A dominant function of p38 mitogen-activated protein kinase signaling in receptor activator of nuclear factor-κB ligand expression and osteoclastogenesis induction by Aggregatibacter actinomycetemcomitans and Escherichia coli lipopolysaccharide

Lipopolysaccharide from gram-negative bacteria is one of the microbial-associated molecular patterns that initiate the immune/inflammatory response, leading to the tissue destruction observed in periodontitis. The aim of this study was to evaluate the role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in lipopolysaccharide-induced receptor activator of nuclear factor-κB ligand (RANKL) expression by murine periodontal ligament cells. Material and Methods:  Expression of RANKL and osteoprotegerin mRNA was studied by reverse transcription-polymerase chain reaction upon stimulation with lipopolysaccharide from Escherichia coli and Aggregatibacter actinomycetemcomitans . The biochemical inhibitor SB203580 was used to evaluate the contribution of the p38 MAPK signaling pathway to lipopolysaccharide-induced RANKL and osteoprotegerin expression. Stable cell lines expressing dominant-negative forms of MAPK kinase (MKK)-3 and MKK6 were generated to confirm the role of the p38 MAPK pathway. An osteoclastogenesis assay using a coculture model of the murine monocytic cell line RAW 264.7 was used to determine if osteoclast differentiation induced by lipopolysaccharide-stimulated periodontal ligament was correlated with RANKL expression. Results:  Inhibiting p38 MAPK prior to lipopolysaccharide stimulation resulted in a significant decrease of RANKL mRNA expression. Osteoprotegerin mRNA expression was not affected by lipopolysaccharide or p38 MAPK. Lipopolysaccharide-stimulated periodontal ligament cells increased osteoclast differentiation, an effect that was completely blocked by osteoprotegerin and significantly decreased by inhibition of MKK3 and MKK6, upstream activators of p38 MAPK. Conditioned medium from murine periodontal ligament cultures did not increase osteoclast differentiation, indicating that periodontal ligament cells produced membrane-bound RANKL. Conclusion:  Lipopolysaccharide resulted in a significant increase of RANKL in periodontal ligament cells. The p38 MAPK pathway is required for lipopolysaccharide-induced membrane-bound RANKL expression in these cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65788/1/j.1600-0765.2007.01013.x.pd

Removing exogenous information using pedigree data

Management of certain populations requires the preservation of its pure genetic background. When, for different reasons, undesired alleles are introduced, the original genetic conformation must be recovered. The present study tested, through computer simulations, the power of recovery (the ability for removing the foreign information) from genealogical data. Simulated scenarios comprised different numbers of exogenous individuals taking partofthe founder population anddifferent numbers of unmanaged generations before the removal program started. Strategies were based on variables arising from classical pedigree analyses such as founders? contribution and partial coancestry. The ef?ciency of the different strategies was measured as the proportion of native genetic information remaining in the population. Consequences on the inbreeding and coancestry levels of the population were also evaluated. Minimisation of the exogenous founders? contributions was the most powerful method, removing the largest amount of genetic information in just one generation.However, as a side effect, it led to the highest values of inbreeding. Scenarios with a large amount of initial exogenous alleles (i.e. high percentage of non native founders), or many generations of mixing became very dif?cult to recover, pointing out the importance of being careful about introgression events in populatio

Short and long term effects of a lifestyle intervention for construction workers at risk for cardiovascular disease: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The prevalence of overweight and elevated cardiovascular disease (CVD) risk among workers in the construction industry is relatively high. Improving lifestyle lowers CVD risk and may have work-related benefits. The purpose of the study was to evaluate the effects on physical activity (PA), diet, and smoking of a lifestyle intervention consisting of individual counseling among male workers in the construction industry with an elevated risk of cardiovascular disease (CVD).</p> <p>Methods</p> <p>In a randomized controlled trial including 816 male blue- and white-collar workers in the construction industry with an elevated risk of CVD, usual care was compared to a 6-month lifestyle intervention. The intervention consisted of individual counseling using motivational interviewing techniques, and was delivered by an occupational physician or occupational nurse. In three face to face and four telephone contacts, the participant's risk profile, personal determinants, and barriers for behavior change were discussed, and personal goals were set. Participants chose to aim at either diet and PA, or smoking. Data were collected at baseline and after six and 12 months, by means of a questionnaire. To analyse the data, linear and logistic regression analyses were performed.</p> <p>Results</p> <p>The intervention had a statistically significant beneficial effect on snack intake (β-1.9, 95%CI -3.7; -0.02) and fruit intake (β 1.7, 95%CI 0.6; 2.9) at 6 months. The effect on snack intake was sustained until 12 months; 6 months after the intervention had ended (β -1.9, 95%CI -3.6; -0.2). The intervention effects on leisure time PA and metabolic equivalent-minutes were not statistically significant. The beneficial effect on smoking was statistically significant at 6 (OR smoking 0.3, 95%CI 0.1;0.7), but not at 12 months (OR 0.8, 95%CI 0.4; 1.6).</p> <p>Conclusions</p> <p>Beneficial effects on smoking, fruit, and snack intake can be achieved by an individual-based lifestyle intervention among male construction workers with an elevated risk of CVD. Future research should be done on strategies to improve leisure time PA and on determinants of maintenance of changed behavior. Considering the rising prevalence of unhealthy lifestyle and CVD, especially in the aging population, implementation of this intervention in the occupational health care setting is recommended.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN60545588">ISRCTN60545588</a></p

Surface modification of Ti-6Al-4V alloy for biomineralization and specific biological response: Part II, Alkaline phosphatase grafting

Titanium and its alloys are the most widespread materials for the realization of orthopaedic and dental implants due to their good mechanical properties and biocompatibility. Surface functionalization of biomaterials aimed to improve and quicken implant integration and tissue regeneration is an active research field. The opportunity to confer biological activity (ability to directly stimulate cells with proper biological signals) to the Ti6Al4 V alloy, previously modified to be bioactive from the inorganic point of view (apatite precipitation), was explored in this research work. The alkaline phosphatase (ALP) enzyme was grafted to metal surface via tresyl chloride activation, maintaining its activity. A synergistic effect between biological functionalization and inorganic bioactivity was observed

Long-term carbon loss in fragmented Neotropical forests

Tropical forests play an important role in the global carbon cycle, as they store a large amount of carbon (C). Tropical forest deforestation has been identified as a major source of CO2 emissions, though biomass loss due to fragmentation—the creation of additional forest edges—has been largely overlooked as an additional CO2 source. Here, through the combination of remote sensing and knowledge on ecological processes, we present long-term carbon loss estimates due to fragmentation of Neotropical forests: within 10 years the Brazilian Atlantic Forest has lost 69 (±14) Tg C, and the Amazon 599 (±120) Tg C due to fragmentation alone. For all tropical forests, we estimate emissions up to 0.2 Pg C y−1 or 9 to 24% of the annual global C loss due to deforestation. In conclusion, tropical forest fragmentation increases carbon loss and should be accounted for when attempting to understand the role of vegetation in the global carbon balance.This study was part of the project ‘Biodiversity conservation in a fragmented landscape at the Atlantic Plateau of São Paulo’ (BIOTA/Caucaia and BioCAPSP) funded by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, project no. 99/05123-4, 01/13309-2, 02/02125-0, 02/02126-7), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, project no. 690144/01-6), Fundação O Boticário de Proteção à Natureza, and by BMBF (German Federal Ministry of Education and Research, project n. 01LB0202). J.P.M. and M.C.R. thank the Brazilian Science Council (Conselho Nacional de Desenvolvimento Científico) for his research fellowship (process no. 307934/2011-0 and 312045/2013-1, respectively). A.H. and S.P. were supported by the ERC advanced grant 233066. M.M. has been supported by BMBF (project n. 01LB0202), and the Department of Ecological Modelling of the Helmholtz Centre for Environmental Research (UFZ). We thank Birgit Felinks for the support during the Mata Atlântica project. Florian Hartig provided valuable comments on an earlier version of this manuscript. S.P. has been funded by the Helmholtz Association of German Research Centres within the project ‘Biomass and Bioenergy systems’. A.H. was also supported by the Helmholtz-Alliance Remote Sensing and Earth System Dynamics. A.H. thanks C. Wissel and H. Bossel for supporting the FORMIND project over the years

Food-dependent, exercise-induced gastrointestinal distress

Among athletes strenuous exercise, dehydration and gastric emptying (GE) delay are the main causes of gastrointestinal (GI) complaints, whereas gut ischemia is the main cause of their nausea, vomiting, abdominal pain and (blood) diarrhea. Additionally any factor that limits sweat evaporation, such as a hot and humid environment and/or body dehydration, has profound effects on muscle glycogen depletion and risk for heat illness. A serious underperfusion of the gut often leads to mucosal damage and enhanced permeability so as to hide blood loss, microbiota invasion (or endotoxemia) and food-born allergen absorption (with anaphylaxis). The goal of exercise rehydration is to intake more fluid orally than what is being lost in sweat. Sports drinks provide the addition of sodium and carbohydrates to assist with intestinal absorption of water and muscle-glycogen replenishment, respectively. However GE is proportionally slowed by carbohydrate-rich (hyperosmolar) solutions. On the other hand, in order to prevent hyponatremia, avoiding overhydration is recommended. Caregiver's responsibility would be to inform athletes about potential dangers of drinking too much water and also advise them to refrain from using hypertonic fluid replacements

A group randomized trial of a complexity-based organizational intervention to improve risk factors for diabetes complications in primary care settings: study protocol

<p>Abstract</p> <p>Background</p> <p>Most patients with type 2 diabetes have suboptimal control of their glucose, blood pressure (BP), and lipids – three risk factors for diabetes complications. Although the chronic care model (CCM) provides a roadmap for improving these outcomes, developing theoretically sound implementation strategies that will work across diverse primary care settings has been challenging. One explanation for this difficulty may be that most strategies do not account for the complex adaptive system (CAS) characteristics of the primary care setting. A CAS is comprised of individuals who can learn, interconnect, self-organize, and interact with their environment in a way that demonstrates non-linear dynamic behavior. One implementation strategy that may be used to leverage these properties is practice facilitation (PF). PF creates time for learning and reflection by members of the team in each clinic, improves their communication, and promotes an individualized approach to implement a strategy to improve patient outcomes.</p> <p>Specific objectives</p> <p>The specific objectives of this protocol are to: evaluate the effectiveness and sustainability of PF to improve risk factor control in patients with type 2 diabetes across a variety of primary care settings; assess the implementation of the CCM in response to the intervention; examine the relationship between communication within the practice team and the implementation of the CCM; and determine the cost of the intervention both from the perspective of the organization conducting the PF intervention and from the perspective of the primary care practice.</p> <p>Intervention</p> <p>The study will be a group randomized trial conducted in 40 primary care clinics. Data will be collected on all clinics, with 60 patients in each clinic, using a multi-method assessment process at baseline, 12, and 24 months. The intervention, PF, will consist of a series of practice improvement team meetings led by trained facilitators over 12 months. Primary hypotheses will be tested with 12-month outcome data. Sustainability of the intervention will be tested using 24 month data. Insights gained will be included in a delayed intervention conducted in control practices and evaluated in a pre-post design.</p> <p>Primary and secondary outcomes</p> <p>To test hypotheses, the unit of randomization will be the clinic. The unit of analysis will be the repeated measure of each risk factor for each patient, nested within the clinic. The repeated measure of glycosylated hemoglobin A1c will be the primary outcome, with BP and Low Density Lipoprotein (LDL) cholesterol as secondary outcomes. To study change in risk factor level, a hierarchical or random effect model will be used to account for the nesting of repeated measurement of risk factor within patients and patients within clinics.</p> <p>This protocol follows the CONSORT guidelines and is registered per ICMJE guidelines:</p> <p>Clinical Trial Registration Number</p> <p>NCT00482768</p

Is the process of delivery of an individually tailored lifestyle intervention associated with improvements in LDL cholesterol and multiple lifestyle behaviours in people with Familial Hypercholesterolemia?

<p>Abstract</p> <p>Background</p> <p>More insight in the association between reach, dose and fidelity of intervention components and effects is needed. In the current study, we aimed to evaluate reach, dose and fidelity of an individually tailored lifestyle intervention in people with Familial Hypercholesterolemia (FH) and the association between intervention dose and changes in LDL-Cholesterol (LDL-C), and multiple lifestyle behaviours at 12-months follow-up.</p> <p>Methods</p> <p>Participants (n = 181) randomly allocated to the intervention group received the PRO-FIT intervention consisting of computer-tailored lifestyle advice (<it>PRO-FIT*advice</it>) and counselling (face-to-face and telephone booster calls) using Motivational Interviewing (MI). According to a process evaluation plan, intervention reach, dose delivered and received, and MI fidelity were assessed using the recruitment database, website/counselling logs and the Motivational Interviewing Treatment Integrity (MITI 3.1.1.) code. Regression analyses were conducted to explore differences between participant and non-participant characteristics, and the association between intervention dose and change in LDL-C, and multiple lifestyle behaviours.</p> <p>Results</p> <p>A 34% (n = 181) representative proportion of the intended intervention group was reached during the recruitment phase; participants did not differ from non-participants (n = 623) on age, gender and LDL-C levels. Of the participants, 95% received a <it>PRO-FIT*advice</it> log on account, of which 49% actually logged on and completed at least one advice module. Nearly all participants received a face-to-face counselling session and on average, 4.2 telephone booster calls were delivered. None of the face-to-face sessions were implemented according to MI guidelines. Overall, weak non-significant positive associations were found between intervention dose and LDL-C and lifestyle behaviours.</p> <p>Conclusions</p> <p>Implementation of the PRO-FIT intervention in practice appears feasible, particularly <it>PRO-FIT*advice</it>, since it can be relative easily implemented with a high dose delivered. However, only less than half of the intervention group received the complete intervention-package as intended. Strategies to let participants optimally engage in using web-based computer-tailored interventions like <it>PRO-FIT*advice</it> are needed. Further, more emphasis should be put on more extensive MI training and monitoring/supervision.</p> <p>Trial registration</p> <p>NTR1899 at ww.trialregister.nl.</p