Radiative Particle-in-Cell Simulations of Turbulent Comptonization in Magnetized Black-Hole Coronae.

We report results from the first radiative particle-in-cell simulations of strong Alfvénic turbulence in plasmas of moderate optical depth. The simulations are performed in a local 3D periodic box and self-consistently follow the evolution of radiation as it interacts with a turbulent electron-positron plasma via Compton scattering. We focus on the conditions expected in magnetized coronae of accreting black holes and obtain an emission spectrum consistent with the observed hard state of Cyg X-1. Most of the turbulence power is transferred directly to the photons via bulk Comptonization, shaping the peak of the emission around 100 keV. The rest is released into nonthermal particles, which generate the MeV spectral tail. The method presented here shows promising potential for ab initio modeling of various astrophysical sources and opens a window into a new regime of kinetic plasma turbulence.

Training in basic gastrointestinal endoscopic procedures: a European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement.

This ESGE Position Statement provides structured and evidence-based guidance on the essential requirements and processes involved in training in basic gastrointestinal (GI) endoscopic procedures. The document outlines definitions; competencies required, and means to their assessment and maintenance; the structure and requirements of training programs; patient safety and medicolegal issues. 1: ESGE and ESGENA define basic endoscopic procedures as those procedures that are commonly indicated, generally accessible, and expected to be mastered (technically and cognitively) by the end of any core training program in gastrointestinal endoscopy. 2: ESGE and ESGENA consider the following as basic endoscopic procedures: diagnostic upper and lower GI endoscopy, as well as a limited range of interventions such as: tissue acquisition via cold biopsy forceps, polypectomy for lesions ≤ 10 mm, hemostasis techniques, enteral feeding tube placement, foreign body retrieval, dilation of simple esophageal strictures, and India ink tattooing of lesion location. 3: ESGE and ESGENA recommend that training in GI endoscopy should be subject to stringent formal requirements that ensure all ESGE key performance indicators (KPIs) are met. 4: Training in basic endoscopic procedures is a complex process and includes the development and acquisition of cognitive, technical/motor, and integrative skills. Therefore, ESGE and ESGENA recommend the use of validated tools to track the development of skills and assess competence. 5: ESGE and ESGENA recommend incorporating a multimodal approach to evaluating competence in basic GI endoscopic procedures, including procedural thresholds and the measurement and documentation of established ESGE KPIs. 7: ESGE and ESGENA recommend the continuous monitoring of ESGE KPIs during GI endoscopy training to ensure the trainee's maintenance of competence. 9: ESGE and ESGENA recommend that GI endoscopy training units fulfil the ESGE KPIs for endoscopy units and, furthermore, be capable of providing the dedicated personnel, infrastructure, and sufficient case volume required for successful training within a structured training program. 10: ESGE and ESGENA recommend that trainers in basic GI endoscopic procedures should be endoscopists with formal educational training in the teaching of endoscopy, which allows them to successfully and safely teach trainees.

Perspectives and awareness of endoscopy healthcare professionals on sustainable practices in gastrointestinal endoscopy: results of the LEAFGREEN survey.

BACKGROUND: Gastrointestinal (GI) endoscopy is one of healthcare's main contributors to climate change. We aimed to assess healthcare professionals' attitudes and the perceived barriers to implementation of sustainable GI endoscopy. METHODS: The LEAFGREEN web-based survey was a cross-sectional study conducted by the European Society of Gastrointestinal Endoscopy (ESGE) Green Endoscopy Working Group. The questionnaire comprised 39 questions divided into five sections (respondent demographics; climate change and sustainability beliefs; waste and resource management; single-use endoscopes and accessories; education and research). The survey was available via email to all active members of the ESGE and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) in March 2023. RESULTS: 407 respondents participated in the survey (11% response rate). Most participants (86%) agreed climate change is real and anthropogenic, but one-third did not consider GI endoscopy to be a significant contributor to climate change. Improvement in the appropriateness of endoscopic procedures (41%) and reduction in single-use accessories (34%) were considered the most important strategies to reduce the environmental impact of GI endoscopy. Respondents deemed lack of institutional support and knowledge from staff to be the main barriers to sustainable endoscopy. Strategies to reduce unnecessary GI endoscopic procedures and comparative studies of single-use versus reusable accessories were identified as research priorities. CONCLUSIONS: In this survey, ESGE and ESGENA members acknowledge climate change as a major threat to humanity. Further improvement in sustainability beliefs and professional attitudes, reduction in inappropriate GI endoscopy, and rational use of single-use accessories and endoscopes are critically required.

Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024.

1: ESGE recommends cold snare polypectomy (CSP), to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of diminutive polyps (≤ 5 mm).Strong recommendation, high quality of evidence. 2: ESGE recommends against the use of cold biopsy forceps excision because of its high rate of incomplete resection.Strong recommendation, moderate quality of evidence. 3: ESGE recommends CSP, to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of small polyps (6-9 mm).Strong recommendation, high quality of evidence. 4: ESGE recommends hot snare polypectomy for the removal of nonpedunculated adenomatous polyps of 10-19 mm in size.Strong recommendation, high quality of evidence. 5: ESGE recommends conventional (diathermy-based) endoscopic mucosal resection (EMR) for large (≥ 20 mm) nonpedunculated adenomatous polyps (LNPCPs).Strong recommendation, high quality of evidence. 6: ESGE suggests that underwater EMR can be considered an alternative to conventional hot EMR for the treatment of adenomatous LNPCPs.Weak recommendation, moderate quality of evidence. 7: Endoscopic submucosal dissection (ESD) may also be suggested as an alternative for removal of LNPCPs of ≥ 20 mm in selected cases and in high-volume centers.Weak recommendation, low quality evidence. 8: ESGE recommends that, after piecemeal EMR of LNPCPs by hot snare, the resection margins should be treated by thermal ablation using snare-tip soft coagulation to prevent adenoma recurrence.Strong recommendation, high quality of evidence. 9: ESGE recommends (piecemeal) cold snare polypectomy or cold EMR for SSLs of all sizes without suspected dysplasia.Strong recommendation, moderate quality of evidence. 10: ESGE recommends prophylactic endoscopic clip closure of the mucosal defect after EMR of LNPCPs in the right colon to reduce to reduce the risk of delayed bleeding.Strong recommendation, high quality of evidence. 11: ESGE recommends that en bloc resection techniques, such as en bloc EMR, ESD, endoscopic intermuscular dissection, endoscopic full-thickness resection, or surgery should be the techniques of choice in cases with suspected superficial invasive carcinoma, which otherwise cannot be removed en bloc by standard polypectomy or EMR.Strong recommendation, moderate quality of evidence.

The Use of Inflammatory Markers for Treatment Response Monitoring in Acute Cholangitis: A Retrospective Cohort Study.

INTRODUCTION: In acute cholangitis (AC), monitoring treatment response to antimicrobial therapy allows for making timely decisions on early biliary decompression. The aims of this study were to compare the discriminating powers of traditional blood inflammatory markers and propose new inflammatory markers that have a better ability to distinguish between patients with and without biliary tract infection. METHODS: This was a retrospective cohort study. Patients who underwent endoscopic retrograde cholangio-pancreaticography for AC and those without biliary tract inflammation were randomly selected in the 4:3 ratio of their hospital admissions from our hospital endoscopic retrograde cholangio-pancreaticography database. The exclusion criterion was the absence of C-reactive protein (CRP) measurements. RESULTS: The discriminating powers of the neutrophil count, lymphocytes, albumin, neutrophil-to-lymphocyte ratio, and CRP were superior to that of white blood cell (P1 < 0.005; P2 = 0.004; P3 < 0.0005; P4 < 0.0005; P5 < 0.0005). In monitoring treatment response in AC, lymphocyte count, albumin, neutrophil-to-lymphocyte ratio, and CRP were better than neutrophil count (P6 = 0.037, P7 < 0.005, P8, 9 < 0.0005). The area under the receiver operating characteristic curve (AUC) of CRP was higher than the AUC for lymphocytes, 96% (95% confidence interval [CI]: 94-98%) versus 81% (95% CI: 76-86%) (P < 0.0005), and larger than the AUC for albumin, 88% (95% CI: 84-92%) (P < 0.0005), indicating a greater discriminating power of CRP. However, the discriminating power of CRP-to-lymphocyte ratio (CLR) was more than that for CRP (P = 0.006) but equal to CRP-to-(lymphocytes∗albumin) ratio (CLAR) (P = 0.249). The AUCs of CLR and CLAR were both 98% (95% CI: 96-99%). CONCLUSIONS: CLR and CLAR have superior discriminating powers than traditional inflammatory markers used for monitoring treatment response in AC.

Supplementation of a High-Fat Diet with Pentadecylresorcinol Increases the Representation of Akkermansia muciniphila in the Mouse Small and Large Intestines and May Protect against Complications Caused by Imbalanced Nutrition.

Imbalanced nutrition, such as a high-fat/high-carbohydrate diet, is associated with negative effects on human health. The composition and metabolic activity of the human gut microbiota are closely related to the type of diet and have been shown to change significantly in response to changes in food content and food supplement administration. Alkylresorcinols (ARs) are lipophilic molecules that have been found to improve lipid metabolism and glycemic control and decrease systemic inflammation. Furthermore, alkylresorcinol intake is associated with changes in intestinal microbiota metabolic activity. However, the exact mechanism through which alkylresorcinols modulate microbiota activity and host metabolism has not been determined. In this study, alterations in the small intestinal microbiota (SIM) and the large intestinal microbiota (LIM) were investigated in mice fed a high-fat diet with or without pentadecylresorcinol (C15) supplementation. High-throughput sequencing was applied for jejunal and colonic microbiota analysis. The results revealed that C15 supplementation in combination with a high-fat diet could decrease blood glucose levels. High-throughput sequencing analysis indicated that C15 intake significantly increased (p < 0.0001) the abundance of the probiotic bacteria Akkermansia muciniphila and Bifidobacterium pseudolongum in both the small and large intestines and increased the alpha diversity of LIM (p < 0.05), but not SIM. The preliminary results suggested that one of the mechanisms of the protective effects of alkylresorcinol on a high-fat diet is the modulation of the content of SIM and LIM and metabolic activity to increase the probiotic bacteria that alleviate unhealthy metabolic changes in the host.

Artificial pore blocker acts specifically on voltage-gated potassium channel isoform KV1.6.

Among voltage-gated potassium channel (KV) isoforms, KV1.6 is one of the most widespread in the nervous system. However, there are little data concerning its physiological significance, in part due to the scarcity of specific ligands. The known high-affinity ligands of KV1.6 lack selectivity, and conversely, its selective ligands show low affinity. Here, we present a designer peptide with both high affinity and selectivity to KV1.6. Previously, we have demonstrated that KV isoform-selective peptides can be constructed based on the simplistic α-hairpinin scaffold, and we obtained a number of artificial Tk-hefu peptides showing selective blockage of KV1.3 in the submicromolar range. We have now proposed amino acid substitutions to enhance their activity. As a result, we have been able to produce Tk-hefu-11 that shows an EC50 of ≈70 nM against KV1.3. Quite surprisingly, Tk-hefu-11 turns out to block KV1.6 with even higher potency, presenting an EC50 of ≈10 nM. Furthermore, we have solved the peptide structure and used molecular dynamics to investigate the determinants of selective interactions between artificial α-hairpinins and KV channels to explain the dramatic increase in KV1.6 affinity. Since KV1.3 is not highly expressed in the nervous system, we hope that Tk-hefu-11 will be useful in studies of KV1.6 and its functions.

Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial.

BACKGROUND: Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant, but modest, clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle cell (ASMC) area in COPD is associated with ICS responsiveness. METHODS: In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, Global Initiative for Chronic Obstructive Lung Disease stage B-D, underwent bronchoscopy with endobronchial biopsy. Patients were divided into groups A and B, with high ASMC area (HASMC: >20% of the bronchial tissue area) and low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively, and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium (ACL)/formoterol (FOR)/budesonide (BUD) (400/12/400 µg twice daily). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/placebo and followed for 12 months. The primary end-point of the study was the difference in post-bronchodilator forced expiratory volume in 1 s (FEV1) over 12 months between patients with LASMC and HASMC receiving or not receiving ICS. RESULTS: In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo (p=0.675). However, in patients with HASMC, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo (p=0.020). Over 12 months, the difference of FEV1 change between the ACL/FOR/BUD group and the ACL/FOR/placebo group was 50.6 mL·year-1 within the group of patients with LASMC and 183.0 mL·year-1 within the group of patients with HASMC. CONCLUSION: COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.

A simple clinical score to stratify the risk of procedure-related adverse events in ERCP procedures with trainee involvement.

BACKGROUND : Optimal training strategies in endoscopic retrograde cholangiopancreatography (ERCP) remain controversial despite the shift toward competence-based training models, with limited data available on patient safety during training. We aimed to assess whether pre-procedural clinical predictors could identify patients at low risk of developing procedure-related adverse-events (AEs) in a training environment. METHODS : We performed a prospective, multicenter, cohort study in five training centers. A data collection system documenting indication, clinical data, trainee performance (assessed using a validated competence assessment tool), technical outcomes, and AEs over a 30-day follow-up was utilized. We developed a clinical risk score (Trainee Involvement in ERCP Risk Score [TIERS]) for patients undergoing ERCP and compared the rate of AEs in a training environment between low-risk and high-risk groups. The association between trainee performance and AE rate was also evaluated. RESULTS : 1283 ERCPs (409 [31.9 %, 95 %CI 29.3 %-34.4 %] with trainee involvement) performed by 11 trainers and 10 trainees were analyzed. AEs were more frequent in the high-risk compared with the low-risk group: 26.7 % (95 %CI 20.5 %-34.7 %) vs. 17.1 % (95 %CI 12.8 %-22.2 %). TIERS demonstrated a high negative predictive value for AEs (82.9 %, 95 %CI 79.4 %-85.8 %) and was the only predictor of AEs on multivariable analysis (odds ratio 1.38, 95 %CI 1.09-1.75). Suboptimal trainee performance was associated with an increase in AE rates. CONCLUSION : Simple, clinical-based predictive tools could improve ERCP training by selecting the most appropriate cases for hands-on training, with the aim of increasing patient safety.

Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota.

Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.

Scattering of Ultrastrong Electromagnetic Waves by Magnetized Particles.

Observations of powerful radio waves from neutron star magnetospheres raise the question of how strong waves interact with particles in a strong background magnetic field B_{bg}. This problem is examined by solving the particle motion in the wave. Remarkably, waves with amplitudes E_{0}>B_{bg} pump particle energy via repeating resonance events, quickly reaching the radiation reaction limit. As a result, the wave is scattered with a huge cross section. This fact has implications for models of fast radio bursts and magnetars. Particles accelerated in the wave emit γ rays, which can trigger an e^{±} avalanche and, instead of silent escape, the wave will produce x-ray fireworks.

Heating of Magnetically Dominated Plasma by Alfvén-Wave Turbulence.

Magnetic energy around astrophysical compact objects can strongly dominate over plasma rest mass. Emission observed from these systems may be fed by dissipation of Alfvén wave turbulence, which cascades to small damping scales, energizing the plasma. We use 3D kinetic simulations to investigate this process. When the cascade is excited naturally, by colliding large-scale Alfvén waves, we observe quasithermal heating with no nonthermal particle acceleration. We also find that the particles are energized along the magnetic field lines and so are poor producers of synchrotron radiation. At low plasma densities, our simulations show the transition to "charge-starved" cascades, with a distinct damping mechanism.

Reducing the environmental footprint of gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement.

Climate change and the destruction of ecosystems by human activities are among the greatest challenges of the 21st century and require urgent action. Health care activities significantly contribute to the emission of greenhouse gases and waste production, with gastrointestinal (GI) endoscopy being one of the largest contributors. This Position Statement aims to raise awareness of the ecological footprint of GI endoscopy and provides guidance to reduce its environmental impact. The European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) outline suggestions and recommendations for health care providers, patients, governments, and industry. MAIN STATEMENTS 1: GI endoscopy is a resource-intensive activity with a significant yet poorly assessed environmental impact. 2: ESGE-ESGENA recommend adopting immediate actions to reduce the environmental impact of GI endoscopy. 3: ESGE-ESGENA recommend adherence to guidelines and implementation of audit strategies on the appropriateness of GI endoscopy to avoid the environmental impact of unnecessary procedures. 4: ESGE-ESGENA recommend the embedding of reduce, reuse, and recycle programs in the GI endoscopy unit. 5: ESGE-ESGENA suggest that there is an urgent need to reassess and reduce the environmental and economic impact of single-use GI endoscopic devices. 6: ESGE-ESGENA suggest against routine use of single-use GI endoscopes. However, their use could be considered in highly selected patients on a case-by-case basis. 7: ESGE-ESGENA recommend inclusion of sustainability in the training curricula of GI endoscopy and as a quality domain. 8: ESGE-ESGENA recommend conducting high quality research to quantify and minimize the environmental impact of GI endoscopy. 9: ESGE-ESGENA recommend that GI endoscopy companies assess, disclose, and audit the environmental impact of their value chain. 10:  ESGE-ESGENA recommend that GI endoscopy should become a net-zero greenhouse gas emissions practice by 2050.

Positron annihilation signatures associated with the outburst of the microquasar V404 Cygni.

Microquasars are stellar-mass black holes accreting matter from a companion star and ejecting plasma jets at almost the speed of light. They are analogues of quasars that contain supermassive black holes of 10(6) to 10(10) solar masses. Accretion in microquasars varies on much shorter timescales than in quasars and occasionally produces exceptionally bright X-ray flares. How the flares are produced is unclear, as is the mechanism for launching the relativistic jets and their composition. An emission line near 511 kiloelectronvolts has long been sought in the emission spectrum of microquasars as evidence for the expected electron-positron plasma. Transient high-energy spectral features have been reported in two objects, but their positron interpretation remains contentious. Here we report observations of γ-ray emission from the microquasar V404 Cygni during a recent period of strong flaring activity. The emission spectrum around 511 kiloelectronvolts shows clear signatures of variable positron annihilation, which implies a high rate of positron production. This supports the earlier conjecture that microquasars may be the main sources of the electron-positron plasma responsible for the bright diffuse emission of annihilation γ-rays in the bulge region of our Galaxy. Additionally, microquasars could be the origin of the observed megaelectronvolt continuum excess in the inner Galaxy.

Complete anatomic surgical myocardial revascularisation during postinfarction ventricular septal defect and ventricular aneurysm repair is associated with improved short- and long-term outcomes.

BACKGROUND: Coronary artery bypass grafting (CABG) is recommended during acute postinfarction ventricular septal defect (PIVSD) repair, but clinical benefits of surgical revascularization in patients with subacute PIVSD have not been established. We aimed to evaluate the association of primary complete anatomic surgical myocardial revascularization (CASMR) during PIVSD and ventricular aneurysm (VA) repair on patients' short- and long-term outcomes. METHODS: This was a retrospective observational study. The inclusion criterion was PIVSD. Patients with previous CABG and those with PIVSD due to vasospasm and normal coronary arteries on angiography were excluded. RESULTS: From March 2002 to April 2021, 53 patients met the eligibility criteria. The median patient age was 65 years, and 28 (53%) were male. Compared to the non-CABG group, CABG patients had higher values of the median postoperative left ventricular (LV) end-diastolic volume, 100 ml, and 128.5 ml, respectively (p = .012), and the mean LV stroke volume, 49 ml, and 61 ml, respectively (p = .048). The mortality rates in the CABG and non-CABG groups were 3.6/100 person-years (95% confidence interval [CI]: 1.5-8.6/100 person-years) and 16.3/100 person-years (95% CI: 8.5-31.3/100 person-years), respectively. Cox regression adjusted for between groups imbalances demonstrated a 4-fold greater mortality risk (hazard ratio = 4.3; 95% CI: 1.1-16.7; p = .036) among the non-CABG patients than in the CABG patients. Kaplan-Meier survival analysis yielded a poorer overall survival of the non-CABG patients (p = .011). CONCLUSION: Primary CASMR during PIVSD and VA repair is associated with improved postoperative cardiac function, lower hospital mortality, and better long-term survival. We recommend CASMR during PIVSD and VA repair.

The combination of Euroscore II with a new variable "Nongraftable coronary artery lesions" improves the discriminating power of the test in surgical patients with postinfarction ventricular septal defect and ventricular aneurysm.

BACKGROUND: We aimed to establish whether Euroscore II can be used for the prediction of hospital mortality in surgical patients with postinfarction intraventricular septal defect (PIVSD) and ventricular aneurysm (VA), and coexisting coronary artery lesions (CALs), and identify perioperative mortality risk factors to improve the discriminating power of Euroscore II. METHODS: This was a retrospective observational study. The inclusion criterion was PIVSD. Exclusion criteria were previous CABG, conservative treatment, percutaneous transcatheter closure of PIVSDs, and PIVSDs with normal coronary arteries on coronary angiography. RESULTS: Among 53 patients with PIVSDs and VAs who met eligibility criteria, 12 (22.6%) patients died in the hospital. Logistic regression demonstrated that Euroscore II was associated with in-hospital mortality (odds ratio [OR] = 1.13; 95% confidence interval [CI]: 1.03-1.23; p = .006), well-calibrated (Hosmer-Lemeshow χ2 (8) = 9.75; p = .283), and had fair discriminating power, area under receiver operating characteristic curve (AUC) = 77% (95% CI: 58%-96%). A newly identified variable "Nongraftable CALs" was associated with in-hospital mortality (OR = 6.65; 95% CI: 1.24-35.53; p = .027), and had a fair discriminating power, AUC = 70% (95% CI: 54%-85%). When Euroscore II and Nongraftable CALs were combined, the discriminating power of the test increased to 83% (95% CI: 71%-95%), p = .036. CONCLUSION: Euroscore II has adequate discriminating power and good calibration in predicting in-hospital mortality of surgical patients with PIVSDs and VAs. The combination of Euroscore II with a new variable "Nongraftable CALs" significantly improves the performance of the model.

Postmyocardial infarction ventricular septal defect and ventricular aneurysm repair with a "double-patch frame" technique.

BACKGROUND: Postmyocardial infarction intraventricular septal rupture is a life-threatening medical condition. Surgical management of postmyocardial infarction ventricular septal defects (PIVSDs) is associated with a 60% mortality and a 40% incidence of residual ventricular septal defects (rVSDs). Our study aimed to describe our modification of the "Double-patch" technique of PIVSD repair without using a biological glue and present its postoperative complications and survival. METHODS: This was a retrospective observational study. The Bakoulev's Scientific Center of Cardiac Surgery patient admission and discharge database was reviewed from March 2002 to April 2021. The inclusion criterion was PIVSD. Exclusion criteria were conservative treatment, transcatheter closure of PIVSD, PIVSD closure with an interventricular septum patch, and chronic PIVSDs. The study outcomes were echocardiographic parameters of cardiac function, postoperative complications, and mortality. RESULTS: Forty nine patients met the study eligibility criteria. Comparison of echocardiographic data of cardiac function demonstrated reduction in the postoperative period end-diastolic (201.4 ± 59.6 ml vs. 118 [range: 76-207] ml; p < .0005) and end-systolic volumes (106 [51-208] ml vs. 66 [40-147] ml; p < .0005). One (2%) patient developed hemodynamically significant rVSD that required the second run of cardiopulmonary bypass and rVSD closure. Thirteen (26.5%) patients died in the hospital. The overall mortality rate for the study period was 11.4/100 person-years (95% confidence interval [CI]: 6.9-19.0/100 person-years). In these patients, 1-year survival was 68.2% (95% CI: 52.3%-79.8%) and 5-year survival was 63.1% (95% CI: 45.1%-76.7%). CONCLUSION: The "Double-patch frame" technique restores LV dimensions, has a low rate of hemodynamically significant rVSDs and mortality.

Potassium channel blocker crafted by α-hairpinin scaffold engineering.

The α-Hairpinins are a family of plant defense peptides with a common fold presenting two short α-helices stabilized by two invariant S-S-bridges. We have shown previously that substitution of just two amino acid residues in a wheat α-hairpinin Tk-AMP-X2 leads to Tk-hefu-2 that features specific affinity to voltage-gated potassium channels KV1.3. Here, we utilize a combined molecular modeling approach based on molecular dynamics simulations and protein surface topography technique to improve the affinity of Tk-hefu-2 to KV1.3 while preserving its specificity. An important advance of this work compared with our previous studies is transition from the analysis of various physicochemical properties of an isolated toxin molecule to its consideration in complex with its target, a membrane-bound ion channel. As a result, a panel of computationally designed Tk-hefu-2 derivatives was synthesized and tested against KV1.3. The most active mutant Tk-hefu-10 showed a half-maximal inhibitory concentration of ∼150 nM being >10 times more active than Tk-hefu-2 and >200 times more active than the original Tk-hefu. We conclude that α-hairpinins provide an attractive disulfide-stabilized scaffold for the rational design of ion channel inhibitors. Furthermore, the success rate can be considerably increased by the proposed "target-based" iterative strategy of molecular design.

Coherent Electromagnetic Emission from Relativistic Magnetized Shocks.

Relativistic magnetized shocks are a natural source of coherent emission, offering a plausible radiative mechanism for fast radio bursts (FRBs). We present first-principles 3D simulations that provide essential information for the FRB models based on shocks: the emission efficiency, spectrum, and polarization. The simulated shock propagates in an e^{±} plasma with magnetization σ>1. The measured fraction of shock energy converted to coherent radiation is ≃10^{-3}σ^{-1}, and the energy-carrying wave number of the wave spectrum is ≃4ω_{c}/c, where ω_{c} is the upstream gyrofrequency. The ratio of the O-mode and X-mode energy fluxes emitted by the shock is ≃0.4σ^{-1}. The dominance of the X mode at σ≫1 is particularly strong, approaching 100% in the spectral band around 2ω_{c}. We also provide a detailed description of the emission mechanism for both X and O modes.

Impact of socioeconomic deprivation on incidence and outcomes of acute type A aortic dissection repair in New Zealand.

BACKGROUND: Socioeconomic deprivation (SED) has been associated with increased 30-day mortality and reduced long-term survival after surgical repair of acute type A aortic dissection (ATAAD). The study aimed to determine the incidence rate ratio of ATAAD in New Zealand population with higher and lower SED indices and to evaluate any association between SED and outcomes after ATAAD repair. METHODS: This was a retrospective cohort study. Patients who underwent ATAAD repair from March 2003 to May 2020 were identified. Overseas patients, those with chronic aortic dissection, and those who died in hospital before the operation were excluded. The total number of New Zealand residents was estimated based on the national 2018 Census. RESULTS: A total of 363 ATAAD patients met the eligibility criteria. The incidence of ATAAD was 70% greater in those who were more socioeconomically deprived (higher SED) compared with less socioeconomically deprived (lower SED) New Zealanders (odds ratio = 1.7; 95% confidence interval [CI] = 1.4-2.1; p < .0005). Postoperative cardiogenic shock, renal failure, pulmonary embolism, and respiratory failure were more common in the higher than in the lower SED group. Both groups had similar operative and in-hospital mortality and time intervals in the intensive care unit and hospital. Both groups had similar freedom from reoperation (hazards ratio [HR] = 1.1; 95% CI = 0.5-2.6; p = .746) and long-term survival (HR = 0.73; 95% CI = 0.5-1.1; p = .115). CONCLUSION: The incidence of ATAAD is greater in more socioeconomically deprived New Zealand residents. Following ATAAD repair, SED is not associated with worse short- or long-term outcomes in the universal health care system.