Background: Cardiac resynchronisation therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. Methods: Data was collected from three CRT-D implanting centres between October 2008 – September 2017. In total 631 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of ‘cephalic’ (ICD lead via cephalic) vs ‘non-cephalic’ (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. Results: The cephalic and non-cephalic cohorts were equally male (82.2% vs 78.3%, p=0.28), similar in age (69.7±11.5 vs 68.7 ± 11.9, p=0.33) and body mass index (BMI) (27.7±5.1 vs 27.1±5.7, p=0.33). Most ICD leads were implanted via the cephalic vein (73.7%) and patients had a median of 2.8 leads implanted via this route. The rate of ICD lead failure was low and similar between both groups (0.4%/year vs 0.14%/year, p=0.34). Female gender was more common in the lead failure cohort than non-failure (50% vs 18.2%, respectively, p=0.01) as was hypertension (90% vs 54%, respectively, p=0.03). On multivariate Cox regression, female sex (p=0.007), hypertension (p=0.041) and BMI (p=0.042) were significantly associated with ICD lead failure. Conclusion: CRT-D implantation via the cephalic route is not associated with premature ICD lead failure. Female gender, BMI and hypertension correlate with lead failure.

The coronavirus disease 2019 pandemic (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented global social and economic impact, and numerous deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung disease, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type-I interferon secretion capacity, and pregnancy. Possible complications include acute respiratory distress syndrome, shock, disseminated coagulopathy, acute kidney injury, pulmonary embolism, and secondary bacterial pneumonia. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1, Krebs von den Lungen-6 (KL-6) and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of COVID-19.

Abstract Objectives: The use of minimally invasive or transcatheter interventions rather than standard full sternotomy operations to treat Tricuspid valve disease is increasing. Debate however is still open regarding venous drainage management during cardiopulmonary bypass and wheatear or not superior and inferior vena cava should be occluded during opening of the right atrium to avoid air entrance in the venous line. The aim of the present study is to report operative outcomes and mid-term follow-up results of minimally invasive tricuspid valve surgery performed without caval occlusion. Methods: This is a retrospective outcome evaluation from institutional records with prospective data entry. We searched for all the patients who underwent right mini-thoracotomy tricuspid valve surgery isolated or combined with mitral valve surgery during the period June 2013 – February 2020. Results: During the study period 68 consecutive patients underwent minimally invasive tricuspid valve surgery without occlusion of cava veins. Survival at a 5-year and 8-year follow up was 100% and 79%, respectively. At follow-up no patient had an NHYA class greater than two, only one patient was re-hospitalized for heart failure for an atrial fibrillation episode. One patient was hospitalized for a pericardiocentesis twenty days after discharge No severe tricuspid regurgitation was evident at echocardiographic follow up. Five patients had 2+ TR. Conclusion Our results show that performing tricuspid surgery without caval occlusion is safe. There is no clinical evidence of gas embolism. Mid-term follow up data confirm that minimally invasive approach does not alter the quality of surgery.

Background: Powered transvenous lead extraction (TLE) tools are commonly required to remove the leads that have long implant duration due to fibrotic adhesions. However, comparative data are lacking among different types of TLE tools. Aim: To compare the efficacy and safety of two different rotational mechanical dilator sheaths in retrospectively analyzed patients who underwent TLE. Methods and results: A total of 566 lead extractions from 302 patients using TightRailTM (333 lead extractions from 169 patients) and Evolution® (233 lead extractions from 133 patients) mechanical dilator sheaths were performed between July 2009 and June 2018. Acute and long term outcomes of study groups were compared. There is no statistically significant difference between Evolution® and TightRailTM groups in procedural success (93.9% vs. 94%), clinical success (99.2% vs. 98%) and major complications (3.8% vs. 1.2%), respectively (p>0.05). In multivariate regression analysis, lead dwell time, the number of extracted leads, and baseline leukocyte count was found as independent predictors of procedural success (p<0.05). During the median follow-up of 36.6 (0.2-118) months, all-cause mortality was observed in 73 patients (25.6% in the Evolution® vs. 23.1 in the TightRailTM group, p>0.05). Chronic renal disease, heart failure, and coagulopathy were shown as independent predictors of all-cause mortality in multivariate regression analysis (p<0.05). Conclusions: TLE using TightRailTM or Evoluation® mechanical dilator sheaths is a safe and effective therapeutic option. Both mechanical dilator sheaths showed similar efficacy, safety, and all-cause mortality at acute and long-term follow-up of patients who underwent TLE.

The burbot (Lota lota) is the only member of the cod family (Gadidae) that is adapted solely to freshwater. This species shows the widest longitudinal range of freshwater fish in the world. The burbot is a good model for studies on adaptive genome evolution from marine to freshwater environment. However, no high-quality reference genome has been released. Here, the first chromosome-level genome of the burbot was constructed using PacBio long sequencing and Hi-C technology. A total of 95.24 Gb polished PacBio sequences were generated, and the preliminary genome assembly was 575.83 Mb in size with a contig N50 size of 2.15 Mb. The assembled sequences were anchored to 22 pseudo-chromosomes by using the Hi-C data. The final assembled genome after Hi-C correction was 575.92 Mb, with a contig N50 of 2.01 Mb and a scaffold N50 of 22.10 Mb. A total of 22,067 protein-coding genes were predicted, 94.82% of which were functionally annotated. Phylogenetic analyses indicated that burbot diverged with the Atlantic cod about 44.4 million years ago. In addition, 377 putative genes that appear to be under positive selection in burbot were identified. These positively selected genes might adapt to the freshwater environment. These genome data provide an invaluable resource for the ecological and evolutionary study of the order Gadiformes.

This manuscript reviews the book ‘Process Intensification – Breakthrough in Design, Industrial Innovation Practices, and Education’, published by Jan Harmsen and Maarten Verkert, De Gruyter (2020), ISBN: 978-3-11-065734-0, 219 pages.

Recent decades have seen a change in the runoff characteristics of the Suntar River in Eastern Siberia. This study attempts to attribute these changed hydrological conditions through parameterizing a hydrological model based on historical short-term observations conducted in 1957-1959 at the Suntar-Khayata research station. The Hydrograph model is applied as it has the advantage of using observed physical properties of landscapes as its parameters. The developed parametrization of the goltsy landscape (rocky-talus) is verified by comparison of the results of simulations of variable states of snow and frozen ground with observations carried out in 1957-1959. Continuous simulations of streamflow on a daily time step are conducted for the period 1957-2012 in the Suntar River (area 7680 km2, altitude 828-2794 m) with mean and median values of Nash-Sutcliff criteria reaching 0.58 and 0.67 respectively. The results of simulations have shown that the largest component of runoff (about 70%) is produced in the high-altitude area which comprises only 44% of the Suntar River basin area. The simulated streamflow reproduces the patterns of recently observed changes, including the increase in low flows, suggesting that the increase in the proportion of liquid precipitation in autumn due to air temperature rise is an important factor in driving streamflow changes in the region. The data presented are unique for the vast mountainous parts of North-Eastern Eurasia which play an important role in global climate system. The results indicate that parameterizing a hydrological model based on observations rather than blind calibration allows the model to be used in studying the response of river basins to climate change with greater confidence.

In this article, the Cauchy problem of three-dimensional (3-D) incompressible magnetohydrodynamic system with infinite energy initial data is investigated. Via some elaborate analysis of the time evolution of both the vorticity ω=: ▽×u and the current density j=: ▽×b , the local-in-time well-posedness of mild solutions with arbitrarily large initial data in Morrey spaces is established.

Temozolomide (TMZ) is a standard of care treatment for Glioblastoma Multiforme (GBM). We report a fatal outcome of a 55 years old female with GBM who developed persistent aplastic anemia (AA) while being treated with TMZ. This case highlights the possibility of a dose-independent and fatal AA secondary to TMZ.

Incoordination during the pharyngeal phase in severe dysphagia due to lateral medullary syndromeRunning title: Severe dysphagia due to LMS

We report a 56-year-old male with methemoglobinemia and hemolytic anemia, secondary to fava bean ingestion. Methylene blue administration worsened the hemolysis as he was G6PD deficient but not diagnosed before. We have discussed the mechanism of hemolysis in such patients and the management of such cases.

Inhibition of interleukin 6 (IL-6) signalling has been proposed as a potential cardioprotective strategy for patients with chronic kidney disease (CKD) but the direct renal effects of IL-6 inhibition are not established. A Mendelian randomization (MR) study was performed to investigate the association of genetically proxied inhibition of IL-6 signalling with estimated glomerular filtration rate (eGFR), CKD and blood urea nitrogen (BUN). Inverse variance weighted MR was used as the main analysis, with sensitivity analyses performed using simple median, weighted median and MR-Egger methods. There was no evidence for an association of genetically proxied inhibition of IL-6 signalling (scaled per unit decrease in natural log transformed C-reactive protein) with log eGFR (0.002, 95% confidence interval -0.004 – 0.008), BUN (0.088, 95% confidence interval -0.003 – 0.019) and CKD (odds ratio 1.018, 95% confidence interval 0.899 – 1.153). These findings suggest that inhibition of IL-6 signalling is unlikely to have a direct effect on renal function.

Background and Purpose The cyclic nucleotides cAMP and cGMP are ubiquitous second messengers participating in the regulation of several biological processes. Interference of cNMP signalling is linked to multiple diseases and thus is an important component of pharmaceutical research. The existing optogenetic toolbox in C. elegans is restricted to soluble adenylyl cyclases, the membrane-bound Blastocladiella CyclOp and hyperpolarizing rhodopsins, yet missing are membrane-bound photoactivatable adenylyl cyclases and hyperpolarizers on the basis of K+-currents. Experimental Approach For the characterization of the photoactivatable nucleotidyl cyclases, we expressed the proteins alone or in combination with cyclic-nucleotide gated channels in C. elegans muscle cells and cholinergic motor neurons. To investigate the extent of optogenetic cNMP production and the ability of the systems to de- or hyperpolarize the cells, we performed behavioural analyses (locomotion, muscle contraction) and measured the cNMP content in vitro. Key Results We implemented Catenaria CyclOp as a new tool for cGMP production, allowing fine-control of cGMP levels. As photoactivatable membrane-bound adenylyl cyclases, we established YFP::BeCyclOp(A-2x) and YFP::CaCyclOp(A-2x), enabling more specific optogenetic cAMP signalling compared to soluble ACs. For the hyperpolarization of excitable cells by K+-currents, we introduced the cAMP-gated K+-channel SthK from Spirochaeta thermophila with either bPAC or BeCyclOp(A-2x), and the Blastocladiella emersonii cGMP-gated K+-channel BeCNG1 with BeCyclOp. Conclusion and Implications We established a comprehensive suite of optogenetic tools for cNMP manipulation for the nematode, which will be useful for applications in many cell types, including sensory neurons which use mainly cGMP as second messenger, and for potent hyperpolarization using K+-ions.

Stuttering is a childhood onset fluency disorder, intertwined with physiological, emotional and anxiety factors. The present study was designed to evaluate the recurrence of the reported mutations among three previously implicated (GNPTAB, GNPTG, NAGPA) candidate genes, in persons with stuttering (PWS) from south India. Mutation screening was performed on 64 probands on 12 specific exons, by Sanger sequencing. A total of 12 variants were identified, which included five nonsynonymous missense, five synonymous and two non coding variants. Only three unrelated probands, harbored heterozygous likely pathogenic missense variants (c.3598G>A in GNPTAB, c.802A>C in GNPTG and c.131G>C in NAGPA) resulting in an overall frequency of 4.7% and an allele frequency of 2.3% (3/128*100). Among the three likely pathogenic variants only two co-segregated (c.3598G>A in GNPTAB - STU 29 and c.802A>C in GNPTG - STU 63) with the affected status reducing the likely pathogenic allele frequency to 1.6% (2/128*100). The recurrence of pathogenic variants in our study corroborate the causative role of these genes in stuttering but still remains unknown as to how the speech dysfluency occurs even in its heterozygous condition. Keywords: Stuttering, candidate genes, GNPTAB, GNPTG, NAGPA

A document by Igor Vendramin. Click on the document to view its contents.

Residual or recurrent symptoms after septal reduction therapy are most often related to inadequate relief of left ventricular outflow gradients. We recently encountered a 71-year-old woman with hypertrophic cardiomyopathy (HCM) and prior alcohol septal ablation who had a unique constellation of findings causing her symptoms. She was found to have four potential causes for her symptoms, residual midventricular obstruction, apical distribution of hypertrophy reducing end-diastolic volume, constrictive pericarditis, and marked arterial stiffness, as reflected by aortic atherosclerosis. She underwent complete pericardiectomy, transaortic septal myectomy, transapical myectomy, and replacement of a heavily calcified ascending aorta.

I read with interest the manuscript by Masroor and co-authors on the strategy of surgical repair for left atrial appendage perforation following implantation of Watchman device. The authors present the successful management of this complications and they comment on the preferred therapeutic strategy. This is a particular sensitive subject nowadays, since the widespread use and the constant growth of a variety of transcatheter cardiac interventions has inevitably increased the number of patients who are exposed to this type of complication.

The role of eosinophils in allergic inflammation is well recognized. In homeostasis these cells are found in multiple healthy tissues including the lung parenchyma, but the function of these resident eosinophils is unknown. Circulating eosinophils are easily quantifiable and have been used to define “eosinophilic phenotype”, and to select patients who are likely to respond to anti-eosinophil and anti-Th2—directed therapies. However, presence of eosinophils in circulation may not necessarily indicate that the eosinophils are key effector cells for an airway disease such as asthma and this may be reason for not all patients responding well to anti-IL5 therapies despite normalization of blood eosinophils. This pro-con commentary examines the role of enumerating circulating vs luminal (sputum) eosinophils (and their activation status) not only to initiate therapies with monoclonal antibodies, but to monitor their clinical response while on therapy.