Optogenetic Interrogation of Electrophysiological Dendritic Properties and Their Effect on Pacemaking Neurons from Acute Rodent Brain Slices.

Understanding dendritic excitability is essential for a complete and precise characterization of neurons' input-output relationships. Theoretical and experimental work demonstrates that the electrotonic and nonlinear properties of dendrites can alter the amplitude (e.g., through amplification) and latency of synaptic inputs as viewed in the axosomatic region where spike timing is determined. The gold-standard technique to study dendritic excitability is using dual-patch recordings with a high-resistance electrode used to patch a piece of distal dendrite in addition to a somatic patch electrode. However, this approach is often impractical when distal dendrites are too fine to patch. Therefore, we developed a technique that utilizes the expression of Channelrhodopsin-2 (ChR2) to study dendritic excitability in acute brain slices through the combination of a somatic patch electrode and optogenetic activation. The protocol describes how to prepare acute slices from mice that express ChR2 in specific cell types, and how to use two modes of light stimulation: proximal (which activates the soma and proximal dendrites in a ~100 µm diameter surrounding the soma) with the use of a high-magnification objective and full-field stimulation through a low-magnification objective (which activates the entire somato-dendritic field of the neuron). We use this technique in conjunction with various stimulation protocols to estimate model-based spectral components of dendritic filtering and the impact of dendrites on phase response curves, peri-stimulus time histograms, and entrainment of pacemaking neurons. This technique provides a novel use of optogenetics to study intrinsic dendritic excitability through the use of standard patch-clamp slice physiology. Key features • A method for studying the effects of electrotonic and nonlinear dendritic properties on the sub- and suprathreshold responses of pacemaking neurons. • Combines somatic patch clamp or perforated patch recordings with optogenetic activation in acute brain slices to investigate dendritic linear transformation without patching the dendrite. • Oscillatory illumination at various frequencies estimates spectral properties of the dendrite using subthreshold voltage-clamp recordings and studies entrainment of pacemakers in current clamp recordings. • This protocol uses Poisson white noise illumination to estimate dendritic phase response curves and peri-stimulus time histograms.

Transcatheter heart valve explant with infective endocarditis-associated prosthesis failure and outcomes: the EXPLANT-TAVR international registry.

BACKGROUND AND AIMS: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE. METHODS: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD). RESULTS: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant due to IE and 188 (50.5%) patients due to BVD. At the index transcatheter aortic valve replacement, patients undergoing THV explant for IE were older (74.3 ± 8.6 vs. 71 ± 10.6 years) and had a lower Society of Thoracic Surgeons risk score [2.6% (1.8-5.0) vs. 3.3% (2.1-5.6), P = .029] compared to patients with BVD. Compared to BVD, IE patients had longer intensive care unit and hospital stays (P < .05) and higher stroke rates at 30 days (8.6% vs. 2.9%, P = .032) and 1 year (16.2% vs. 5.2%, P = .010). Adjusted in-hospital, 30-day, and 1-year mortality was 12.1%, 16.1%, and 33.8%, respectively, for the entire cohort, with no significant differences between groups. Although mortality was numerically higher in IE patients 3 years postsurgery (29.6% for BVD vs. 43.9% for IE), Kaplan-Meier analysis showed no significant differences between groups (P = .16). CONCLUSIONS: In the EXPLANT-TAVR registry, patients undergoing THV explant for IE had higher 30-day and 1-year stroke rates and longer intensive care unit and hospital stays. Moreover, patients undergoing THV explant for IE had a higher 3-year mortality rate, which did not reach statistical significance given the relatively small sample size of this unique cohort and the reduced number of events.

Phase Delays between Mouse Globus Pallidus Neurons Entrained by Common Oscillatory Drive Arise from Their Intrinsic Properties, Not Their Coupling.

A hallmark of Parkinson's disease is the appearance of correlated oscillatory discharge throughout the cortico-basal ganglia (BG) circuits. In the primate globus pallidus (GP), where the discharge of GP neurons is normally uncorrelated, pairs of GP neurons exhibit oscillatory spike correlations with a broad distribution of pairwise phase delays in experimental parkinsonism. The transition to oscillatory correlations is thought to indicate the collapse of the normally segregated information channels traversing the BG. The large phase delays are thought to reflect pathological changes in synaptic connectivity in the BG. Here we study the structure and phase delays of spike correlations measured from neurons in the mouse external GP (GPe) subjected to identical 1-100 Hz sinusoidal drive but recorded in separate experiments. First, we found that spectral modes of a GPe neuron's empirical instantaneous phase response curve (iPRC) elucidate at what phases of the oscillatory drive the GPe neuron locks when it is entrained and the distribution of phases at which it spikes when it is not. Then, we show that in this case the pairwise spike cross-correlation equals the cross-correlation function of these spike phase distributions. Finally, we show that the distribution of GPe phase delays arises from the diversity of iPRCs and is broadened when the neurons become entrained. Modeling GPe networks with realistic intranuclear connectivity demonstrates that the connectivity decorrelates GPe neurons without affecting phase delays. Thus, common oscillatory input gives rise to GPe correlations whose structure and pairwise phase delays reflect their intrinsic properties captured by their iPRCs.

Striatal Neurons Are Recruited Dynamically into Collective Representations of Self-Initiated and Learned Actions in Freely Moving Mice.

Striatal spiny projection neurons are hyperpolarized-at-rest (HaR) and driven to action potential threshold by a small number of powerful inputs-an input-output configuration that is detrimental to response reliability. Because the striatum is important for habitual behaviors and goal-directed learning, we conducted a microendoscopic imaging in freely moving mice that express a genetically encoded Ca2+ indicator sparsely in striatal HaR neurons to evaluate their response reliability during self-initiated movements and operant conditioning. The sparse expression was critical for longitudinal studies of response reliability, and for studying correlations among HaR neurons while minimizing spurious correlations arising from contamination by the background signal. We found that HaR neurons are recruited dynamically into action representation, with distinct neuronal subsets being engaged in a moment-by-moment fashion. While individual neurons respond with little reliability, the population response remained stable across days. Moreover, we found evidence for the temporal coupling between neuronal subsets during conditioned (but not innate) behaviors.

Contemporary Management and Outcomes of Patients With High-Risk Pulmonary Embolism.

BACKGROUND: Contemporary care patterns/outcomes in high-risk pulmonary embolism (PE) patients are unknown. OBJECTIVES: This study sought to characterize the management of high-risk PE patients and identify factors associated with poor outcomes. METHODS: A retrospective analysis of the PERT (Pulmonary Embolism Response Team) Consortium Registry was performed. Patients presenting with intermediate-risk PE, high-risk PE, and catastrophic PE (those with hemodynamic collapse) were identified. Patient characteristics were compared with chi-square testing for categorical covariates and Student's t-test for continuous covariates. Multivariable logistic regression was used to assess associations between clinical characteristics and outcomes in the high-risk population. RESULTS: Of 5,790 registry patients, 2,976 presented with intermediate-risk PE and 1,442 with high-risk PE. High-risk PE patients were more frequently treated with advanced therapies than intermediate-risk PE patients (41.9% vs 30.2%; P < 0.001). In-hospital mortality (20.6% vs 3.7%; P < 0.001) and major bleeding (10.5% vs. 3.5%; P < 0.001) were more common in high-risk PE. Multivariable regression analysis demonstrated vasopressor use (OR: 4.56; 95% CI: 3.27-6.38; P < 0.01), extracorporeal membrane oxygenation use (OR: 2.86; 95% CI: 1.12-7.30; P = 0.03), identified clot-in-transit (OR: 2.26; 95% CI: 1.13-4.52; P = 0.02), and malignancy (OR: = 1.70; 95% CI: 1.13-2.56; P = 0.01) as factors associated with in-hospital mortality. Catastrophic PE patients (n = 197 [13.7% of high-risk PE patients]) had higher in-hospital mortality (42.1% vs 17.2%; P < 0.001) than those presenting with noncatastrophic high-risk PE. Extracorporeal membrane oxygenation (13.3% vs. 4.8% P < 0.001) and systemic thrombolysis (25% vs 11.3%; P < 0.001) were used more commonly in catastrophic PE. CONCLUSIONS: In the largest analysis of high-risk PE patients to date, mortality rates were high with the worst outcomes among patients with hemodynamic collapse.

Stroke After Acute Type A Dissection Repair Using Right Axillary Cannulation First Approach.

BACKGROUND: This study sought to analyze the details of strokes after acute type A dissection repair (ATAD) using a right axillary artery (RAX) first approach. METHODS: A total of 356 consecutive ATAD repairs from 2005 to 2022 were analyzed on the basis of arterial cannulation site. Strokes were evaluated by head computed tomography. RESULTS: The rate of RAX cannulation was 82.6% (n = 294), with a 38.2% rate of antegrade cerebral perfusion use, both of which had increased over the years. The non-RAX group had more cardiogenic shock (RAX, 16.3% vs non-RAX, 37.1%; P < .001), cerebral malperfusion (8.8% vs 25.8%, respectively; P < .001), and innominate artery dissection (45.9% vs 69.2%, respectively; P = .007). Eight patients died before undergoing a full neurologic assessment. The overall stroke rate was 8.4% (n = 30), and it was lower in the RAX group (5.1% vs 24.2%; P < .001). All strokes were ischemic, with concomitant hemorrhagic strokes occurring in 6 patients. Strokes diagnosed immediately after surgery (perioperative stroke) accounted for 70% (n = 21 of 30) of cases. Strokes predominantly affected the right anterior circulation (right anterior, 80% vs left anterior, 46.7% vs left posterior, 26.7%; P = .013), independent of arterial cannulation site. The proposed mechanism of perioperative strokes was not uniform (embolism, 33.3%; hypoperfusion, 42.8%; embolism and hypoperfusion, 14.3%; lacunar infarct, 10%), whereas most postoperative strokes were embolic (77.8%). The mean National Institutes of Health Stroke Scale score was 20.6 ± 9.9, and the modified Rankin score at discharge was 4.1±2.2. CONCLUSIONS: Most strokes in ATAD occurred perioperatively from various mechanisms predominantly affecting the right anterior circulation irrespective of the arterial cannulation site. This complication is most likely the result of unstable hemodynamics and dissection of the innominate artery (IA) or its downstream vessels.

Practical approach to confirm femoral artery patency after percutaneous closure for veno-arterial extracorporeal membrane oxygenation decannulation.

BACKGROUND: We describe a technique to assess blood flow distal to the decannulation site after deployment of Perclose ProGlide (Abbott Vascular, Abbott Park, Ill) in patients on femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. TECHNIQUE: An antegrade distal perfusion catheter was placed in all patients, and decannulation was primarily performed at bedside (N = 11/12). With the VA-ECMO circuit switched off, a needle was inserted into the arterial tubing, passed through the femoral arterial cannula into the artery. The arterial cannula was removed over a wire and the previously placed Proglide Perclose sutures were secured. Back bleeding from the antegrade distal perfusion catheter, confirmed using a three-way connector, indicated blood flow to the superficial femoral artery. This was followed by confirmation of blood flow to the lower leg using a Doppler ultrasound. Hemostasis of the antegrade perfusion catheter was achieved through manual compression. RESULTS: We implemented this technique in 12 patients with a technical success rate of 100%. There were no ipsilateral leg ischemia, bleeding, pseudoaneurysm, or infection after decannulation. CONCLUSIONS: This technique allows prompt assessment of blood flow to the distal leg immediately following arterial decannulation.

Acetylcholine waves and dopamine release in the striatum.

Striatal dopamine encodes reward, with recent work showing that dopamine release occurs in spatiotemporal waves. However, the mechanism of dopamine waves is unknown. Here we report that acetylcholine release in mouse striatum also exhibits wave activity, and that the spatial scale of striatal dopamine release is extended by nicotinic acetylcholine receptors. Based on these findings, and on our demonstration that single cholinergic interneurons can induce dopamine release, we hypothesized that the local reciprocal interaction between cholinergic interneurons and dopamine axons suffices to drive endogenous traveling waves. We show that the morphological and physiological properties of cholinergic interneuron - dopamine axon interactions can be modeled as a reaction-diffusion system that gives rise to traveling waves. Analytically-tractable versions of the model show that the structure and the nature of propagation of acetylcholine and dopamine traveling waves depend on their coupling, and that traveling waves can give rise to empirically observed correlations between these signals. Thus, our study provides evidence for striatal acetylcholine waves in vivo, and proposes a testable theoretical framework that predicts that the observed dopamine and acetylcholine waves are strongly coupled phenomena.

Zone 2 arch repair for acute type A dissection: Evolution from arch-first to proximal-first repair.

Objective: With growing experience of acute type A aortic dissection repair, Zone 2 arch repair has been advocated. The aim of this study is to compare the outcome between "proximal-first" and "arch-first" Zone 2 repair. Methods: From January 2015 to March 2023, 45 patients underwent Zone 2 arch repair out of 208 acute type A aortic dissection repairs: arch-first, N = 19, and proximal-first technique, N = 26, since January 2021. Indications were aortic arch or descending tear, complex dissection in neck vessels, cerebral malperfusion, or aneurysm of the aortic arch. Results: The lowest bladder temperature was higher in the proximal-first technique (24.9 °C vs 19.7 °C, P < .001). Cardiopulmonary bypass (230 vs 177.5 minutes, P < .001), myocardial ischemic (124 vs 91 minutes, P < .001), and lower-body circulatory arrest (87 vs 28 minutes, P < .001) times were shorter in the proximal-first technique. The arch-first group required more packed red blood cells (arch-first, 2 units vs proximal-first, 0 units, P = .048), platelets (arch-first, 4 units vs proximal-first, 2 units, P = .003), and cryoprecipitates (arch-first, 2 units vs proximal-first, 1 unit, P = .024). Operative mortality and major morbidities were higher in the arch-first group (57.9% vs 11.5%, P = .001). One-year survival was comparable (arch-first, 89.5% ± 7.0% vs proximal-first, 92.0% ± 5.5%, P = .739). Distal intervention was successfully performed in 5 patients (endovascular, N = 3, and open repair, N = 2). Conclusions: Zone 2 arch repair using the proximal-first technique for acute type A aortic dissection repair yields shorter lower-body ischemic time with a warmer core temperature, resulting in shorter cardiopulmonary bypass time, less blood product use, and fewer morbidities when compared with the arch-first technique.

del Nido versus blood cardioplegia in cardiac surgery: A multicenter analysis of over 40,000 patients.

OBJECTIVES: The use of del Nido cardioplegia in adult cardiac surgery is rising in popularity. The objective of this large multicenter study was to evaluate the use and associated outcomes of del Nido versus blood cardioplegia in adult cardiac surgery. METHODS: Patients undergoing coronary artery bypass grafting (CABG) and/or valve (mitral, aortic), and/or nondescending thoracic aortic surgery (July 2014 to March 2022) across 39 centers were extracted from the Perfusion Measures and Outcomes registry. Patients were stratified by cardioplegia type for unadjusted analysis and multivariable mixed-effects models were used for risk adjustment. RESULTS: Of 44,175 patients, 42.5% used del Nido, with use increasing 48% over time. Overall, the del Nido group had shorter median crossclamp time (74 minutes vs 87 minutes, P < .001) and lower median peak intraoperative glucose levels (161 mg/dL vs 180 mg/dL, P < .001). Use of del Nido was not associated with operative mortality (adjusted odds ratio [ORadj], 1.16; P = .075) nor major morbidity (ORadj, 1.05; P = .25). Findings for valve cases were similar, except crossclamp time differences were variable by type of valve procedure. Within the CABG subgroup there was a trend toward increased operative mortality with del Nido (ORadj, 1.24; P = .069), whereas the risk of renal failure approaches statistical significance in the aortic subgroup (ORadj, 1.54; P = .056). CONCLUSIONS: In this large, multicenter study, the use of del Nido was associated with variable crossclamp time differences, lower intraoperative glucose levels, and no significant difference in major morbidity or mortality. Efficiency benefits of del Nido may be limited in valve cases, whereas outcomes in CABG and aortic cases warrant further study.

Dispelling the Saddle Pulmonary Embolism Myth (from a Comparison of Saddle Versus Non-Saddle Pulmonary Embolism).

In the setting of an acute pulmonary embolism (PE), there is often an assumed association between a saddle PE (SPE) and increased clinical severity. We aimed to determine the magnitude of SPE proximal pulmonary artery (PA) flow obstruction and its impact on right ventricular (RV) function in the setting of acute PE in a single-center series. From 2005 to 2022, patients with acute PE presenting with acute RV dysfunction requiring intervention were classified as SPE and non-SPE based on presenting computed tomography (CT) scans. SPE flow obstruction was determined by the ratio of the orthogonal cross-sectional surface area measurements of clot and native PA at the location of maximum clot burden in the right PA and left PA. Presenting RV function based on clinical and imaging parameters (CT and transthoracic echocardiography) were compared between SPE and non-SPE cohorts. A total of 174 patients were identified (SPE 92 [52.9%] and non-SPE 82 [47.1%]). Demographics and co-morbidities were similar. In patients with SPE, there was a mean 25.9% total flow obstruction (right PA 26.9% and left PA 25.5%). Non-SPE had greater clinical RV dysfunction on presentation as reflected by more high-risk PE (43.9% vs 26.1%, p = 0.01), need for venoarterial extracorporeal membrane oxygenation (21.9% vs 10.9%, p = 0.05), and more preoperative cardiopulmonary resuscitation (16.7% vs 7.8%, p = 0.08). RV:left ventricular ratio (CT and transthoracic echocardiography) and RV fractional area change were statistically similar between groups. In-hospital mortality was statistically similar between cohorts (4.9% non-SPE vs 2.1% SPE, p = 0.32). In conclusion, in a single-center series of patients with acute PE with RV dysfunction, SPE did not cause proximal flow-limiting obstruction. Non-SPE was associated with more clinical RV dysfunction than SPE. Thus, it should not be assumed that a non-SPE is a marker of patient stability.

Significant increase in mortality and risk of acute ischemic stroke in infective endocarditis patients with subarachnoid hemorrhage secondary to mycotic aneurysms.

Infective Endocarditis (IE) patients are known to have a variety of complications with one of the rarest, but serious being cerebral mycotic aneurysm, which can result in subarachnoid hemorrhage (SAH). Using the National In-Patient Sample database, we sought to determine the rate of acute ischemic stroke (AIS) and outcomes in IE- patients with and without SAH. In total, we identified 82,844 IE-patients from 2010 to 2016, of which 641 had a concurrent diagnosis of SAH. IE patients with SAH had a more complicated course, higher mortality rate (OR 4.65 CI 95% 3.9-5.5, P < 0.001), and worse outcomes. This patient population also had a significantly higher rate of AIS (OR 6.3 CI 95% 5.4-7.4, P < 0.001). Overall, 41.5% of IE-patients with SAH had AIS during their hospitalization as compared to 10.1% of IE only patients. IE-patients with SAH were more likely to undergo endovascular treatment (3.6%) with 0.8% of the IE patients with AIS undergoing mechanical thrombectomy. While IE-patients are at risk for various complications, our study suggests a significant increase in the mortality and risk of AIS in those with SAH.

Fire-driven animal evolution in the Pyrocene.

Fire regimes are a major agent of evolution in terrestrial animals. Changing fire regimes and the capacity for rapid evolution in wild animal populations suggests the potential for rapid, fire-driven adaptive animal evolution in the Pyrocene. Fire drives multiple modes of evolutionary change, including stabilizing, directional, disruptive, and fluctuating selection, and can strongly influence gene flow and genetic drift. Ongoing and future research in fire-driven animal evolution will benefit from further development of generalizable hypotheses, studies conducted in highly responsive taxa, and linking fire-adapted phenotypes to their underlying genetic basis. A better understanding of evolutionary responses to fire has the potential to positively influence conservation strategies that embrace evolutionary resilience to fire in the Pyrocene.

Explant vs Redo-TAVR After Transcatheter Valve Failure: Mid-Term Outcomes From the EXPLANTORREDO-TAVR International Registry.

BACKGROUND: Valve reintervention after transcatheter aortic valve replacement (TAVR) failure has not been studied in detail. OBJECTIVES: The authors sought to determine outcomes of TAVR surgical explantation (TAVR-explant) vs redo-TAVR because they are largely unknown. METHODS: From May 2009 to February 2022, 396 patients in the international EXPLANTORREDO-TAVR registry underwent TAVR-explant (181, 46.4%) or redo-TAVR (215, 54.3%) for transcatheter heart valve (THV) failure during a separate admission from the initial TAVR. Outcomes were reported at 30 days and 1 year. RESULTS: The incidence of reintervention after THV failure was 0.59% with increasing volume during the study period. Median time from index-TAVR to reintervention was shorter in TAVR-explant vs redo-TAVR (17.6 months [IQR: 5.0-40.7 months] vs 45.7 months [IQR: 10.6-75.6 months]; P < 0.001], respectively. TAVR-explant had more prosthesis-patient mismatch (17.1% vs 0.5%; P < 0.001) as the indication for reintervention, whereas redo-TAVR had more structural valve degeneration (63.7% vs 51.9%; P = 0.023), with a similar incidence of ≥moderate paravalvular leak between groups (28.7% vs 32.8% in redo-TAVR; P = 0.44). There was a similar proportion of balloon-expandable THV failures (39.8% TAVR-explant vs 40.5% redo-TAVR; P = 0.92). Median follow-up was 11.3 (IQR: 1.6-27.1 months) after reintervention. Compared with redo-TAVR, TAVR-explant had higher mortality at 30 days (13.6% vs 3.4%; P < 0.001) and 1 year (32.4% vs 15.4%; P = 0.001), with similar stroke rates between groups. On landmark analysis, mortality was similar between groups after 30 days (P = 0.91). CONCLUSIONS: In this first report of the EXPLANTORREDO-TAVR global registry, TAVR-explant had a shorter median time to reintervention, with less structural valve degeneration, more prosthesis-patient mismatch, and similar paravalvular leak rates compared with redo-TAVR. TAVR-explant had higher mortality at 30 days and 1 year, but similar rates on landmark analysis after 30 days.

Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone.

The subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the adult SVZ control NSC behavior are unclear. We found that Cx43 is highly expressed by SVZ NSCs and ECs, and its deletion in either leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence. This is further supported by single-cell RNA sequencing and in vitro studies showing that ECs control NSC proliferation by regulating expression of genes associated with NSC quiescence and/or activation in a Cx43-dependent manner. Cx43 mediates these effects in a channel-independent manner involving its cytoplasmic tail and ERK activation. Such insights inform adult NSC regulation and maintenance aimed at stem cell therapies for neurodegenerative disorders.

Does the evolution of ontogenetic niche shifts favour species coexistence? An empirical test in Trinidadian streams.

A major question in ecology is how often competing species evolve to reduce competitive interactions and facilitate coexistence. One untested route for a reduction in competitive interactions is through ontogenetic changes in the trophic niche of one or more of the interacting species. In such cases, theory predicts that two species can coexist if the weaker competitor changes its resource niche to a greater degree with increased body size than the superior competitor. We tested this prediction using stable isotopes that yield information about the trophic position (δ15 N) and carbon source (δ13 C) of two coexisting fish species: Trinidadian guppies Poecilia reticulata and killifish Rivulus hartii. We examined fish from locations representing three natural community types: (1) where killifish and guppies live with predators, (2) where killifish and guppies live without predators and (3) where killifish are the only fish species. We also examined killifish from communities in which we had introduced guppies, providing a temporal sequence of the community changes following the transition from a killifish only to a killifish-guppy community. We found that killifish, which are the weaker competitor, had a much larger ontogenetic niche shift in trophic position than guppies in the community where competition is most intense (killifish-guppy only). This result is consistent with theory for size-structured populations, which predicts that these results should lead to stable coexistence of the two species. Comparisons with other communities containing guppies, killifish and predators and ones where killifish live by themselves revealed that these results are caused primarily by a loss of ontogenetic niche changes in guppies, even though they are the stronger competitor. Comparisons of these natural communities with communities in which guppies were translocated into sites containing only killifish showed that the experimental communities were intermediate between the natural killifish-guppy community and the killifish-guppy-predator community, suggesting contemporary evolution in these ontogenetic trophic differences. These results provide comparative evidence for ontogenetic niche shifts in contributing to species coexistence and comparative and experimental evidence for evolutionary or plastic changes in ontogenetic niche shifts following the formation of new communities.

Surgical Management and Mechanical Circulatory Support in High-Risk Pulmonary Embolisms: Historical Context, Current Status, and Future Directions: A Scientific Statement From the American Heart Association.

Acute pulmonary embolism is the third leading cause of cardiovascular death, with most pulmonary embolism-related mortality associated with acute right ventricular failure. Although there has recently been increased clinical attention to acute pulmonary embolism with the adoption of multidisciplinary pulmonary embolism response teams, mortality of patients with pulmonary embolism who present with hemodynamic compromise remains high when current guideline-directed therapy is followed. Because historical data and practice patterns affect current consensus treatment recommendations, surgical embolectomy has largely been relegated to patients who have contraindications to other treatments or when other treatment modalities fail. Despite a selection bias toward patients with greater illness, a growing body of literature describes the safety and efficacy of the surgical management of acute pulmonary embolism, especially in the hemodynamically compromised population. The purpose of this document is to describe modern techniques, strategies, and outcomes of surgical embolectomy and venoarterial extracorporeal membrane oxygenation and to suggest strategies to better understand the role of surgery in the management of pulmonary embolisms.

Aortic Reoperation After Prior Acute Type A Aortic Dissection Repair: Don't Despair the Repair.

BACKGROUND: There is paucity of data regarding reoperation after acute type A aortic dissection (ATAD) repair. METHODS: From October 2006 to March 2022, 75 patients received 123 reoperations after ATAD (proximal, n = 17; distal, n = 103; and both, n = 3) utilizing redo sternotomy (RS, n = 68), left thoracotomy (LT, n = 44), and endovascular approach (TEVAR, n = 11). The axillary artery cannulation was utilized in 97.1% of the RS cases. A classic elephant trunk technique was used as a 2-staged procedure for distal pathology. Most LT repairs (95.5%) were completed above the celiac axis. RESULTS: Index ATAD repairs were predominantly ascending/hemiarch repair (73.3%). The median duration from the index repair was 2.0 years. Most reoperations were elective procedures (82.1%). Hospital mortality was 2.4% (RS, 1.5%; LT, 4.5%; TEVAR, 0%), and the stroke rate was 1.6%. There was no spinal cord ischemia. The 5-year overall survival and freedom from aortic mortality or procedure were 85.2% ± 5.6% and 80.6% ± 6.1%, respectively. There were 7 distal reinterventions (prior TEVAR, n = 3; prior LT, n = 4). Two patients required LT repair after prior TEVAR and 3 patients received infrarenal aortic repair after prior LT repair. Computed tomography after completion of the distal repair (n = 45) showed an increase of distal aorta at each level as follows: celiac axis 1.2 mm/y; renal artery 1.0 mm/y; and terminal aorta 1.2 mm/y. CONCLUSIONS: Reoperation after ATAD repair can be safely performed as an elective procedure at experienced centers. Staged distal interventions utilizing classic elephant trunk insertion and open repair above the celiac axis showed durable outcomes.

Morin and isoquercitrin protect against ischemic neuronal injury by modulating signaling pathways and stimulating mitochondrial biogenesis.

Objetive: The search for the etiology of Alzheimer's disease has revealed dysregulation of amyloid protein precursors, ß-secretase, mitophagy, apoptosis, and Tau protein genes after ischemic brain injury. Due to this and the fact that some flavonoids have demonstrated anti-amyloidogenic effects on AD targets, we aimed to investigate whether they are effective against an ischemic neuronal injury not only by its antioxidant effects and clarify their mechanism.We simulated the energy depletion that characterizes ischemic processes using iodoacetic acid on HT22 cells. In vitro ischemic assays were also performed under OXPHOS inhibition using inhibitors of the different mitochondrial complexes and intracellular ATP, NADH and NADPH levels were determined. The signaling pathways of MAP kinase (MAPK) and of the PI3K/Akt mTOR were analyzed for its close association with post-ischemic survival.Results: Morin and isoquercitrin showed a significant neuroprotective effect against IAA toxicity, favored the activity of the mitochondrial complexes and prevented the decrease in ERK phosphorylation and activation of the stress proteins JNK and p38 caused by IAA treatment, as well as prevented satisfactorily mTOR and p70 dephosphorylation. They provide a considerable resistance to ischemic brain injury by modulating signaling pathways that stimulate mitochondrial biogenesis and promoting the activity of electron transport chain.Highlights Morin and isoquercitrin showed a significant neuroprotective effect against IAA toxicity.Morin and isoquercitrin favor the activity of the mitochondrial complexes I, III and V.Morin and isoquercitrin prevent the decrease in ERK phosphorylation caused by IAA.Morin shows a better profile avoiding Akt dephosphorylation than isoquercetrin.Morin and isoquercitrin prevent dephosphorylation of mTOR and p70.