Changes in leisure time and occupational physical activity over 8 years: The Cornellà health Interview Survey Follow-Up Study

Aim: To describe changes in leisure time and occupational physical activity status in an urban Mediterranean population-based cohort, and to evaluate sociodemographic, health-related and lifestyle correlates of such changes. Methods: Data for this study come from the Cornellè Health Interview Survey Follow-Up Study, a prospective cohort study of a representative sample (n¿=¿2500) of the population. Participants in the analysis reported here include 1246 subjects (567 men and 679 women) who had complete data on physical activity at the 1994 baseline survey and at the 2002 follow-up. We fitted Breslow-Cox regression models to assess the association between correlates of interest and changes in physical activity. Results: Regarding leisure time physical activity, 61.6% of cohort members with ¿sedentary¿ habits in 1994 changed their status to ¿light/moderate¿ physical activity in 2002, and 70% who had ¿light/moderate¿ habits in 1994 did not change their activity level. Regarding occupational physical activity, 74.4% of cohort members who were ¿active¿ did not change their level of activity, and 64.3% of participants with ¿sedentary¿ habits in 1994 changed to ¿active¿ occupational physical activity. No clear correlates of change in physical activity were identified in multivariate analyses. Conclusion: While changes in physical activity are evident in this population-based cohort, no clear determinants of such changes were recognised. Further longitudinal studies including other potential individual and contextual determinants are needed to better understand determinants of changes in physical activity at the population level.

Boring activity of Epibionts in an Early Holocene molluscan fauna of Spanish Catalunya

Using X-Ray techniques, the boring activities of various Invertebrates on Bivalvia of wmian age were studied. Emphasis is placed on the boring activity of Porifera and their apparent preselection of the species bored, based on: a) the mineralogical composition, and/or b) the microstucture, andlor c) some special environmental conditions, or d) combinations of these three posibilities.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Self reported physical activity, public health, and perceived environment: results from a comparative European study

The focus of physical activity promotion is moving from methods for increasing health enhancing physical activity on the individual level to higher level strategies including environmental and policy approaches. Scientific inquiry, traditionally related to individual-based strategies, requires adaptation and refinement when environmental and policy changes become more relevant. The objective of this study is to investigate the significance for behaviour and health of community-based environments that encourage physical activity. DESIGN AND SETTING The article presents data and results from a cross sectional comparative survey of the general population in six European countries (Belgium, Finland, Germany (East and West), Netherlands, Spain, Switzerland). Specifically, the relation between perceived community-based opportunities for physical activity, self reported physical activity, and self rated health status is investigated. PARTICIPANTS Representative samples of general populations (adults 18 years or older). Overall response rate: 53.5%. Sample sizes realised: Belgium: n=389; Finland: n=400; Germany (East): n = 913; Germany (West): n=489; Netherlands: n=366; Spain: n=380; Switzerland: n=406. MAIN RESULTS Analyses show that best opportunities are reported by people who are lightly to moderately physically active. People's self rated health is moderately, but significantly associated with both perceived opportunities, and physical activity itself. These predictors interact in that especially for women, the health impact of physical activity is more pronounced in case of good opportunities. CONCLUSIONS The paper shows the potential of opportunities within residential and community environments with regard to physical activity, both for behaviour and health. Opportunities may enable the population, especially women, to develop an active lifestyle, and thus improve their health. Future studies with objective indicators for physical activity related environments should test the findings that are based on perceptions.

Somatostatin Subtype‑2 Receptor-Targeted Metal-Based Anticancer Complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η6-bip)Os(4-CO2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η6-p-cym)RuCl(dap)]+ (p-cym = p-cymene) (5), and [(η6-p-cym)RuCl(imidazole-CO2H)(PPh3)]+ (6), were synthesized by using a solid-phase approach. Conjugates 35 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC50 = 63 ± 2 μM in MCF-7 cells and IC50 = 26 ± 3 μM in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC50 = 45 ± 2.6 μM in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically.

Do walking strategies to increase physical activity reduce reported sitting in workplaces: a randomized control trial

Background: Interventions designed to increase workplace physical activity may not automatically reduce high volumes of sitting, a behaviour independently linked to chronic diseases such as obesity and type II diabetes. This study compared the impact two different walking strategies had on step counts and reported sitting times. Methods: Participants were white-collar university employees (n = 179; age 41.3 ± 10.1 years; 141 women), who volunteered and undertook a standardised ten-week intervention at three sites. Preintervention step counts (Yamax SW-200) and self-reported sitting times were measured over five consecutive workdays. Using pre-intervention step counts, employees at each site were randomly allocated to a control group (n = 60; maintain normal behaviour), a route-based walking group (n = 60; at least 10 minutes sustained walking each workday) or an incidental walking group (n = 59; walking in workday tasks). Workday step counts and reported sitting times were re-assessed at the beginning, mid- and endpoint of intervention and group mean± SD steps/day and reported sitting times for pre-intervention and intervention measurement points compared using a mixed factorial ANOVA; paired sample-t-tests were used for follow-up, simple effect analyses. Results: A significant interactive effect (F = 3.5; p < 0.003) was found between group and step counts. Daily steps for controls decreased over the intervention period (-391 steps/day) and increased for route (968 steps/day; t = 3.9, p < 0.000) and incidental (699 steps/day; t = 2.5, p < 0.014) groups. There were no significant changes for reported sitting times, but average values did decrease relative to the control (routes group = 7 minutes/day; incidental group = 15 minutes/day). Reductions were most evident for the incidental group in the first week of intervention, where reported sitting decreased by an average of 21 minutes/day (t = 1.9; p < 0.057). Conclusion: Compared to controls, both route and incidental walking increased physical activity in white-collar employees. Our data suggests that workplace walking, particularly through incidental movement, also has the potential to decrease employee sitting times, but there is a need for on-going research using concurrent and objective measures of sitting, standing and walking.

Referral from primary care to a physical activity programme: establishing long-term adherence? A randomized controlled trial. Rationale and study design

Background: Declining physical activity is associated with a rising burden of global disease. There is little evidence about effective ways to increase adherence to physical activity. Therefore, interventions are needed that produce sustained increases in adherence to physical activity and are cost-effective. The purpose is to assess the effectiveness of a primary care physical activity intervention in increasing adherence to physical activity in the general population seen in primary care. Method and design: Randomized controlled trial with systematic random sampling. A total of 424 subjects of both sexes will participate; all will be over the age of 18 with a low level of physical activity (according to the International Physical Activity Questionnaire, IPAQ), self-employed and from 9 Primary Healthcare Centres (PHC). They will volunteer to participate in a physical activity programme during 3 months (24 sessions; 2 sessions a week, 60 minutes per session). Participants from each PHC will be randomly allocated to an intervention (IG) and control group (CG). The following parameters will be assessed pre and post intervention in both groups: (1) health-related quality of life (SF-12), (2) physical activity stage of change (Prochaska's stages of change), (3) level of physical activity (IPAQ-short version), (4) change in perception of health (vignettes from the Cooperative World Organization of National Colleges, Academies, and Academic Associations of Family Physicians, COOP/WONCA), (5) level of social support for the physical activity practice (Social Support for Physical Activity Scale, SSPAS), and (6) control based on analysis (HDL, LDL and glycated haemoglobin).Participants' frequency of visits to the PHC will be registered over the six months before and after the programme. There will be a follow up in a face to face interview three, six and twelve months after the programme, with the reduced version of IPAQ, SF-12, SSPAS, and Prochaska's stages. Discussion: The pilot study showed the effectiveness of an enhanced low-cost, evidence-based intervention in increased physical activity and improved social support. If successful in demonstrating long-term improvements, this randomised controlled trial will be the first sustainable physical activity intervention based in primary care in our country to demonstrate longterm adherence to physical activity. Trial Registration: A service of the U.S. National Institutes of Health. Developed by the National Library of Medicine. ClinicalTrials.gov ID: NCT00714831.

The Effect of a Physical Activity Program on the Total Number of Primary Care Visits in Inactive Patients: A 15-Month Randomized Controlled Trial

Abstract Background: Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity. Objectives: To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period. Research Design: Randomized controlled trial. Subjects: Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources. Measures: The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15). Results: The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002). Conclusions: Our findings indicate that a 3-month physical activity program linked to community resources is a shortduration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits. Trial Registration: ClinicalTrials.gov NCT00714831

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: caveats from a very revealing single clinical case

Background: We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation: Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions: The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

Background: Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results: We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer- approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion: Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.

The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.