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Funding Acknowledgements Type of funding sources: None. Background Previous studies have demonstrated that cardiac biomarkers elevate after both cryoballoon (CB) and radiofrequency atrial fibrillation (AF) ablation, depending on the amount of energy delivered and the site of ablation. To date no comparison has been made between these thermal energy source and a novel non-thermal pulsed-field ablation (PFA) technology based on cells electroporation. Purpose Our analysis aims to compare acute myocardial injury through cardiac troponin I variation after pulmonary vein isolation (PVI) performed with different technologies (PFA vs CB). Methods All consecutive patients undergoing paroxysmal AF ablation with CB and PFA at our center from July to November 2022 were included. Protocol-directed cryoablation (CBA) was delivered for 180 sec or 240 sec according to operator’s preference for isolation achieved in ≤60 sec, or 240 sec if isolation occurred >60 sec or when time to isolation was not available. A standard PFA protocol-directed PVI was applied using 2kV with eight applications per vein (four applications each in the basket and flower poses). The ablation endpoint was PVI as assessed by entrance and exit block. Pre- and post-procedure samples of cardiac troponin I (CTpI) were collected before CBA/PFA and at 24h after ablation. Only patients with normal baseline values for myocardial injury were included. Results A total of 71 patients met inclusion criteria and were included in this analysis. The CBA group consists of 50 (70%) patients and the PFA group comprises 21 (30%) patients. The number of CBA applications to reach PVI was 5.0±1.4 and the number of PFA applications to achieve PVI was 32±4. All (100%) patients were in sinus rhythm at the time of the procedure. Evaluating the kinetic of CTpI, baseline values were homogeneous between CBA and PFA groups (p=0.979) whereas CTpI values significantly rose from baseline (7±2 ng/L) to 24h (8979±3691 ng/L, p Conclusion Our preliminary results showed that cardiac troponin I enzyme level increased after PVI by means of both cryoballoon and pulsed-field ablation and were higher after cellular electroporation by PFA than cryoablation.

Funding Acknowledgements Type of funding sources: None. Introduction Pulsed-field ablation (PFA) is a new non-thermal, tissue-specific ablation technique. Through the application of a local electric field, it is possible to induce a selective electroporation of cardiomyocytes membranes, resulting in myocytic apoptosis and sparing of non-myocardial structures (nerves, connective tissue, esophagus, vessels). Purpose A new PFA system for atrial fibrillation (AF) ablation has recently been introduced in our hospital. The aim of this retrospective review is to share the initial results of our experience in terms of acute efficacy and safety. Methods A total of 41 adult patients suitable for AF percutaneous ablation underwent PFA between April and November 2022 in our Institute. PFA system consisted of a current generator, a deflectable sheath and a multielectrode PFA catheter. Once inside the left atrium (LA), the PFA catheter was directed to the pulmonary veins (PVs) ostia through an over-the-wire system. Then, 8 electric impulses were applied for each PV to achieve electrical isolation; in some cases, applications to the posterior left atrium wall (LAPW) were delivered to obtain LAPW isolation (LAPWI). A moderate-to-deep sedation was provided by an anesthesiologist during all the procedures. Acute ablation efficacy was defined as absence of intracavitary signals at the electroanatomic mapping and local capture failure at the pacing maneuvers. Intra and peri-procedural safety was defined as the absence of major complications (pericardial effusion/ tamponade, stroke, vascular complications, death) during the procedure and the hospitalization period. Results Of the 41 patients included, 24 (58.5%) were treated for paroxysmal AF and 17 (41.5%) for persistent AF. In almost all cases (n=40, 97.6%) pulmonary veins isolation (PVI) was performed; in 14 cases (34.1%, almost all persistent AF patients) a LAPWI was performed with the application of a variable number of pulses (mean value = 13). In most of the cases (n=28, 68.3%) an electroanatomic mapping was acquired before and after the ablation. Acute efficacy was observed in all PVI cases (n=40, 100%) and in all LAPWI cases (n=14, 100%). No periprocedural major complications were observed (n=0, 0%). Conclusions PFA is a promising ablation technique capable of inducing selective myocytic apoptosis through electroporation, causing a thick damage across the muscle with no injury of other tissues, and could become a game changer in electrophysiology in the next future. Our initial data report a combination of ease of use and high efficacy and safety profiles.

Funding Acknowledgements Type of funding sources: None. Background Intracardiac echocardiography (ICE) is becoming more common during the ablation of atrial fibrillation (AF) and it may improve procedural effectiveness. However, there is no evidence evaluating efficiency, effectiveness, and safety outcomes of ICE in the context of the novel pulsed-field ablation (PFA) of AF. Purpose We aimed to evaluate the impact of ICE on procedural parameters in consecutive patients (pts) indicated for AF ablation with a new PFA technology. Methods All consecutive pts undergoing AF ablation with PFA at 5 experienced centers were included. Protocol-directed PVI was delivered using 2000 V with eight applications per vein, that is, four applications each in the basket and flower poses. Additional lesions were performed at the operator’s discretion. In procedures during which an ICE catheter was used, the ICE catheter was utilized to manipulate the PFA catheter in the left atrium to reach an optimal contact on the atrial structures. At the end of procedures, ICE was utilized for identification of procedure-related complications. Data are reported as median [IQ range]. Results One-hundred eighty pts were included in this analysis (36[32-40] pts per center; n=124, 69% paroxysmal AF; n=56, 31% persistent AF). The ICE-guided PFA procedures consisted of 35 (19.4%) cases. PVI was achieved in all pts with a 32[32-32.5] PFA applications per pt. Additional applications outside the PVs (i.e. posterior wall ablation) were performed in 31 (17%) cases, requiring 18[12.5-26] PFA deliveries on the lesion sets, all validated through 3D mapping and/or differential pacing. Fluoroscopy time was 17[13-22]min, LA dwell time was 22.5[18.5-27.5]min, skin-to-skin time was 60[52-80]min and total support time (procedural plus patient preparation) was 75[60-90]min. Considering PVI only cases, the use of ICE did not improve procedural metrics (ICE vs no ICE: 23[20-26]min vs 23[19-27]min for the time to PVI, p=0.4141; 65[64-85]min vs 70[60-82]min for support time, p=0.8271; 60[58-60]min vs 60[50-75]min for skin-to-skin time, p=0.8681 and 19[16-23]min vs 15[12-18]min for fluoroscopy time, p=0.0012). On the contrary, when looking at procedures with additional lesion sets, ICE-guided PFA showed some improvements (ICE vs no ICE: 27.5[25-30]min vs 16[13-20]min for the time to PVI, p=0.0003; 75[65-80]min vs 120[90-145]min for support time, p=0.0032; 70[60-74]min vs 82.5[74-112.5]min for skin-to-skin time, p=0.0077 and 20[16.5-22]min vs 20[17-30]min for fluoroscopy time, p=0.3328). No major procedure-related adverse events were reported. Conclusion In our preliminary experience, the use of a novel PFA system for AF ablation was safe and effective. The integration of ICE in guiding ablation, may provide some beneficial aspects, especially in the context of complex AF ablation with additional lesion sets.

Issue The aim of the Horizon 2020 unCoVer project (Unravelling Data for Rapid Evidence-Based Response to COVID-19) is to coordinate research expertise in utilising Real World Data (RWD) to investigate the underlying risk factors for COVID-19 infection and severity, the effectiveness of treatments and the impact on health systems. RWD is particularly useful in a dynamic health context as it is relevant, timely, and more ecologically valid. Pooling clinical databases and integrating epidemiological principles and powerful biostatistical tools optimises resources and fully exploits routinely-collected data. Description of the problem RWD sharing poses new practical and ethical challenges to research. The unCoVer network has developed a federated data platform to access diverse databases for advanced analytics. This data access process entails GDPR, and regulatory and ethical nuances. The use of large-scale data from heterogeneous sources across multiple jurisdictions for research purposes presents a complex systems challenge. Effects & Lessons A dedicated team of unCoVer network members is responsible for addressing these challenges. Here, we describe the ethical and regulatory aspects of RWD sources, the role of the Data Protection Authorities and the Data Protection External Authority Board (DP-EAB) of the Uncover project, and the documentation involved, including a data processing agreement and a data transfer agreement. We provide an overview of the main principles for sharing RWD whilst maintaining integrity and security and how this translates into procedures to protect the rights, security, and well-being of human research participants. This represents a practical framework for researchers. Key messages

Funding Acknowledgements Type of funding sources: None. Background Complete electrical pulmonary vein isolation (PVI) by cryo-balloon approach is a well-established ablation strategy of atrial fibrillation (AF). Recently, a new cryoablation system (POLARx) with unique features has been made available for clinical use. To date, limited data exist on acute and follow-up outcome of this system in a multicentric clinical practice. Purpose We reported the preliminary experience of this novel technology in a multicenter Italian registry. Methods Consecutive patients (pts) undergoing AF ablation from the CHARISMA registry at 6 Italian centres were included. Protocol-directed cryoablation was delivered for 180 sec or 240 sec according to operator’s preference for isolation achieved in ≤60 sec, or 240 sec if isolation occurred >60 sec or when time to isolation (TTI) was not available. The ablation endpoint was PV isolation as assessed by entrance and exit block. Rhythm monitoring during the follow-up examinations was performed via the clinical assessment of AF recurrence, ECG and Holter monitoring, according to the clinical practice of each center. All patients were followed-up for at least 6 months after the procedure. Arrhythmia recurrences within the first 3 months (blanking period) were classified as early recurrences and were not considered procedural failures Results Six-hundred twenty-four cryoapplications from 112 pts (439 PVs) were analyzed (n=89, 79.5% paroxysmal AF, n=23, 20.5% persistent AF, mean age 61.5±9 years, 76% male, 22% with an history of AT, mean LVEF 49±10%). PVI was achieved in all pts using only cryoablation. The mean number of freeze applications per pt was 5.6±2.1 (1.4±1.2 for LSPV, 1.5±1.1 for LIPV, 1.3±0.8 for RSPV and 1.3±0.8 for RIPV), with 318 (72.4%) PVs treated with a single cryoablation (92, 21% with 2 cryoablation; 29, 6.6% with more than 2 cryoablations). Fourty-four (39.3%) pts were treated with a single application to each of the PVs. Over a median of 296[245 to 382] days of follow-up, five (4.5%) patients experienced an early recurrence of AF/AT during the 90-day blanking period. Overall, 12 patients (10.7%) suffered an AF/AT recurrence after the 90-day blanking period (median time to recurrence 200[124 to 297] days). Specifically, 8 (7.1%) patients had AF recurrence only, 3 (2.7%) had AT recurrence only and 1 (0.9%) experienced both events. One (0.9%) patient underwent a repeated ablation procedure. The proportion of patients exhibiting AF/AT recurrences was similar between AF types (10 out 89, 11.2% for paroxysmal AF vs 2 out 23, 8.7% for persistent AF, p=1.00) with a hazard ratio of 0.9 (95%CI: 0.2 to 3.9, log-rank p=0.8894). One transient phrenic nerve palsy was observed, with full recovery in the 48-h post procedure; no major procedure-related adverse events were reported. Conclusion In this first multicentric experience, the novel cryo-balloon system proved to be safe and effective and resulted in a very low rate of AF/AT recurrence during follow-up.

A 22–year–old healthy athlete was referred to our hospital for electrocardiographic findings consistent with intermittent type–1 Brugada pattern. A routine electrocardiogram (ECG) performed during a check–up showed sinus rhythm, normal PR interval and QRS duration, rSR’ with a coved type ST–segment elevation in V2 lead (Figure 1).The patients denied history of syncope or palpitations and his family history did not show sudden cardiac death or Brugada syndrome (BrS). Transthoracic echocardiography was normal and a 12–lead Holter monitoring revealed the intermittence of the type–1 Brugada pattern. The patient was hospitalized for further investigation. On admission, ECG showed a type–2 Brugada pattern; therefore, Ajmaline challenge test (1 mg/kg injection in 10 minutes) was performed and resulted positive. Subsequently, the patient underwent an electrophysiological study (EPS) which was negative for induction of sustained arrhythmias. The protocol adopted consisted of double extrastimuli programmed electrical stimulation until refractoriness (drive 600/220 ms and 400/210 ms), at double sites (right ventricle apex and right ventricular outflow tract). Furthermore a genetic test was performed using next–generation sequencing, showing a heterozygous mutation in the SCN5A gene, encoding for sodium channel alpha subunit (variant c.5363delA), not previously described in the literature. Since the low arrhythmic risk, the patient was implanted with a loop recorder (ILR, Medtronic Reveal LINQ), entering a program of home monitoring. After a 15–months follow–up, an episode of ventricular polymorphic tachycardia lasting 2 minutes and 11 seconds, associated with lightheadedness and palpitations, was detected by the remote monitoring (Figure 2). The patient was therefore hospitalized. During the in–hospital stay a cardiac magnetic resonance was performed to exclude other underlying diseases, identifying an enlarged right ventricle (EDVi 114 ml/m2) and abnormal free wall motion (Figure 3), thus reaching one major criteria of arrhythmogenic cardiomyopathy (however not sufficient for the diagnosis). The patient was then implanted with a subcutaneous implantable cardiac defibrillator (Boston Scientific EMBLEM MRI S–ICD). We presented a case of complex arrhythmic risk stratification in a possible overlap of an arrhythmogenic cardiomyopathy and a Brugada Syndrome in a young athlete who experienced a sustained ventricular tachycardia during loop–recorder monitoring.

The visible light driven water oxidation reaction (WOR) by the organic electron acceptor 2,3,5,6-tetrafluoro-7,7,8,8-tetracyano-quinodimethane (TCNQF(4)) was studied at the water|butyronitrile interface. The WOR was performed at neutral pH, and without any metal or organometallic catalysts. The oxygen generated was measured by GC-MS and cyclic voltammetry, and the protons produced were monitored by measuring the aqueous pH. This work opens novel perspectives for water photo-oxidation in liquids and artificial photosynthesis.

Purely pairwise interactions of the core-softened type, i.e., featuring a soft repulsion followed by a hard-core interaction at shorter distance, give rise to nontrivial equilibrium structures entirely different from the standard close packing of spheres. In particular, in a suitable low-temperature region of their phase diagram, such interactions are well known to favor a transition from a fluid to a cluster crystal. The residual mutual interaction between individual clusters can lead to the formation of patterns of their reciprocal orientations. In this work, we investigate two examples of such models in two dimensions, at the density most appropriate to the dimer phase, whereby clusters consist of just two particles, studying them with optimization techniques and Monte Carlo simulations. We focus on the dimer crystal, and unveil a second phase transition at extremely low temperature. This transition leads from a triangular dimer lattice with randomly disordered dimer orientations at high temperature to a reduced-symmetry ground state with nematic orientational order and a slightly distorted structure characterized by a centered-rectangular lattice at low temperature.

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From carbonyls to chiral alcohols via asymmetric biocatalysis: exploiting the substrate promiscuity of hydroxysteroid dehydrogenases (HSDHs

Background The number of master athletes is increasing and treatment of AF is mandatory for sports continuation. However, few data exist about the effectiveness of catheter ablation (CA) in athletes and the feasibility of resuming vigorous exercise afterwards. Objectives Aim of our study was to analyze the efficacy and safety of AF CA in athletes and to evaluate the feasibility of resuming vigorous exercise. Methods We report a retrospective registry of athletes referred to our center for AF CA in the last five years. All athletes were previously declared non-eligible to competitive sport because of recurrences of AF or evidence of persistent asymptomatic AF. CA was performed as per practice and recurrences were defined as recrudescence of symptoms and/or any documentation of AF lasting more than 30 sec. At the end of the follow-up all pts were asked about resuming sport. Results We ablated 40 athletes (38 males, 95%) with a mean age of 48±13 years. Mean left atrium volume was 36±11 ml/m2 and mean ejection fraction was 61±5%. Distribution between AF characteristics was: 31 (78%) paroxysmal AF, 8 (20%) early-persistent AF, 1 (2%) long-persistent AF. After a median follow-up of 787 days, 62,5% of athletes were free from recurrences after one CA procedure and mostly without antiarrhythmic drugs (87%). 7 athletes underwent a redo procedure and all of them were then free of recurrences with an overall freedom from recurrences of 84%. No major complication was observed. Athletes practicing endurance sports showed a negative trend in terms of recurrences (p = ns). Most (72%) of the athletes resumed vigorous exercise after at least 3 months from the CA as per Italian sport protocols. Conclusions CA is safe and efficient in treating AF also in athletes. Resuming high intensity sports is often possible after 3 months from CA. Funding Acknowledgement Type of funding source: None

Background Premature ventricular complexes (PVCs) are a common clinical problem and a critical issue with regard to sports eligibility in sportsmen. Although PVCs can be considered a benign feature of the athlete's heart adaptive phenotype, they may also be the only clinical manifestation of a concealed cardiomyopathy, potentially heralding sudden cardiac death (SCD) during sports activity. The optimal diagnostic evaluation of athletes with PVCs is currently uncertain. Purpose To evaluate the diagnostic contribution and the implications for sports eligibility assessment of a thorough non-invasive and invasive work-up including electroanatomical mapping (EAM) and endomyocardial biopsy (EMB) in athletes with PVCs. Methods We conducted a prospective, single-arm, open-label double center study. All consecutive athletes presenting for evaluation at our institution after being disqualified from participating in sports due to PVCs were included in our study. These athletes underwent a baseline non-invasive diagnostic protocol with transthoracic echocardiogram and gadolinium enhanced cardiac magnetic resonance imaging (cMRI). Subsequently, an invasive diagnostic work-up was performed, including EPS with programmed electrical stimulation, EAM and EAM-guided EMB if deemed necessary. When clinically indicated, catheter ablation was performed. Sports eligibility status was re-assessed at six months' follow-up according to Italian sports medicine guidelines. Results After diagnostic evaluation, 20 subjects out of 107 (19%) had a diagnosis of heart disease, most commonly myocarditis (n=8), arrhythmogenic right ventricular cardiomyopathy (ARVC, n=7) or dilated cardiomyopathy (DCM, n=2). On multivariate logistic-regression analysis, QRS complex/T wave abnormalities on ECG (OR 23), non left bundle branch block and inferior axis PVC morphology (OR 13), echocardiogram abnormalities (OR 24) and low-voltage areas on EAM (OR 33) were significantly associated with diagnosis of a concealed cardiac disease. Nondiagnostic abnormalities on cMRI were common in this population of athletes, prevalently involving the right ventricle. EAM-guided EMB was performed in 12 subjects (11%) and catheter ablation in 56 (52.3%). After six months, 63 athletes (59%) were judged eligible to participate in competitive sports and 23 subjects (21%) were deemed eligible to participate in non-competitive sports. Conclusions Almost one fifth of sportsmen presenting with PVCs have a concealed heart disease, most commonly myocarditis or ARVC. Non-outflow tract PVCs' morphology and abnormalities on ECG, echocardiogram and EAM are predictive of structural heart disease's detection, whereas nondiagnostic findings on cMRI can be misleading in athletes. Invasive diagnostic tests, including EAM and EAM-guided EMB, play a critical role in case of diagnostic uncertainty. More than ¾ of subjects were judged eligible to participate in sports at 6 months' follow-up. Funding Acknowledgement Type of funding source: None

Summary Objective Fibroblast growth factor 18 (FGF18) is involved in chondrogenesis and articular cartilage repair. We investigated tissue distribution and pharmacokinetics of radioactive [3H]sprifermin, a recombinant human FGF18, in rats after a single intravenous (i.v.) or intra-articular (i.a.) injection. Design In two studies (48–96-h [n = 23] and 28-day [n = 12]), 35 male albino (Sprague Dawley) rats received single i.v. or i.a. dose [3H]sprifermin (0.24 mg/kg). Radioactivity was measured in blood, serum, and (in animals receiving i.a. administration) in the knee joint by liquid scintillation counting. Radioactivity in organs, tissues, and distribution in the whole body were measured with whole-body autoradiography. Results After i.v. injection, radioactivity peaked in serum and whole blood after 4 and 24 h, respectively, with greater total radioactivity in serum. After i.a. injection, radioactivity peaked in serum and whole blood after 24 and 48 h, respectively; intact [3H]sprifermin was not detected in vena caval serum and systemic exposure was low, approximately 20% of that with i.v. injection. Following i.v. injection, radioactivity was mainly found in the liver, adrenal glands, kidney, and spleen; following i.a. injection, radioactivity was preferentially concentrated in articular cartilage after initial distribution in the joint capsule, and still evident in the joint after 28 days. Conclusions After i.a. injection of [3H]sprifermin in rats, radioactivity was concentrated in the knee joint, particularly articular cartilage, with low levels in other investigated tissues. Systemic exposure to sprifermin was greater with i.v. than i.a. injection. Subsequent clinical investigation in patients with osteoarthritis has reported consistent results.

Background ventricular Arrhythmias (VAs) are a common clinical problem and a critical issue with regards to sports" eligibility in athletes. Although VAs can be considered a benign feature of the athlete’s heart adaptive phenotype, they may also be the only clinical manifestation of a concealed cardiomyopathy, potentially heralding sudden cardiac death (SCD) during sports activity. Purpose to evaluate the diagnostic contribution and the implications for sports eligibility assessment of a thorough non-invasive and invasive work-up including electrophysiology study (EPS), electroanatomical mapping (EAM) and endomyocardial biopsy (EMB) in athletes with complex VAs and to derive a multiparametric risk score in order to easily predict structural heart diseases’ diagnosis. Methods we conducted a prospective, single-arm, open-label single center, observational study. All consecutive athletes presenting for evaluation at our institution after being disqualified from participating in sports due to complex VAs were enrolled. The athletes underwent a baseline non-invasive diagnostic protocol with transthoracic echocardiogram and gadolinium enhanced cardiac magnetic resonance imaging (cMRI). Subsequently EPS, EAM and EAM-guided EMB were performed if deemed necessary. Sports eligibility status was re-assessed at 6 months’ follow-up. A multivariable logistic regression model was built, considering cMRI as the gold standard exam. Results after diagnostic evaluation, 55 subjects (26.4%) had a diagnosis of heart disease, most commonly myocarditis (n = 27) and arrhythmogenic right ventricular cardiomyopathy (ARVC, n = 16). After 6 months, 100 athletes (48.1%) were judged eligible to participate in competitive sports and 46 subjects (22.1%) were deemed eligible to participate in non-competitive sports. On multivariable logistic-regression analysis, abnormalities on ECG (OR 5.3) or on echocardiogram (OR 3.7), sustained VA inducibility on EPS (OR 17.7) and low-voltage areas on EAM (OR 7.7) proved all predictive of concealed structural heart diseases’ diagnosis. We derived two simple risk scores: a 40-points risk score and an 8-points risk score (obtained by weighing each variable according to the regression model’s ORs). Both these risk scores’ performance proved very good (AUC = 0.856 for the 40-points score and AUC = 0.852 for the 8-points score, figure 1). Conclusions approximately 1/4 of athletes presenting with complex VAs have a concealed heart disease, most commonly myocarditis or ARVC. ECG, echocardiogram and EAM abnormalities and sustained VAs inducibility on EPS are predictive of structural heart diseases’ detection. Therefore, these diagnostic tests should be routinely included in the evaluation of athletes with complex VAs. A risk score including the results of these tests can greatly help in the prediction of concealed structural heart diseases’ diagnosis. More than 2/3 of subjects were judged eligible to participate in sports at 6 months’ follow-up. Abstract Figure 1. ROC curves for diagnosis

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Introduction Myocarditis represents a not negligible cause of sudden death (SD) in athletes, representing the cause of 4%-14% cardiac arrests and deaths in athletes. Preparticipation screening including 12-leads basal electrocardiogram could drastically reduce SD in athletes and screening programs are therefore now recommended by most medical and sport association. At the moment, no data in literature are available about incidence of concealed myocarditis in athletes but there is general consensus about disqualification from competitive sport in the presence of myocardial fibrosis (MF). Purpose Purpose of our study was to quantify incidence of MF consistent with past myocarditis in athletes that referred to our Sport Cardiology Center for ventricular arrhythmias (VA) +/− repolarization abnormalities (RA) detected at preparticipation screening. Methods In our study we retrospectively evaluated all athletes with VA +/− RA and we quantified how many were found to have MF consistent with myocarditis at cardiac MRI. Furthermore, we evaluated characteristics of presentation in terms of clinical symptoms of myocarditis and frequency and morphology of VA. Finally, we analyzed findings of invasive diagnostic workout when performed. Results In the last two years we evaluated 111 athletes for VA +/− RA and we found MF consistent with myocarditis in 18 (16%) of them. Only 2/18 referred past febrile status probably correlated with myocarditis and 1 had symptoms consistent with acute myocarditis. Number of VA was not correlated with MF fibrosis, while polymorphic VA and exercise-correlated VA were the most frequent finding. 5/18 (28%) had also rest and/or exercise induced RA. 10/18 (55%) athletes underwent electrophysiological study without any induction of arrhythmias. 7/18 (39%) underwent also electroanatomical mapping (EAM) with pathological findings in 5/7 (71%). All of these 5 underwent endomyocardial biopsy guided by EAM and in 2 cases bioptic findings were consistent with arrhythmogenic cardyomyopahty (ACM). All 18 athletes were disqualified from competitive sport as for Italian Sport Medicine protocols. Conclusion MF consistent with past myocarditis is a not infrequent finding in athletes with VA with or without RA. Morphology and exercise behavior of VA are the most important “alarm bell”, while VA number is not correlated with MRI pathological findings. Sometimes MF interpreted as consistent with past myocarditis is actually the manifestation of ACM. Identification of these diseases is of extreme importance for athletes' safety.

Background The diagnosis of concealed cardiomyopathies in patients with ventricular arrhythmias (VAs) is one of the major challenging issues faced by physicians. Purpose We aimed at reporting the cardiomyopathic substrate in patients with recurrent arrhythmias of ventricular origin. Methods Consecutive patients with unexplained VAs underwent a complete diagnostic work-out, including endomyocardial biopsy (EMB). Results Ninety-seven patients were enrolled (76.3% male, age 39.7±13.3 yrs). The presenting arrhythmic manifestation was aborted cardiac arrest in 30 (30.9%) patients, sustained ventricular tachycardia (VT) in 9 (9.3%), nonsustained VT in 15 (15.5%) and frequent premature ventricular complexes in 43 (44.3%). Overall, 350 biopsies were collected (3.6/patient). The incidence of procedure-related complications was 5.1% (n=5): 4 major complications (1 rupture of a tricuspid chorda tendinea w/o hemodynamic impairment, 1 dissection of right external iliac artery treated with stent, 1 thrombotic occlusion of left superficial femoral artery which required surgical treatment, 1 TIA) and 1 minor complication (groin hematoma) occurred. The final diagnosis was arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) (n=41; 42.3%), followed by myocarditis (n=20; 20.6%), dilated cardiomyopathy (n=6; 6.2%), cardiac sarcoidosis (n=6; 6.2%), and myocarditis in ARVD/C (n=5; 5.1%). Among the 25 patients whose final diagnosis was consistent with myocarditis, an acute stage of the disease was documented in 7 (7.2%), while a chronic myocarditis in 18 (18.5%). Additionally, according to medical history and diagnostic workout, in 2 of the 6 patients the dilated cardiomyopathy had a likely post-inflammatory etiology. Absence of myocardial abnormalities was documented in 15 (15.5%) patients: this group included 1 case of methadone-induced torsade de pointes. The remaining 4 (4.1%) patients were diagnosed with a cardiac hypertrophy (n=2, 2.1%, secondary to exercise or Fabry disease), a dilated mitochondrial cardiomyopathy (n=1, 1.0%), a dilated cardiomyopathy in Emery-Dreifuss muscular dystrophy (n=1; 1.0%). Conclusion In our series, approximately 45% of patients with unexplained VAs had a final diagnosis of ARVD/C.

Background Arrhythmogenic Cardio-Myopathy (ACM) is characterized by epi-endocardial fibro-fatty replacement. Depending on the most affected ventricle, right dominant (RDACM) or left dominant (LDACM) phenotypes can be defined. RDACM voltage mapping characteristics have already been described, with late potentials strongly correlating with arrhythmia recurrence risk; LDACM voltage features have not been described yet. Purpose To analyze voltage map characteristics in LDACM patients (pts) and compare them with RDACM; to assess if there is any correlation between late potentials and recurrence rate in LDACM as well. Methods We retrospectively enrolled all consecutive ACM patients treated c/o our center and diagnosed according to the 2010 Task Force Criteria. Procedural and follow up data were collected. Patient were sorted by ventricular involvement lateralization. Recurrence rates were evaluated and linearly regressed for the presence of late potentials. Results 89 ACM patients were enrolled (67 RDACM, 22 LDACM; 76% males, 69±4 y.o.) in our study. All patients underwent endocardial voltage mapping; procedurally, 43 (48%) pts underwent catheter ablation, while 46 (52%) were managed conservatively with anti-arrhythmic drugs. Bipolar pathological potentials were found in 43 (64%) and 13 (59%), unipolar pathological potentials in 45 (67%) and 14 (63%), while late potentials in 19 (31%) and 8 (36%) in the RDACM and LDACM group respectively [p = 0.66, p=0.63, and p=0.33]. The average follow-up was 18 months [14–48]; 15 (22%) in the RDACM and 9 (40%) in LDACM arrhythmic recurrences were respectively encountered; recurrences in both groups were regressed for the presence of late potentials. Results were as follows: the presence of late potentials correlated with recurrences with an 4,3 [1.15–16.1; p=0.03] OR and with an 11 [0.4–85; p=0.022] OR in the RDACM and LDACM group respectively. Conclusion Pathologically low unipolar, bipolar and late potentials can be found in comparable % both in RDACM and LDACM; like in RDACM, late potentials represent an important risk factor for arrhythmic recurrence in LDACM as well.

Introduction Patients with myocarditis may fulfill the cardiac magnetic resonance (CMR) criteria set forth by the 2010 Task Force for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), thereby increasing the risk of misdiagnosis. Purpose We sought to evaluate the role of CMR and endomyocardial biopsy (EMB) in the differential diagnosis between myocarditis and ARVD/C. Methods Consecutive patients presenting with ventricular arrhythmias, underwent a complete diagnostic work-out, which included CMR and EMB. The final diagnosis served as the gold standard to assess the diagnostic accuracy of CMR and EMB. Results Overall, 74 consecutive patients presenting with VAs underwent a complete diagnostic workout at our institution. The cohort was 70.3% male, with a mean age of 38.9±12.1 years. A final diagnosis of ARVD/C was made in 30 (40.5%) patients, whereas 19 (25.7%) had a diagnosis of myocarditis. The McNemar's test showed significant differences in the diagnostic performance of EMB and cardiac MRI (p=0.003 for ARVD/C, p=0.04 for myocarditis). At receiver operating characteristic (ROC) analyses, the area under the curve (AUC) to discriminate between controls and ARVD/C patients was 0.711 (95% CI: 0.59–0.83) for MRI and 0.944 (95% CI: 0.88–1.00) for biopsy (p Diagnostic performance of CMR and EMB Conclusion Even though CMR has good diagnostic performances as single technique, a complete diagnostic work-out including EMB may frequently reduce the risk of misdiagnoses.

An experiment was conducted on in vitro regeneration and multiplication of Dendrobium bensoniae. Different concentrations of BA and IBA alone or combination of both hormones were used as treatment for regeneration. It was revealed that shoot regeneration from node was the best at 2.0 mg/l BA supplemented to MS medium. It gave better responses than all other concentrations and combinations of BA and BA+IBA, used in the present study. The highest number of shoots and leaves were found when 1.0 mg/l BA with 1.5 mg/l IBA was supplemented into MS medium. For rooting, 0.5 mg/l BA with 1.0 mg/l IBA was found to be the most effective. The well-rooted plantlets were successfully acclimatized under 70-80% humidity and planted in pots and transferred to the shade house for establishment. Around 85% of plantlets survived in the field. From the present result, it may be recommended that MS medium supplemented with 2.0 mg/l BA may be used for rapid shoot induction and regeneration of D. bensoniae.The Agriculturists 2016; 14(2) 24-31

Chirality is a property of matter which manifests at any length scale and can equally appear as quantum phenomena and in three-dimensional macroscopic structures. However, while chirality can be easily achieved by removing the inversion symmetry operation in hexagonal or tetragonal metal structures, chirality in metals is an unusual and barely developed phenomenon. Nevertheless, chirality can greatly alter mechanical and functional features of materials, making them suitable for catalysis, optics, electromagnetism, thermoelectricity and superconductivity; properties strictly dependent on the anisotropy of the crystal and on the direction of the applied force. This review aims to extend the definition of chirality to describe nanoclusters, metal surfaces and crystals and to provide an interdisciplinary overview on how symmetry can affect their properties.This review was submitted as part of the 2016 Materials Literature Review Prize of the Institute of Materials, Minerals and Mining run by the Editorial Bo...

Butyronitrile is an organic solvent stable enough to be used in photochemical reactions at liquid/liquid interfaces. However, it provides a rather short polarisation window making the analysis of ion transfer across the water|butyronitrile interface challenging. Here, steady-state cyclic voltammetry, at microhole-supported micro-interfaces, was used to measure Gibbs energies of transfer. A linear relationship between the standard Gibbs energies of ion partition for the water|butyronitrile interface and the water|1,2-dichloroethane and water|nitrobencene interfaces was found, making easy to extrapolate the Gibbs energy of other ions from this empiric correlation. Fil: Riva, Julieta Soledad. Swiss Federal Institute Of Technology Epfl; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina Fil: Bassetto, V. C.. Swiss Federal Institute Of Technology Epfl; Suiza Fil: Girault, Hubert. Swiss Federal Institute Of Technology Epfl; Suiza Fil: Olaya, A. J.. Swiss Federal Institute Of Technology Epfl, Lausanne

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Background Atacicept is an antagonist of the B cell regulatory factors BLyS (B lymphocyte stimulator) and APRIL (a proliferation inducing ligand). It is capable of binding to all known conformations of BLyS and APRIL and is thus expected to modulate the maturation, differentiation, and effector function of B cells. We aimed to define the relationship between atacicept drug exposure and pharmacodynamic (PD) effects in vivo. Here, we report results of our study examining the effects of atacicept on the immune response in a keyhole limpet hemocyanin (KLH) challenge model in cynomolgus monkeys. Methods Cynomolgus monkeys (Macaca fascicularis) were injected with KLH on Day −33, and on Day 1 received the first dose of either atacicept (0.3, 3, or 30 mg/kg) or vehicle followed by a KLH challenge. Animals were dosed weekly (Day 1, 8, 15) and were subsequently monitored for 2 weeks before the study ended on Day 29. Clinical signs, total and free drug levels, peripheral blood B and T cell subpopulations, and total and KLH-specific immunoglobulin (Ig) levels were monitored. Additionally, gene expression in blood was analysed using the NanoString nCounter platform. Results Atacicept was well-tolerated at all dose levels tested. All animals in the treatment arms had quantifiable levels of atacicept in serum throughout the study. Reduction of serum IgM and IgG was detected 7 days after treatment, with a continuous reduction in the mean serum IgM and IgG levels observed until Day 29 (table 1). In animals treated with 3 and 30 mg/kg atacicept, a significant decrease in serum anti-KLH IgG levels was observed versus vehicle-treated controls, beginning at Day 11 (table 2). A minor reduction in absolute CD3-CD20+, IgD +B cell numbers was seen in response to treatment, but no changes in T cell subsets were detected. Changes in gene expression following atacicept treatment were predominantly observed in B cell-related and Ig genes. Conclusions This study showed that atacicept modulates B cell responses, IgM and IgG levels, and Ig isotype switching in a KLH-antigen-challenged cynomolgus monkey model, thus supporting its use in the treatment of antibody-mediated diseases. Additionally, gene expression PD markers identified in this study will be used in subsequent clinical trials as exploratory PD readouts. Disclosure of Interest E. Samy Employee of: EMD Serono Research and Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), A. Bender Employee of: EMD Serono Research and Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Y. Wu Employee of: EMD Serono Research and Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), V. Castagna Employee of: Istituto di Ricerche Biomediche Antoine Marxer RBM SpA, an affiliate of Merck KGaA, E. Bertotti Employee of: Istituto di Ricerche Biomediche Antoine Marxer RBM SpA, an affiliate of Merck KGaA, R. Boggio Employee of: Istituto di Ricerche Biomediche Antoine Marxer RBM SpA, an affiliate of Merck KGaA, A. Paoletti Employee of: Istituto di Ricerche Biomediche Antoine Marxer RBM SpA, an affiliate of Merck KGaA, S. Riva Employee of: Istituto di Ricerche Biomediche Antoine Marxer RBM SpA, an affiliate of Merck KGaA, P. Schneider Grant/research support from: EMD Serono Research and Development Institute, Inc. and Merck KGaA, P. Haselmayer Employee of: Merck KGaA, J. DeMartino Employee of: EMD Serono Research and Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany)

Study Design: Resident's case study. Background and Purpose: Functional Movement Analysis (FMA) including observational gait analysis are powerful tools that can be used to guide patient examination and differential diag- nosis process. Case description: An 18-year-old female was referred to physical therapy with a diagnosis of gait abnormality and a chief complaint of left medial knee and left medial hip pain. Two orthopedic surgeons suspected neurologic pathology due to inconclusive findings on physical examination, an abnormal antalgic gait pattern, and negative findings on Magnetic Resonance Imaging (MRI) and radiographic studies. The physical therapist gathered a comprehensive sub- jective history, and performed a functional movement analysis including observational gait analysis. The findings were used to guide a full musculoskeletal examination. Correlating the functional movement analysis with subjective history and comprehensive musculoskeletal ex- amination, the therapist found the patient to have subtle but definite lateral knee joint laxity. This was hypothesized to be driving the abnormal gait pattern and causing her hip and knee pain. Outcomes: Stress radiographs, suggested by the physical therapist, were ordered and confirmed the therapist's finding of lateral knee instability. The patient subsequently had surgery to repair and augment her popliteal fibular ligament and lateral collateral ligament. She underwent post- operative physical therapy, and returned to her prior level of function with full resolution of her gait deviations and pain. Discussion: Functional movement analysis is a powerful and unique tool that clinicians can use when evaluating and treating patients. Level of Evidence: Therapy, level 4.

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