Background Post-Cardiotomy ECMO (PC-ECMO) represents a unique subset of critically ill patients, with a paucity of data regarding long-term survival, and characteristics correlated with short and long-term outcomes. We present a retrospective cohort PC patients supported with ECMO at a single institution, with outcomes at 1 and 3-year follow-up. Methods Data was collected retrospectively for all patients requiring ECMO within 72 hours of index cardiac operation, excluding assist devices and heart transplantation. Operative data, frozen mediastinum status, cannulation site, postoperative hemorrhage, and timing of cannulation (immediate versus delayed) were all collected and examined. Primary outcomes were ability to wean from ECMO, hospital survival, and long-term survival. Results 33 patients required PC ECMO, representing a total of 179 days of ECMO support. Overall survival data were: ability to wean 61%, hospital survival 55%, one month survival 45%. The estimated 12 and 36 month survival for all PC ECMO patients was 40% and 33% respectively. Twelve and 36 month survival for all hospital survivors was 66% and 60% respectively. Operative times, type of operation performed, open chest status, reoperation for hemorrhage and cannulation location (central/peripheral) were all compared. There were no statistically significant relationships of these variables short or long-term survival. Conclusions Overall 12 month survival for PC-ECMO patients was 40%, and was 33% at 36 months. For hospital survivors, 1 year survival was 66%, and was 60% at 36 months. These data support PC-ECMO as a reasonable salvage strategy, with mid-term survival comparable to other surgically treated diseases.
Isoflavonoid is one of the groups of flavonoids that play pivotal roles in the survival of land plants. Chalcone synthase (CHS), the first enzyme of the isoflavonoid biosynthetic pathway, catalyzes the formation of a common isoflavonoid precursor. We have previously reported that an isozyme of soybean CHS (termed GmCHS1) is a key component of the isoflavonoid metabolon, a protein complex to enhance efficiency of isoflavonoid production. Here, we determined the crystal structure of GmCHS1 as a first step of understanding the metabolon structure, as well as to better understand the catalytic mechanism of GmCHS1.
Minimum energy structures of neutral and radical cations of end substituted thia[n]helicenes (n=1-10) in DCM solvent are reported. For both neutral and radical cations of these helicenes, calculated structures are non-planar for n=3-10. Helical structures are obtained for higher helicenes and thiahelicene system has a helical structure with one complete turn. Equilibrium geometries are predicted applying B3LYP-D/6-311++G(d,p) method in conjunction with SMD solvent model. Single point energy calculations are also performed at MP2 level to improve certain energy parameters. Excited state calculations are performed using Time-Dependent Density Functional Theory (TDDFT) formalism to predict UV-Visible spectra of neutral and radical cations of thia[n]helicenes in DCM solvent. Thia[n]helicenes radical cation have strong absorption in the near IR region. Calculations also suggest that dimerization is not a favourable process in DCM solvent for the end substituted neutral and radical cation of thiahelicene. The present theoretical study examines the molecular and electronic properties of thia[n]helicenes in search of near infrared electronic devices.
The pandemic outbreaks of coronavirus disease 2019 (COVID-19) was first discovered in Wuhan, Hubei, China in December 2019. The COVID-19 was caused by the novel coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It took 30 days to spread to all provinces of China . Recently, the confirmed cases of COVID-19 have been reported from about 200 countries or regions on March 30, 2020, and killed almost 30 thousand people . Efficient identification of the infection by SARS-CoV-2 has been one of the most important tasks to facilitate all the following counter measurements in dealing with infectious disease. In Taiwan, a COVID-19 Open Science Platform adhering to the spirit of open science: sharing sources, data, and methods to promote progress in academic research while corroborating findings from various disciplines has established in mid-February 2020, for collaborative research in support of the development of detection methods, therapeutics, and a vaccine for COVID-19. Research priorities include infection control, epidemiology, clinical characterization and management, detection methods (including viral RNA detection, viral antigen detection, and serum antibody detection), therapeutics (neutralizing antibody and small molecule drugs), vaccines, and SARS-CoV-2 pathogenesis. In addition, research on social ethics and the law are included to take full account of the impact of the COVID-19 virus.
Membranes with asymmetric wettability-Janus membranes-have recently received considerable attention for a variety of critical applications. Nonetheless, the current methods for making such membranes are still challenging. Here, we report on a simple approach to introduce asymmetric wettability into hydrophilic porous domains. Our approach is based on the physicochemical-selective deposition of polytetrafluoroethylene (PTFE) on hydrophilic polymeric substrates. The physicochemical inhibition was achieved through prefilling the substrates with glycerol, containing a known amount of free radical inhibitors. We showed that the glycerol/inhibitor mixture hinders the deposition of PTFE within the membrane pores. As a result, the surface of the substrates remains open and porous. The fabricated Janus membranes show stable wetting-resistant properties, evaluated through sessile drop contact angle measurements and direct contact membrane distillation (DCMD).
We present a patient with a rare ectopic retrosternal goitre that underwent a right hemithyroidectomy via an open cervical and video assisted thoracoscopic surgery (VATS). This case report reviews the work-up and radiological features of retrosternal goitre(RSG) and provides an update on the management of RSG.
Abstract: The objective of this study was to identify patient and hospitalization characteristics associated with in-hospital mortality in infants with truncus arteriosus. We conducted a retrospective analysis of a large administrative database, the National Inpatient Sample dataset of the Healthcare Cost and Utilization Project for the years 2002–2017. We also sought to evaluate the resource utilization in the subgroup of subjects with truncus arteriosus and 22q11.2 deletion syndrome. Neonates with truncus arteriosus were identified by ICD-9 and ICD-10 codes. Hospital and patient factors associated with inpatient mortality were analyzed. Overall, 3009 neonates met inclusion criteria; a total of 326 patients died during the hospitalization (10.8%). Extracorporeal membrane oxygenation utilization was 7.1 %. Univariate and multivariate logistic regression analyses were used to identify risk factors for in-hospital mortality. Independent risk factors for mortality were prematurity (aOR = 2.43, 95% CI: 1.40–4.22, p = 0.002), diagnosis of stroke (aOR = 26.2, 95% CI: 10.1–68.1, p < 0.001), necrotizing enterocolitis (aOR = 3.10, 95% CI: 1.24–7.74, p = 0.015) and presence of venous thrombosis (aOR = 13.5, 95% CI: 6.7–27.2, p < 0.001). Patients who received ECMO support or had cardiac catheterization procedure during the hospitalization had increased odds of mortality (aOR = 82.0, 95% CI: 44.5–151.4, p < 0.001, and aOR = 1.65, 95% CI: 0.98–2.77, p = 0.060, respectively). 22q11.2 deletion syndrome was associated with an inverse risk of death despite having more non-cardiac comorbidities; this patient subpopulation also had a higher length of stay and increased cost of hospitalization.
Introduction: The clinical efficacy and safety of hot balloon ablation (HBA) for treatment of persistent AF (PerAF) remain unclear. We aimed to evaluate the clinical efficacy and safety of HBA vs. cryoballoon ablation (CBA) as treatment for PerAF. Methods: Of 195 consecutive patients who underwent initial catheter ablation for PerAF (AF lasting >7 days but <12 months), 158 propensity score-matched (79 HBA and 79 CBA) patients were included in our study. All patients who underwent HBA received applications of energy to the upper posterior LA wall with a larger balloon in addition to single shots to each pulmonary vein (PV) ostium, whereas those who underwent CBA received simple single-shot applications. The electrically isolated surface area (ISA), including the PV antrum and part of the posterior LA wall, was assessed by high-resolution mapping. Results: Success of the PV isolation with balloon shots alone did not differ between HBA and CBA (81% vs. 85%; P = 0.52). The ISA was generally wide in both groups and significantly larger in the HBA group than in the CBA group (61 ± 16% vs. 51 ± 12%, P < 0.001). The incidence of procedure-related complications did not differ significantly (HBA 4% vs. CBA 1%; P = 0.62) nor did the arrhythmia recurrence rate (HBA 11% vs. CBA 18% at 18 months; P = 0.26). Conclusion: Despite the difference in protocols, HBA and CBA performed for PerAF appear comparable in terms of wide antral lesion creation, clinical efficacy, and safety.
Nitric oxide (NO) is a unique signaling molecule in the mammalian species. NO is produced by a variety of cell types to elicit distinct physiological actions. In the vascular system, NO is produced by the endothelium, a single layer of cells forming the inner lining of all blood vessels. Endothelium-derived NO has several different functions, one of which is vascular smooth muscle relaxation, resulting in vasodilation and a consequent decrease in blood pressure and increase in local blood flow. In the erectile tissue, NO is released as a neurotransmitter from the nerves innervating the corpus cavernosum during sexual stimulation, and causes profound smooth muscle relaxation and increased blood flow to the erectile tissue. This results in engorgement with blood and consequent penile erection.The uniqueness of NO as a signaling molecule derives, at least in part, by the fact that it is a gaseous molecule in its native state. However, despite being a gas, NO, like oxygen (O2), elicits its pharmacological effects as a solute in aqueous solution. Another unique characteristic of NO is its fleeting action because of its highly unstable chemical nature and reactivity. Unlike many other signaling molecules, NO elicits its wise array of physiological effects by distinct mechanisms. For example, vascular and nonvascular smooth muscle relaxation, and inhibition of platelet function are mediated by intracellular cyclic GMP (cyclic 3’, 5’-guanosine monophosphate). NO elicits many cyclic GMP-independent effects as well. For example, nitric oxide is a reactive free radical that can covalently modify protein function. One good example is protein S-nitrosylation, which can result in both regulatory and aberrant effects. By this and a variety of other mechanisms, NO also reacts with other molecules, such as reactive oxygen species, in invading cells such as bacteria, parasites and viruses to kill them or inhibit their replication or spread.The first pharmacological action of nitric oxide, demonstrated several years before it’s production in mammals was actually discovered, was vascular and nonvascular smooth muscle relaxation. One of many examples of the latter is the smooth muscle enveloping the sinusoidal cavities within the corpus cavernosum. Another important example is the airway smooth muscle in the trachea and bronchioles of the lungs. Indeed, inhalation of NO gas causes bronchodilation and increased delivery of air into the lungs. However, perhaps more significant than the bronchodilator effect of inhaled NO is its vasodilator effect. In fact, advantage was taken of the vasodilator action of NO in the lungs by Warren Zapol, MD, from the Massachusetts General Hospital in Boston, who discovered that inhalation of very small amounts of NO gas by newborn babies with life-threatening, persistent pulmonary hypertension (PPHN) results in a dramatic and permanent reversal of pulmonary vasoconstriction. Inhaled NO (INO) literally turned blue babies into pink babies. Without INO, most babies would have died while others would have required highly invasive procedures (extracorporeal membrane oxygenation; ECMO) to oxygenate their lungs, and may not have survived.Regarding its antiviral action, NO has been shown to increase the survival rate of mammalian cells infected with SARS-CoV (Severe Acute Respiratory Syndrome caused by coronavirus). In an in vitrostudy, NO donors (i.e., S-nitroso-N-acetylpenicillamine) greatly increased the survival rate of SARS-CoV-infected eukaryotic cells, suggesting direct antiviral effects of NO (1). In this study, NO significantly inhibited the replication cycle of SARS CoV in a concentration-dependent manner. NO also inhibited viral protein and RNA synthesis. Furthermore, NO generated by inducible nitric oxide synthase inhibited the SARS CoV replication cycle. The coronavirus responsible for SARS-CoV shares most of the genome of COVID- 19 indicating potential effectiveness of inhaled NO therapy in these patients.In 2004, during the SARS-CoV outbreak in China, the administration of inhaled NO reversed pulmonary hypertension, improved severe hypoxia and shortened the length of ventilatory support as compared to matched control patients with SARS-CoV (2). The mechanism of action was thought to be pulmonary vasodilation and consequent improved oxygenation in the blood of the lungs, thereby killing the virus, which does not do well in a high oxygen environment. In addition, however, I would offer the opinion that the NO also interacts directly with the virus to kill it and/or inhibit its replication, as shown in a prior study (1).Although studies have not yet been reported with COVID-19, NO has been shown to have an antiviral effect on several DNA and RNA virus families (3). The NO-mediated S-nitrosylation of viral molecules might be an intriguing general mechanism for the control of the virus life cycle. In this regard, it is conceivable that NO could nitrosylate cysteine-containing enzymes and proteins, including nucleocapsid proteins and glycoproteins, present in the coronavirus.In view of the knowledge gained by treating SARS-CoV patients with INO, it follows that INO might be effective in patients with the current SARS CoV-2 (COVID-19) infection. Indeed, a clinical trial of inhaled nitric oxide in patients with moderate to severe COVID-19 with pneumonia and under assisted ventilatory support recently received IRB (Institutional Review Board) approval at the Massachusetts General Hospital. Warren Zapol is director of this project. This trial has now been expanded to include at least two additional hospitals in the U.S. In the successful treatment of persistent pulmonary hypertension in newborns, the amount of NO inhaled is generally one ppm (part per million). In the clinical trial using COVID-19 patients, the amount of NO will be approximately 100-fold higher, about 100 ppm. This is a safe dose of INO, which could prove to be effective in killing the virus and allowing recovery of the patient. The effective use of INO would also lessen the need for oxygen, ventilators, and beds in the ICU.One thing I urge everyone to practice during this coronavirus pandemic is to breathe or inhale through your NOSE and exhale through your mouth. Swedish investigators at the Karolinska Institute in Stockholm have shown that the cells and tissues in the nasal sinusoids, but not the mouth, constantly and continuously produce nitric oxide, which is a gas, and can be easily detected in the exhaled breath. The physiological significance of this is that nasally-derived NO, when inhaled through the nose, improves oxygen delivery into the lungs by causing bronchodilation. This physiological action of inhaled NO is well-known by competitive athletes, especially runners. Moreover, when inhaling through the nose, your nasal nitric oxide is inhaled into your lungs where it stands a chance of meeting up with the coronavirus particles and killing them or inhibiting their replication. Inhaling through your mouth will NOT accomplish this. By the same token, exhaling through your nose is highly wasteful in that you would be expelling the NO away from the lungs, where it is needed most.“INHALE THROUGH YOUR NOSE, AND EXHALE THROUGH YOUR MOUTH!”
Background: This bibliometric analysis is used to identify publications and highlights the key areas that have significantly shaped modern clinical practice for aortic valve replacement (AVR), which is becoming increasingly relevant. The top 100 most cited manuscripts for AVR were analysed. Method: The Thomson Reuters Web of Science database was searched using the terms ‘aortic valve replacement’, ‘replacement’, ‘aortic valve’ and/or ‘AVR’ for full manuscripts in English Language. The results were ranked by citation number and the top 100 articles were further analysed by subject, author, journal, year of publication, institution and country of origin. Results: 26,782 eligible papers were returned and accumulated 76,680 citations in total, with a mean citation of 767 per manuscript (350-3667). The New England Journal of Medicine accumulated the most citations whereas Circulation published the most papers. Majority of manuscripts examined patients with aortic stenosis, of which half also included aortic regurgitation. The United States of America contributed 51 manuscripts, accumulating 43629 citations. Conclusion: The most cited manuscript, by Leon et al., assessed the outcomes of transcatheter aortic valve implantation in patients with severe aortic stenosis who were unfit for surgical replacement. By providing the most influential references this work serves as a guide to topics of interest in the field of AVR.
We report a case of 41-year-old woman who presented with chest tightness and shortness of breath. Transthoracic echocardiogram (TTE) showed left ventricular (LV) pseudo-aneurysm of the inferior wall with preserved LV systolic function. Coronary angiogram was normal. Surgical repair of the pseudo-aneurysm with a pericardial patch was performed, and pathological results confirmed rupture of an isolated congenital LV diverticulum.as the most likely etiology.
The 2019–20 coronavirus (COVID-19) pandemic was affirmed to have spread to Bangladesh on March 2020. The initial three known cases were accounted for by the nation’s Institute of Epidemiology, Disease Control and Research (IEDCR) on 7 March 2020 . As of 9th April 2020, the Government of Bangladesh has reported that there is a total of 330 confirmed cases, 33 recoveries, and 21 deaths in the whole country . In this research, I try to forecast the COVID-19 outbreak in Bangladesh by using a well-known epidemiological model, Susceptible-Infectious-Recovered (SIR) model.
In hemophilia A and B, analysis of the F8 and F9 variants has become standard over recent decades, giving information on the severity of hemophilia, inhibitor formation and allowing counseling for the families. The PedNet Registry collects data on hemophilia in children and has more than 2000 children listed. Genetic reports are collected uniformly and re-evaluated following international guidelines. We report 90 novel variants in the F8 and F9 gene, respectively, causing hemophilia with detailed information on severity, factor level and inhibitor formation. This will lead to further guidance for genetic laboratories and the treating physician. These findings can be implemented in hemophilia variant databases. The study highlights the need to re-evaluate and update earlier genetic reports in hemophilia both locally but also in variant databases in the light of changed nomenclature, the use of in silico prediction and new sequencing techniques.
The complement system is a well-characterised cascade of extracellular serum proteins that is activated by pathogens and unwanted waste material. Products of activated complement signal to host cells via cell-surface receptors, illicting responses such as removal of the stimulus by phagocytosis. The complement system therefore functions as a warning system, resulting in removal of unwanted material. This review describes how extracellular activation of the complement system can also trigger autophagic responses within cells, upregulating protective homeostatic autophagy in response to perceived stress, but also intiating targeted anti-microbial autophagy in order to kill intracellular cyto-invasive pathogens. In particular, we will focus on recent discoveries that complement may also have roles in detection and autophagy-mediated disposal of unwanted materials within the intracellular environment. We therefore summarize the current evidence for complement involvement in autophagy, both by transducing signals across the cell membrane, as well as roles within the cellular environment.
Most cell penetrating peptides (CPPs) are unstructured and susceptible to proteolytic degradation. One alternative is to incorporate D-chirality amino acids into unstructured CPPs to allow for enhanced uptake and intracellular stability. This work investigates CPP internalization using a series of time, concentration, temperature, and energy dependent studies, resulting in a three-fold increase in uptake and 50-fold increase in stability of D-chirality peptides over L-chirality counterparts. CPP internalization occurred via a combination of direct penetration and endocytosis, with a percentage of internalized CPP expelling from cells in a time-dependent manner. Mechanistic studies identified that cells exported the intact internalized D-chirality CPPs via an exocytosis independent pathway, analogous to a direct penetration method out of the cells. These findings highlight the potential of D-chirality CPPs as bio-vectors in therapeutic and biosensing applications, but also identify a new expulsion method suggesting a relationship between uptake kinetics, intracellular stability, and export kinetics
This paper reports on the results of research aimed to translate biometric 3D face recognition concepts and algorithms into the field of protein biophysics in order to precisely and rapidly classify morphological features of protein surfaces. Both human faces and protein surfaces are free-forms and some descriptors used in differential geometry can be used to describe them applying the principles of feature extraction developed for computer vision and pattern recognition. The first part of this study focused on building the protein dataset using a simulation tool and performing feature extraction using novel geometrical descriptors. The second part tested the method on two examples, first involved a classification of tubulin isotypes and the second compared tubulin with the FtSZ protein, which is its bacterial analogue. An additional test involved several unrelated proteins. Different classification methodologies have been used: a classic approach with a Support Vector Machine (SVM) classifier and an unsupervised learning with a k-means approach. The best result was obtained with SVM and the radial basis function (RBF) kernel. The results are significant and competitive with the state-of-the-art protein classification methods. This opens a new area for protein structure analysis.