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SGLT2–i have been shown to improve prognosis in patients with heart failure with reduced ejection fraction (HFrEF) in randomized clinical trials (RCTs). However, at the moment, we have little data on the use of these drugs in clinical practice, both in terms of safety and efficacy profile. Objectives To describe the characteristics of HFrEF outpatients who started SGLT2–i in clinical practice; evaluate tolerability and the effect on clinical and biohumoral parameters. Methods We prospectively analyzed patients who started SGLT2–i in our Heart Failure clinic. The baseline characteristics, the variations of bio–humoral and clinical parameters were recorded, as well as the onset of adverse effects leading to drug suspension after one month. Results We evaluated 37 patients, with a mean age of 77.7± 8.5 years (65% over 75). The baseline characteristics of the population compared to that of the treatment arms of the RCTs are shown in Fig.1. Most patients were in NYHA II (62%), with ischemic etiology (65%), with reduced EF (mean 34.7± 5.1%) and nearly half of the patients received ICD or CRT–D (43.2%). At the one month follow–up, there was a significant reduction in NYHA class (Fig. 2)and furosemide dose (36.3 vs 53.2 mg, p Conclusions In this preliminary analysis, after one month of SGLT2–i therapy in elderly patients, there was a clinical and hemodynamic improvement as demonstrated by the improvement of the NYHA class and the reduction of the diuretic therapy. SGLT2–i have been shown to be relatively safe, with no adverse effects and no increased risk of orthostatic hypotension or significant worsening of renal function.

In July 2022 C.M., a 58–year–old woman, was admitted to our Heart Failure Outpatient Clinic. Patient with permanent AF undergoing DOAC therapy, previous double mitral and tricuspid valve replacement with bioprosthesis. As comorbidities she had stage IIIb CKD, previous ischemic stroke without outcome, multifactorial anaemia, asthma, ulcerative rectocolitis non–responsive to biological therapy. Since April 2022 progressive reduction in exercise tolerance with dyspnoea for previously well–tolerated exertion, with finding of severe left ventricular systolic dysfunction (FE 25%) due to widespread hypokinesia previously unknown. In September angiographic control confirmed the absence of coronary artery disease. Amiodarone therapy was started for frequent runs of VT. Cardiac MRI confirmed FE 27% with fibrosis of the interventricular septum and lower basal wall of non–ischemic appearance. In view of the clinical–instrumental findings, a single–chamber ICD pacemaker was implanted and the therapy for heart failure with reduced FE was optimised with the introduction of Sacubitril/Valsartan (later discontinued due to hypotension), MRA and SGLT2–I (Empagliflozin). Due to the persistence of labile haemodynamic compensation, an indication was given to perform three cycles of Levosimendan infusion at our Day Hospital. The routine EGA taken during the first infusion cycle showed metabolic acidosis in the absence of significant worsening of renal function (Fig. 1) with mild hypobicarbonatemia and electrolytes in the normal range. On the assumption that the acidosis was secondary to the introduction of SGLT2–I (about two months earlier), Empagliflozin was discontinued. One week after discontinuation, the control EGA (Fig. 1) showed resolution of the acidosis, with a substantially stable glomerular filtrate, so that discontinuation of the drug was confirmed. Conclusions In the literature there are reviews and case reports of euglycaemic diabetic ketoacidosis (euDKA) in DM2 patients on SGLT2–I therapy although there are currently only hypotheses regarding the pathophysiological mechanism. The possibility of inducing acidosis with hypobicarbonatemia in the absence of worsening renal function is unclear. A ‘Fanconi–like‘ mechanism could be hypothesised with induction of type 2 tubular acidosis with bicarbonate loss due to glycosuria.

Introduction Heart failure (HF) is a risk factor for postoperative mortality in major non–cardiac surgery. Collaboration between the Multimodal Preoperative Prehabilitation unit (MPP) and Heart Failure Clinic (HFC) could allow optimization of heart failure therapy and negative prognostic factors such as reduced functional capacity (FC), malnutrition, and sarcopenia to improve the prognosis of these patients. Case report: Mrs. C.M. is a 58–year–old patient who presents to the MPP unit in anticipation of total colectomy for drug–refractory ulcerative colitis. Mrs. C.M. has a past medical history significant for heart failure with reduced ejection fraction (EF 25%) of presumably valvular–arrhythmic etiology. She underwent tricuspid annuloplasty and mitral replacement surgery some years ago and is affected by atrial fibrillation. At the MPP unit, Mrs. C.M. had a reduced FC and was malnourished and sarcopenic. Blood tests showed iron deficiency anemia. Heart failure therapy (NYHA II) was not optimized according to guidelines. Therefore, the patient started multimodal prehabilitation consisting of aerobic and resistance exercise, nutritional intervention, intravenous iron infusion, and optimization of HF therapy. After the patient was evaluated at the HFC, she started empagliflozin, sacubitril/valsartan, and ranolazine; intermittent levosimendan therapy was also performed. She also underwent cardiac NMR, which showed non–ischemic fibrosis, and coronary angiography, which was negative. Finally, she underwent PM–ICD implantation. After six months of multimodal prehabilitation, there was an increase in EF (38% vs. 25%), a reduction in NT–proBNP (700 vs 4988 pg/mL), and mitigation of HF symptoms. There was also a marked improvement in FC (383 vs 269 meters at 6–minute walking test), nutritional status (stage B vs stage C at PG–SGA test), and muscle strength (handgrip strength test 14.6 vs 8.5 kg). Considering the excellent preoperative optimization response, it was decided to proceed with surgery after a collegial discussion (anesthetist, heart failure cardiologist, surgeon, and patient). Conclusions Multimodal preoperative prehabilitation, based on the collaboration between the Multimodal Preoperative Prehabilitation Unit and Heart Failure Clinic, can effectively improve the preoperative functional capacity of HF patients.

Heart failure (HF), despite new therapeutic strategies, remains a condition characterized by an inauspicious prognosis and poor quality of life. The management of advanced and then terminal SC proves to be a current challenge, especially in elderly patients. A.C, 87 years old is autonomous and cognitively intact (BADL preserved 5/6, MMSE 28/30). In June ‘21 femur fracture complicated by cerebral hemorrhage (no relics) and anterior STEMI (FE 25%). Not performed coronarography (contraindication to antiplatelet therapy). Discharged to NYHA II with ARNI, MRA and beta blocker. After 1 month hospitalized for HF in the course of AF, performed infusion of levosimendan. In September ‘21 taken over by our "HF clinic" with progressive titration of therapy and insertion of SGLT2–i. In January ‘22 due to precarious clinical compensation (NYHA III–IV) progressive increase in furosemide dosage and undertaken sequential nephron blockade with metolazone, with good response. Given advanced–HF situation, performed Levosimendan infusions under DH regimen (8 h; 0.05–>0.2 mcg/Kg/min; three times every 2 weeks) with clinical stabilization. In April, hospitalization for decompensation flare–up with worsening creatinine (0.8 >>>2 mg/dL). On discharge, given the precarious compensation, activated the "Hospital–Territory Rapid Intervention Group" with home diuretic infusions and stabilization of the clinical picture and subsequent new referral from the "heart failure clinic" with monthly FU. By November 2022, clinical (NYHA IV with diuretic resistance), cognitive and functional (MMSE 22/30, BADL preserved 2/6) worsening. Evaluated as an end–stage scenario (in the absence of further treatment options), family interview was performed, home nursing service activated for infusions of furosemide, and referred to the palliative care service to assist the patient in the terminal phase of illness at home (Fig. 1). Conclusion in order to ensure the best quality of life in the terminal phase of the disease, the management of advanced SC in the elderly patient must involve individualization of the care pathway, through multidimensional assessment of the patient and sharing of goals at the different stages: from intensive FU with optimization of therapy in the early stages to early activation of home and palliative care services in the more advanced stages.

Hyperkalimia (HK) is a condition that occurs very frequently in patients with heart failure (HF). HK often limits and discourages the implementation and optimization of RAASI therapy in patients with HFrEF. The introduction of the new K–binders drugs has made it possible to overcome this obstacle by allowing optimization of therapy even in patients with persistent hyperkalemia. Mr. AB aged 83 years cognitively intact and autonomous ( Katz‘s BADL and Lawton‘s IADL preserved; MMSE 29/30). February 2022 accessed DEA for aggravating exertional dyspnea; at that time echocardiogram finding reduced left ventricular systolic function, FE 35%. March 2022 performed elective coronarography: coronary tree free of critical lesions, confirmed on echocardiogram reduced FE. Post indication to undertake Sacubitril/Valsartan, beta blocker and SGLT2i therapy. For moderate CKD (eGFR 33 ml/min) with tendency to hyperkalemia not initiated MRA. April 2022 the patient was taken to our Heart Failure Outpatient Clinic–UTIG– AOU Careggi. June 2022 considered improvement in renal function and Kaliemia in optimized range GDMTs therapy with Potassium Canreonate 25 mg/day. At control EEs in July 2022 found hyperKalemia with K values 5.5 mEq/L but stability of renal function. Reduced therefore the dosage of Potassium Canreonate (25 mg every other day) with indication to repeat blood tests soon. September 2022 despite reduction in MRA dosage further increase in Kaliemia values to 5.8 mEq/L. Suspended Potassium Canreonate and started Sodium Zirconium Cyclosilicate therapy initially at loading dosage of 10 g three times daily for two days then continued with maintenance dosage of 5 g. At follow–up performed the following week K 4.5 mEq/L. Re–introduced Potassium Canreonate 25 mg/day with initial tight control of potassium values that remained stably at optimal values. Hyperkalemia is an obstacle in titrating HFrEF, especially in elderly patients with CKD. However, we have new drugs available that may allow the implementation of guideline–recommended treatments by controlling potassium values.

Background Intermittent infusions of Levosimendan (L) have been shown to reduce hospitalizations and improve quality of life in patients with advanced heart failure (HF). "Real–world" experience is currently insufficient, particularly in older patients. Purpose: Since November 2020 we treated elderly outpatients with advanced HF with repeated L infusions. Here, we present the preliminary analysis of the collected data. Methods The protocol involves three infusions of L given 14 days apart. The duration of each session was approximately 8 hours. The starting infusion rate is 0.05 μg/Kg/min, titrated every 30/60‘ to a maximum of 0.2 μg/Kg/min based on blood pressure, heart rate and rhythm recorded on telemetry. We evaluated patients by clinical, labatorily and echocardiographic at baseline and two weeks after the end of treatment. Results The treated population had a mean age of 79 years, a long history of disease (mean 12 years) and high comorbidities (mean Charlson Comorbidity Index of 6.8). As shown in Table 1, we compared our population with that of leading international trials on this type of treatment, and we found that our population was significantly older and more complex. Of the 19 patients enrolled, 15 completed the expected treatment of infusions while 4 were lost due to hospitalizations for cardiovascular causes and/or social issues. In the 50 infusions performed, we observed good tolerance to the therapy with a failure rate of 2 % and good safety profile in the absence of major adverse effects, particularly in terms of arrhythmias (Figure 1). At the end of the infusion cycles, there was significant improvement of clinical and hemodynamic parameters (Figure 2). Moreover, we found a decrease in systemic congestion in terms of VD–AD gradient reduction (p=0.031) associated with a downward trend in average daily furosemide dose, clinical congestion scores and mean NTproBNP value. Conclusions Our preliminary analysis seems to confirm the safety and tolerability of the developed treatment scheme. Further data are needed to confirm its efficacy in clinical, hemodynamic, and therapy effects.

Background After the lockdown imposed by the COVID19 pandemic, physicians had to limite ambulatory visits to exceptional cases to reduce interpersonal contact. We structured a telephone follow–up developing a standardized 23 item questionnaire to administrate to our HF outpatient clinic and from whom we obtained the Covid–19–HFscore. Methods The patients were identified by a numeric code, date of birth and gender. The questionnaire was designed for rapid administration during telephone interview (on average 6 minutes) and was administered directly by physicians to patients and/or to their caregiver. It was built to reproduce our usual clinical evaluation. Results As shown in Figure 1, we investigated seven domains: 1) social and functional condition 2) mood 3) adherence to pharmacological and non–pharmacological recommendations (blood pressure, heart rate, weight monitoring and fluid intake control) 4) clinical and hemodynamic status 5) recording of laboratory tests 6) current pharmacological treatment 7) recent evaluation by family physician or need to contact emergency services followed or not by hospitalisation. General and pharmacological recommendations as well as the following telephone contact were finally recorded. To determine the timing of the next telephonic evaluation, we decided to weight questions regarding clinical and hemodynamic status, adherence to pharmacological and non–pharmacological recommendations, therapeutic changes and need for hospitalisation by scoring the answers (from 1 to 3) to build a score. The sum of individual scores represented the novel TeleHFCovid19–score, ranging from 0 to 29. Based on such score, three groups of patients were identified by arbitrary cut–off levels: the green (score Conclusion During this emergency situation this questionnaire could be a useful clinical tool to help physicians maintaining a regular FU of their patients and identifying patients at greatest risk of imminent instability. Furthermore, this instrument could also represent a useful resource in the management of low–risk HF patients.

Background The use of intermittent infusion of Levosimendan (L) demonstrated to be able to reduce hospitalisations and to improve functional capacity and quality of life in patients with advanced heart failure (HF). Purpose To describe our preliminary experience regarding L intermittent infusions in advanced HF older outpatients. Methods A maximum of three consecutive L infusions were carried out 14 days apart. The duration of each session was 8 hours. The starting infusion rate was 0.05 μg/Kg/min, titrated every 30/60‘ up to a maximum of 0.2 μg/Kg/min based on blood pressure, heart rate and arrhythmias recorded during telemetry. We evaluated patients by clinical, laboratory and echocardiographic controls at baseline and two weeks after the end of treatment. Results Since November 2020 we enrolled 17 patients with a mean age of 77 years; 12% were women. HF etiology was ischemic in 64% of cases and the mean ejection fraction was 30%. A total of 41 infusions were performed, the mean dose of L administered was 5.4 mg/infusion. Three patients did not complete the expected treatment, one due to an intercurrent COVID–19 infection and two because of social issues. In 28 sessions the maximum infusion rate was reached, while in 12 a lower rate; in one case drug infusion was suspended (Figure 1). The main complication observed was marked non–symptomatic hypotension, followed by the onset of atrial fibrillation or frequently ventricular extrasystole. As shown in Figure 2, at the end of the infusion cycles, there was an improvement of clinical and hemodynamic parameters. Moreover, at the end of the infusion cycles, we observed a reduction in the mean dose of loop diuretic prescribed and an increase in the prescription of disease–modify treatment, according to HF guidelines (Figure 3). Conclusions In our preliminary experience repeated infusions of L appear to be well tolerated in older patients with advanced HF. Although there was an improvement in congestion parameters and targeted therapy for HF, more data will be needed in the future to confirm its safety and efficacy, also in terms of guidelines–directed medical therapy.

Introduction The Coronavirus Disease (COVID–19) pandemic and its consequences has forced physicians to develop telematic methods in order to follow up patients with cronic diseases, such as heart failure (HF). Objectives To evaluate TeleHFCovid–19 score as a mid–term (six months) prognostic score in terms of prediction of hospitalitazion and cardiovascular mortality in patients with chronic HF during Covid–19 pandemic. Methods During COVID–19 pandemic (from March 2020 to May 2020), we were forced to cancel nearly all follow–up checks in our HF outpatient clinic. We hence standardized a telephone follow–up by developing a questionnaire (Fig. 1) from which we then obtained a score, later called the “TeleHFCovid–19 score” (0–29). This score stratified patients in three risk score groups: green (0–3), yellow (4–8), and red (≥9), for which the next telefonic evaluation was planned after 4, 2 and 1 weeks, respectively. Results 146 patients were enrolled: 112 were classified as green, 21 as yellow and 13 as red. Mean age was 81 years, females were 40%. Approximately one third had EF Conclusions The TeleHFCovid–19 score was able to correctly identify patients with good outcomes at six months. Furthermore, it has the ability to stratify the adverse event risk and this could represent a useful tool to appropriately schedule the reevaluation timing of these patients and to identify those who may need urgent hospital evaluation.

Background Although older patients with heart failure (HF) with reduced ejection fraction enrolled in PARADIGM–HF showed a good tolerance to sacubitril/valsartan (Sa/Va), more real–word data are needed to define their tolerability in this population. Aim: To describe the Sa/Va tolerability and titration in older HFrEF patients followed by our HF outpatient. Methods HFrEF patients aged ≥65 years and treated with Sa/Va from November 2016 to June 2021 were enrolled, assessing Sa/Va tolerability at six months and its clinical and hemodynamic effects. Results We enrolled 101 patients with a mean age of 78 years (⁓20% female). The aetiology was ischemic in 59% of cases while the mean ejection fraction was 31%. Sa/Va was prescribed at the starting dose (24/26mg) and intermediate dose (49/51mg) in 91% and 9% of cases, respectively. After six months, 9 of the 100 patients still alive had discontinued treatment with Sa/Va (4 for symptomatic hypotension, 3 for suspected allergic reaction and 2 for worsening renal function). Of the 91 patients still on therapy, only 17 had reached the target dose (97/103mg) while 28 were at the intermediate dose (Figure 1). Symptomatic hypotension (62%), hyperkalaemia (15%) and worsening of renal function (4%) were the main causes of maintaining Sa/Va therapy at the starting dose; note, in 15% of cases a specific cause of non–titration was not identified. Comparing HF treatment between starting dose vs higher–dose patients, after six months in low–dose patients there was a slight improvement in mineralcorticosteroid receptor antagonist (MRA) prescription and in combination therapy (Sa/Va, beta–blocker and MRA) while in patients at higher–doses there was a significant decrease (Figure 2). In patients still receiving Sa/Va, significant clinical improvement was observed while renal function, K+ levels and systolic blood pressure remained stable (Figure 3). Conclusions After six months of treatment, Sa/Va was well tolerated in most of our older patients and used in combination with a beta–blocker and an MRA in a high percentage of cases, although a reduction in MRA prescription is observed in patients taking higher dosages of Sa/Va. In addition, there was a marked improvement in the clinical variables.

The demand of powertrain technologies able to efficiently employ several non-fossil fuels types, as bio or synthetic ones, compels to develop simplified strategies to accelerate the engines industrial optimization. High-tumble ultra-lean SI engines are currently an attractive option, thanks to their fuel flexibility and the potential of extending the lean combustion limit with novel ignition strategies. This work presents a methodology to initialize tumble flow fields at closed-valves inside pent-roof SI engines, without the need of simulating the gas exchange process. First, assuming an elliptical-shaped vortex, a velocity field is initialized into the cylinder according to the target tumble ratio at inlet valve closing (IVC). Then, the flow field is evolved at fixed piston position for a time duration proportional to the integral time scale of turbulence. This process is essential to adapt the vortex morphology to the surrounding geometrical details, despite some kinetic energy is lost due to frictions. To compensate this last effect, the velocity field is re-scaled at the end of the process to match the initial tumble ratio. Finally, the parameters affecting the tumble initialization are calibrated by comparing the development of the flow-field during the compression stroke with the results from a full-cycle simulation in a pent-roof SI engine. The methodology is validated on the Darmstadt optical engine. First, the numerical velocity fields are compared against PIV measurements at different crank-angles. Then, the combustion prediction is also evaluated, to assess the quality of the initialized tumble flow field. The achieved results are satisfactory, demonstrating the industrial applicability of the presented methodology.

Interkingdom communication between bacteria and host organisms is one of the most interesting research topics in biology. Quorum sensing molecules produced by Gram-negative bacteria, such as acylated homoserine lactones and quinolones, have been shown to interact with host cell receptors, stimulating innate immunity and bacterial clearance. To our knowledge, there is no evidence that these molecules influence CNS function. Here, we have found that low micromolar concentrations of the Pseudomonas aeruginosa quorum sensing autoinducer, 2-heptyl-3-hydroxy-4-quinolone (PQS), inhibited polyphosphoinositide hydrolysis in mouse brain slices, whereas four selected acylated homoserine lactones were inactive. PQS also inhibited forskolin-stimulated cAMP formation in brain slices. We therefore focused on PQS in our study. Biochemical effects of PQS were not mediated by the bitter taste receptors, T2R4 and T2R16. Interestingly, submicromolar concentrations of PQS could be detected in the serum and brain tissue of adult mice under normal conditions. Levels increased in five selected brain regions after single i.p. injection of PQS (10 mg/kg), peaked after 15 min, and returned back to normal between 1 and 4 h. Systemically administered PQS reduced spontaneous locomotor activity, increased the immobility time in the forced swim test, and largely attenuated motor response to the psychostimulant, methamphetamine. These findings offer the first demonstration that a quorum sensing molecule specifically produced by Pseudomonas aeruginosa is centrally active and influences cell signaling and behavior. Quorum sensing autoinducers might represent new interkingdom signaling molecules between ecological communities of commensal, symbiotic, and pathogenic microorganisms and the host CNS.

Summary Plitidepsin is a cyclic peptide that inhibits the host protein elongation factor alpha 1, thus blocking viral replication. A hospitalized patient with stage IIIB gastric signet ring cell carcinoma and multiple comorbidities developed Coronavirus disease (COVID-19) shortly after receiving his first chemotherapy course. He was treated with plitidepsin on a compassionate use basis. The patient showed a substantial acute reduction in viral load 4 days after initiating plitidepsin treatment and was negative for SARS-CoV-2 by day 14. Therapy was well-tolerated, and no COVID-19-related complications were observed. The patient was discharged 18 days after plitidepsin treatment having received a full second course of chemotherapy, with only a 1-week delay from the planned schedule.

EFV12 is a small bioactive peptide produced by

Additional file 1. National health record systems.

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe. The workshop participants received funding from the European Union Seventh Program for Research, Technological Development and Demonstration (FP7) and Horizon Research and Innovation Program (H2020) and other European Union programs under the following grant agreements: AETIONOMY (Developing an Aetiology-based Taxonomy of Human Disease—Approaches to Develop a New Taxonomy for Neurological Disorders, IMI-no115568), ANTI-SUPERBUG PCP (ANTISUPERBUG Precommercial Procurement, H2020-no688878), B-CAST (Breast CAncer Stratification understanding the determinants of risk and prognosis of molecular sub-types, H2020-no633784), BRIDGE Health (Bridging information and data generation for evidence-based health policy and research, H2020-no664691), CASyM (Coordinating Action Systems Medicine—Implementation of Systems Medicine across Europe, FP7-n°305033), CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI, FP7-no602150), CECM (Centre for New Methods in Computational Diagnostics and Personalized Therapy, H2020-no763734), COLOSSUS (Advancing a Precision Medicine Paradigm in Metastatic Colorectal Cancer: Systems based patient stratification solutions, H2020-no754923), COMPARE (COllaborative Management Platform for detection and Analyses of (Re-)emerging and foodborne outbreaks in Europe, H2020-no643476), CONNECARE (Personalized Connected Care for Complex Chronic Patients, H2020-no689802), CREATIVE (Collaborative REsearch on ACute Traumatic brain Injury in intensiVe care medicine in Europe, FP7-no602714), DEFORM (Define the global and financial impact of research misconduct H2020-no710246), ECCTR (European Cornea and Cell Transplant Registry, FP7-n°709723), E-COMPARED (European COMPARative Effectiveness Research on online Depression, FP7-no603098), ECRIN-IA (European Clinical Research Infrastructures Network- Integrating Activity, FP7-no284395), EHR4CR (Electronic Health Records Systems for Clinical Research, IMI-no115189) eInfraCentral (European E-infrastructures Services Gateway, H2020-no731049), ELIXIR (European Life-science Infrastructure for Biological Information, FP7-n°211601), ELIXIR-EXCELERATE (Fast track ELIXIR implementation and drive early user exploitation across the life sciences, H2020-no676559), eMEN (e-mental health innovation and transnational implementation platform North West Europe, H2020), EMIF (European Medical Information Framework, IMI-no115372), ERA PerMed (ERA-net Cofund in Personalized Medicine, H2020-no779282), eTRIKS (Delivering European Translational Information and Knowledge Management Services, IMI-1-no115446), EuroPOND (Data-driven models for progression of neurological diseases, H2020-n°666992), EurValve (Personalized Decision Support for Heart Valve disease, H2020-no689617), HBP SGA1/SGA2 (Human Brain Project specific grant agreements, H2020-n°720270/785907), ICT4DEPRESSION (User-friendly ICT tools to enhance self-management and effective treatment of depression in the EU, FP7-n°248778), ImpleMentAll (Towards evidence-based tailored implementation strategies for eHealth, H2020-no733025), INSTRUCT-ULTRA (Releasing the full potential of instruct to expand and consolidate infrastructure services for integrated structural life sciences research, H2020-no731005), MASTERMIND (Management of Mental Disorders through Advanced Technologies, CIP-no621000), MeDALL (Mechanisms of the Development of ALLergy, FP7-n°261357), MedBioinformatics (Creating medically-driven integrative bioinformatics applications focused on oncology, CNS disorders and their comorbidities, H2020-n°634143), MIDAS (Meaningful Integration of Data, Analytics and Services, H2020-no727721), MultipleMS (Multiple manifestations of genetic and non-genetic factors in Multiple Sclerosis disentangled with a multi-omics approach to accelerate personalized medicine, H2020-no733161), myPEBS (Randomized Comparison Of Risk-Stratified versus Standard Breast Cancer Screening European Women Aged 40–74, H2020-no755394), OpenAIRE-Advance (Advancing Open Scholarship, H2020-no777541), OpenMedicine (OpenMedicine, H2020-n°643796), PanCareSurFup (PanCare Childhood and Adolescent Cancer Survival Care and Follow-up Studies, FP7-n°257505), PIONEER (Prostate Cancer DIagnOsis and TreatmeNt Enhancement through the Power of Big Data in EuRope, H2020-IMI-2-n°777492), PREPARE (Platform for European Preparedness Against (Re-)emerging Epidemics, FP7-n°602525), Regions4PerMed (Interregional coordination for a deep and fast uptake of personalized health, H2020-no825812), RD-CONNECT (An integrated platform connecting registries, biobanks and clinical bioinformatics for rare disease research, FP7-no305344), Solve-RD (Solving the unsolved Rare Diseases, H2020-no779257), SPIDIA4P (SPIDIA for Personalized Medicine-Standardization of generic Pre-analytical procedures for In-vitro DIAgnostics for Personalized Medicine, H2020-no733112), SYSCID (A Systems medicine approach to chronic inflammatory disease, H2020-no733100), SysCLAD (Systems prediction of Chronic Allograft Dysfunction, FP7-n°305457), SYSCOL (Systems Biology of Colorectal Cancer, FP7-no258236), SysMedPD (Systems Medicine of Mitochondrial Parkinson’s Disease, H2020-n°668738), U-BIOPRED (Unbiased BIOmarkers for the PREDiction of respiratory disease outcomes, IMI-n°115010), VPH-share (Virtual Physiological Human: Sharing for Healthcare—A Research Environment, FP7-n°269978).

In this study the physicochemical evolution of soot particles in a laminar premixed flame has been investigated. The evolution of the particle size distribution as function of the different heights above the burner has been explored in conjunction with changes of particle chemical/physical properties retrieved by Raman and Electron Paramagnetic Resonance spectroscopy. In addition, the results obtained by Raman spectroscopy on flame formed soot particles were compared to those obtained by analyzing some standard carbon-based materials such as commercial carbon black, activated carbon, disordered graphite and highly oriented pyrolytic graphite.

Synthetic associative acrylic monomers functionalized by oxo alcohol based hydrophobic group have been synthetized and then used in “Hydrophobic Alkali Swellable Emulsion (HASE)”. One of the features of use these associative acrylic monomers resides in that once added into the aqueous phase containing a latex and possessing an alkaline nature, they lead to a phenomenon of increased viscosity over a wide range of shearing gradients without adding a neutralization agent. This constitutes a major asset compared to the conventional HASE polymers, which thickened a medium after adding a neutralization agent to it; such an addition has not possible in the emulsion as it has, as it might increase its viscosity to a level that would make it unworkable [1]. Higher thickening efficiency is achieved by the self-associating properties of the attached hydrophobic groups to the polymer backbone. The importance of HASE polymers is due to the great market demand since they are used in a wide range of industrial applications such as viscosizers, paint formulations, cosmetics, cleaning products and coatings paper [2]. The synthesis of the associative monomers has been carried out by an esterification reaction. The reagents used are methacrylic acid, an ethoxylated alcohol and sulfuric acid to catalyze the reaction. Because the properties of the HASE polymers are certainly related to the structure and composition, several associative acrylic monomers can be synthetized changing the ethoxylated alcohol structure (i.e. number of ethoxy groups, length of alkyl chain, linear or branched chain). The characterization of associative monomers has been performed by acid-base titration and IR spectroscopy for structural information. Another aim of the present work, as mentioned above, is to use these associative monomers synthetized in HASE polymers formulation. An example of the polymeric structure is reported in Figure 1. Figure 1 – Molecular structure of a hydrophobically modified alkali-soluble emulsion polymer. x, y, z are structural parameters. n is the number of poly(ethylene oxide). HASE polymers have been synthetized by emulsion polymerization. In particular, have been synthetize HASE with higher molecular weight, low residual solid and with a correct value of polydispersity index. To characterize the HASE polymers have been performed rheological tests to analyze the increasing of viscosity.

The mechanism by which unilateral testicular torsion leads to injury of the contralateral testis is still controversial. The present study aimed to evaluate immunohistopathological changes in the contralateral testis of rats after acute testicular torsion.40 pubertal rats were randomly divided into 3 groups. Group 1 (n=10) functioned as controls. Group 2 rats (n=10) underwent a sham operation, and Group 3 (n=20) underwent 720° torsion of the left spermatic cord (3 h) followed by detorsion (24 h).Immunofluorescence tests were done to investigate contralateral lesions in half of the animals in Group 3. Nitro blue tetrazolium (NBT) was injected in both testes to identify the presence of oxygen-derived free radicals. 24 h after reperfusion, bilateral samples of the testes were obtained for histological analysis. Fisher's exact test was used for statistical analysis with p-values0.05 considered significant.Immunofluorescence tests were positive for the contralateral (right) testis but with a lower intensity than that of the testis submitted to torsion. NBT reaction was intense all over the left testis while a minor reaction was visible in the right testis. In Group 3 the left distorted testicle showed diffuse edema with cell elimination and extensive necrosis of the seminiferous tubules. Histological lesions were moderate to mild in the contralateral testis.An autoimmune IgG-mediated mechanism deposited on the basement membrane of seminiferous tubules seems to be involved in the genesis of contralateral testis injury.

This paper focuses on the development of a new generation of interoperable simulators of micro activities in a logistics node; the proposed example focuses on a real-time full-scope virtual simulator of port activities able to simulate the activities of the whole port by having ships, cranes, trucks and containers interoperating in a federation. The technologies adopted in terms of architecture and installation were very effective in creating a mobile laboratory open to further extension by online interoperation with other simulators and with biomedical devices for assessing human capabilities within this framework. This approach allows us to face the existing challenges in extending the capabilities of a logistics node over their current capabilities limited by technological and human factors.

Polymers of natural polyphenols have so far received little attention as bioavailable, biocompatible antioxidants for several applications e.g. in packaging and related technologies. Expected advantages with respect to the monomers would include greater chemical stability under processing conditions and lower tendency to be released into the contact medium (food, water, etc.) with reduced adverse effects. As an example we have recently found that a polymer obtained by oxidation of caffeic acid methyl ester is highly efficient in stabilizing polyethylene against oxidative degradation.1 We have also observed that acid treatment significantly improves the antioxidant properties of natural phenolic pigments.2 Herein we report the results of a systematic investigation of the reducing and free radical scavenging properties of bioinspired polymers prepared by horseradish/H2O2 oxidation of a series of natural phenolic compounds (e.g. ferulic acid, caffeic acid and pyrogallol) and of the effects of acid treatment on these properties.3 Both 2,2-diphenylpicrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays indicated a significant increase (up to 230 times) in the antioxidant properties of almost all the phenolic polymers investigated. Details on the structural modifications induced by the acid treatment will be reported. This study furnishes important information to tailor synthetic phenolic polymers as novel easily accessible materials for use in packaging and biomedical applications.

The results of this study support the hypothesis that couples who perceived themselves as having actively participated in the development of their own divorce decrees were more satisfied with their custody and financial arrangements and obligations. These same couples, however, reported more postdivorce conflict with their ex-spouses and more emotional maladjustment. It is concluded that there are costs and benefits attached to self-determined divorce decrees. Such decrees tend to require greater cooperation between ex-spouses, which in turn creates more opportunities for disagreements. Thus more attention needs to be paid to helping couples deal with the strife that is likely to occur after the divorce is final.

Saliva traces in forensic casework can be found in many different samples such as cigarette butts, stamps or balaclavas (Fig. 1). In these cases, we are able to test for saliva presence by a-amylase testing [1] (BNP-Amylase test, Sclavo), an enzymatic method that utilises blocked p-nitrophenyl-maltoheptaoside (BpNPG7) as substrate. The a-amylase (1,4-a-D-glucan glucanhydrolase) catalyses the endohydrolysis of a-1,4 glucosidic linkages to produce p-NP-labelled fragments ( p-NPGn). Glucoamylase (exo-1,4-a-D-glucosidase) and maltase (a-glucosidase) quickly hydrolyse nonreducing ends of the chains, liberating p-nitrophenol; the absorbance of p-nitrophenol ( p-NP), stoichiometrically formed, can be measured at 405 nm. The rate of its liberation is directly proportional to the a-amylase activity in the sample. This test is rapid, highly sensitive and allows forensic scientists to determine exactly and localise saliva traces. When we have a positive response with the a-amylase test, we extract the DNA directly from the same region of the substrate with a modified phenol– chloroform method. We performed over 200 tests with reference saliva samples on cigarette butts, stamps and balaclavas. No differences were observed between a-amylase tested versus nontested samples in DNA recovery and successful STR typing.

Recurrent vaginitis and cystitis are a daily challenge for the woman and the physician. The recurrence worsens the symptoms' severity, increases comorbidities, both pelvic (provoked vestibulodynia, bladder pain syndrome, levator ani hyperactivity, introital dyspareunia, obstructive constipation, chronic pelvic pain) and cerebral (neuroinflammation and depression), increases health costs, worsens the quality of life. Antibiotics increase the risk of bacterial resistences and devastate the ecosystems: intestinal, vaginal and mucocutaneous. Pathogenic biofilms are the (still) neglected etiology of recurrences. Biofilms are structured communities of bacteria and yeasts, protected by a self-produced polymeric matrix adherent to a living or inert structures, such as medical devices. Biofims can be intra or extracellular. Pathogens live in a resting state in the deep biofilm layers as "persister cells", resistant to antibiotics and host defences and ready to re-attack the host. The paper updates the evidence on biofilms and introduces new non-antibiotic strategies of preventing and modulating recurrent vaginitis and cystitis.