100 Years of Immunotherapy: The Monaco Charter

Aims of the Monaco Charter: (1) to present the current evidence on the efficacy and safety of allergen-specific immunotherapy (SIT) and to address the reasons for its underuse in clinical practice; (2) to develop strategies to increase the awareness about the benefits and the hazards of SIT in allergic patients, lay public and healthcare professionals not trained in allergy, and (3) to make SIT accessible and affordable to eligible patient

Benefits of outdoor sports for society. A systematic literature review and reflections on evidence

The combination of physical activity and being in nature is recognized as providing a range of significant benefits. The objective of this literature review was to compile an overview of the social benefits and costs associated with outdoor sports within the academic literature and to reflect on the quality of underlying evidence that supports the relationship. A systematic review was carried out with seven partners from different European countries, including Bulgaria, France, Germany, United Kingdom, Italy, Portugal, and Spain. From a total of 17,560 studies identified, 133 studies were selected with relevant data extracted to standardized forms. The selected studies have been analyzed with qualitative research methods. A meta-analysis could not be conducted due to the heterogeneity of the study designs and outcome measures. As a result, the review gives an overview of the social impacts associated with outdoor sports which have been clustered to six broad categories: physical health, mental health and wellbeing, education and lifelong learning, active citizenship, crime reduction, and anti-social behavior, as well as additional benefits. The review furthermore revealed gaps in the evidence base which are especially notable in the long-term effects that outdoor sports can have on personal and social development

Antithrombotic regimens for the prevention of major adverse cardiac events in chronic coronary syndrome: A systematic review and network meta-analysis

BackgroudAntithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS.MethodsWe used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality.ResultsFive trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39–0.71); and 0.68 (95% CrI, 0.54–0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low.ConclusionsThese results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options

Differential scanning calorimetry and elasticity of textured, heat set and mechanical strained polylactide multifilaments

Industrially textured PLA multifilaments were heat set under different conditions at 110 ºC for 1 min and subjected to one cycle of deformation up to 20%. Thermal transitions of the original textured, heat set and cyclic strained filaments were measured using differential scanning calorimetry from 25 to 250 ºC. Cyclic deformation induces an endo-exo transition at peak temperatures between 55 - 60 ºC that is not observed in the original textured and heat set multifilaments. There is another endo-exo transition with peak temperatures between 67 and 72 ºC in all filaments, the intensity of which varies according to texturing conditions, heat setting and cycle strain. Texturing conditions, heat setting and cyclic strain play a role in thermal transitions, the strain at breaking and elastic properties of the filaments. The crystallinity and magnitude of the endo-exo thermal events detected by DSC are related to the strain at breaking and elasticity of polylactide textured multifilamentsPostprint (published version

Streitkultur und Öffentlichkeit im konfessionellen Zeitalter (Volume 95, Edition 1)

Öffentlich ausgetragene Debatten gehören zu den Grundmerkmalen moderner Gesellschaften. Eine entwickelte »demokratische Streitkultur« gilt mithin geradezu als Voraussetzung für das Funktionieren einer Demokratie. Die dieser Wahrnehmung oft implizit zu Grunde liegende These vom »Strukturwandel der Öffentlichkeit« ist in den letzten Jahrzehnten von Seiten der Geschichtswissenschaft verschiedentlich relativiert worden.Was hatten diese unterschiedlichen Formen des öffentlich ausgetragenen Streits gemeinsam? Inwieweit prägten und strukturierten sie die jeweilige(n) historische(n) Öffentlichkeit(en)? Wie wurde das Phänomen des Streits von den Zeitgenossen jeweils wahrgenommen und bewertet? Lassen sich diesbezüglich signifikante Unterschiede zur Zeit der frühen Reformation oder der Frühaufklärung konstatieren? Gab es so etwas wie eine spezifische Streitkultur des konfessionellen Zeitalters

Trehalose Metabolism: From Osmoprotection to Signaling

Trehalose is a non-reducing disaccharide formed by two glucose molecules. It is widely distributed in Nature and has been isolated from certain species of bacteria, fungi, invertebrates and plants, which are capable of surviving in a dehydrated state for months or years and subsequently being revived after a few hours of being in contact with water. This disaccharide has many biotechnological applications, as its physicochemical properties allow it to be used to preserve foods, enzymes, vaccines, cells etc., in a dehydrated state at room temperature. One of the most striking findings a decade ago was the discovery of the genes involved in trehalose biosynthesis, present in a great number of organisms that do not accumulate trehalose to significant levels. In plants, this disaccharide has diverse functions and plays an essential role in various stages of development, for example in the formation of the embryo and in flowering. Trehalose also appears to be involved in the regulation of carbon metabolism and photosynthesis. Recently it has been discovered that this sugar plays an important role in plant-microorganism interactions

Sperm protein 17 is expressed in human nervous system tumours

BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells

Risk and safety requirements for diagnostic and therapeutic procedures in allergology : World Allergy Organization Statement

Peer reviewe

Inactivation of alpha1-antiproteinase (alpha1-AT) and changes in antioxidants plasma levels in subarachnoid hemorrhage

Recent studies have suggested that a quantitative or a qualitative imbalance between the activity of proteases and its inhibitors hypothetically might be involved in intracranial aneurysm rupture. In the present study we test the hypothesis that the systemic reduction of α1-antitrypsin activity might be related to the elevated oxidative potential exerted by cigarette smoking and/or to a systemic low antioxidant capacity. We studied, in a series of 57 patients bearing intracranial aneurysms, the relationship between α1-antitrypsin activity, cigarette smoking and the following variables measured in plasma: vitamin A, vitamin E, thiol groups, urate and lipid peroxide levels. Serum levels of α1-antitrypsin are higher in patients with subarachnoid hemorrhage than in cases of unruptured aneurysms, while the levels of vitamin A and vitamin E are significantly lower in patients that suffered subarachnoid hemorrhage than in controls. Both vitamin A and E levels are related to the occurrence of rupture of the aneurysm, as elicited by logistic regression analysis (P=0.017 and P=0.014, respectively), with a protective effect of higher levels of the variables, as shown by their odds ratio (0.028 and 0.84, respectively). No significant changes in the strength of the association could be appreciated when controlling for smoking habit. None of the other tested variables could be related to the occurrence of the aneurysm rupture. Both α1-antitrypsin serum level and the level of vitamin A appeared to be independently related to α1-antitrypsin collagenase inhibitory capacity percentage (P=0.03 and P=0.025), with no independent influence of the type of aneurysm and the smoking habit. The results of the present study show that the qualitative pattern of α1-antitrypsin is significantly related to the serum level of liposoluble vitamin A, while the type of aneurysm and the smoking habit have no independent influence. This suggests that in a situation in which systemic levels of vitamin A are reduced, the risk of a reduced activity of α1-antitrypsin as controller of proteases is elevated, with the consequent increased risk of aneurysm bleedin