Transfer of efficient anti-melanocyte T cells from vitiligo donors to melanoma patients as a novel immunotherapeutical strategy

BACKGROUND: Vitiligo is a relatively common progressive depigmentary condition that is believed to be due to the autoimmune-mediated loss of epidermal melanocytes. High frequencies of self-reactive T lymphocytes directed toward melanocyte differentiation antigens are found in vitiligo patients and might be directly responsible for the pathogenesis of the disease. An interesting aspect of vitiligo is its relation to melanoma: cytotoxic T lymphocytes directed to self antigens shared by normal melanocytes and melanoma cells are found in both conditions, but the resulting immune reactions are completely different. From this standpoint, the selective destruction of pigment cells that occurs in cases of vitiligo is the therapeutic goal sought in melanoma research. PRESENTATION OF THE HYPOTHESIS: Our working hypothesis is that vitiligo patients might represent a unique source of therapeutic cells to be used in allo-transfer for HLA-matched melanoma patients. The adoptive transfer of ex-vivo generated autologous tumor-specific T cells is a therapy that has met with only limited success, essentially because of inability to isolate therapeutically valuable T cells from the majority of tumor patients. Ideally, model systems where strong and efficient responses against the same (tumor) antigens are achieved would represent a better source of therapeutic cells. We believe it is possible to identify one such model in the melanoma-vitiligo dichotomy: T lymphocytes specific for different melanocyte differentiation antigens are found in vitiligo and represent the effective anti-melanocyte reactivity that is often ineffective in melanoma. TESTING THE HYPOTHESIS: Melanocyte-specific T cell clones can be isolated from the peripheral blood of vitiligo patients and tested for their capacity to efficiently expand in vitro without loosing their cytotoxic activity and to migrate to the skin. Cytotoxicity against melanoma patients' non-tumor cells can also be tested. In addition, it would be interesting to attempt an in vivo animal model. If the results obtained from these validation steps will be satisfactory, it might be possible to plan the clinical grade preparation of relevant clones for transfer. IMPLICATIONS OF THE HYPOTHESIS: When translated into a clinical trial, the possibility of in vitro selecting few effective tumor-specific T cell clones for infusion, inherent with this approach, could enhance the therapeutic graft-versus-tumor effect while possibly decreasing the risk of graft-versus-host disease

Hydrological Effectiveness of an Extensive Green Roof in Mediterranean Climate

In urban water management, green roofs provide a sustainable solution for flood risk mitigation. Numerous studies have investigated green roof hydrologic effectiveness and the parameters that influence their operation; many have been conducted on the pilot scale, whereas only some of these have been executed on full-scale rooftop installations. Several models have been developed, but only a few have investigated the influence of green roof physical parameters on performance. From this broader context, this paper presents the results of a monitoring analysis of an extensive green roof located at the University of Calabria, Italy, in the Mediterranean climate region. To obtain this goal, the subsurface runoff coefficient, peak flow reduction, peak flow lag-time, and time to the start of runoff were evaluated at an event scale by considering a set of data collected between October 2015 and September 2016 consisting of 62 storm events. The mean value of subsurface runoff was 32.0% when considering the whole dataset, and 50.4% for 35 rainfall events (principally major than 8.0 mm); these results indicate the good hydraulic performance of this specific green roof in a Mediterranean climate, which is in agreement with other studies. A modeling approach was used to evaluate the influence of the substrate depth on green roof retention. The soil hydraulics features were first measured using a simplified evaporation method, and then modeled using HYDRUS-1D software (PC-Progress s.r.o., Prague, Czech Republic) by considering different values of soil depth (6 cm, 9 cm, 12 cm, and 15 cm) for six months under Mediterranean climate conditions. The results showed how the specific soil substrate was able to achieve a runoff volume reduction ranging from 22% to 24% by increasing the soil depth

IMPACT OF PHYSICAL EXERCISE ON PSYCHOLOGICAL WELL-BEING AND PSYCHIATRIC DISORDERS

Background: Physical exercise is one of the major features of human health, as it is involved in several physiological processes and related to major benefits in reducing body fat, myocardial infarction, hypertension and insulin resistance risk. Physical exercise also plays a positive role in achieving psychological well-being that can be defined as a state of happiness and serenity, with low levels of distress, overall good physical and mental health and outlook and a good quality of life. Aim of the paper: To review the positive effects of physical activity on psychological well-being and its possible neurobiological underpinnings, as well as its impact on several neuropsychiatric disorders, such as depression, anxiety, eating disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, schizophrenia and some neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Methods: The PubMed, Scopus, Embase, PsycINFO and Google Scholar databases were searched for full text articles published in the latest thirty years on the benefits that physical activity exerts on psychological well-being. Objectives: This study aims to identify the common and differential elements of the DLD (SLI) and LD through a quantitative and qualitative analysis. Results: An impressive amount of data support the positive role of physical activity on psychological well-being and a large amount of research has focused on its beneficial effects in improving the symptoms of the main neuropsychiatric disorders, while highlighting its usefulness as an adjuvant option to psychopharmacological treatments and psychotherapy. In particular, exercise would deeply affect CNS morphology and function, through heterogeneous mechanisms including, amongst the others, the production of hormones, neurotransmitters and neurotrophins, the promotion of angiogenesis and neuroplasticity, and the regulation of gene expression. Conclusion: Literature indicates that the promotion of physical activity may work like an adjunctive and/or augmentation strategy to enhance drugs or psychological treatments, or even as an alternative option in major depression

Management of Osteoporosis in Men: A Narrative Review

Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women

Chronotropic Incompentence and Functional Capacity in CHF

SUMMARY Aim: To assess the effect of chronotropic incompetence on functional capacity in chronic heart failure (CHF) patients, as evaluated as NYHA and peak oxygen consumption (pVO2), focusing on the presence and dose of β-blocker treatment. Methods: Nine hundred and sixty-seven consecutive CHF patients were evaluated, 328 of whom were discarded because they failed to meet the study criteria. Of the 639 analyzed, 90 were not treated with β-blockers whereas the other 549 were. The latter were further subdivided in high (n = 184) and low (n = 365) β-blockers daily dose group in accordance with an arbitrary cut-off of 25 mg for carvedilol and of 5 mg for bisoprolol. Failure to achieve 80% of the percentage of maximum age predicted peak heart rate (%Max PHR) or of HR reserve (%HRR) constituted chronotropic incompetence. Results: No differences were found in NYHA or pVO2 between patients with and without β-blockers and, similarly, between high and low β-blocker dose groups. Twenty and sixty-nine percent of not β-blocked patients showed chronotropic incompetence according to %Max PHR and %HRR, respectively, whereas this prevalence rose to 61% and 84% in those on β-blocker therapy. Patients taking β-blockers without chronotropic incompetence, as inferable from both %Max PHR and %HRR, showed higher NYHA and pVO2 regardless of drug dose, whereas, in not β-blocked patients, only %HRR revealed a difference in functional capacity. At multivariable analysis, HR increase during exercise (ΔHR) was the variable most strongly associated to pVO2 (β: 0.572; SE: 0.008; P < 0.0001) and NYHA class (β: −0.499; SE: 0.001; P < 0.0001). Conclusions: ΔHR is a powerful predictor of CHF severity regardless of the presence of β-blocker therapy and of β-blocker daily dose

Management of Urban Waters with Nature-Based Solutions in Circular Cities—Exemplified through Seven Urban Circularity Challenges

Nature-Based Solutions (NBS) have been proven to effectively mitigate and solve resource depletion and climate-related challenges in urban areas. The COST (Cooperation in Science and Technology) Action CA17133 entitled “Implementing nature-based solutions (NBS) for building a resourceful circular city” has established seven urban circularity challenges (UCC) that can be addressed effectively with NBS. This paper presents the outcomes of five elucidation workshops with more than 20 European experts from different backgrounds. These international workshops were used to examine the effectiveness of NBS to address UCC and foster NBS implementation towards circular urban water management. A major outcome was the identification of the two most relevant challenges for water resources in urban areas: ‘Restoring and maintaining the water cycle’ (UCC1) and ‘Water and waste treatment, recovery, and reuse’ (UCC2). s Moreover, significant synergies with ‘Nutrient recovery and reuse’, ‘Material recovery and reuse’, ‘Food and biomass production’, ‘Energy efficiency and recovery’, and ‘Building system recovery’ were identified. Additionally, the paper presents real-life case studies to demonstrate how different NBS and supporting units can contribute to the UCC. Finally, a case-based semi-quantitative assessment of the presented NBS was performed. Most notably, this paper identifies the most typically employed NBS that enable processes for UCC1 and UCC2. While current consensus is well established by experts in individual NBS, we presently highlight the potential to address UCC by combining different NBS and synergize enabling processes. This study presents a new paradigm and aims to enhance awareness on the ability of NBS to solve multiple urban circularity issues.publishedVersio

Mediterranean monitoring and forecasting operational system for Copernicus Marine Service

The MEDiterranean Monitoring and Forecasting Center (Med-MFC) is part of the Copernicus Marine Environment Monitoring Service (CMEMS, http://marine.copernicus.eu/), provided on an operational mode by Mercator Ocean in agreement with the European Commission. Specifically, Med MFC system provides regular and systematic information about the physical state of the ocean and marine ecosystems for the Mediterranean Sea. The Med-MFC service started in May 2015 from the pre-operational system developed during the MyOcean projects, consolidating the understanding of regional Mediterranean Sea dynamics, from currents to biogeochemistry to waves, interfacing with local data collection networks and guaranteeing an efficient link with other Centers in Copernicus network. The Med-MFC products include analyses, 10 days forecasts and reanalysis, describing currents, temperature, salinity, sea level and pelagic biogeochemistry. Waves products will be available in MED-MFC version in 2017. The consortium, composed of INGV (Italy), HCMR (Greece) and OGS (Italy) and coordinated by the Euro-Mediterranean Centre on Climate Change (CMCC, Italy), performs advanced R&D activities and manages the service delivery. The Med-MFC infrastructure consists of 3 Production Units (PU), for Physics, Biogechemistry and Waves, a unique Dissemination Unit (DU) and Archiving Unit (AU) and Backup Units (BU) for all principal components, guaranteeing a resilient configuration of the service and providing and efficient and robust solution for the maintenance of the service and delivery. The Med-MFC includes also an evolution plan, both in terms of research and operational activities, oriented to increase the spatial resolution of products, to start wave products dissemination, to increase temporal extent of the reanalysis products and improving ocean physical modeling for delivering new products. The scientific activities carried out in 2015 concerned some improvements in the physical, biogeochemical and wave components of the system. Regarding the currents, new grid-point EOFs have been implemented in the Med-MFC assimilation system; the climatological CMAP precipitation was replaced by the ECMWF daily precipitation; reanalysis time-series have been increased by one year. Regarding the biogeochemistry, the main scientific achievement is related to the implementation of the carbon system in the Med-MFC biogeochemistry model system already available. The new model is able to reproduce the principal spatial patterns of the carbonate system variables in the Mediterranean Sea. Further, a key result consists of the calibration of the new variables (DIC and alkalinity), which serves to the estimation of the accuracy of the new products to be released in the next version of the system (i.e. pH and pCO2 at surface). Regarding the waves, the system has been validated against in-situ and satellite observations. For example, a very good agreement between model output and in-situ observations has been obtained at offshore and/or well-exposed wave buoys in the Mediterranean Sea.PublishedVienna3SR. AMBIENTE - Servizi e ricerca per la Societ

Multicentre harmonisation of a six-colour flow cytometry panel for naïve/memory T cell immunomonitoring

Background. Personalised medicine in oncology needs standardised immunological assays. Flow cytometry (FCM) methods represent an essential tool for immunomonitoring, and their harmonisation is crucial to obtain comparable data in multicentre clinical trials. The objective of this study was to design a harmonisation workflow able to address the most effective issues contributing to intra- and interoperator variabilities in a multicentre project. Methods. The Italian National Institute of Health (Istituto Superiore di Sanita, ISS) managed a multiparametric flow cytometric panel harmonisation among thirteen operators belonging to five clinical and research centres of Lazio region (Italy). The panel was based on a backbone mixture of dried antibodies (anti-CD3, anti-CD4, anti-CD8, anti-CD45RA, and anti-CCR7) to detect naive/memory T cells, recognised as potential prognostic/predictive immunological biomarkers in cancer immunotherapies. The coordinating centre distributed frozen peripheral blood mononuclear cells (PBMCs) and fresh whole blood (WB) samples from healthy donors, reagents, and Standard Operating Procedures (SOPs) to participants who performed experiments by their own equipment, in order to mimic a real-life scenario. Operators returned raw and locally analysed data to ISS for central analysis and statistical elaboration. Results. Harmonised and reproducible results were obtained by sharing experimental set-up and procedures along with centralising data analysis, leading to a reduction of cross-centre variability for naive/memory subset frequencies particularly in the whole blood setting. Conclusion. Our experimental and analytical working process proved to be suitable for the harmonisation of FCM assays in a multicentre setting, where high-quality data are required to evaluate potential immunological markers, which may contribute to select better therapeutic options