186 research outputs found

    A Primary Care Nurse-Delivered Walking Intervention in Older Adults: PACE (Pedometer Accelerometer Consultation Evaluation)-Lift Cluster Randomised Controlled Trial.

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    Background: Brisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity (MVPA) in ≥10-minute bouts, as advised in World Health Organization guidelines. Previous interventions have reported step-count increases, but not change in objectively measured MVPA in older people. We assessed whether a primary care nurse-delivered complex intervention increased objectively measured step-counts and MVPA. Methods and Findings: A total of 988 60–75 year olds, able to increase walking and randomly selected from three UK family practices, were invited to participate in a parallel two-arm cluster randomised trial; randomisation was by household. Two-hundred-ninety-eight people from 250 households were randomised between 2011 and 2012; 150 individuals to the intervention group, 148 to the usual care control group. Intervention participants received four primary care nurse physical activity (PA) consultations over 3 months, incorporating behaviour change techniques, pedometer step-count and accelerometer PA intensity feedback, and an individual PA diary and plan. Assessors were not blinded to group status, but statistical analyses were conducted blind. The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months, with change at 12 months a secondary outcome. Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts, accelerometer counts, and counts/minute at 3 months and 12 months. Other outcomes were adverse events, anthropometric measures, mood, and pain. Qualitative evaluations of intervention participants and practice nurses assessed the intervention’s acceptability. At 3 months, eight participants had withdrawn or were lost to follow-up, 280 (94%) individuals provided primary outcome data. At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control group: by 1,037 (95% CI 513–1,560) steps/day and 63 (95% CI 40–87) minutes/week, respectively. At 12 months corresponding differences were 609 (95% CI 104–1,115) steps/day and 40 (95% CI 17–63) minutes/week. Counts and counts/minute showed similar effects to steps and MVPA. Adverse events, anthropometry, mood, and pain were similar in the two groups. Participants and practice nurses found the intervention acceptable and enjoyable. Conclusions : The PACE-Lift trial increased both step-counts and objectively measured MVPA in ≥10-minute bouts in 60–75 year olds at 3 and 12 months, with no effect on adverse events. To our knowledge, this is the first trial in this age group to demonstrate objective MVPA increases and highlights the value of individualised support incorporating objective PA assessment in a primary care setting. Trial Registration: Controlled-Trials.com ISRCTN4212256

    Early changes in Orthopteran assemblages after grassland restoration : a comparison of space-for-time substitution versus repeated-measures monitoring

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    Grasslands harbour significant biodiversity and their restoration is a common intervention in biodiversity conservation. However, we know very little on how grassland restoration influences arthropod groups. Here we compared orthopteran assemblages in croplands, natural grasslands and one to four-year-old grasslands restored in a large-scale restoration on former croplands in Hortobágy National Park (E-Hungary). Sampling was done by standardized sweep-netting both in a repeated measures design and space-for-time substitution (chronosequence) design. General linear models with repeated measures from five years showed that species richness, abundance and Shannon diversity of orthopterans decreased in the year following restoration but increased afterwards. By the fourth year, species richness almost doubled and abundance increased almost ten-fold in restored grasslands compared to croplands. Multivariate analyses showed that species composition in the first two years did not progress much but by the third and fourth year there was partial overlap with natural grasslands. Local restoration conditions (last crop, seed mixture) and landscape configuration (proportion of natural grasslands < 1 km away) did not influence the above patterns in either the repeated measures or the chronosequence design, whereas time since restoration affected almost all community variables. Our results suggest that generalist ubiquitous species appeared in restored grasslands first and the more sensitive species colonized the restored fields gradually in later years. The qualitative and quantitative properties of the orthopteran assemblages in restored fields did not yet reach those of natural grasslands, therefore, our study suggests that the full regeneration of the orthopteran assemblages takes more than four years

    Cough and its importance in COPD

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    Patients with COPD most frequently complain of breathlessness and cough and these are both increased during exacerbations. Studies have generally focused on quality of life during end-stage disease, where breathlessness becomes dominant and cough less important. There are very little data on the frequency and severity of cough in COPD or its impact on quality of life at different stages of disease. Little is known about the factors that influence objective cough counts in COPD. Cough may be a marker for progressive disease in milder COPD patients who continue to smoke, and it may be useful in case-finding for milder disease in the community. The cough reflex sensitivity is heightened in COPD compared with healthy volunteers and similar to that in subjects with asthma. The degree of airflow obstruction does not predict cough reflex sensitivity or objective cough counts, implying an independent process. Effective treatments for cough in COPD have not yet been identified. Improved outcome measures of cough, a better understanding of cough in the natural history of COPD, and its importance to patients are needed

    Health Locus of Control and Assimilation of Cervical Cancer Information in Deaf Women

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    This study assessed the relationship between Deaf women's internal health locus of control (IHLC) and their cervical cancer knowledge acquisition and retention. A blind, randomized trial evaluated Deaf women's (N = 130) baseline cancer knowledge and knowledge gained and retained from an educational intervention, in relation to their IHLC. The Multidimensional Health Locus of Control scales measured baseline IHLC, and a cervical cancer knowledge survey evaluated baseline to post-intervention knowledge change. Women's IHLC did not significantly predict greater cervical cancer knowledge at baseline or over time. IHLC does not appear to be a characteristic that must be considered when creating Deaf women's cancer education programs

    Experimental Rugged Fitness Landscape in Protein Sequence Space

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    The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12–130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7×10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18–24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region

    An Incomplete TCA Cycle Increases Survival of Salmonella Typhimurium during Infection of Resting and Activated Murine Macrophages

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    In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice.We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence.Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous

    Behavioral and molecular genetics of reading-related AM and FM detection thresholds

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    Auditory detection thresholds for certain frequencies of both amplitude modulated (AM) and frequency modulated (FM) dynamic auditory stimuli are associated with reading in typically developing and dyslexic readers. We present the first behavioral and molecular genetic characterization of these two auditory traits. Two extant extended family datasets were given reading tasks and psychoacoustic tasks to determine FM 2 Hz and AM 20 Hz sensitivity thresholds. Univariate heritabilities were significant for both AM (h2 = 0.20) and FM (h2 = 0.29). Bayesian posterior probability of linkage (PPL) analysis found loci for AM (12q, PPL = 81 %) and FM (10p, PPL = 32 %; 20q, PPL = 65 %). Bivariate heritability analyses revealed that FM is genetically correlated with reading, while AM was not. Bivariate PPL analysis indicates that FM loci (10p, 20q) are not also associated with reading

    Histone H1 Depletion Impairs Embryonic Stem Cell Differentiation

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    Pluripotent embryonic stem cells (ESCs) are known to possess a relatively open chromatin structure; yet, despite efforts to characterize the chromatin signatures of ESCs, the role of chromatin compaction in stem cell fate and function remains elusive. Linker histone H1 is important for higher-order chromatin folding and is essential for mammalian embryogenesis. To investigate the role of H1 and chromatin compaction in stem cell pluripotency and differentiation, we examine the differentiation of embryonic stem cells that are depleted of multiple H1 subtypes. H1c/H1d/H1e triple null ESCs are more resistant to spontaneous differentiation in adherent monolayer culture upon removal of leukemia inhibitory factor. Similarly, the majority of the triple-H1 null embryoid bodies (EBs) lack morphological structures representing the three germ layers and retain gene expression signatures characteristic of undifferentiated ESCs. Furthermore, upon neural differentiation of EBs, triple-H1 null cell cultures are deficient in neurite outgrowth and lack efficient activation of neural markers. Finally, we discover that triple-H1 null embryos and EBs fail to fully repress the expression of the pluripotency genes in comparison with wild-type controls and that H1 depletion impairs DNA methylation and changes of histone marks at promoter regions necessary for efficiently silencing pluripotency gene Oct4 during stem cell differentiation and embryogenesis. In summary, we demonstrate that H1 plays a critical role in pluripotent stem cell differentiation, and our results suggest that H1 and chromatin compaction may mediate pluripotent stem cell differentiation through epigenetic repression of the pluripotency genes
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