Multi-level assessment of obsessive-compulsive disorder (OCD) reveals relations between neural and neurochemical levels.

BACKGROUND: While considerable progress has been made in exploring the psychological, the neural, and the neurochemical dimensions of OCD separately, their interplay is still an open question, especially their changes during psychotherapy. METHODS: Seventeen patients were assessed at these three levels by psychological questionnaires, fMRI, and venipuncture before and after inpatient psychotherapy. Seventeen controls were scanned at comparable time intervals. First, pre/post treatment changes were investigated for all three levels separately: symptom severity, whole-brain and regional activity, and the concentrations of cortisol, serotonin, dopamine, brain-derived neurotrophic factor (BDNF), and immunological parameters (IL-6, IL-10, TNFα). Second, stepwise linear modeling was used to find relations between the variables of the levels. RESULTS: The obsessive-compulsive, depressive, and overall symptom severity was significantly reduced after psychotherapy. At the neural level, the activity in the anterior cingulate cortex (ACC), in frontal regions, in the precuneus, and in the putamen had significantly decreased. No significant changes were found on the neurochemical level. When connecting the levels, a highly significant model was found that explains the decrease in neural activity of the putamen by increases of the concentrations of cortisol, IL-6, and dopamine. CONCLUSION: Multivariate approaches offer insight on the influences that the different levels of the psychiatric disorder OCD have on each other. More research and adapted models are needed.

Acute Exposure to Environmental Tobacco Smoke: A Controlled Study in Adults with Asthma.

BACKGROUND: Short-term, indoor exposure to environmental tobacco smoke (ETS) is still highly prevalent; however, little is known about the acute lung response in adult asthma. OBJECTIVES: We investigated whether acute, experimental ETS exposure influences symptoms, lung function, and inflammatory parameters. METHODS: Human subjects with asthma (n = 23) were exposed for 180 min to either room air or ETS at 250, 450, or 850 µg/m3. Respiratory symptoms, lung function, and exhaled nitric oxide (FeNO) were measured. Additionally, blood samples were analyzed for pro- and anti-inflammatory cytokines. RESULTS: Humans with asthma demonstrate an increase in respiratory symptoms at all levels of ETS exposure, while the forced expiratory volume in 1 s (FEV1) and FeNO decrease with increasing ETS. The anti-inflammatory cytokine interleukin (IL)-10 increases at intermediate ETS concentrations, whereas tumor necrosis factor (TNF)-α and IL-8 increase only at the highest ETS concentration. CONCLUSION: Following 180 min of acute, experimental ETS exposure, we observed a significant increase in respiratory symptoms, a decrease in lung function, and an increase in inflammatory cytokines, indicating an acute lung response in asthma.

Upregulation of mitotic bookmarking factors during enhanced proliferation of human stromal cells in human platelet lysate.

BACKGROUND: Innovative human stromal cell therapeutics require xeno-free culture conditions. Various formulations of human platelet lysate (HPL) are efficient alternatives for fetal bovine serum (FBS). However, a consistent lack of standardized manufacturing protocols and quality criteria hampers comparability of HPL-products. Aim of this study was to compare the biochemical composition of three differential HPL-preparations with FBS and to investigate their impact on stromal cell biology. METHODS: Stromal cells were isolated from bone marrow (BM), white adipose tissue (WAT) and umbilical cord (UC) and cultured in medium supplemented with pooled HPL (pHPL), fibrinogen-depleted serum-converted pHPL (pHPLS), mechanically fibrinogen-depleted pHPL (mcpHPL) and FBS. Biochemical parameters were analyzed in comparison to standard values in whole blood. Distinct growth factors and cytokines were measured by bead-based multiplex technology. Flow cytometry of stromal cell immunophenotype, in vitro differentiation, and mRNA expression analysis of transcription factors SOX2, KLF4, cMYC, OCT4 and NANOG were performed. RESULTS: Biochemical parameters were comparable in all pHPL preparations, but to some extent different to FBS. Total protein, glucose, cholesterol and Na+ were elevated in pHPL preparations, K+ and Fe3+ levels were higher in FBS. Compared to FBS, pHPL-based media significantly enhanced stromal cell propagation. Characteristic immunophenotype and in vitro differentiation potential were maintained in all four culture conditions. The analysis of growth factors and cytokines revealed distinct levels depending on the pre-existence in pHPL, consumption or secretion by the stromal cells. Interestingly, mRNA expression of the transcription and mitotic bookmarking factors cMYC and KLF4 was significantly enhanced in a source dependent manner in stromal cells cultured in pHPL- compared to FBS-supplemented media. SOX2 mRNA expression of all stromal cell types was increased in all pHPL culture conditions. CONCLUSION: All pHPL-supplemented media equally supported proliferation of WAT- and UC-derived stromal cells significantly better than FBS. Mitotic bookmarking factors, known to enable a quick re-entry to the cell cycle, were significantly enhanced in pHPL-expanded cells. Our results support a better characterization and standardization of humanized culture media for stromal cell-based medicinal products.

Green exercise and mg-ca-SO4 thermal balneotherapy for the treatment of non-specific chronic low back pain: a randomized controlled clinical trial.

BACKGROUND: Non-specific chronic low back pain (nscLBP) has a high socio-economic relevance due to its high incidence, prevalence and associated costs. Therefore, it is essential to evaluate effective therapeutic strategies. This study examines the effects of moderate mountain exercise and spa therapy on orthopedic and psychophysiological parameters. Based on a three-armed randomized controlled trial, guided mountain hiking tours and balneotherapy in thermal water were compared to a control group. METHODS: Eighty patients with diagnosed nscLBP were separated into three groups: The two intervention groups GE (green exercise) and GEBT (green exercise and balneotherapy) undertook daily mountain hiking tours, whereas the GEBT group got an additional treatment with baths in Mg-Ca-SO4 thermal water. The third group (CO) received no intervention. GE and GEBT group were treated for 6 days; all groups were followed up for 120 days. RESULTS: Compared to GE and CO group, the GEBT treatment showed significant improvements of pain, some orthopedic parameters, health-related quality of life and mental well-being in patients with nscLBP. CONCLUSIONS: The results of this study confirmed a benefit of mountain hiking combined with Mg-Ca-SO4 spa therapy as a multimodal treatment of patients with nscLBP. Further studies should focus on long-term-effects of this therapeutic approach. TRIAL REGISTRATION: ISRCTN, ISRCTN99926592 . Registered 06. July 2018 - Retrospectively registered.

Radon balneotherapy and physical activity for osteoporosis prevention: a randomized, placebo-controlled intervention study.

Low-dose radon hyperthermia balneo treatment (LDRnHBT) is applied as a traditional measure in the non-pharmacological treatment of rheumatic diseases in Europe. During the last decades, the main approach of LDRnHBT was focused on the treatment of musculoskeletal disorders, but scientific evidence for the biological background of LDRnHBT is weak. Recently, evidence emerged that LDRnHBT influences bone metabolism. We investigated, whether combined LDRnHBT and exercise treatment has an impact on bone metabolism and quality of life in a study population in an age group at risk for developing osteoporosis. This randomized, double-blind, placebo-controlled trial comprised guided hiking tours and hyperthermia treatment in either radon thermal water (LDRnHBT) or radon-free thermal water (PlaceboHBT). Markers of bone metabolism, quality of life and somatic complaints were evaluated. Statistics was performed by linear regression and a linear mixed model analysis. Significant changes over time were observed for most analytes investigated as well as an improvement in self-assessed health in both groups. No significant impact from the LDRnHBT could be observed. After 6 months, the LDRnHBT group showed a slightly stronger reduction of the osteoclast stimulating protein receptor activator of nuclear kB-ligand compared to the PlaceboHBT group, indicating a possible trend. A combined hyperthermia balneo and exercise treatment has significant immediate and long-term effects on regulators of bone metabolism as well as somatic complaints. LDRnHBT and placeboHBT yielded statistically equal outcomes.

Effects of Alpine Natural Health Resources on Human Health and Wellbeing.

As humanity becomes progressively urban, a huge number of people could lose the opportunity to benefit from or develop an appreciation for nature [...].

Uncovering placemaking needs with(in) a kindergarten community: a cross-disciplinary approach to participatory design.

Introduction: The design of early childhood education and care facilities faces the double challenge of creating a stimulating environment for young children and a supportive workplace for staff. The existing body of research suggests that placemaking strategies serve both requirements. A promising approach to meet placemaking needs is the participation of future occupants in the building design. Methods: We pursued a participatory design study with the community of an Austrian kindergarten aiming to inform the future building renovation. We combined novel cultural fiction probes methods with conventional inquiry methods to gather information from children and teachers about their experience of the built environment. Using thematic and content analyzes we explored placemaking needs from different epistemic perspectives and converged findings through iterative exchange. Results: Returns of children and teachers were interconnected and complementary. From a design-oriented perspective, children's experience of place was relatable to spatial, temporo-spatial, and acoustic qualities as well as control needs. From a human-centered perspective, teachers' experience of place was relatable to the needs of feeling embedded, protected, enacted, and socially connected. The converged findings revealed dynamic placemaking processes involving the elements of space, time, and control at different levels. Discussion: Cross-disciplinary collaboration and research consolidation brought forth valuable insights on supportive structures for both children and teachers, facilitated timely knowledge transfer, and converted into design solutions that foster enacted placemaking. Albeit general transferability is limited, findings are interpretable within a solid framework of existing theories, concepts and evidence.

Long-Term Effects of Mountain Hiking vs. Forest Therapy on Physical and Mental Health of Couples: A Randomized Controlled Trial.

BACKGROUND: Lifelong physical activity is related to longer health span, which is reflected at an individual level, and is of substantial socioeconomic relevance. Sedentary lifestyles, on the other hand, pose an increasingly major public health problem. In addition, the COVID-19 pandemic had a negative impact on activity levels and well-being. Previous research indicates that contact with nature might improve exercise levels as well as well-being. METHODS: This randomized, controlled clinical trial (ANKER-study) investigated the effects of two types of nature-based therapies (forest therapy and mountain hiking) in couples (FTG: n = 23; HG: n = 22;) with a sedentary or inactive lifestyle on health-related quality of life, relationship quality and other psychological and physiological parameters. RESULTS: The results of this study displayed that healthy and highly functioning women and men with sedentary lifestyles mentally benefit from contact with nature (quality of life, satisfaction with life, mood, internal and external health-related control beliefs). The gender-specific effect on women is most visible in the physiological outcomes (hemopoietic system, aerobic capacity, skeletal muscle mass and hydration) of mountain hiking. Men and women showed small improvements in blood pressure as a result of the interventions. CONCLUSIONS: The ANKER-study provides a method for valid comparison of forest therapy interventions for the first time. Regarding the COVID-19 pandemic, the nature-based intervention presented could offer a multimodal contribution to maintaining a more active lifestyle, further contact with nature that affects peoples physical as well as mental health, and an improvement in social interaction.

Nature-based biopsychosocial resilience: An integrative theoretical framework for research on nature and health.

Nature-based solutions including urban forests and wetlands can help communities cope better with climate change and other environmental stressors by enhancing social-ecological resilience. Natural ecosystems, settings, elements and affordances can also help individuals become more personally resilient to a variety of stressors, although the mechanisms underpinning individual-level nature-based resilience, and their relations to social-ecological resilience, are not well articulated. We propose 'nature-based biopsychosocial resilience theory' (NBRT) to address these gaps. Our framework begins by suggesting that individual-level resilience can refer to both: a) a person's set of adaptive resources; and b) the processes by which these resources are deployed. Drawing on existing nature-health perspectives, we argue that nature contact can support individuals build and maintain biological, psychological, and social (i.e. biopsychosocial) resilience-related resources. Together with nature-based social-ecological resilience, these biopsychosocial resilience resources can: i) reduce the risk of various stressors (preventive resilience); ii) enhance adaptive reactions to stressful circumstances (response resilience), and/or iii) facilitate more rapid and/or complete recovery from stress (recovery resilience). Reference to these three resilience processes supports integration across more familiar pathways involving harm reduction, capacity building, and restoration. Evidence in support of the theory, potential interventions to promote nature-based biopsychosocial resilience, and issues that require further consideration are discussed.

Conditional deletion of histone deacetylase 1 in T cells leads to enhanced airway inflammation and increased Th2 cytokine production.

Chromatin modifications, such as reversible histone acetylation, play a key role in the regulation of T cell development and function. However, the role of individual histone deacetylases (HDACs) in T cells is less well understood. In this article, we show by conditional gene targeting that T cell-specific loss of HDAC1 led to an increased inflammatory response in an in vivo allergic airway inflammation model. Mice with HDAC1-deficient T cells displayed an increase in all critical parameters in this Th2-type asthma model, such as eosinophil recruitment into the lung, mucus hypersecretion, parenchymal lung inflammation, and enhanced airway resistance. This correlated with enhanced Th2 cytokine production in HDAC1-deficient T cells isolated from diseased mice. In vitro-polarized HDAC1-deficient Th2 cells showed a similar enhancement of IL-4 expression, which was evident already at day 3 of Th2 differentiation cultures and restricted to T cell subsets that underwent several rounds of cell divisions. HDAC1 was recruited to the Il4 gene locus in ex vivo isolated nonstimulated CD4(+) T cells, indicating a direct control of the Il4 gene locus. Our data provide genetic evidence that HDAC1 is an essential HDAC that controls the magnitude of an inflammatory response by modulating cytokine expression in effector T cells.

Effects of ionized waterfall aerosol on pediatric allergic asthma.

OBJECTIVE: Ionized water aerosols have been suggested to exert beneficial health effects on pediatric allergic asthma. Their effect was evaluated in a randomized controlled clinical trial as part of a summer asthma camp. METHODS: Asthmatic allergic children (n = 54) spent 3 weeks in an alpine asthma camp; half of the group was exposed to water aerosol of an alpine waterfall for 1 hour per day, whereas the other half spent the same time at a "control site". Immunological analysis, lung function testing, and fractional exhaled nitric oxide (FeNO) testing were performed during the stay, and sustaining effects were evaluated 2 months later. Symptom score testing was done over a period of 140 days. RESULTS: The water aerosol group showed a significant improvement in all lung function parameters, whereas only the peak expiratory flow improved in the control group. All patients showed a significant improvement in symptom score and a significant decrease in FeNO after the camp. Only the water aerosol group exhibited a long-lasting effect on asthma symptoms, lung function, and inflammation in the follow-up examination. Induction of interleukin (IL)-10 and regulatory T (Treg) cells was measured in both groups, with a pronounced increase in the water aerosol group. IL-13 was significantly decreased in both groups, whereas IL-5 and eosinophil cationic protein were decreased only in the water aerosol group. CONCLUSIONS: Our findings confirm the induction of Treg cells and reduction in inflammation by climate therapy. They indicate a synergistic effect of water aerosols resulting in a long-lasting beneficial effect on asthma symptoms, lung function, and airway inflammation.

Sustainability of Hiking in Combination with Coaching in Cardiorespiratory Fitness and Quality of Life.

Although strong evidence shows that physical inactivity and sedentary behavior are associated with many negative health outcomes, inactive lifestyles are still increasing. Consequently, new approaches must be developed to increase adherence to an active lifestyle and hence a longer life. Green exercise and health coaching could be effective ways to induce long-lasting lifestyle changes geared towards more physical activity. In this randomized controlled trial, we investigated the effects of mountain hiking and psychological coaching on adults with a sedentary lifestyle. The coaching group (n = 26) participated in a 7-day guided hiking program with three personal coaching sessions, whereas the hiking group (n = 32) received no coaching. The effects on aerobic capacity, spirometry and quality of life were assessed at baseline (day 0), after the intervention week (day 7) and after 80 days. Fully nonparametric statistical analysis revealed a gender-based effect for aerobic capacity-the female participants of the coaching group showed a greater improvement (p = 0.03) than the hiking group. No significant effects were found for spirometry. Quality of life parameters improved in both groups. In conclusion, both green exercise and health coaching are capable of inducing improvements in health-related quality of life and cardiorespiratory fitness. No superior effects of health coaching were found.

Mountain Hiking vs. Forest Therapy: A Study Protocol of Novel Types of Nature-Based Intervention.

INTRODUCTION: The global rise of urbanization has much triggered scientific interest in how nature impacts on human health. Natural environments, such as alpine landscapes, forests, or urban green spaces, are potential high-impact health resources. While there is a growing body of evidence to reveal a positive influence of these natural environments on human health and well-being, further investigations guided by rigorous evidence-based medical research are very much needed. OBJECTIVE: The present study protocol aims at testing research methodologies in the context of a prospective clinical trial on nature-based interventions. This shall improve the standards of medical research in human-nature interactions. METHODS: The ANKER Study investigates the influence of two novel types of nature-based therapy-mountain hiking and forest therapy-on physiological, psychological, and immunological parameters of couples with a sedentary lifestyle. Two intervention groups were formed and spent a seven-day holiday in Algund, Italy. The "forest therapy group" participated in daily guided low-power nature connection activities. The "hiking group", by contrast, joined in a daily moderate hiking program. Health-related quality of life and relationship quality are defined as primary outcomes. Secondary outcomes include nature connection, balance, cardio-respiratory fitness, fractional exhaled nitric oxide, body composition and skin hydration. Furthermore, a new approach to measure health-related quality of life is validated. The so-called "intercultural quality of life" comic assesses the health-related quality of life with a digitally animated comic-based tool.

Designing hypoallergenic derivatives for allergy treatment by means of in silico mutation and screening.

BACKGROUND: The incidence of allergic diseases in developed countries has been increasing constantly in the last 2 decades. The only curative treatment available thus far is specific immunotherapy (SIT). The problematic side effects that can occur during SIT with allergen extracts led to the search for safer alternatives, such as recombinant hypoallergenic proteins with reduced allergenic potential and preserved T-cell immunogenicity. OBJECTIVE: We created hypoallergenic variants of the allergens Bet v 1a and Phl p 5b by using in silico mutation and screening and characterized the biochemical and immunologic properties of selected mutant proteins. METHODS: Knowledge-based potentials were used to estimate structural changes of the protein structures under sequence variation. IgE antibodies and their cross-linking capacity were determined by using a basophil release assay, binding of human birch pollen-specific IgE was investigated by means of ELISA, and ELISPOT assays were performed to examine the T-cell immunogenicity. RESULTS: Selected mutated proteins showed significantly reduced IgE-binding and cross-linking ability but retained their T cell-stimulating properties. Immunization with the hypoallergenic mutants induced blocking antibodies against murine and human IgE epitopes. CONCLUSION: In silico calculation and selection of mutations that render a protein hypoallergenic represents a novel and rapid tool to create candidate molecules for SIT with recombinant allergens.

Modulation of allergen-specific T-lymphocyte function by virus-like particles decorated with HLA class II molecules.

BACKGROUND: T(H)2 lymphocytes play an important role in the induction and maintenance phase of type I allergy. Modulation of the responses of T(H)2 lymphocytes by novel forms of antigen-presenting platforms may help shape the immune response to allergen and palliate allergic diseases. OBJECTIVE: To present HLA class II/allergen-peptide complexes on virus-like particles (VLPs) and to evaluate their potential to modulate allergen-specific T-cell responses. METHODS: Virus-like particles that express the immunodominant T-cell epitope Art v 1(25-34) of the major mugwort pollen allergen in the context of HLA-DR1 and costimulatory molecules were produced by transfection of 293 cells. The effect of VLPs on IL-2 promoter activity, proliferation, and cytokine production of allergen-specific T cells derived from donors with and without mugwort pollen allergy was determined. RESULTS: Flow-cytometric analyses showed that HLA class II molecules, invariant chain::Art v 1 fusion proteins, and costimulatory molecules were expressed on 293 cells. Biochemical analyses confirmed that these molecules were efficiently targeted to VLPs. The engineered VLPs activated Art v 1-specific T cells in a costimulation-dependent manner. VLPs lacking costimulators induced T-cell unresponsiveness, which was overcome by addition of exogenous IL-2. Costimulation could be provided by CD80, CD86, or CD58 and induced distinct cytokine profiles in allergen-specific T cells. Unlike the other costimulatory molecules, CD58 induced IL-10/IFN-gamma-secreting T cells. CONCLUSION: Virus-like particles represent a novel, modular, acellular antigen-presenting system able to modulate the responses of allergen-specific T cells in a costimulator-dependent fashion. Allergen-specific VLPs show promise as tools for specific immunotherapy of allergic diseases.

Winter Exercise and Speleotherapy for Allergy and Asthma: A Randomized Controlled Clinical Trial.

(1) Background: The prevalence of allergic respiratory diseases is still rising and efforts towards holistic treatments should be made. Although speleotherapy is widely applied in Europe to treat chronic airway diseases, the existing scientific evidence is rather low. Recreational winter exercise has been shown to improve allergic airway inflammation, but little is known about the combined effects of speleotherapy and recreational winter exercise. (2) Methods: In this clinical study we investigated the effects of winter exercise and speleotherapy on adults with allergic rhinitis and/or asthma. The speleotherapy group (n = 23) participated in a ten-day combined winter exercise and speleotherapy program and the exercise group (n = 18) joined a full-day winter sports program. The effects on allergic airway inflammation, quality of life, spirometry and cardiorespiratory fitness were assessed. (3) Results: No significant effects were found for fractional exhaled nitric oxide or nasal nitric oxide. Quality of life (p < 0.001 time effect) and allergic symptoms (p < 0.001 time effect) were improved in the speleotherapy and in the exercise group. (4) Conclusions: Winter exercise alone and winter exercise in combination with speleotherapy improve quality of life and allergic symptoms in adults with allergic rhinitis and/or asthma. Further studies are required to investigate the specific effects of speleotherapy. To our knowledge, this is the first investigation examining speleotherapy in combination with winter exercise. Recreational outdoor winter exercise and speleotherapy may be recommended for highly functioning patients with good disease control.

Endurance Athletes Are at Increased Risk for Early Acute Mountain Sickness at 3450 m.

INTRODUCTION: Acute mountain sickness (AMS) may develop in nonacclimatized individuals after exposure to altitudes ≥2500 m. Anecdotal reports suggest that endurance-trained (ET) athletes with a high maximal oxygen uptake (V˙O2max) may be at increased risk for AMS. Possible underlying mechanisms include a training-induced increase in resting parasympathetic activity, higher resting metabolic rate (RMR), and lower hypoxic ventilatory response (HVR). METHODS: In 38 healthy, nonacclimatized men (19 ET and 19 untrained controls [UT], V˙O2max 66 ± 6 mL·min·kg vs 45 ± 7 mL·min·kg; P < 0.001) peripheral oxygen saturation (SpO2), heart rate variability, RMR, and poikilocapnic HVR were assessed at 424 m and during 48 h at 3450 m after passive ascent by train (~2 h). Acute mountain sickness was evaluated by AMS cerebral (AMS-C) score. RESULTS: On day 1 at altitude, ET presented with a higher AMS incidence (42% vs 11%; P < 0.05) and severity (AMS-C score: ET, 0.48 ± 0.5 vs UT, 0.21 ± 0.2; P = 0.03), but no group difference was found on days 2 and 3. SpO2 decreased upon arrival at altitude (ET: 82% ± 6% vs UT: 83% ± 4%; ptime <0.001) with a significantly different time course between ET and UT (ptime × group = 0.045). Parasympathetic activity decreased at altitude (P < 0.001) but was always higher in ET (P < 0.05). At altitude RMR increased (P < 0.001) and was higher in ET (P < 0.001). Hypoxic ventilatory response increased only in ET (P < 0.05) and was greater than in UT after 24 and 48 h (P < 0.05). CONCLUSIONS: Endurance-trained athletes are at higher risk for developing AMS on the first day after passive and rapid ascent to 3450 m, possibly due to an increased parasympathetic activity and an increased RMR, while HVR appeared to be of minor importance. Differences in AMS time course and physiological responses should be taken into consideration when ET are planning high-altitude sojourns.

The phytostilbene resveratrol induces apoptosis in INS-1E rat insulinoma cells.

We investigated the effect of resveratrol on proliferation and induction of apoptosis of INS-1E rat insulinoma cells by cell counting, crystal violet staining, flow cytometry and immunoblotting. Resveratrol treatment of INS-1E cells at concentrations > or =50 microM resulted in a dose-dependent inhibition of cell proliferation, accumulation of the cells in the S and G0/G1 phase and a significant increase of the percentage of apoptotic cells. This was paralleled by an increase of cell granularity, apoptotic volume decrease (AVD), exposure of phosphatidylserine at the outer leaflet of the plasma membrane, an increase of the 7-AAD signal and caspase activation. The AMP-kinase (AMPK) inhibitor compound C (10 microM) significantly inhibited cell proliferation and induced caspase activation within 48 hours but this effect was not modified by resveratrol suggesting that AMPK is not a major target involved in mediating the proapoptotic effect of resveratrol in INS-1E cells. Immunoblotting revealed a significant inhibition of Akt (PKB) phosphorylation by 100 muM resveratrol within 1 hour. Addition of insulin (10 microM) to the culture medium strongly enhanced basal Akt phosphorylation. This enhancement was significantly attenuated by 50 and 100 microM resveratrol. We conclude that the antiproliferative/proapoptotic effect of resveratrol on INS-1E cells is due to negative interference with Akt signaling and most likely disruption of auto/paracrine insulin signaling.

Molecular and functional analysis of the antigen receptor of Art v 1-specific helper T lymphocytes.

BACKGROUND: Ninety-five percent of patients with mugwort allergy are sensitized to Art v 1, the sole major allergen in mugwort (Artemisia vulgaris) pollen. Sixty-nine percent of patients recognizing the single immunodominant T-cell epitope Art v 1(25-36) have an HLA-DRB1*01 phenotype. OBJECTIVE: We studied cloning and functional expression of a human alphabeta T-cell receptor (TCR) specific for Art v 1(25-36). METHODS: TCR chains were RT-PCR amplified from an Art v 1(25-36)-specific T-cell clone, retrovirally transferred, and functionally tested in Jurkat T cells or alternatively in peripheral blood T lymphocytes of nonallergic individuals. RESULTS: The alpha-chain of the TCR is composed of TRAV17 and TRAJ45 segments, and the beta-chain uses TRBV18, TRBD1, and TRBJ2-7. Analyses of 23 other Art v 1-specific T-cell clones did not reveal preferential usage of the TRAV17, TRBV18, or other TCR gene families. Efficient TCR transfer into Jurkat T cells was shown by binding of TCR Vbeta18-specific mAb and DRB1*0101/Art v 1 tetramers. Transgenic Jurkat T cells specifically recognized syngeneic EBV B cells pulsed with Art v 1(25-36) peptide and artificial antigen-presenting cells expressing invariant chain::Art v 1 fusion proteins. Moreover, transfer of the TCR into peripheral blood lymphocytes generated T cells that were Art v 1 reactive. Activation of transgenic T cells by artificial antigen-presenting cells was strictly dependent on costimulation. CONCLUSION: For the first time, a detailed molecular and functional analysis of a human allergen-specific TCR is presented.

The Role of Anthropogenic Elements in the Environment for Affective States and Cortisol Concentration in Mountain Hiking-A Crossover Trial.

Green exercise might have positive effects on health and affective states. Little is known about the ideal characteristics of the natural environment, where exercise is conducted in. Thus, the primary aim of the present study was to investigate the effects of anthropogenic elements on acute stress-related physiological responses and affective states in green exercise. Using a crossover field study design, 52 healthy participants were exposed to two different mountain hiking conditions: An environment with less anthropogenic elements and an environment with more anthropogenic elements. Pre and post conditions, affective states and salivary cortisol concentration were measured. Repeated measures ANOVAs were used to analyze if pre-post changes differed between the conditions. Pre-post changes in affective states and salivary cortisol concentration did not significantly differ, partial η² < 0.06. Positive affective states showed significantly higher values post compared to pre-condition, partial η² > 0.13. The present results indicate that anthropogenic elements have a minor role in the influence on affective states and salivary cortisol concentration during mountain hiking. It is concluded that a single bout of mountain hiking independent of anthropogenic elements in the environment is effective in influencing affective states positively.