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Heart failure is associated with systemic insulin resistance and abnormalities in glucose metabolism but the underlying mechanisms are poorly understood. In the skeletal muscle, the major peripheral site of glucose utilization, we observe an increase in miR-133b in heart failure mice, which reduces the insulin-sensitive glucose transporter (GLUT4), glucose uptake, and metabolism in C2C12 and in myocytes. The antagomir for miR-133b restores GLUT4 protein and markers of metabolism in skeletal myocytes from heart failure mice demonstrating that miR-133b is an exciting target for systemic insulin resistance in heart failure and an important player in the cross talk between the heart and the periphery in the heart failure syndrome.

The ion transport properties of ionomers comprised of polydimethylsiloxanes with amidinium or imidazolinium attached side chains and alkyldithiocarbamate anions (where alkyl is hexyl or octadecyl) have been investigated in chloroform solutions principally and as neat liquids. The influence of modifying the molecular weights of the polydimethylsiloxanes, the frequency of their amidininium or imidazolinium side groups, and temperature on the conductivity have been explored. When a solvent more polar than chloroform

Purpose In children and adolescents, preoperative planning for a semi-implantable bone conduction device (SIBCD) is crucial. The geometric changes of the new version of a common SIBCD should enable a higher rate of successful implantation due to its flatter actuator. Thus, this radioanatomic study compared the rate of successful implantation of both device versions at the traditional mastoidal localization and two alternative sites, retrosigmoidal, and parietal, and investigated parameters helping to estimate the feasibility. Methods A retrospective analysis of 136 CT scans of 0 to 20-year-old patients, evaluation of demographic parameters, radioanatomy, and assessment of head diameter was conducted. The feasibility was investigated for certain age groups at three implantation sites. Prediction of feasible implantation by means of different parameters was calculated. Results A significant higher implantation rate was observed with the new device for all three sites and age groups. The age group of 6–8 years (n = 19) had most striking differences with a 58.1% rate of successful implantation with the new device without spacer (80% with spacer) at the mastoidal localization, whereas none with the old implant. Head diameter was identified as the most predictive parameter regarding all implantation sites (mastoidal: p = 0.030; retrosigmoidal: p = 0.006; parietal: p p p p = 0.001). Conclusion The geometric changes of the actuator lead to a higher rate of successful implantation in all age-groups and all three localizations with reducing the requirement for spacers. Parameters age and head diameter might aid in estimating the rate of successful implantation in young patients and may be a novel tool to assist in the decision-making process for a SIBCD.

Background : One of the most competitive surgical sub-specialty fellowships remains Pediatric Surgery (PS), which requires candidates to develop a strong and research-oriented curriculum vitae. Although some objective factors of matriculation are known, factors for the interview selection and ranking per the program directors (PDs) have not been reviewed in over a decade. Methods : A web-based survey of US and Canadian PS program directors (PDs) (n=58) was used to evaluate a comprehensive list of factors in the selection criteria for PS fellowships. A mix of dichotomous, ranking, five-point Likert scale, and open-ended questions evaluated applicant characteristics, ABSITE scores, research productivity, interview day, and rank order criteria. Results : Fifty-five programs responded to the survey for a 95% participation rate. PDs desired an average of two years in dedicated research and weighted first authorship and total number of publications heavily. Only 38% of programs used an ABSITE score cutoff for offering interviews; however, the majority agreed that an overall upward trend was important. Quality letters of recommendation, especially from known colleagues, carried weight when deciding to offer interviews. Interview performance, being a team player, observed interpersonal interactions, perceived operative skills and patient care, and leadership were some of the notable factors when finalizing rank lists. Conclusions : A multitude of factors define a successful matriculant, including quality of letters of recommendation, quality and quantity of publications, supportive phone calls, observed interactions, interview performance, perceptions of being team player with leadership skills as well as perceptions of good operative skills and patient care.

BACKGROUND: Patients with ≥2 ventricular arrhythmia (VA) events within 3 months (clustered VA) have increased risk for mortality. OBJECTIVES: The aim of this study was to examine the association of risk factors including scar characteristics on cardiovascular magnetic resonance imaging with clustered VA and VA cycle length in nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM). METHODS: Data from 329 primary prevention implantable cardioverter-defibrillator recipients (mean age 57 years, 26% women) were analyzed from the Left Ventricular Structural Predictors of Sudden Cardiac Death study. RESULTS: Twenty-one patients developed clustered VA (median time 2.7 years after implantable cardioverter-defibrillator placement). Men had the greatest risk for recurrent VA. Patients with NICM and scar had the highest incidence rate of clustered VA. In patients with NICM, each 1-g increase in core scar correlated with greater clustered VA risk (HR: 1.19; 95% CI: 1.07–1.32). Gray scar was similar among subgroups. Patients with NICM with clustered VA had the longest mean VA cycle length (297 ± 40 milliseconds). Higher core scar burden correlated with longer VA cycle length in patients with NICM (P = 0.002), and higher body mass index correlated with shorter VA cycle length in those with ICM (P = 0.02). Type of VA was similar between cardiomyopathy subgroups, and no scar pattern predominated. CONCLUSIONS: Clustered VA was most common in patients with NICM and scar, with greatest risk among those with larger core scar. Core scar correlated with slower VA in patients with NICM, and higher body mass index correlated with faster VA in those with ICM. Type of VA was similar by cardiomyopathy etiology, and no dominant scar pattern was associated with clustered VA. (J Am Coll Cardiol EP 2022;8:957–966) © 2022 by the American College of Cardiology Foundation.

Este artículo trata de los muy numerosos individuos que hacen posible la gobernanza global. Indaga el papel de intermediarios ocultos, por lo general alejados de la mirada académica: profesionales, equipos de servicio y otros que actúan entre bastidores. No están en la cima de las organizaciones públicas y privadas (donde imperan “gobernantes [es decir, líderes] globales”; global governors en la bibliografía especializada), pero ayudan a mantener firme la pirámide. Realizan el trabajo político, operativo y de apoyo para impulsar las instituciones de gobernanza en todos los planos, del local al mundial. Estos elementos, en gran medida invisibles y olvidados en los escritos académicos y políticos, hacen posible la gobernanza global. Las aportaciones de los intermediarios ocultos, o “sector medio desconocido”, no se circunscriben al ámbito de las entidades intergubernamentales, porque la gobernanza global contemporánea no es sinónimo de organización internacional, sino que atañe más bien a la coordinación de autoridades públicas, que pueden o no incluir secretarías o estados.

Objective: Betahistine is frequently used in the pharmacotherapy for Menière’s Disease (MD). Little is known about its mode of action and prescribed dosages vary. While betahistine had an increasing effect on cochlear microcirculation in earlier studies, low dose betahistine of 0.01 mg/kg bw or less was not able to effect this. Selegiline inhibits monoaminooxidase B and therefore potentially the breakdown of betahistine. The goal of this study was to examine whether the addition of selegiline to low dose betahistine leads to increased cochlear blood flow. Methods: Twelve Dunkin-Hartley guinea pigs were anesthetized, the cochlea was exposed and a window opened to the stria vascularis. Blood plasma was visualized by injecting fluoresceinisothiocyanate-dextrane and vessel diameter and erythrocyte velocity were evaluated over 20 minutes. One group received low dose betahistine (0.01 mg/kg bw) and selegiline (1 mg/kg bw) i.v. while the other group received only selegiline (1 mg/kg bw) and saline (0.9% NaCl) as placebo i.v. Results: Cochlear microcirculation increased significantly ( P Conclusions: Low dose betahistine increased cochlear microcirculation significantly when combined with selegiline. This should be investigated in further studies regarding dose-effect relation in comparison to betahistine alone. Side effects, in particular regarding circulation, should be considered carefully in view of the clinical applicability of a combination therapy in patients with MD.

BACKGROUND: People living with HIV (PLWH) on antiretroviral therapy (ART) are at increased risk of atherosclerotic disease. Abnormal adipose distribution is common in PLWH and may contribute to atherosclerosis. Because coronary artery endothelial function (CEF) is impaired in early atherosclerosis, predicts future cardiovascular events, and is reduced in PLWH, we investigated associations between body fat distribution and CEF in PLWH. SETTING: Prospective cohort study. METHODS: PLWH on stable ART underwent MRI to quantify CEF, measured as change in coronary cross-sectional area (CSA) from rest to that during isometric handgrip exercise, an endothelial-dependent stressor. Abdominal visceral and subcutaneous fat area (axial L4 level) and liver fat fraction were quantified via MRI. Linear regression was used to determine associations between CEF and independent variables. RESULTS: Among 84 PLWH (52±11 years; 33% women), mean CSA change was 0.74±11.7’%, indicating impaired CEF. On univariable regression analysis, CEF was inversely related to waist circumference (R=−0.31, p =0.014), hip circumference (R=−0.27, p =0.037), and subcutaneous fat area (R=−0.25, p =0.031). We did not observe significant relationships between CEF and liver fat fraction, waist/hip ratio, or visceral fat area. On multivariable regression adjusted for age, sex, and race, CEF was associated with waist circumference, hip circumference, subcutaneous fat, and liver fat fraction. CONCLUSION: Waist and hip circumference, and subcutaneous fat area are associated with impaired CEF, an established metric of abnormal vascular health in PLWH on stable ART, and may contribute to the increased rate of heart disease in this population.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by recurrent episodes of upper airway obstruction and subsequent hypoxia. In patients with OSA, severity and number of these hypoxic events positively correlate with the extent of associated cardiovascular pathology. The molecular mechanisms underlying intermittent hypoxia (IH)-driven cardiovascular disease in OSA, however, remain poorly understood—partly due to the lack of adequate experimental models. Here, we present a novel experimental approach that utilizes primary human endothelial cells cultivated under shear stress. Oxygen partial pressure dynamics were adopted in our in vitro model according to the desaturation-reoxygenation patterns identified in polysomnographic data of severe OSA patients (n = 10, with 892 severe desaturations, SpO2in vitro model for deciphering OSA-elicited effects on the vascular endothelium. First data obtained in this model point to the endothelial activation of pro-inflammatory rather than hypoxia-associated pathways in OSA. Future studies in this model might contribute to the development of targeted strategies against OSA-induced, secondary cardiovascular disease.

BACKGROUND: MicroRNAs constitute promising biomarkers. OBJECTIVE: The aim was to investigate diagnostic and prognostic implications of miR-182-5p and miR-205-5p in p16-positive and p16-negative oropharyngeal squamous cell carcinomas (OPSCCs). METHODS: Expression of miR-182-5p, miR-205-5p were determined via quantitative real-time-PCR in fresh frozen tissues of 26 p16-positive, 19 p16-negative OPSCCs and 18 HPV-negative oropharyngeal controls. Associations between miRNA-expression, clinicopathological characteristics and prognosis were analyzed. RESULTS: Higher miR-182-5p expression was associated with significant inferior disease-specific survival for p16-positive OPSCCs (HR = 1.98E+09, 95% CI 0–Inf; P= 0.028) and a similar trend was observed for p16-negative OPSCCs (HR = 1.56E+09, 95% CI 0–Inf; P= 0.051). Higher miR-205-5p expression was associated with an inferior progression-free survival (HR = 4.62, 95% CI 0.98–21.83; P= 0.034) and local control rate (HR = 2.18E+09, 95% CI 0–Inf; P= 0.048) for p16-positive OPSCCs. CONCLUSIONS: Results indicate that miR-182-5p and miR-205-5p can further stratify patients with p16-positive OPSCC into prognostic groups.

This article focuses on the vast number of people who make global governance happen. It probes the role of the unknown people in the “middle” who are largely absent from scholarly gaze: professionals, service teams, and others who act behind the scenes. They are not at the top of public and private organizations (“global governors” in the literature), but they keep the lights on. They accomplish the policy, operational, and support work to move the needle of global governance institutions of all varieties from the local to global. These largely invisible and unheard populations—at least in the scholarly and policy literatures—make global governance work. The “missing middle” is not confined to the everyday contributions of professionals in intergovernmental secretariats because contemporary global governance is not synonymous with international organization, but concerns networked forms of public authority that may or may not include secretariats or states.

Polymer brushes, consisting of densely end-tethered polymers to a surface, can exhibit rapid and sharp conformational transitions due to specific stimuli, which offer intriguing possibilities for surface-based sensing of the stimuli. The key toward unlocking these possibilities is the development of methods to readily transduce signals from polymer conformational changes. Herein, we report on single-fluorophore integrated ultrathin (40 nm) polymer brush surfaces that exhibit changing fluorescence properties based on polymer conformation. The basis of our methods is the change in occupied volume as the polymer brush undergoes a collapse transition, which enhances the effective concentration and aggregation of the integrated fluorophores, leading to a self-quenching of the fluorophores' fluorescence and thereby reduced fluorescence lifetimes. By using fluorescence lifetime imaging microscopy, we reveal spatial details on polymer brush conformational transitions across complex interfaces, including at the air-water-solid interface and at the interface of immiscible liquids that solvate the surface. Furthermore, our method identifies the swelling of polymer brushes from outside of a direct droplet (

Small structural changes to side chain groups have large consequences to the structures and dynamics of corresponding polysiloxane-based ionomers.

Single port surgery (SPS) was introduced as an attractive, minimally invasive surgical technique that ensures esthetic results for many types of visceral surgery. Initially, surgeons immediately set about performing SPS without preliminary knowledge or training, which resulted in higher complication rates. Today, current studies conclusively show that SPS is scientifically rehabilitated and indicated for simple and complex laparoscopic procedures. We here describe the astonishing analogies between Greek mythology and modern surgery.

OBJECTIVE Persons living with HIV (PLWH) and co-infected with hepatitis C (PLWH + HCV) have increased risk of cardiovascular disease (CVD). Peri-coronary inflammation, measured by fat attenuation index (FAI) on coronary CT angiography (CCTA), independently predicts cardiovascular risk in the general population but has not been studied in the PLWH + HCV population. We tested whether peri-coronary inflammation is increased in PLWH or PLWH + HCV, and whether inflammation changes over time. DESIGN Cross-sectional analysis to determine FAI differences among groups. Longitudinal analysis in PLWH to assess changes in inflammation over time. METHODS Age- and sex-matched seropositive groups (PLWH and PLWH + HCV) virologically suppressed on antiretroviral therapy (ART), HCV viremic, and without prior CVD and matched controls underwent CCTA. Peri-coronary FAI was measured around the proximal right coronary artery (RCA) and left anterior descending artery (LAD). Follow-up CCTA was performed in 22 PLWH after 20.6-27.4 months. RESULTS 101 participants (48 women) were studied (60 PLWH, 19 PLWH + HCV and 22 controls). In adjusted analyses, peri-coronary FAI did not differ between seropositive groups and controls. Low attenuation coronary plaque was significantly less common in seropositive groups compared to controls (LAD, p = 0.035; and RCA, p = 0.017, respectively). Peri-coronary FAI values significantly progressed between baseline and follow-up in PLWH (RCA: p = 0.001, LAD: p =

Background The prognostic impact of hsa-miRNA-182-5p in oral cancer remains unexplored. Therefore, the aim of this study was to investigate the prognostic value of hsa-miRNA-182-5p and its predicted target kinectin 1 (KTN1) in oral squamous cell carcinoma (OSCC). Method Expression level of hsa-miRNA-182-5p was analyzed in tumor tissue (n = 36) and healthy oral mucosal tissue (n = 17) using quantitative real-time polymerase chain reaction. Protein level of the predicted target KTN1 was detected via immunohistochemistry. Results were validated in a cohort of The Cancer Genome Atlas (TCGA). Results After dividing the data into a subgroup with high and low hsa-miRNA-182-5p expression level, a significant better overall (p = 0.016), recurrence-free (p = 0.009), and progression-free survival (p = 0.004) was observed in an upregulation of hsa-miRNA-182-5p. Staining intensity of KTN1 showed a reciprocal impact on the prognosis. Validation in a TCGA cohort confirmed these results. Conclusion Our results indicate hsa-miRNA-182-5p and KTN1 as potential biomarkers for OSCC.

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

HYPOTHESIS The ability of JWH-133, an agonist at the cannabinoid receptor 2, to abrogate the effects of lipopolysaccharide on cochlear microcirculation was investigated. BACKGROUND Cochlear inflammation and subsequent impairment of microcirculation is part of numerous pathologies affecting inner ear function, including suppurative labyrinthitis, noise trauma, and sudden sensorineural hearing loss. One way of causing cochlear inflammation is exposing the cochlea to lipopolysaccharide, a bacterial endotoxin. METHODS Twenty Dunkin-hartley guinea pigs were divided into four groups of five animals each. Two groups received topic treatment with JWH-133 and two received treatment with placebo. One group that had been treated with JWH-133 and one with placebo were then exposed to lipopolysaccharide or placebo, respectively. Cochlear microcirculation was quantified before, in between and after treatments by in vivo fluorescence microscopy. RESULTS Significantly different changes in cochlear blood flow were only seen in the group that was treated with placebo and subsequently lipopolysaccharide. Every other group showed no significant change in cochlear blood flow. CONCLUSION JWH-133 is capable of abrogating the effects of lipopolysaccharide on cochlear microcirculation. It may therefore be clinical interest in treating numerous inflammation associated cochlear pathologies.

Martin Heidegger has been labeled the philosopher of “home” (Heimat) and “homelessness” (Heimatlosigkeit). But he is also the philosopher of “the uncanny” (das Unheimliche). The present paper first explores the uncanniness provoked by anxiety as Heidegger describes it in Being and Time. It then shows how this uncanniness is based on the relationship between thinking and being, as already described by Parmenides and exemplified by Heidegger in his interpretation of the first chorus in Sophocles’ tragedy Antigone. Heidegger shows that the uncanny in the relationship between thinking and being, i.e. between “Humanity” and “Being”, is not based in their difference but their identity. Humans, understood as “being-there” (Da-sein), have to cope with the fact that they have to disclose in their actions – be it thinking, writing poetry or fabricating – the essence of Being, which consists in being the autonomous appearing of beings. Thus, humanity has to accept the uncanniness of not being the independent subject dominating Earth, but a part of evolving nature itself.

Colorectal cancer (CRC) screening guidelines recommend frequent colonoscopies and consideration of genetic testing in individuals with ≥10 cumulative adenomas. However, it is unclear how these guidelines apply to routine practice. We estimated the proportion of participants found to have ≥10 cumulative adenomas in a screening population and described their outcomes of advanced neoplasia (AN), CRC, and extra-colonic malignancy. We performed a secondary analysis of VA CSP#380, which includes 3121 veterans aged 50–75 who were followed up to 10 years after screening colonoscopy. We calculated the cumulative risk of ≥10 cumulative adenomas by Kaplan–Meier method. We compared baseline risk factors in those with and without ≥10 cumulative adenomas as well as the risk for AN (adenoma ≥1 cm, villous adenoma or high-grade dysplasia, or CRC) and extra-colonic malignancy by multivariate logistic regression. The cumulative risk of ≥10 cumulative adenomas over 10.5 years was 6.51% (95% CI 4.38%–9.62%). Age 60–69 or 70–75 at baseline colonoscopy was the only factors associated with the finding of ≥10 cumulative adenomas. Compared to those with 0–9 cumulative adenomas, participants with ≥10 cumulative adenomas were more likely to have had AN (OR 17.03; 95% CI 9.41–30.84), including CRC (OR 7.00; 95% CI 2.84–17.28), but not extra-colonic malignancies. Approximately 6.5% of participants in this screening population were found to have ≥10 cumulative adenomas over 10.5 years, which was uncommon before age 60. These participants were found to have AN and CRC significantly more often compared to those with lower cumulative adenomas.

Zusammenfassung Hintergrund Durch die Digitalisierung hat sich das Internet zu einem wesentlichen Informationsmedium für Patienten entwickelt. Patienten mit Hörsturz haben aufgrund unsicherer wissenschaftlicher Erkenntnisse einen besonders großen Informationsbedarf. In der vorliegenden Arbeit wurden daher die Ergebnisse einer Internetsuche zum Thema Hörsturz untersucht. Material und Methoden Die ersten 30 Treffer einer Google-Suche mit dem Begriff „Hörsturz“ wurden kategorisiert, eine Lesbarkeitsstatistik anhand verschiedener Formeln (Flesch-Reading-Ease-Score; 0=schwer, 100=leicht lesbar) berechnet und falsche Informationen dokumentiert. Eine strukturierte inhaltliche Bewertung erfolgte mit dem DISCERN-Fragebogen (1=niedrige, 5=hohe Qualität) getrennt durch 2 verblindete Untersucher. Die Einhaltung empfohlener Standards wurde anhand einer Health-On-The-Net-Zertifizierung erfasst. Ergebnisse 18 Internetseiten (60,0%) waren Informationsportale, 7 (23,3%) von Medizinprodukteunternehmen (davon 3 Hörgerätehersteller), 2 (6,7%) von öffentlichen Einrichtungen und je 1 (3,3%) von einem Ärzteverband und einer Selbsthilfeorganisation sowie ein wissenschaftlicher Artikel. Im Mittel lag die Wortanzahl bei 1307,0±840,2 Wörtern, die letzte Aktualisierung war vor 17,1±32,5 Monaten und der Flesch-Reading-Ease-Score lag bei 36,1±13,9. Am schwierigsten lesbar war der wissenschaftliche Artikel (13,7). Insgesamt lag der DISCERN bei 2,2±0,7 mit schlechtester Bewertung von Medizinprodukteunternehmen (1,6±0,5). Zwei Internetseiten (6,7%) hatten ein Health-On-The-Net-Zertifikat, 14 (46,7%) zeigten falsche Informationen. Schlussfolgerung Patienteninformationen im Internet sind aufgrund geringer Lesbarkeit, potenzieller Interessenkonflikte, niedriger Qualität oder falscher Informationen kritisch zu bewerten. Eine mögliche Konsequenz wäre eine Bereitstellung verlässlicher Gesundheitsinformationen im Internet durch medizinische Leistungserbringer und Fachgesellschaften.

Study question What is the clinical outcome of collapsed blastocysts without signals of re-expansion in frozen embryo transfers (FET)? Summary answer FET of non-re-expanded blastocysts after thawing showed a live-birth rate in 11.5% of the cases. Embryos vitrified on day 5 revealed the best results. What is known already Embryo viability is crucial for FET to be successful. Since the introduction of vitrification techniques, outcomes have improved substantially and are even comparable to fresh transfers. Nevertheless, some indicators may help predict the outcome of frozen-thawed blastocysts. Blastocoele re-expansion after thawing has been widely studied and is a strong predictor of clinical pregnancy outcome. However, accurate data on non-re-expanded blastocysts after FET is still not available. Hence, this study aims to evaluate the clinical outcome of non-re-expanded blastocyst after FET. Study design, size, duration The retrospective study was designed and conducted at the Kinderwunsch Institut Schenk GmbH (Dobl, Austria). Data was collected from FET performed between 2017 and 2021. In total, 104 FET cycles of collapsed blastocysts were analysed. All the transfers performed were single embryo transfers (SET). Patient’s average age was of 33.6 years at the time of embryo vitrification. Embryos were excluded if they showed more fragmentation than before vitrification. Participants/materials, setting, methods Patients were divided into two groups following the time of blastocyst cryopreservation: day 5 (44 SET) and day 6 (60 SET); which was dependant on the time of blastocoel expansion. They were further divided according to the trophectoderm quality: good (42 SET) and poor (62 SET) and the overall embryo quality, considering trophectoderm and inner cell mass (ICM): good (37 SET) and poor (67 SET). In both cases quality was assessed before vitrification. Main results and the role of chance A total of 104 collapsed blastocysts were transferred (SET). 16.3% of the patients had a positive biochemical pregnancy. 11.5% of the pregnancies resulted in a live birth and 4.8% of the pregnancies ended in abortion. FET with day 5 non-re-expanded blastocysts after thawing showed better results than day 6 thawed blastocysts regarding biochemical pregnancy (29.5% vs 6.6%, p = 0.02) and live birth rate (20.4% vs 5%, p = 0.017). Good embryo quality before vitrification showed a trend for better clinical outcome, however, results were not significant. A good trophectoderm quality before vitrification revealed a live birth rate of 16.7% compared to 8.1% in poor trophectoderm quality. Regarding overall embryo quality (trophectoderm and ICM quality) the results were 14.3% deliveries for good quality blastocysts vs 7.6% for poor quality blastocysts. Limitations, reasons for caution The sample size may be seen as a study limitation. However, statistically significant results were obtained. Nonetheless, results should be confirmed with a bigger sample size. Wider implications of the findings The present study revealed a lower chance of live birth for non-re-expanded blastocysts after thawing, which should nevertheless not be overlooked; specially in cases with good quality embryos frozen and thawed on day 5. Transfer of collapsed embryos after thawing would be recommended taking into consideration the study results. Trial registration number Not Applicable

BACKGROUNDSudden cardiac death (SCD) remains a worldwide public health problem in need of better noninvasive predictive tools. Current guidelines for primary preventive SCD therapies, such as implantable cardioverter defibrillators (ICDs), are based on left ventricular ejection fraction (LVEF), but these guidelines are imprecise: fewer than 5% of ICDs deliver lifesaving therapy per year. Impaired cardiac metabolism and ATP depletion cause arrhythmias in experimental models, but to our knowledge a link between arrhythmias and cardiac energetic abnormalities in people has not been explored, nor has the potential for metabolically predicting clinical SCD risk.METHODSWe prospectively measured myocardial energy metabolism noninvasively with phosphorus magnetic resonance spectroscopy in patients with no history of significant arrhythmias prior to scheduled ICD implantation for primary prevention in the setting of reduced LVEF (≤35%).RESULTSBy 2 different analyses, low myocardial ATP significantly predicted the composite of subsequent appropriate ICD firings for life-threatening arrhythmias and cardiac death over approximately 10 years. Life-threatening arrhythmia risk was approximately 3-fold higher in patients with low ATP and independent of established risk factors, including LVEF. In patients with normal ATP, rates of appropriate ICD firings were several-fold lower than reported rates of ICD complications and inappropriate firings.CONCLUSIONTo the best of our knowledge, these are the first data linking in vivo myocardial ATP depletion and subsequent significant arrhythmic events in people, suggesting an energetic component to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of metabolic strategies that limit ATP loss to treat or prevent life-threatening cardiac arrhythmias and herald noninvasive metabolic imaging as a complementary SCD risk stratification tool.TRIAL REGISTRATIONClinicalTrials.gov NCT00181233.FUNDINGThis work was supported by the DW Reynolds Foundation, the NIH (grants HL61912, HL056882, HL103812, HL132181, HL140034), and Russell H. Morgan and Clarence Doodeman endowments at Johns Hopkins.

The multiphysics object-oriented simulation environment (moose) is a code package that couples a variety of physics modules, allowing for highly accessible multiphysics simulations. The physics modules include a finite element Navier–Stokes (N–S) module that is designed to solve laminar fluid dynamics problems. The usage of this module in multiple recent studies coupled with the growing interest in moose for usage in nonlight water reactor safety studies by the Nuclear Regulatory Commission (NRC) prompted the authors to investigate the computational fluid dynamics capabilities of moose. A two-dimensional laminar flow past a circular cylinder scenario is simulated in the moose framework to investigate the effectiveness of the N–S module. Simulations assumed an unsteady laminar flow with a Reynolds number of 200. To verify the results from moose, similar simulations were conducted using the well-utilized simulation of turbulent flow in arbitrary regions—computational continuum mechanics C++ (star-ccm+) finite volume code. Results from both codes are also compared to some results from literature. Velocity and pressure profiles of both transient simulations were compared. The numerical and input errors in moose are also visualized with contour plots to qualitatively understand the evolution of the errors across time and space. The comparisons between moose and star-ccm+ showed nearly perfect agreement between the codes for velocity and pressure, especially after the development of the vortex street in later time-steps. The force coefficients showed excellent agreement after the development of the vortex street, but demonstrated notable discrepancies prior to the vortex street development, which is likely due to how each code simulated the approach to the vortex street in earlier time-steps.

Persistence of a left-to-right shunt caused by a patent ductus arteriosus (PDA) leads to significant sequelae in extremely premature infants as a result of pulmonary overcirculation and systemic steal. Although timing and duration of treatment for a persistent clinically significant PDA differ among institutions, standard pharmacologic interventions are the nonsteroidal anti-inflammatory drugs indomethacin and ibuprofen. Acetaminophen has emerged as an alternative to indomethacin and ibuprofen with less significant adverse effects, but there is no consensus regarding its use. This review summarizes the most recent evidence for the use of acetaminophen in PDA treatment.