Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Effect of Torrefaction on Water Vapor Adsorption Properties and Resistance to Microbial Degradation of Corn Stover

The equilibrium moisture content (EMC) of biomass affects transportation, storage, downstream feedstock processing, and the overall economy of biorenewables production. Torrefaction is a thermochemical process conducted in the temperature regime between 200 and 300 °C under an inert atmosphere that, among other benefits, aims to reduce the innate hydrophilicity and susceptibility to microbial degradation of biomass. The objective of this study was to examine water sorption properties of torrefied corn stover. The EMC of raw corn stover, along with corn stover thermally pretreated at three temperatures, was measured using the static gravimetric method at equilibrium relative humidity (ERH) and temperatures ranging from 10 to 98% and from 10 to 40 °C, respectively. Five isotherms were fitted to the experimental data to obtain the prediction equation that best describes the relationship between the ERH and the EMC of lignocellulosic biomass. Microbial degradation of the samples was tested at 97% ERH and 30 °C. Fiber analyses were conducted on all samples. In general, torrefied biomass showed an EMC lower than that of raw biomass, which implied an increase in hydrophobicity. The modified Oswin model performed best in describing the correlation between ERH and EMC. Corn stover torrefied at 250 and 300 °C had negligible dry matter mass loss due to microbial degradation. Fiber analysis showed a significant decrease in hemicellulose content with the increase in pretreatment temperature, which might be the reason for the hydrophobic nature of the torrefied biomass. The outcomes of this work can be used for torrefaction process optimization, and decision-making regarding raw and torrefied biomass storage and downstream processing

Outcomes of the rope skipping \u27STAR\u27 programme for schoolchildren

Physical activity in children and adolescents is on a decline trend. To this end, we conducted a matched-pair randomized controlled trial to examine the effects of a 4-week STAR (School-based; Train-the-trainer; Accessibility of resources; Recreational) skipping programme. 1,386 schoolchildren from 20 primary and secondary schools were recruited. Schools were randomized into the experimental or wait-list control group. Participants self-reported their health-related quality of life using the KIDSCREEN-27. Accelerometers were used to measure the time a subgroup of participants (n = 480) spent in moderate-to-vigorous physical activity during school hours on five consecutive days. Measures were taken at pre- and post-test. At post-test, students in the experimental group, compared to those in the control group, engaged in less moderate-to-vigorous physical activity during school hours. Health-related quality of life from two groups of students was similar, but the experimental group reported higher levels of autonomy and parent relationships. Results suggested that although the intervention did not increase students\u27 physical activity levels, it slightly improved their health-related quality of life. Future studies should explore personal factors that might mediate the effect of the intervention

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.Supported by a MRC Clinician Scientist award (G0701911), a Brain and Behaviour Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and Wellcome Trust (G1000183 and 093875/Z/10Z respectively); by awards from the Wellcome Trust (095692) and the Bernard Wolfe Health Neuroscience Fund to Professor Fletcher, and by awards from the Wellcome Trust Institutional Strategic Support Fund (097814/Z/11) and Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.37

Adiposity is Associated with Regional Cortical Thinning

BACKGROUND: Although obesity is associated with structural changes in brain grey matter, findings have been inconsistent and the precise nature of these changes is unclear. Inconsistencies may partly be due to the use of different volumetric morphometry methods, and the inclusion of participants with comorbidities that exert independent effects on brain structure. The latter concern is particularly critical when sample sizes are modest. The purpose of the current study was to examine the relationship between cortical grey matter and body mass index (BMI), in healthy participants, excluding confounding comorbidities and using a large sample size. SUBJECTS: A total of 202 self-reported healthy volunteers were studied using surface-based morphometry, which permits the measurement of cortical thickness, surface area and cortical folding, independent of each other. RESULTS: Although increasing BMI was not associated with global cortical changes, a more precise, region-based analysis revealed significant thinning of the cortex in two areas: left lateral occipital cortex (LOC) and right ventromedial prefrontal cortex (vmPFC). An analogous region-based analysis failed to find an association between BMI and regional surface area or folding. Participants' age was also found to be negatively associated with cortical thickness of several brain regions; however, there was no overlap between the age- and BMI-related effects on cortical thinning. CONCLUSIONS: Our data suggest that the key effect of increasing BMI on cortical grey matter is a focal thinning in the left LOC and right vmPFC. Consistent implications of the latter region in reward valuation, and goal control of decision and action suggest a possible shift in these processes with increasing BMI.We thank all the participants and the staff of the Wolfson Brain Imaging Centre. This work was supported by the Bernard Wolfe Health Neuroscience Fund (NM, HZ, ISF, PCF), the Wellcome Trust (RGAG/144 to N.M, RGAG/188 to ISF, RNAG/259 to PCF) and the Medical Research Council (G0701497 to KDE).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ijo.2016.42

Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation

Background: Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. in our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.Methods: the beta 1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and beta 1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Results: Differential association among Timp1, CD63 and beta 1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. in human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Conclusions: Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and beta 1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. in addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilLudwig Inst Canc Res, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/12306-1FAPESP: 2010/18715-8CAPES: 2867/10Web of Scienc

Cost-Effectiveness of a Community First Responder System for Out-of-Hospital Cardiac Arrest in Poland

Jerzy Jaskuła,1 Goran Medic,2 Sanjay Verma,2 Joachim Maurer,3 Tom A Kooy,4 Bianca de Greef2 1Department of Medical Education, Centre for Innovative Medical Education, Jagiellonian University Medical College, Krakow, Poland; 2Chief Medical Office – Health Economics and Outcome Research, Philips, Amsterdam, Netherlands; 3Connected Care – Emergency Care, Philips, Amsterdam, Netherlands; 4Research Department, Stan BV, Udenhout, NetherlandsCorrespondence: Goran Medic, Email [email protected]: Out-of-Hospital Cardiac Arrest (OHCA) is a significant public health issue in Poland, with only an 8.4% survival rate to hospital discharge. Early initiation of Basic Life Support and defibrillation through a Community First Responder (CFR) system can markedly improve survival rates and neurological outcomes.Methods: A decision tree and Markov model compared the cost-effectiveness of three scenarios against standard care by estimating costs and quality-adjusted life years (QALYs). Scenario 1 involved raising public awareness and educating on the 30:2 CPR protocol. Scenario 2 added equipping blue-light service vehicles with Automated External Defibrillators (AEDs) and training personnel. Scenario 3 implemented a full CFR system with integrated AEDs, dispatch centers, and trained citizen responders. The analysis included survival to hospital discharge, with sensitivity analyses assessing robustness.Results: The incremental cost-effectiveness ratios (ICERs) were € 15,221 for Scenario 1, € 30,659 for Scenario 2, and € 16,205 for Scenario 3 per QALY gained—all below the threshold of € 50,197. Improvements were observed in all stages, including survival to hospital discharge and neurologically intact survival. Probabilistic sensitivity analyses confirmed the robustness of the results.Conclusion: Implementing a CFR system in Poland is a cost-effective strategy that enhances survival rates after OHCA at an acceptable cost per QALY. The study emphasizes the importance of AED accessibility, trained CFRs, and streamlined emergency responses to improve survival and quality of life for OHCA patients. These findings support policy development and resource allocation to strengthen Poland’s emergency medical response to OHCA.Keywords: out-of-hospital cardiac arrest, community first responder, automated external defibrillator, cost-effectiveness, defibrillatio

Influence of Higenamine on Exercise Performance of Recreational Female Athletes: A Randomized Double-Blinded Placebo-Controlled Trial

The aim of this study was to determine the ergogenic effects and the safety profile of a one-component higenamine supplement in female recreational athletes. Twelve recreational female basketball players (age 29–41 years, oxygen consumption (VO2max) > 30 ml⋅kg–1⋅min–1, with training > 5 h wk–1) were randomized either to the higenamine group, or to the placebo group for 3 weeks. In order to determine ergogenic effects and safety profile of higenamine administration, we assessed the following variables before and after 3 weeks of supplementation: anthropometric parameters, resting metabolic rate (RMR), exercise testing variables, serum free fatty acids (FFAs), blood pressure, enzyme activity, urea, lipid profile, and complete blood count. There were no differences between groups in anthropometric parameters, including basal metabolic rate (BMR), RMR and body fat [p = 0.706 (Cohen’s d 0.223), p = 0.169 (Cohen’s d 0.857), and p = 0.223 (Cohen’s d 0.750), respectively], FFAs [0.43 ± 0.03 vs. 0.54 ± 0.23, p = 0.206 (Cohen’s d 0.540)], neither significant differences in cardiopulmonary parameters after the intervention period. Furthermore, all measured outcome variables in the safety assessment were not significant, with values remaining stable during the intervention period for participants in both groups. This is the first study to document the effects and the safety profile of higenamine-based dietary supplements at a specified dose in female recreational athletes. Our data indicate that 21-day of supplementation with 75 mg higenamine would not result in improving cardiopulmonary exercise fitness and weight loss in female recreational athletes. Moreover, supplementation with 75 mg higenamine is safe and well-tolerated in younger recreational female athletes