This work aims to investigate the anisotropic fracture and energy dissipation characteristics of marbles cored along an angle of 0°, 30°, 60° and 90° with respect to interbed planes, subjected to multi-level cyclic loading conditions. Rock fatigue deformation, strength, lifetime and dissipated energy first decreases and then increases with increasing interbed orientation, they get to the minimum for sample having 30° interbed orientation. Rock stiffness degradation is significant with the increase of cyclic level and the stiffness evolution is affected by interbed structure. The incremental rate of dissipated energy becomes faster with increase of cyclic loading level and it presents an abrupt increasing trend at the last cyclic loading level. A damage evolution model was first established based on the dissipated energy to describe the two-phase damage accumulation characteristics. It suggests that the proposed model fits well to the testing data and favorably represents the non-linear characteristics of damage accumulation.

With the arrival of the coronavirus disease (SARS-CoV-2) in the U.S., care practice paradigms have drastically changed. Data from China suggests the new virus poses additional risks as case fatality of patients with cancer was higher at 5.6% compared to 2.3% of the general population. There are three proposed major strategies to address care for patients with cancer in this SARS-CoV-2 pandemic with postponing treatment for those with stable cancer, increasing personal protection provisions for cancer patients, and increasing monitoring if a patient becomes infected with SARS-CoV-2.  In this present commentary, we discuss the unique mental health challenges and burdens of head and neck cancer (HNC) patients in the times of the SARS-CoV-2 pandemic and approaches to mitigate these stressors through telemedicine to reduce future burdens to the patient and the health care system.

Aim: Prevention of type 2 diabetes is enabled by identification and effective management of risk factors. The study was conducted to evaluate the risk factors associated with the development of type 2 diabetes. Methods: A cross-sectional survey was conducted on persons without diabetes in two secondary hospitals using Canadian diabetes risk assessment questionnaire. Data analysis was done using SPSS version 18. Result: A total of 300 respondents participated in the study and 160 (53.3%) were at high risk of developing type 2 diabetes. From the risk evaluation, males (62.5%), overweight (65.1%) and obese (82.6%) participants; were at high risk for type 2 diabetes. Others found to be at high risk were; respondents with high waist circumference (55.6%), respondents who did not exercise (77.0%), those who did not eat fruits and vegetable daily (54.4% ), those with high blood pressure (67.5% ) and those who have had raised blood sugar in the past (71.0% ). Conclusion: Majority of the study participants was at high risk for type 2 diabetes and male participants had higher risks than their female counterparts. Other socio-demographic factors also presented major risks for type 2 diabetes.

Rationale, aims and objective Clinical audit plays a fundamental role in improving the quality of patient care and hence, is considered a cornerstone of clinical governance. This study evaluates clinical audit as a newly introduced quality improvement tool in the healthcare system of the Gaza Strip. Methods: Medical students and healthcare professionals who completed audits between 2015 and 2018 were invited to fill in an online survey from October 12 to November 2, 2018. Data was collected on applied methods, supervision, training, re-auditing and subsequent improvements in practice. Results A total of 62 audits was collected. Former training in clinical governance was received by 55 authors (88.7%) while a senior supervision was available in 56 audits (90.3%). Audits were performed across different hospitals and specialties with 18 audits (29%) in obstetrics, 16 audits (25.8%) in medicine and 11 audits (17.7%) each in surgery and paediatrics. A clear trend of increasing numbers of audits was observed with four audits (6.4%) completed in 2015 and 24 audits (38.7%) in 2018. Only 32 audits (51.6%) were presented to the local staff. The audit cycle was only completed in 14 projects (22.5%) with seven of them reporting improvements in practice. Conclusions A rise in the numbers of audits reflects a growing awareness of its key role in healthcare and patient safety. However, closure of loops and the actual implementation of recommendations are still lagging behind. Therefore, more focused efforts are needed to implement changes and ensure continuous evaluation of their effectiveness.

African swine fever (ASF) is emerging in Vietnam and poses a continuing severe threat to the swine industry. A histopathological study of clinical samples collected during the August to September 2019 outbreak of ASF was performed to determine the characteristic lesions. We analyzed samples from eight ASFV-infected farms. Histopathological results revealed the characteristic lesions of the acute to the subacute clinical form of ASF. Immunohistochemical results showed ASFV viral antigen distribution in mononuclear cells/macrophage in various organs, hepatocytes, and renal tubular epithelium. Molecular analysis of partial capsid protein 72 gene revealed that ASFV strain from the eight separate outbreaks belonged to genotype II.

Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials. Drugs with previous efficacy against related betacoronaviruses like SARS and MERS were also systematically evaluated as potentially promising candidates for drug repositioning.

New technologies in the field of vaccinology arise as necessity for treatment and control of many diseases. Currently modified live virus and inactivated vaccines used for Bovine Herpesvirus-1 (BoHV-1) have several disadvantages. Previous works for preventive treatment of BoHV-1 with DNA based vaccines have demonstrated the capability to induce humoral and cellular immune response. Nevertheless, it is well known that “naked” DNA induces low immunogenic response. Thus, loading of antigen encoding DNA sequences in liposomal formulations targeting dendritic cell receptors could be a promising strategy to better activate these antigen presenting cells (APC). In this work, DNA based vaccine encoding the truncated version of gD glycoprotein (pCIgD) of BoHV-1 was investigated alone and upon encapsulation on liposomal formulation coated with MANα1-2MAN-PEG-DOPE and LPS from Brucella ovis (pCIgD-Man-L) in mice and cattle assay. Results showed that the use of pCIgD-Man-L was capable to enhance the immune response in both animal models. Significant levels of humoral immunity were achieved when total antibody titers and isotypes were detected in sera and mucosa. For cellular immunity, specific viral lymphoproliferation was detected in the animals inoculated with pCIgD-Man-L. In addition, positively modulation of CD40 molecules on the surface of bovine dendritic cells (DCs) was observed when cells were stimulated and activated with vaccine formulations. When challenge assay was performed, bovines inoculated with pCIgD and liposome decorated with MANα1-2MAN-PEG-DOPE elicited better protection and diminished viral excretion. The results demonstrate the targeting of the MANα1-2MAN coated liposomes toward dendritic cells and their ability to boost the immunogenicity according to an adjuvant effect that results in long-lasting immunity. Liposome decorated with MANα1-2MAN-PEG-DOPE were for the first time tested as DNA based vaccine in cattle as preventive treatment of BoHV-1. These results open up new perspectives for the design of vaccine for the control of bovine rhinotracheitis.

BACKGROUND AND PURPOSE Neutrophil overactivation is crucial in the pathogenesis of acute lung injury (ALI). Bletinib (3,3′-dihydroxy-2′,6′-bis(p-hydroxybenzyl)-5-methoxybibenzyl), a natural bibenzyl first extracted from Bletilla striata in 1983, has anti-inflammatory, antibacterial, and antimitotic potential. In this study, we evaluated the therapeutic effects of Bletinib in human neutrophilic inflammation and lipopolysaccharide (LPS)-mediated ALI. EXPERIMENTAL APPROACH We assessed integrin expression, superoxide anion production, degranulation, neutrophil extracellular trap (NET) formation, and adhesion in activated human neutrophils through flow cytometry, spectrophotometry, and immunofluorescence microscopy. Moreover, phosphorylation of Src family kinases (SFKs) and downstream proteins was evaluated through immunoblotting. Finally, a murine LPS-induced ALI model was used to investigate the potential therapeutic effects of Bletinib treatment. KEY RESULTS In activated human neutrophils, Bletinib reduced degranulation, respiratory burst, NET formation, adhesion, migration, and integrin expression; suppressed the enzymatic activity of SFKs, including Src, Lyn, Fgr, and Hck; and inhibited the phosphorylation of SFKs as well as Vav and Bruton’s tyrosine kinase (Btk). In our mice with ALI, the pulmonary sections demonstrated considerable amelioration of prominent inflammatory changes, such as haemorrhage, pulmonary oedema, and neutrophil infiltration, after Bletinib treatment. CONCLUSION AND IMPLICATIONS This is the first study to provide evidence that Bletinib regulates neutrophilic inflammation by inhibiting the SFKs–Btk–Vav pathway and that Bletinib ameliorates LPS-induced ALI in mice. Further biochemical optimisation of Bletinib may be a promising strategy for the development of novel therapeutics for inflammatory diseases.

Near-field Signals Detected by a Standard Bipolar Electrode without Detection of Corresponding Signals by Microelectrode: What is the Mechanism?Short title ; Near-filed Microelectrode signalTakashi Nakashima, MD*, Cyril Goujeau, MD, Yosuke Nakatani, MD,Ghassen Cheniti, MD, Pierre Jaïs, MD, Frédéric Sacher, MDAll authors have no conflicts of interest to disclose.Department of Cardiac Electrophysiology, Service de Rhythmologie, Hôpital Cardiologique du Haut-Lévêque (Centre Hospitalier Universtaire de Bordeaux)Avenue de Magellan, 33604, Bordeaux-Pessac, FranceCorrespondence to Takashi Nakashima, MDDepartment of Cardiac Electrophysiology, Service de Rhythmologie, Hôpital Cardiologique du Haut-Lévêque (Centre Hospitalier Universtaire de Bordeaux)Avenue de Magellan, 33604, Bordeaux-Pessac, FranceTel: +33 5 57 65 68 63 19, Fax: +33 5 57 65 68 96 20, Email; takashin727jw@yahoo.co.jp, ORCID: 0000-0002-8538-9259Key words: Ablation; Electrogram analysis; Microelectrode; Ventricular tachycardia

Background: End stage renal disease (ESRD) is a well-recognized risk factor for development of sudden cardiac arrest (SCA). There is limited data on baseline characteristics and outcomes after an in-hospital SCA event in ESRD patients. Methods: For the purpose of this study, data were obtained from National Inpatient Sample from January 2007 to December 2017. In-hospital SCA was identified using International Classification of Disease, 9th Revision, Clinical Modification and International Classification of Disease, 10th Revision, Clinical Modification codes of 99.60, 99.63 and 5A12012. ESRD patients were subsequently identified using codes of 585.6 and N18.6. Baseline characteristics and outcomes were compared among ESRD and non-ESRD patients in crude and propensity matched (PS) cohorts. Predictors of mortality in ESRD patients after an in-hospital SCA event were analyzed using a multivariate logistic regression model. Results: A total of 1,412,985 patients sustained in-hospital SCA during our study period. ESRD patients with in-hospital SCA were younger and had a higher burden of key co-morbidities. Mortality was similar in ESRD and non-ESRD patients in PS matched cohort (70.4% vs. 70.7%, p = 0.45) with an overall downward trend over our study years. Advanced age, Black race, diabetes, hypertension and peripheral vascular disease were independently associated with increased mortality in ESRD patients after an in-hospital SCA event. Conclusion: In the context of in-hospital SCA, mortality is similar in ESRD and non-ESRD patients in adjusted analysis. Adequate risk factor modification could further mitigate the risk of in-hospital SCA among ESRD patients.

Introduction: His-Purkinje system (HPS) pacing emerges as an ideal strategy to restore cardiac synchrony. However, there is insufficient evidence to confirm the safety of HPS pacing in advanced age patients who are vulnerable to invasive procedures. Methods: We aimed to evaluate the short-term feasibility and safety of HPS pacing in symptomatic bradycardia patients over 85 years of age by comparing the pacing parameters and clinical outcomes with a younger cohort. 189 out of 198 consecutive patients underwent HPS pacing with symptomatic bradycardia were included. Among them 37 and 152 were aged over 85 years and below 85 years respectively. Peri- and post-procedure pacing parameters, cardiac function and clinical events were thoroughly evaluated during follow-up. Results: Compared with the younger cohort, the elderly had worse renal function and cardiac function. All 189 patients underwent successful HPS pacing, among whom 28 were paced at His-bundle. Paced QRS duration was shortened non-significantly compared with intrinsic, which showed no difference between cohorts. Pacing threshold and impedance decreased significantly without difference between cohorts. Lead dislodgement and pocket hematoma/infection only occurred in 2 (1.3%) and 4 (0.7%) younger patients, respectively. Through a 10.5±3.0 months follow-up, A non-significant improvement in cardiac function was indicated by echocardiographic indices. Clinical events incidences were comparable, except a higher incidence of myocardial infarction (8.1% vs 0.7%) observed in the advanced age cohort. Conclusion: Compared with the younger, HPS pacing could safely restore physiological conduction and reserve cardiac function in advanced age patients with symptomatic bradycardia.

Introduction: Previous studies on radiofrequency catheter ablation of premature ventricular complexes (PVCs) arising from the left ventricle (LV) papillary muscles (PM) show a modest procedural success rate with higher recurrence rate. This study explored the utility of using a multipolar catheter for ablating the PM PVCs. Methods and Results: Endocardial mapping was performed via retrograde aortic approach using a steerable duodecapolar catheter in 6 patients and conventional point-by-point catheter in 5 patients, respectively. Compared with patients in point-by-point catheter group, duodecapolar catheter mapping demonstrated higher efficiency with an average procedure time and fluoroscopy time. The values of earliest activation time during mapping using duodecapolar catheter were significantly greater (32.3 ± 3.9 ms vs. 25.4 ± 2.8 ms). The mean number of ablation applications points in the duodecapolar catheter group was 6.8 ± 1.9 with an average overall ablation duration of 6.1 ± 3.0 minutes, which was significantly less compared to the point-by-point catheter group. There were no complications in duodecapolar catheter group whereas one cardiac tamponade occurred in the point-by-point catheter group. All 6 patients (100%) in the duodecapolar catheter group demonstrated acute successful ablation whereas only 3 of the 5 patients (60%) with point-by-point catheter ablation succeeded, and the intermediate success rate remained the same after an average follow-up of 9.7 ± 3.2 months. Conclusions: Mapping and ablation of PM PVCs using a duodecapolar catheter facilitated identification of earliest activation potentials and pace mapping, and demonstrated a high success rate during follow-up when compared to conventional mapping techniques.

Objectives: To elucidate the impact of regulation of tricuspid regurgitation (TR) using tricuspid annuloplasty on postoperative changes in right ventricular (RV) systolic and diastolic functions. Methods: We enrolled 69 patients who underwent aortic or mitral valve surgery between July 2016 to March 2018 without recurrence. Patients with concomitant coronary artery bypass grafting or a history of previous cardiovascular surgery were excluded, remaining 45 patients enrolled. Patients were divided into 2 groups according to concomitant tricuspid annuloplasty (T: n=12 vs non-T: n=33). RV global longitudinal strain (RVGLS), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio (tricuspid E/e’) were assessed as functional indices at preoperative, postoperative and 1-year follow-up periods. Results: RVFAC deteriorated postoperatively but recovered at follow-up in group T, whereas that in group non-T showed gradual deterioration overtime. RVGLS and TAPSE showed similar temporary deterioration and recovery between groups. Tricuspid E in group T increased postoperatively and showed significant difference, which was kept until follow-up period. Tricuspid e’ decreased postoperatively, and recovered slightly in both groups. As a result, postoperative RV diastolic function (tricuspid E/e’) showed significant difference between groups. This difference was maintained until follow-up. Conclusions: RV systolic function deteriorated postoperatively, but there was a tendency to improve at follow-up regardless of tricuspid annuloplasty. RV diastolic function may potentially be impaired when TR was regulated by tricuspid annuloplasty.

Viruses are considered as one of the primary drivers for human evolution. Humans in return have also offered them an ideal habitat for their growth and evaluation. However, both, humans and viruses are diverse, astute, competitive, and avaricious in nature, which engage them in a never-ending battle. Today, the world goes to win the battle against COVID-19 for sure. However, this never ending merciless battle between viruses and humans looks like an arms race for their survival in which neither a virus wins nor a human but each battle provides them an opportunity to bounce back for the next.

A document by Maryam Azimzadeh Irani, written on Authorea.

The SARS-CoV-2 infection has been considered a global pandemic due to its widespread transmission and high rate of fatality. As of April 11, 2020, globally, there are 1.76 million confirmed cases of COVID-19, of which 108,281 people succumbed to the disease. In the absence of therapeutic intervention and a possible vaccine candidate, the spread of the disease and associated fatalities are on the rise. The epidemiological data indicate age and country-specific bias in the spread and severity of COVID-19. In this review, we discussed the recent update on the pathogenesis of SARS-CoV-2 among men and women, including children. Further, we also discuss the role of the cellular receptors and co-receptors used by the virus to enter host cells in the virus pathogenesis on differential infection among men and women. Further, highlighted the co-morbidity of COVID-19 with cardio-metabolic disease, and the potential treatments to control SARS-CoV-2 infection. Finally, we summarize the prospective treatment options that have been evaluated or are in the pipeline at different stages of clinical trials to fight against COVID-19.

Oxidized low-density lipoproteins (oxLDL) and oxysterols play a key role in the endothelial dysfunction and atherosclerosis development. Loss of vascular endothelium integrity impacts vasomotion, cell growth, adhesiveness and barrier functions. While for some of these disturbances we can give a reasonable explanation from a mechanistic point of view, for many others the involved molecular players are unknown. Caveolae, specific plasma membrane domains, have recently emerged as targets and mediators of oxLDL-induced endothelial cell dysfunction. The current knowledge on oxLDL/caveolae interplay and the associated signal transduction pathways are here reviewed and discussed in light of the possible cross-talk between transducers (from receptors to membrane cholesterol) and/or effectors. A better understanding of how oxLDL interact with endothelial cells (EC) and, in turn, modulate metabolic/signaling pathways in EC is crucial to define their role in atherogenesis and find new targets of intervention.

We read with great interest the recent study by Rogers, et al. describing lesion formation with continuous versus intermittent radiofrequency ablation.1 The authors applied 50 (ex-vivo) or 10 (in-vivo) watts with either intermittent (15-seconds x4, 30-seconds x2, or 60-seconds x1) or continuous (1, 2, 3, or 5 minutes) radiofrequency applications and examined lesion size with each strategy. Continuous lesions resulted in significantly larger lesion size with possibly increased risk of steam pops at high power. In the ex-vivo model, they saw rapid lesion formation in the first minute of ablation with substantial drop-off in expansion of lesion size over time especially after 3 minutes (down to 0.35mm/min at 5 minutes), and suggest that there is only minimal incremental benefit of prolonging ablation lesion duration beyond 3 minutes in normal tissue.They have, however, appropriately recognized the limitation of their model which lacks significant fibrosis, limiting the generalizability of their findings to ablation in patients with scar. It is important to recognize that lesion formation in scar-related ventricular tachycardia (VT) is likely to differ dramatically compared to normal myocardial tissue. Barkargan, et al. have shown in an in-vivo porcine model of anterior myocardial infarction that lesion formation in normal versus scar tissue can be substantially different.2Specifically, ablation lesions in scar tissue were histologically quite heterogeneous, and connective tissue tended to be more resistant to thermal injury than normal myocardium.We have seen many cases where after identifying critical VT circuit components with activation and entrainment mapping, VT slowing and termination could only be achieved very late (4-5 minutes) into radiofrequency application, suggesting continued lesion expansion due to delayed effect of conductive heating in scar tissue can persist well beyond 3 minutes. Historical data from Nath, et al. have demonstrated that tissue temperature of >50°C must be reached in order to achieve nonreversible cellular damage.3 In the setting of dense scar, as in patients with healed myocardial infarction or dense basal septal scar in nonischemic cardiomyopathy, dynamics of tissue heating and lesion formation are likely quite different than in normal tissue. Especially in intramural substrates which are “protected” by dense subendocardial (or subepicardial if ablating from the epicardium) scar, ablation with very long (>3 minute) lesions may have a more pronounced effect than in normal tissue. While in our experience, steam pops seem to occur less frequently when ablating in dense scar- even with long, high power lesions, close monitoring of ablation parameters including catheter tip temperature and impedance remain necessary during ablation to assure continued safety to avoid char formation and steam pops.We enthusiastically applaud the authors for their valuable contribution to the literature. While chronic cardiomyopathy models are technically difficult to create and costly to maintain, additional studies examining lesion formation in dense scar would be extremely helpful to delineate optimal ablation strategies in patient with cardiomyopathy and difficult VT substrates. Our clinical experience with late VT termination and prevention of inducibility after 4-5 minute radiofrequency ablation lesions in areas of marked fibrosis would support such additional study.References:1. Rogers AJ, Borne RT, Ho G, Sauer WH, Wang PJ, Narayan SM, Zheng L, Nguyen DT. Continuous Ablation Improves Lesion Maturation Compared with Intermittent Ablation Strategies. J Cardiovasc Electrophysiol 2020.2. Barkagan M, Leshem E, Shapira-Daniels A, Sroubek J, Buxton AE, Saffitz JE, Anter E. Histopathological Characterization of Radiofrequency Ablation in Ventricular Scar Tissue. JACC Clin Electrophysiol 2019;5:920-931.3. Nath S, DiMarco JP, Gallop RG, McRury ID, Haines DE. Effects of dispersive electrode position and surface area on electrical parameters and temperature during radiofrequency catheter ablation. Am J Cardiol 1996;77:765-767.

ABSTRACT Background: Data regarding the use of high-power short-duration (HPSD) radiofrequency (RF) in combination with half-normal saline irrigation for catheter irrigation is limited. Objectives: This study investigated the safety and efficacy of using HPSD RF ablation in combination with half-normal saline irrigation for the treatment of AF. Methods: One hundred consecutive patients with AF underwent RF ablation using HPSD combined with half-normal saline for catheter irrigation. In addition, the following ablation strategies were used: 1 mm tags for the display of ablation lesions on the mapping system, high-frequency jet ventilation (HFJV), low contact force, pacing after ablation to verify areas of noncapture, atrial/ventricular pacing at 500 to 700 ms to aid in catheter stability, use of two skin electrodes to reduce impedance, and post-ablation adenosine infusion. Power was started at 40-45 W and was modulated manually based on impedance changes. Results: The average age of patients was 65.2 years and 70% were male. Forty-seven percent had paroxysmal AF and the average CHA2DS2-VASc score was 2.1±1.6. The average power and lesion duration were 38.1 ± 3.3 W and 8.1 ± 2.3 seconds, respectively. During a median follow-up period of 321 + 139 days, 89% of the patients remained free from any atrial arrhythmias after a single RF ablation procedure. No procedure-related death, stroke, pericardial effusion, or atrioesophageal fistula occurred during follow-up. Conclusions: Catheter ablation using HPSD RF lesions in combination with half-normal saline irrigation and is safe and effective, and results in high rate of freedom from AF.

Introduction: Brugada syndrome is associated with ventricular arrhythmia leading to sudden cardiac death. Risk stratification is challenging, as major arrhythmic events (MAE) are rare. We assessed the utility of drug challenge testing in Brugada syndrome by a systematic review and meta-analysis. Methods and results: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies compared the incidence of MAE between spontaneous and drug challenge induced Type-1. Data were combined using the random-effects, generic inverse variance method, to calculate pooled incidence and odds ratio (OR). Mixed-effects Poisson regression was used to calculated incidence rate ratio (IRR). Eighteen studies from 2006 to 2018 were included (4,099 patients, mean follow-up 4.5 years). Pooled annual incidences of MAE in spontaneous, drug challenge induced (regardless of symptoms), asymptomatic drug challenge induced, and symptomatic drug challenge induced Type-1 were 23.8 (95% confidence interval [CI]: 19.8-27.8), 6.5 (95% CI: 3.9-9.1), 2.1 (95% CI: -0.3-4.4), and 19.6 (95% CI: 9.9-29.3) per 1,000 person-years respectively. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type-1 was not statistically different (IRR=1.0, 95%CI: 0.6-1.7). The presence of ventricular tachyarrhythmia during drug challenge testing was a predictor of MAE (OR=3.73, 95% CI: 1.77-7.86, p=0.001). Conclusions: The incidence of MAE in drug challenge induced Type-1 in asymptomatic patients is low. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type-1 was similar. Ventricular tachyarrhythmia during drug challenge testing could be a useful risk marker for MAE in Brugada syndrome.

Leadless pacemakers have an accepted role with demonstrable benefit in adults. In contrast, implant and follow-up experience in pediatric patients is quite limited. We present our implant experience in a 4-year-old for treatment of high-grade AV block. Implant considerations in small patients and follow-up assessment of the vessel used for implantation are discussed.

Despite extreme and undeniable progress in the concept of implantable cardioverter defibrillator (ICD) therapy over the last 40 years, the endocardial lead is still the weakest link of the system. Many efforts have been taken to improve the construction and consequently the durability of the lead. Not all of them were successful and some of the lead models proved to be technically imperfect, resulting in formal recalls. Similarly, patient- and procedure-related factors may strongly affect the lead reliability. The implantation of cardiac electronic devices (CIED) is considered to be a quite common vascular intervention. Also, there are strongly established opinions of best procedural manners, including the most optimal methods of vascular access during the CIED implantations.In this issue of the Journal of Cardiovascular Electrophysiology, Barbhaiya et al. present an interesting retrospective analysis of 660 patients who underwent the ICD implantations in one center from 2011-2017. The goal of the study was to determine the risk factors for premature lead failure. Four implanted leads models were assessed: Biotronik Linox, Sprint Quattro, Durata and Endotak.The main findings include:The ICD lead implantation via cephalic access in multi-lead ICD systems may be a risk factor for premature ICD lead failure (p<0.001).The overall risk of premature ICD lead failure was similar for all the analyzed lead models.Concerns regarding the durability of Biotronik Linox were discussed and the study showed its equal reliability compared to the other leads.Neither age nor gender were the risk factors for premature lead failure.An optimal vascular access for the endocardial lead implantation was investigated in many studies.1-4 So far, cephalic vein cutdown (CVC) was considered to be the method of choice, with the lowest rate of possible complications.2,4,5 Meta-analysis performed by Benz et al. (30 000 patients, more than 50 000 leads) compared CVC and subclavian puncture (SP) and demonstrated lower risk of lead failure when CVC was adopted.2 Axillary vein puncture (AP), especially when ultrasonography-guided, is a feasible technique and significantly reduces the probability of subclavian crush syndrome.6-8 Unfortunately this method is not used by many operators. EHRA survey from 2013 showed that in more than 80% of participating centers, the preferred method for venous access was either CVC or SP.9 What is worth emphasizing, in the study of Barbhaiya et al., axillary access was most often used for lead insertion – 76.8% (61-88%, dependently on the lead model). This fact may potentially explain the main study finding. It is also consistent with the interesting results of the PAIDLESS study presented in the paper of Shaikh et al.3 They showed that experienced operators preferably choose subclavian and/or axillary access (62% of implants), whereas low-volume implanters generally use cephalic vein approach (63%). High-volume operators are also less likely to experience lead failure.An important issue to discuss is the number of leads inserted via cephalic vein. The routine practice, also applied by Barbhaiya and colleagues, includes the placing of atrial and right ventricular leads via cephalic access, if possible. Inserting one or two leads is usually not a problem. There are many inventive ways for doing this, described in literature. Some operators go even further – they use cephalic vein to implant all three leads of cardiac resynchronization therapy (CRT) systems with the success rate of 87.7% - 91.7%.10,11The question of long-term reliability of the leads implanted in such a way is still open. They are tightly packed in one small vessel and possible lead - lead interaction may contribute to their failure. Especially the ICD leads, by definition more complex and sensitive, are prone to damage in these circumstances.Another possible locus minoris resistentiae is the site of cephalic vein ligation after the lead insertion. The line between an adequate and too strong suture tightening is quite narrow. The effort to stop the bleeding from the vein may cause ligation-induced lead insulation damage. Recently, Kajiyama et al. proposed a novel technique for the ligation of the cephalic vein during a two-in-one insertion of the leads.12 It reduces hemorrhaging without decreasing the lead safety.The discussion about the benefits of different vascular access should include the potential disadvantages of future lead extraction, especially in the multi-lead systems. Inserting more than one lead via cephalic vein may determine more problematic transvenous lead extraction procedure (TLE). It may also necessitate the extraction of the functioning lead because of its periprocedural damage during the TLE of the initially targeted lead.The reliability of ICD leads is certainly the most important feature. During the last decades several lead models produced by different manufacturers were recalled because of their serious technical defects. Numerous concerns and divergent literature data regarding the durability of the Linox lead were the premise for the authors to conduct the discussed study. An important observation is that all analyzed lead models, including Linox, were similar in terms of performance (p=0.769).Young and physically active patients were traditionally believed to have a higher risk of lead damage because of the intensive mechanical interaction between the lead and anatomical structures of costoclavicular space. This observation was not confirmed by the authors of the commented paper.The study has several limitations and they are all listed by the authors. The lack of multivariate risk factors analysis is the most important drawback. It could not be performed due to the low overall event rate. All interesting study findings require validation and further investigation.As the ICD lead failure is still a serious problem, the study investigating possible risk factors is always of great importance. With all the limitations, the paper presented by Barbhaiya et al. may be an important guide in dealing with the vascular access during CIED implantations. It sheds new light on the dogma of superiority of cephalic access. What is particularly important in the study outcome and what I personally find a very strong recommendation – is the conclusion that the multiple lead systems should be avoided, if not indicated, especially when combined with cephalic venous access. One possible solution is to use cephalic vein for one lead only. Prospective randomized studies directly comparing axillary and cephalic access would be highly desirable in order to come closer to the idea of the best vascular approach for the endocardial lead implantation.1. Knight BP, Curlett K, Oral H, Pelosi F, Morady F, Strickberger SA. Clinical predictors of successful cephalic vein access for implantation of endocardial leads. J Interv Card Electrophysiol.2002;7(2):177-180.2. Benz AP, Vamos M, Erath JW, Hohnloser SH. Cephalic vs. subclavian lead implantation in cardiac implantable electronic devices: a systematic review and meta-analysis. Europace.2019;21(1):121-129.3. Shaikh ZA, Chung JA, Kersten DJ, et al. Differences in Approaches and Outcomes of Defibrillator Lead Implants Between High-Volume and Low-Volume Operators: Results From the Pacemaker and Implantable Defibrillator Leads Survival Study (”PAIDLESS”). J Invasive Cardiol. 2017;29(12):E184-E189.4. Chan NY, Kwong NP, Cheong AP. Venous access and long-term pacemaker lead failure: comparing contrast-guided axillary vein puncture with subclavian puncture and cephalic cutdown. Europace.2017;19(7):1193-1197.5. Gallik DM, Ben-Zur UM, Gross JN, Furman S. Lead fracture in cephalic versus subclavian approach with transvenous implantable cardioverter defibrillator systems. Pacing Clin Electrophysiol.1996;19(7):1089-1094.6. Belott P. How to access the axillary vein. Heart Rhythm.2006;3(3):366-369.7. Liccardo M, Nocerino P, Gaia S, Ciardiello C. Efficacy of ultrasound-guided axillary/subclavian venous approaches for pacemaker and defibrillator lead implantation: a randomized study. J Interv Card Electrophysiol. 2018;51(2):153-160.8. Squara F, Tomi J, Scarlatti D, Theodore G, Moceri P, Ferrari E. Self-taught axillary vein access without venography for pacemaker implantation: prospective randomized comparison with the cephalic vein access. Europace. 2017;19(12):2001-2006.9. Bongiorni MG, Proclemer A, Dobreanu D, et al. Preferred tools and techniques for implantation of cardiac electronic devices in Europe: results of the European Heart Rhythm Association survey.Europace. 2013;15(11):1664-1668.10. Vogler J, Geisler A, Gosau N, et al. Triple lead cephalic versus subclavian vein approach in cardiac resynchronization therapy device implantation. Sci Rep. 2018;8(1):17709.11. Hadjis A, Proietti R, Essebag V. Implantation of cardiac resynchronization therapy devices using three leads by cephalic vein dissection approach. Europace. 2017;19(9):1514-1520.12. Kajiyama T, Ueda M, Ishimura M, et al. A novel technique for ligation of the cephalic vein reduces hemorrhaging during a two-in-one insertion of dual cardiac device leads. Indian Pacing Electrophysiol J. 2018;18(4):152-154.

Samia ricini, a gigantic saturniid moth, has the potential to be a novel lepidopteran model species. Since S. ricini is much more tough and resistant to diseases than the current model species Bombyx mori, the former can be easily reared compared to the latter. In addition, genetic resources available for S. ricini rival or even exceed those for B. mori: at least 26 eco-races of S. ricini are reported and S. ricini can hybridise with wild Samia species, which are distributed throughout Asian countries, and produce fertile progenies. Physiological traits such as food preference, integument colour, larval spot pattern, etc. are different between S. ricini and wild Samia species so that those traits can be the target for forward genetic analysis. In order to facilitate genetic research in S. ricini, we determined the whole genome sequence of S. ricini. The assembled genome of S. ricini was 458 Mb with 155 scaffolds, and the N50 length of the assembly was approximately 21 Mb. 16,702 protein coding genes were predicted in the assembly. Although the gene repertoire of S. ricini was not so different from that of B. mori, some genes, such as chorion genes and fibroin genes, seemed to have specifically evolved in S. ricini.

Background The covid 19 positive patient who is subject to a hyperinflammatory condition associated with lung injury with the development of pneumonia is hospitalized in the intensive care unit. Before resolving and overcoming the “cytokine storm”, with overexpression of pro-inflammatory interleukins (IL-, Il-6), this patient will be intubated for more than 48 hours and therefore needs adequate nutrition. Experimental approach Malnutrition can lead to sarcopenia with a decrease in lean body mass and worsening of the inflammatory state underway. In addition, severe debilitation, if not corrected with adequate nutrition, can greatly lengthen rehabilitation times with prolonged hospitalization, increased costs and reduced turn over already in crisis due to the health emergency caused by coronavirus. Key Results The aim of this study is to focus attention on the nutritional importance that must be provided in case of covid 19 together with pharmacological treatments to lower the number of circulating proinflammatory cytokines. Conclusions Oral, enteral and parenteral nutrition should always be carried out according to the patient’s condition and, in the case of a hyperinflammatory patient, such as the one affected by covid 19, it has been shown that the supplementation of amino acids helps to lower the inflammatory state and promotes normal recovery physiological. Keywords: amino acids, nutrition, covid, glutamine, hyperinflammatory, sarcopenia, cytokine.