A platform for efficient, thiol-stable conjugation to albumin's native single accessible cysteine

Herein we report the use of bromomaleimides for the construction of stable albumin conjugates via conjugation to its native, single accessible, cysteine followed by hydrolysis. Advantages over the classical maleimide approach are highlighted in terms of quantitative hydrolysis and absence of undesirable retro-Michael deconjugation

Novice Learner Experiences in Software Development: A Study of Freshman Undergraduates

This paper presents a study that is part of a larger research project aimed at addressing the gap in the provision of educational software development processes for freshman, novice undergraduate learners, to improve proficiency levels. With the aim of understanding how such learners problem solve in software development in the absence of a formal process, this case study examines the experiences and depth of learning acquired by a sample set of novice undergraduates. A novel adaption of the Kirkpatrick framework known as AKM-SOLO is used to frame the evaluation. The study finds that without the scaffolding of an appropriate structured development process tailored to novices, students are in danger of failing to engage with the problem solving skills necessary for software development, particularly the skill of designing solutions prior to coding. It also finds that this lack of engagement directly impacts their affective state on the course and continues to negatively impact their proficiency and affective state in the second year of their studies leading to just under half of students surveyed being unsure if they wish to pursue a career in software development when they graduate

Is there a U-shaped association between physical activity and falling in older persons?

Summary: This study tests whether the relationship between physical activity and (recurrent) falling is U-shaped. Among 1,337 community-dwelling older persons, no evidence for a nonlinear association was found. If all older persons increase their physical activity level with 100 units, 4% may be prevented to become recurrent fallers. Introduction: Previous studies suggest a U-shaped relationship between physical activity and falling. This study tests this hypothesis and examines whether this relationship is modified by level of physical functioning. Methods: Community-dwelling persons (65+) from the Longitudinal Aging Study Amsterdam (LASA) were prospectively followed on falls for 3 years after baseline assessment in 1995/1996 (n=1,337). Outcome measures were time to first fall and time to recurrent falling. The LASA Physical Activity Questionnaire was used to calculate physical activity in minutes per day weighted for intensity (range 0-2000). Physical functioning was measured with physical performance tests and self reported functional limitations. Confounders were age, sex, body mass index, chronic diseases, psychotropic medication, cognitive functioning, depressive symptoms, and fear of falling. Results: No evidence for a nonlinear association was found (p for physical activity > 0.20). No significant association was found between physical activity and time to first fall. An increase in physical activity of 100 units led to a 4% decrease in risk of recurrent falling (adjusted hazard ratio 0.96, 95% confidence interval 0.92, 0.99). No interactions with physical performance or functional limitations were found (p>0.50). Conclusions: The hypothesized U-shaped relationship between physical activity and falling could not be confirmed. At higher levels of physical activity, the risk of recurrent falling decreased, while no association was found with fall risk

Level of daily physical activity in individuals with COPD compared with healthy controls

<p>Abstract</p> <p>Background</p> <p>Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality. COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue. Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults. COPD might worsen this scenario, but it is unclear to what degree. This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA). The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.</p> <p>Results</p> <p>A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar. After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA. Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA. The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%. Correlations of DPA and severity of the disease were low and/or not significant.</p> <p>Conclusions</p> <p>From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects. The intensity of DPA seems to be less affected by COPD than duration and counts. Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA. Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable.</p

Healthy obesity as an intermediate state of risk: a critical review

This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Review of Endocrinology and Metabolism on 12 Aug 2016, available online: http://dx.doi.org/10.1080/17446651.2016.1220298Introduction: Obesity is a top public health priority but interventions to reverse the condition have had limited success. About 1-in-3 obese adults are free of metabolic risk factor clustering and are considered ‘healthy', and much attention has focused on the implications of this state for obesity management. Areas covered: We searched for individual studies, systematic reviews, and meta-analyses which examined correlates and outcomes of metabolically healthy obesity. We discuss the key roles of fat distribution and physical activity in determining healthy vs. unhealthy obesity and report a greatly increased risk of incident type 2 diabetes associated with healthy obesity vs. healthy normal-weight, among other outcomes. We argue that despite inconsistencies in the definition, patterns across studies clearly show that healthy obesity is a state of intermediate disease risk. Expert commentary: Given the current state of population-level evidence, we conclude that obesity and metabolic dysfunction are inseparable and that healthy obesity is best viewed only as a state of relative health but not of absolute health. We recommend that weight loss through energy restriction be a stand-alone target in addition to increased physical activity for minimising risk of future disease

Urban community gardeners' knowledge and perceptions of soil contaminant risks

Although urban community gardening can offer health, social, environmental, and economic benefits, these benefits must be weighed against the potential health risks stemming from exposure to contaminants such as heavy metals and organic chemicals that may be present in urban soils. Individuals who garden at or eat food grown in contaminated urban garden sites may be at risk of exposure to such contaminants. Gardeners may be unaware of these risks and how to manage them. We used a mixed quantitative/qualitative research approach to characterize urban community gardeners' knowledge and perceptions of risks related to soil contaminant exposure. We conducted surveys with 70 gardeners from 15 community gardens in Baltimore, Maryland, and semi-structured interviews with 18 key informants knowledgeable about community gardening and soil contamination in Baltimore. We identified a range of factors, challenges, and needs related to Baltimore community gardeners' perceptions of risk related to soil contamination, including low levels of concern and inconsistent levels of knowledge about heavy metal and organic chemical contaminants, barriers to investigating a garden site's history and conducting soil tests, limited knowledge of best practices for reducing exposure, and a need for clear and concise information on how best to prevent and manage soil contamination. Key informants discussed various strategies for developing and disseminating educational materials to gardeners. For some challenges, such as barriers to conducting site history and soil tests, some informants recommended city-wide interventions that bypass the need for gardener knowledge altogether

Time trends in leisure time physical activity and physical fitness in elderly people: 20 year follow-up of the Spanish population national health survey (1987-2006)

<p>Abstract</p> <p>Background</p> <p>To estimate trends in leisure time physical activity and physical fitness between 1987-2006 in older Spanish people.</p> <p>Methods</p> <p>We analyzed data collected from the Spanish National Health Surveys conducted in 1987 (n = 29,647), 1993 (n = 20,707), 1995-1997 (n = 12,800), 2001 (n = 21,058), 2003 (n = 21,650), and 2006 (n = 29,478). The number of subjects aged ≥ 65 years included in the current study was 29,263 (1987: n = 4,958-16.7%; 1993: n = 3,751-17.8%; 1995-97: n = 2,229-17.4%; 2001: n = 4,356-20.7%; 2003: 6,134-28.3%; 2006: 7,835-26.5%). Main variables included leisure-time physical activity and physical fitness. We analyzed socio-demographic characteristics, self-rated health status, lifestyle habit and co-morbid conditions using multivariate logistic regression models.</p> <p>Results</p> <p>Women exhibited lower prevalence of leisure time physical activity and physical fitness compared to men (P < 0.05). The multivariate analysis for time trends found that practising leisure time physical activity increased from 1987 to 2006 (P < 0.001). Variables associated with a lower likelihood of practicing leisure time physical activity were: age ≥ 80 years old, ≥ 2 co-morbid chronic conditions, and obesity. Variables associated with lower physical fitness included: age ≥ 80 years, worse self rated health; ≥ 2 medications (only for walking), and obesity.</p> <p>Conclusions</p> <p>We found an increase in leisure time physical activity in the older Spanish population. Older age, married status, co-morbid conditions, obesity, and worse self-perceived health status were associated with lower activity. Identification of these factors can help to identify individuals at risk for physical inactivity.</p

Inhibition of the Mitochondrial Enzyme ABAD Restores the Amyloid-β-Mediated Deregulation of Estradiol

Alzheimer's disease (AD) is a conformational disease that is characterized by amyloid-β (Aβ) deposition in the brain. Aβ exerts its toxicity in part by receptor-mediated interactions that cause down-stream protein misfolding and aggregation, as well as mitochondrial dysfunction. Recent reports indicate that Aβ may also interact directly with intracellular proteins such as the mitochondrial enzyme ABAD (Aβ binding alcohol dehydrogenase) in executing its toxic effects. Mitochondrial dysfunction occurs early in AD, and Aβ's toxicity is in part mediated by inhibition of ABAD as shown previously with an ABAD decoy peptide. Here, we employed AG18051, a novel small ABAD-specific compound inhibitor, to investigate the role of ABAD in Aβ toxicity. Using SH-SY5Y neuroblastoma cells, we found that AG18051 partially blocked the Aβ-ABAD interaction in a pull-down assay while it also prevented the Aβ42-induced down-regulation of ABAD activity, as measured by levels of estradiol, a known hormone and product of ABAD activity. Furthermore, AG18051 is protective against Aβ42 toxicity, as measured by LDH release and MTT absorbance. Specifically, AG18051 reduced Aβ42-induced impairment of mitochondrial respiration and oxidative stress as shown by reduced ROS (reactive oxygen species) levels. Guided by our previous finding of shared aspects of the toxicity of Aβ and human amylin (HA), with the latter forming aggregates in Type 2 diabetes mellitus (T2DM) pancreas, we determined whether AG18051 would also confer protection from HA toxicity. We found that the inhibitor conferred only partial protection from HA toxicity indicating distinct pathomechanisms of the two amyloidogenic agents. Taken together, our results present the inhibition of ABAD by compounds such as AG18051 as a promising therapeutic strategy for the prevention and treatment of AD, and suggest levels of estradiol as a suitable read-out

Accelerometer-based physical activity in a large observational cohort - study protocol and design of the activity and function of the elderly in Ulm (ActiFE Ulm) study

<p>Abstract</p> <p>Background</p> <p>A large number of studies have demonstrated a positive effect of increased physical activity (PA) on various health outcomes. In all large geriatric studies, however, PA has only been assessed by interview-based instruments which are all subject to substantial bias. This may represent one reason why associations of PA with geriatric syndromes such as falls show controversial results. The general aim of the Active-Ulm study was to determine the association of accelerometer-based physical activity with different health-related parameters, and to study the influence of this standardized objective measure of physical activity on health- and disability-related parameters in a longitudinal setting.</p> <p>Methods</p> <p>We have set up an observational cohort study in 1500 community dwelling older persons (65 to 90 years) stratified by age and sex. Addresses have been obtained from the local residents registration offices. The study is carried out jointly with the IMCA - Respiratory Health Survey in the Elderly implemented in the context of the European project IMCA II. The study has a cross-sectional part (1) which focuses on PA and disability and two longitudinal parts (2) and (3). The primary information for part (2) is a prospective 1 year falls calendar including assessment of medication change. Part (3) will be performed about 36 months following baseline. Primary variables of interest include disability, PA, falls and cognitive function. Baseline recruitment has started in March 2009 and will be finished in April 2010.</p> <p>All participants are visited three times within one week, either at home or in the study center. Assessments included interviews on quality of life, diagnosed diseases, common risk factors as well as novel cognitive tests and established tests of physical functioning. PA is measured using an accelerometer-based sensor device, carried continuously over a one week period and accompanied by a prospective activity diary.</p> <p>Discussion</p> <p>The assessment of PA using a high standard accelerometer-based device is feasible in a large population-based study. The results obtained from cross-sectional and longitudinal analyses will shed light on important associations between PA and various outcomes and may provide information for specific interventions in older people.</p