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The effects of left ventricular (LV) afterload on longitudinal versus circumferential ventricular mechanics are largely unknown. Our objective was to examine changes in LV deformation before and early after aortic valve replacement (AVR) in patients with severe aortic valve stenosis (AS). Paired echocardiographic studies before and early (7 ± 3 days) after AVR were analyzed in 45 patients (age 67 ± 12 years, 49% men) with severe AS and normal LV ejection fraction without segmental wall motion abnormalities. Longitudinal myocardial function was assessed from 3 apical views (average of 18 segments). Circumferential function was assessed at mid and apical levels (averaging 6 segments per view). Strain, strain rate (SR), and LV twist (relative rotation of the mid and apex) were measured using 2-dimensional strain software. Early post-AVR, (1) LV size and LV ejection fraction did not change; (2) longitudinal systolic strain, which was lower than normal before AVR, increased (−12.8 ± 1.7 to −15.9 ± 2.2, P < .05), whereas mid-LV circumferential strain, which was higher than normal, decreased (−27.0 ± 5.1 to −22.3 ± 4.9, P < .05); (3) longitudinal early diastolic SR increased (0.6 ± 0.1 to 0.7 ± 0.2, P < .05), whereas mid-LV circumferential diastolic SR decreased (1.2 ± 0.5 to 1.0 ± 0.3, P < .05); and (4) LV twist increased (3.7° ± 2.1° to 6.1° ± 2.9°, P < .05). Aortic valve stenosis causes differential changes in longitudinal and circumferential mechanics that partially normalize after AVR. These findings provide new insights into the mechanical adaptation of the LV to chronic afterload elevation and its response to unloading.

Introduction Stress-induced cardiomyopathy (Takotsubo) after bee stings in patients who have received catecholamines is rare. Endogenous as well as exogenous administration of catecholamines is thought to trigger stress-induced cardiomyopathy. Case presentation A 37-year-old healthy white woman was stung by an unknown Hymenoptera that resulted in an anaphylactic reaction. Intravenous adrenaline (0.9 mg) was administered at a nearby clinic; she was transferred to our emergency room. Cardiogenic shock was diagnosed and mechanical ventilation commenced. Hemodynamic stabilization was not achieved by inotropic support and intra-aortic balloon pump insertion. Initial coronary angiography did not demonstrate any coronary obstructive lesions while her left ventricular systolic function was severely depressed. Peripheral femoral venoarterial extracorporeal membrane oxygenation was inserted as a bridge to recovery assuming possible reversible cause of the cardiogenic shock. Over the following 48 hours she was extubated and gradually weaned off venoarterial extracorporeal membrane oxygenation and inotropic support. She was discharged with a near normal left ventricular ejection fraction and in 3 weeks she was asymptomatic with normal electrocardiographic and echocardiographic examinations (left ventricular ejection fraction >65 %). Conclusions A Hymenoptera sting may be a specific cause of catecholamine cardiac depression. The presence of cardiogenic shock and its etiology should prompt aggressive management including extracorporeal membrane oxygenation as a bridge to cardiac functional recovery in such rare scenarios.

Abstract Background  A sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly. Most SVA’s rupture into right heart chambers and can be classified using the modified Sakakibara classification according to the site of rupture. Transoesophageal echocardiography (TOE) is a useful diagnostic tool and aides in treatment planning in patients with congenital anomalies in emergency situations. Three-dimensional TOE (3D-TOE) provides additional value over standard TOE. Case summary A 38-year-old man with a reported history of ventricular septal defect (VSD) presented to the emergency department complaining of chest pain and epigastric pain lasting several days. Physical examination revealed a continuous heart murmur and signs of acute heart failure. A 3D-TOE revealed an SVA rupture into the right ventricle (Type IIIv) but no evidence of a VSD. Urgent aortic valve replacement with correction of the ruptured SVA was performed. Neither a VSD nor signs of endocarditis were found during surgical exploration. The patient was discharged on post-operative Day 5 in good condition. Discussion A sinus of Valsalva aneurysm is a rare cardiac condition. Ventricular septal defect, bicuspid aortic valve, or aortic valve regurgitation may coexist with SVA. Xin-Jin et al. classified a ruptured SVA into five types according to the site of rupture. Transoesophageal echocardiography is an important tool for diagnosis, anatomical description, and typing of the ruptured SVA. Sinus of Valsalva aneurysm may be misdiagnosed as a VSD, as was the case in our patient, and 3D-TOE can be instrumental for providing both correct diagnosis and critical surgical planning.

Pope Francis telephoned the parents of the martyred journalist, James Foley, who was brutally beheaded by Islamist terrorists in Syria. I hope the pope's solace and comfort somewhat eased their pain. I imagine he is a very busy public servant and for him to take the time for this purpose is a noble act. A few weeks ago, three Israeli teenagers were kidnapped, one of whom was a U.S. citizen brutally murdered by an affiliated group of ISIS. This atrocity was followed by the raining of rockets upon cities and towns in Israel for the sole purpose of killing innocent men, women and children. Thanks to God and Israeli preparedness, the damage was minimized. Credit: [Timothy O]'[Neill], Pompano Beach; [Lenore Eisenberg], Lake Worth; [Cantor Zvi Adler], Boynton Beach; [Marilyn Greenbaum], Boca Raton

Redox–enzyme‐mediated electrochemical processes such as hydrogen production, nitrogen fixation, and CO2 reduction are at the forefront of the green chemistry revolution. To scale up, the inefficient two‐dimensional (2D) immobilization of redox enzymes on working electrodes must be replaced by an efficient dense 3D system. Fabrication of 3D electrodes was demonstrated by embedding enzymes in polymer matrices. However, several requirements, such as simple immobilization, prolonged stability, and resistance to enzyme leakage, still need to be addressed. The study presented here aims to overcome these gaps by immobilizing enzymes in a supramolecular hydrogel formed by the self‐assembly of the peptide hydrogelator fluorenylmethyloxycarbonyl‐diphenylalanine. Harnessing the self‐assembly process avoids the need for tedious and potentially harmful chemistry, allowing the rapid loading of enzymes on a 3D electrode under mild conditions. Using the [FeFe] hydrogenase enzyme, high enzyme loads, prolonged resistance against electrophoresis, and highly efficient hydrogen production are demonstrated. Further, this enzyme retention is shown to arise from its interaction with the peptide nanofibrils. Finally, this method is successfully used to retain other redox enzymes, paving the way for a variety of enzyme‐mediated electrochemical applications. A facile method has been developed to efficiently encapsulate [FeFe] hydrogenase on a commercial three‐dimensional carbon felt electrode using peptide self‐assembly. Glue‐like immobilization of the enzyme on carbon fibers is achieved under mild conditions. High enzyme loads, prolonged resistance against electrophoresis, and highly efficient hydrogen production are demonstrated. This strategy is shown to be applicable to other enzymes.

Background Plants respond to abiotic stress on physiological, biochemical and molecular levels. This includes a global change in their cellular proteome achieved by changes in the pattern of their protein synthesis and degradation. The ubiquitin-proteasome system (UPS) is a key player in protein degradation in eukaryotes. Proteins are marked for degradation by the proteasome by coupling short chains of ubiquitin polypeptides in a three-step pathway. The last and regulatory stage is catalyzed by a member of a large family of substrate-specific ubiquitin ligases. Results We have identified AtPUB46 and AtPUB48— two paralogous genes that encode ubiquitin ligases (E3s)—to have a role in the plant environmental response. The AtPUB46, −47, and − 48 appear as tandem gene copies on chromosome 5, and we present a phylogenetic analysis that traces their evolution from an ancestral PUB-ARM gene. Single homozygous T-DNA insertion mutants of AtPUB46 and AtPUB48 displayed hypersensitivity to water stress; this was not observed for similar mutants of AtPUB47 . Although the three genes show a similar spatial expression pattern, the steady state levels of their transcripts are differentially affected by abiotic stresses and plant hormones. Conclusions AtPUB46 and AtPUB48 encode plant U-Box E3s and are involved in the response to water stress. Our data suggest that despite encoding highly homologous proteins, AtPUB46 and AtPUB48 biological activity does not fully overlap.

Monkeypox virus (MPXV) is the most pathogenic Poxvirus in circulation, yet key viral antigens remain immunologically unexplored. We isolate and characterize a panel of monoclonal antibodies (mAbs) targeting MPXV A28 (OPG153), an important membranal protein present on mature MPXV virions. From male convalescent individuals, we isolate anti-A28 mAbs alongside additional mAbs targeting the A35 and H3 proteins. Anti-A28 mAbs potently neutralize MPXV and Vaccinia virus (VACV) through complement-dependent mechanisms involving C1q and C3 deposition. High-resolution crystal structures of two anti-A28 mAbs, 10M2146 and 8M2110, in complex with VACV A26 reveal two distinct and highly conserved proximal epitopes within the N-terminal domain. Passive transfer of 8M2110 modestly attenuates disease in infected female mice. Moreover, immunization with A28 elicits antigen-specific B cells and robust neutralizing antibody responses and provides protection against lethal VACV challenge. These findings identify MPXV A28 as a promising central target for the induction of neutralizing antibodies and antiviral interventions. Recent MPXV outbreaks underscore the need for better vaccines and treatments. Here, the authors isolate and structurally characterize potent antibodies interacting with A28 that they identify as a key viral surface protein essential for viral entry and that induces strong, protective antibody response in mice.

Reinforcement learning models treat the basal ganglia (BG) as an actor–critic network. The ventral pallidum (VP) is a major component of the BG limbic system. However, its precise functional roles within the BG circuitry, particularly in comparison to the adjacent external segment of the globus pallidus (GPe), remain unexplored. We recorded the spiking activity of VP neurons, GPe cells (actor) and striatal cholinergic interneurons (critic) while monkeys performed a classical conditioning task. Here, we report that VP neurons can be classified into two distinct populations. The persistent population displayed sustained activation following visual cue presentation, was correlated with monkeys’ behavior and showed uncorrelated spiking activity. The transient population displayed phasic synchronized responses that were correlated with the rate of learning and the reinforcement learning model’s prediction error. Our results suggest that the VP is physiologically different from the GPe and identify the transient VP neurons as a BG critic.Kaplan et al. characterize the physiological properties of cells in the primate ventral pallidum. They employ a reinforcement learning model to demonstrate that the different neuronal populations play distinct roles in the basal ganglia network.

Background Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM. Methods Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay. Results The total duration of antimicrobial treatment in the study group ( n  = 8) was significantly shorter than the control group ( n  = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p  = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p  = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p  = 0.01). Conclusions The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis. Trial registration The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center ( 0378–17-TLV , 10/17/2017) and Rabin Medical Center ( 0270–18-RMC , 11/11/2018) Ethics committees and conforms to recognized standards.