVE experimental design (Miller et al., 2023; https://doi.org/10.3334/ORNLDAAC/2150). The Supplement provides hyperlinks to extensive maps, tables, and every flight plan as well as individual flight lines. We illustrate the interdisciplinary nature of airborne SAR data with examples of preliminary results from ABoVE studies including boreal forest canopy structure from TomoSAR data over Delta Junction, AK, and the Boreal Ecosystem Research and Monitoring Sites (BERMS) area in northern Saskatchewan and active layer thickness and soil moisture data product validation. This paper is presented as a guide to enable interested readers to fully explore the ABoVE L- and P-band airborne SAR data (https://uavsar.jpl.nasa.gov/cgi-bin/data.pl)

Feeding ecology of five commercial shark species of the Celtic Sea through stable isotope and trace metal analysis

In order to trace their feeding habits, stable carbon and nitrogen isotope ratios (delta(15)N and delta(13)C), as well as trace metal concentrations (Zn, Cd, Fe, Cu, Se and Hg) were analysed in the tissues of five commercial shark species from the Celtic Sea: the tope shark Galeorhinus galeus, the black-mouthed catshark Galeus melastomus, the starry smooth hound Mustelus asterias, the spiny dogfish Squalus acanthias and the lesser-spotted dogfish Scyliorhinus canicula. Our results were compared to previously described stomach contents and isotopic composition of potential preys. Isotopic ratio delta(15)N suggested that tope sharks fed at a higher trophic level (16.7 parts per thousand in the muscle) than the other species, reflecting its piscivorous diet. The lower values of spiny dogfish (11.6 parts per thousand in the muscle) might be explained, amongst other things, by either its migratory behaviour or its preference for preys from lower trophic levels. Cd and Hg were correlated with isotopic ratios delta(13)C and delta(15)N, and were shown to be diet-related whereas Zn, Fe and Cu seemed much more linked to species-specific metabolism. Although this multidisciplinary approach is revealed as a useful tool for the study of shark ecology, the lack of known trophic fractionation suggests that isotopic data be compared to traditional diet analyses. (c) 2005 Elsevier Ltd. All rights reserved.Peer reviewe

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Morpholino-Mediated Increase in Soluble Flt-1 Expression Results in Decreased Ocular and Tumor Neovascularization

BACKGROUND: Angiogenesis is a key process in several ocular disorders and cancers. Soluble Flt-1 is an alternatively spliced form of the Flt-1 gene that retains the ligand-binding domain, but lacks the membrane-spanning and intracellular kinase domains of the full-length membrane bound Flt-1 (mbFlt-1) protein. Thus, sFlt-1 is an endogenous inhibitor of VEGF-A mediated angiogenesis. Synthetic mopholino oligomers directed against splice site targets can modulate splice variant expression. We hypothesize that morpholino-induced upregulation of sFlt-1 will suppress angiogenesis in clinically relevant models of macular degeneration and breast cancer. METHODS AND FINDINGS: In vivo morpholino constructs were designed to target murine exon/intron 13 junction of the Flt-1 transcript denoted VEGFR1_MOe13; standard nonspecific morpholino was used as control. After nucleofection of endothelial and breast adenocarcinoma cell lines, total RNA was extracted and real-time RT-PCR performed for sFlt-1 and mbFlt-1. Intravitreal injections of VEGFR1_MOe13 or control were done in a model of laser-induced choroidal neovascularization and intratumoral injections were performed in MBA-MD-231 xenografts in nude mice. VEGFR1_MOe13 elevated sFlt-1 mRNA expression and suppressed mbFlt-1 mRNA expression in vitro in multiple cellular backgrounds (p<0.001). VEGFR1_MOe13 also elevated sFlt/mbFlt-1 ratio in vivo after laser choroidal injury 5.5 fold (p<0.001) and suppressed laser-induced CNV by 50% (p = 0.0179). This latter effect was reversed by RNAi of sFlt-1, confirming specificity of morpholino activity through up-regulation of sFlt-1. In the xenograft model, VEGFR1_MOe13 regressed tumor volume by 88.9%, increased sFlt-1 mRNA expression, and reduced vascular density by 50% relative to control morpholino treatment (p<0.05). CONCLUSIONS: Morpholino oligomers targeting the VEGFR1 mRNA exon/intron 13 junction promote production of soluble FLT-1 over membrane bound FLT-1, resulting in suppression of lesional volume in laser induced CNV and breast adenocarcinoma. Thus, morpholino manipulation of alternative splicing offers translational potential for therapy of angiogenic disorders