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Abstract Aortic dissection is the most frequently diagnosed lethal disease of the aorta. Half of all patients with acute type-A aortic dissection die within 48 hours of presentation. There is still debate as to the optimal site of arterial cannulation for establishing cardiopulmonary bypass in patients with type-A aortic dissection. Femoral artery cannulation with retrograde perfusion is the most common method but because of the risk of malperfusion of vital organs and atheroembolism related to it different sites such as the axillary artery, the innominate artery and the aortic arch are used. Cannulation of these sites is not without risks of atheroembolism, neurovascular complications and can be time consuming. Another yet to be popularised option is the transapical aortic cannulation (TAC) described in this article. TAC consists of the insertion of the arterial cannula through the apex of the left ventricle and the aortic valve to lie in the sinus of Valsalva. Trans-oesophageal guidance is necessary to ensure correct placement of the cannula. TAC is an excellent method of establishing cardiopulmonary bypass as it is quick, provides a more physiological method of delivering antegrade arterial flow and is the only method to assure perfusion of the true lumen.

Aortic dissection is the most frequently diagnosed lethal disease of the aorta. Half of all patients with acute type-A aortic dissection die within 48 hours of presentation. There is still debate as to the optimal site of arterial cannulation for establishing cardiopulmonary bypass in patients with type-A aortic dissection. Femoral artery cannulation with retrograde perfusion is the most common method but because of the risk of malperfusion of vital organs and atheroembolism related to it different sites such as the axillary artery, the innominate artery and the aortic arch are used. Cannulation of these sites is not without risks of atheroembolism, neurovascular complications and can be time consuming. Another yet to be popularised option is the transapical aortic cannulation (TAC) described in this article. TAC consists of the insertion of the arterial cannula through the apex of the left ventricle and the aortic valve to lie in the sinus of Valsalva. Trans-oesophageal guidance is necessary to ensure correct placement of the cannula. TAC is an excellent method of establishing cardiopulmonary bypass as it is quick, provides a more physiological method of delivering antegrade arterial flow and is the only method to assure perfusion of the true lumen. [ABSTRACT FROM AUTHOR]

Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line, and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adeno-associated viral (AAV) transduction procedures, we describe spatially confined aberrant Ca 2+ microwaves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7, or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer in a titre-dependent fashion. Ca 2+ microwaves developed in hippocampal CA1 and CA3, but not dentate gyrus nor neocortex, were typically first observed at 4 wk after viral transduction, and persisted up to at least 8 wk. The phenomenon was robust and observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca 2+ microwaves depend on the promoter and viral titre of the GECI, density of expression, as well as the targeted brain region. We used an alternative viral transduction method of GCaMP which avoids this artefact. The results show that commonly used Ca 2+ -indicator AAV transduction procedures can produce artefactual Ca 2+ responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca 2+ microwaves, and we provide a potential solution., Competing Interests: NM, MM, EG, DO, FD, PR, FH, RY, MF, HB, MW, TK No competing interests declared, (© 2024, Masala et al.)

In schnauzers, a breed predisposition to squamous cell carcinoma of the digit (dSCC) is well known. The aim of this study was to compare the clinical and macroscopic findings of dSCCs in giant (GSs), standard (SSs), and miniature schnauzers (MSs)., Methods: Pathology reports of 478 dSCCs from 417 schnauzers (227 GSs, 174 SSs, and 16 MSs) were retrospectively evaluated., Results: The MSs were older than the SSs and GSs ( p ≤ 0.01). The male GSs were predisposed to dSCC ( p < 0.05). In the GSs, the nodular dSCCs were larger than in the MSs ( p ≤ 0.05) and SSs ( p ≤ 0.001). The digital SCCs were mostly diagnosed at the forelimbs, especially at digits 1, 2, and 5. At the hindlimbs, the affected toes differed between the GSs and SSs. Multiple dSCCs were more common in SSs than in GSs ( p = 0.003). If dSCC was the cause of death, the survival time was shorter than in dogs dying from other diseases ( p = 0.004). Metastases occurred in 20% of the cases and led to a significantly shorter survival time in both the GSs and SSs ( p < 0.001)., Conclusions: The results showed various differences in the dSCC depending on the size variant of the schnauzer., Competing Interests: The authors declare no conflict of interest. However, the authors H.A.-L. and R.K. do offer diagnostic pathology services.

Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding and deficits in spatial memory. Two-photon glutamate uncaging experiments revealed a marked increase in the fraction of hippocampal first-order CA1 pyramidal cell dendrites capable of generating dendritic spikes in the kainate model of chronic epilepsy. Moreover, in epileptic mice dendritic spikes were generated with lower input synchrony, and with a lower threshold. The Nav1.3/1.1 selective Na+ channel blocker ICA-121431 reversed dendritic hyperexcitability in epileptic mice, while the Nav1.2/1.6 preferring anticonvulsant S-Lic did not. We used in vivo two-photon imaging to determine if aberrant dendritic excitability is associated with altered place-related firing of CA1 neurons. We show that ICA-121431 improves degraded hippocampal spatial representations in epileptic mice. Finally, behavioural experiments show that reversing aberrant dendritic excitability with ICA-121431 reverses hippocampal memory deficits. Thus, a dendritic channelopathy may underlie cognitive deficits in epilepsy and targeting it pharmacologically may constitute a new avenue to enhance cognition., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Dendrites of hippocampal CA1 pyramidal cells amplify clustered glutamatergic input by activation of voltage-gated sodium channels and N-methyl-D-aspartate receptors (NMDARs). NMDAR activity depends on the presence of NMDAR co-agonists such as D-serine, but how co-agonists influence dendritic integration is not well understood. Using combinations of whole-cell patch clamp, iontophoretic glutamate application, two-photon excitation fluorescence microscopy and glutamate uncaging in acute rat and mouse brain slices we found that exogenous D-serine reduced the threshold of dendritic spikes and increased their amplitude. Triggering an astrocytic mechanism controlling endogenous D-serine supply via endocannabinoid receptors (CBRs) also increased dendritic spiking. Unexpectedly, this pathway was activated by pyramidal cell activity primarily in the theta range, which required HCN channels and astrocytic CB1Rs. Therefore, astrocytes close a positive and frequency-dependent feedback loop between pyramidal cell activity and their integration of dendritic input. Its disruption in mice led to an impairment of spatial memory, which demonstrated its behavioral relevance., (© 2022. The Author(s).)

The hippocampal dentate gyrus is an important relay conveying sensory information from the entorhinal cortex to the hippocampus proper. During exploration, the dentate gyrus has been proposed to act as a pattern separator. However, the dentate gyrus also shows structured activity during immobility and sleep. The properties of these activity patterns at cellular resolution, and their role in hippocampal-dependent memory processes have remained unclear. Using dual-color in vivo two-photon Ca 2+ imaging, we show that in immobile mice dentate granule cells generate sparse, synchronized activity patterns associated with entorhinal cortex activation. These population events are structured and modified by changes in the environment; and they incorporate place- and speed cells. Importantly, they are more similar than expected by chance to population patterns evoked during self-motion. Using optogenetic inhibition, we show that granule cell activity is not only required during exploration, but also during immobility in order to form dentate gyrus-dependent spatial memories., Competing Interests: MP, NN, AH, TN, NM, FD, OB, JM, LE, KG, HB No competing interests declared, (© 2021, Pofahl et al.)

Purpose: To implement, optimize, and characterize lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses for fat-suppressed fully self-gated free-running 5D cardiac MRI., Methods: Bloch equation simulations were used to optimize LIBRE parameter settings in non-interrupted bSSFP prior to in vitro validation. Thus, optimized LIBRE pulses were subsequently applied to free-running coronary MRA in 20 human adult subjects, where resulting images were quantitatively compared to those obtained with non-fat-suppressing excitation (SP), conventional 1-2-1 water excitation (WE), and a previously published interrupted free-running (IFR) sequence. SAR and scan times were recorded. Respiratory-and-cardiac-motion-resolved images were reconstructed with XD-GRASP, and contrast ratios, coronary artery detection rate, vessel length, and vessel sharpness were computed., Results: The numerically optimized LIBRE parameters were successfully validated in vitro. In vivo, LIBRE had the lowest SAR and a scan time that was similar to that of WE yet 18% shorter than that of IFR. LIBRE improved blood-fat contrast when compared to SP, WE, and IFR, vessel detection relative to SP and IFR, and vessel sharpness when compared to WE and IFR (for example, for the left main and anterior descending coronary artery, 51.5% ± 10.2% [LIBRE] versus 42.1% ± 6.8% [IFR]). Vessel length measurements remained unchanged for all investigated methods., Conclusion: LIBRE enabled fully self-gated non-interrupted free-running 5D bSSFP imaging of the heart at 1.5T with suppressed fat signal. Measures of image quality, vessel conspicuity, and scan time compared favorably to those obtained with the more conventional non-interrupted WE and the previously published IFR, while SAR reduction offers added flexibility., (© 2020 International Society for Magnetic Resonance in Medicine.)

Neurofeedback based on real-time functional MRI is an emerging technique to train voluntary control over brain activity in healthy and disease states. Recent developments even allow for training of brain networks using connectivity feedback based on dynamic causal modeling (DCM). DCM is an influential hypothesis-driven approach that requires prior knowledge about the target brain network dynamics and the modulatory influences. Data-driven approaches, such as tensor independent component analysis (ICA), can reveal spatiotemporal patterns of brain activity without prior assumptions. Tensor ICA allows flexible data decomposition and extraction of components consisting of spatial maps, time-series, and session/subject-specific weights, which can be used to characterize individual neurofeedback regulation per regulation trial, run, or session. In this study, we aimed to better understand the spatiotemporal brain patterns involved and affected by model-based feedback regulation using data-driven tensor ICA. We found that task-specific spatiotemporal brain patterns obtained using tensor ICA were highly consistent with model-based feedback estimates. However, we found that the DCM approach captured specific network interdependencies that went beyond what could be detected with either general linear model (GLM) or ICA approaches. We also found that neurofeedback-guided regulation resulted in activity changes that were characteristic of the mental strategies used to control the feedback signal, and that these activity changes were not limited to periods of active self-regulation, but were also evident in distinct gradual recovery processes during subsequent rest periods. Complementary data-driven and model-based approaches could aid in interpretation of the neurofeedback data when applied post-hoc, and in the definition of the target brain area/pattern/network/model prior to the neurofeedback training study when applied to the pilot data. Systematically investigating the triad of mental effort, spatiotemporal brain network changes, and activity and recovery processes might lead to a better understanding of how learning with neurofeedback is accomplished, and how such learning can cause plastic brain changes along with specific behavioral effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer system comprising photoactivated adenylyl cyclases (PACs) and the small cyclic nucleotide-gated potassium channel SthK. Activation of this 'PAC-K' silencer by brief pulses of low-intensity blue light causes robust and reversible silencing of cardiomyocyte excitation and neuronal firing. In vivo expression of PAC-K in mouse and zebrafish neurons is well tolerated, where blue light inhibits neuronal activity and blocks motor responses. In combination with red-light absorbing channelrhodopsins, the distinct action spectra of PACs allow independent bimodal control of neuronal activity. PAC-K represents a reliable optogenetic silencer with intrinsic amplification for sustained potassium-mediated hyperpolarization, conferring high operational light sensitivity to the cells of interest.

Objective: The authors aimed to validate the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) classification of postoperative complications in patients undergoing coronary artery bypass grafting (CABG)., Design: Retrospective, observational study., Setting: University hospital., Participants: A total of 2,764 patients with severe coronary artery disease. Complete baseline, operative, and postoperative data were available for patients who underwent isolated CABG., Interventions: Isolated CABG., Measurements and Main Results: The E-CABG complication classification was used to stratify the severity and prognostic impact of adverse postoperative events. Primary outcome endpoints were 30-day, 90-day, and long-term all-cause mortality. The secondary outcome endpoints was the length of intensive care unit stay. Both the E-CABG complication grades and additive score were predictive of 30-day (area under the receiver operating characteristics curve 0.866, 95% confidence interval [CI] 0.829-0.903; and 0.876; 95% CI 0.844-0.908, respectively) and 90-day (area under the receiver operating characteristics curve 0.850, 95% CI 0.812-0.887; and 0.863, 95% CI 0.829-0.897, respectively) all-cause mortality. The complication grades were independent predictors of increased mortality at actuarial (log-rank: p<0.0001) and adjusted analysis (p<0.0001; grade 1: hazard ratio [HR] 1.757, 95% CI 1.111-2.778; grade 2: HR 2.704, 95% CI 1.664-4.394; grade 3: HR 5.081, 95% CI 3.148-8.201). When patients who died within 30 days were excluded from the analysis, this grading method still was associated with late mortality (p<0.0001). The grading method (p<0.0001) and the additive score (rho, 0.514; p<0.0001) were predictive of the length of intensive care unit stay., Conclusions: The E-CABG postoperative complication classification seems to be a promising tool for stratifying the severity and prognostic impact of postoperative complications in patients undergoing cardiac surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Clinical evidence in coronary surgery is usually derived from retrospective, single institutional series. This may introduce significant biases in the analysis of critical issues in the treatment of these patients. In order to avoid such methodological limitations, we planned a European multicenter, prospective study on coronary artery bypass grafting, the E-CABG registry., Design: The E-CABG registry is a multicenter study and its data are prospectively collected from 13 centers of cardiac surgery in university and community hospitals located in six European countries (England, Italy, Finland, France, Germany, Sweden). Data on major and minor immediate postoperative adverse events will be collected. Data on late all-cause mortality, stroke, myocardial infarction and repeat revascularization will be collected during a 10-year follow-up period. These investigators provided a score from 0 to 10 for any major postoperative adverse events and their rounded medians were used to stratify the severity of these complications in four grades. The sum of these scores for each complication/intervention occurring after coronary artery bypass grafting will be used as an additive score for further stratification of the prognostic importance of these events., Discussion: The E-CABG registry is expected to provide valuable data for identification of risk factors and treatment strategies associated with suboptimal outcome. These information may improve the safety and durability of coronary artery bypass grafting. The proposed classification of postoperative complications may become a valuable research tool to stratify the impact of such complications on the outcome of these patients and evaluate the burden of resources needed for their treatment., Clinical Trials Number: NCT02319083.

Proteoglycan 4 (PRG4, or lubricin) is a lubricating mucin-like glycoprotein recently discovered at the ocular surface, where it functions as a boundary lubricant and appears to play a protective role. Recent technological advances have enabled abundant expression of full-length recombinant human PRG4 (rhPRG4). The objectives of this study were to 1) biochemically characterize the gross structure and glycosylations of full-length rhPRG4, and 2) assess the ocular surface boundary lubricating ability of rhPRG4 at both human cornea-eyelid and human cornea-polydimethylsiloxane (PDMS) biointerfaces. rhPRG4 expressed by a Chinese hamster ovary cell line was characterized and compared to native bovine PRG4 by SDS-PAGE western blotting, and protein identity was assessed by tandem mass spectrometry (MS/MS). Human corneas were articulated against PDMS or human eyelids, at effective sliding velocities of 0.3-30 mm/s under physiological loads of ∼15 kPa, to assess and compare the ocular lubricating ability of rhPRG4 to PRG4. Samples were tested serially in PRG4, rhPRG4 (both 300 μg/ml), then saline. Western blotting indicated that rhPRG4 had immunoreactivity at the appropriate apparent molecular weight, and possessed O-linked glycosylation consistent with that of PRG4. rhPRG4 protein identity was confirmed by MS/MS. Both PRG4 and rhPRG4 significantly, and similarly, reduced friction compared to saline at both human cornea - PDMS and human cornea-eyelid biointerfaces. In conclusion, the rhPRG4 studied here demonstrated appropriate higher order structure, O-linked glycosylations, and ocular surface boundary lubricating. Purified rhPRG4 may have clinical utility as a topical treatment of dry eye disease or contact lens biomaterial coating to promote more comfortable wear., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

Social isolation (SI) is a notable model of prolonged mild stress, characterized by multiple neurochemical and behavioral alterations, that appears particularly suitable for studying different aspects of the interplay between stress and ethanol (EtOH) consumption in order to characterize potential molecular mechanisms, including changes in the function of inhibitory GABAergic synapses, underlying such interaction. In C57BL/6J mice, SI is associated with an altered hippocampal concentration of the neuroactive steroids 3α-hydroxy-5α-pregnan-20-one (3α-5α-THP), an increased expression of the α4 and δ subunit of γ-aminobutyric acid type A receptors (GABAARs) in the dentate gyrus (DG), and a parallel enhancement of the stimulatory action of 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) on GABAergic tonic currents recorded in voltage-clamped DG granule cells (DGGCs). In addition, SI in C57BL/6J mice determines an increase in voluntary EtOH consumption and EtOH preference when compared to group-housed (GH) control animals. Furthermore, in hippocampal slices of SI mice we also observed a marked reduction of both cellular excitability and long term potentiation (LTP) in pyramidal neurons of the CA1 hippocampal sub-region, effects that were prevented by the long term treatment of SI mice with the neuroactive steroid precursor progesterone. In this article, we summarize some of our recent findings on the effects of SI in C57BL/6J mice on voluntary EtOH intake, regulation of GABAARs gene expression and function and hippocampal long term synaptic plasticity.

Background: Solitary (localized) fibrous tumors of the pleura (SFTP) are rare slow-growing neoplasms that generally have a favorable prognosis. The aim of this paper is to evaluate the predictors of outcome in a series of 110 patients with SFTP., Methods: The records of 110 patients (63 men; mean age 56.4 years; range, 17 to 79) surgically treated for SFTP from July 1990 to February 2008, were evaluated for demographics, operative procedure, histopathology, morbidity, mortality, postoperative chemotherapy or radiotherapy, and long-term follow-up., Results: Operative mortality was 0.9% (1 of 110) and the overall morbidity was 10.9% (12 of 110). The main surgical approach was video-assisted thoracoscopic surgery (69 procedures with a conversion rate of 14.5%); 40 patients underwent thoracotomy and 1 had sternotomy. The visceral pleura was the site of origin in 95 tumors, the parietal pleura in 13, the mediastinal pleura in 2 cases. Sixty-three tumors were pedunculated, 35 were sessile, and 12 were inverted fibroma. Tumors were pathologically benign in 95 cases (86.4%), and malignant in 15 (13.6%). Symptomatic patients presented with malignant tumors more often than asymptomatic (19.1% versus 9.5%). Overall 10-year survival rate was 97.5%. The overall disease-free survival rate was 90.8% (95.7% in benign cases and 67.1% in malignant cases; p < 0.05). Eight patients presented with recurrence of disease, 4 cases of which were malignant and 4 were benign., Conclusions: Solitary fibrous tumor of the pleura is a rare disease that includes both benign and malignant variants.The outcome is mostly benign, with an overall 10-year survival rate of 97.5%. Pathologically benign lesions show a better disease-free survival rate than malignant lesions (95.7% versus 67.1%; p < 0.05). Surgery is the gold standard of treatment as neither radiotherapy nor chemotherapy proved to be effective.

Background and Aim of the Study: Aortic stentless bioprostheses provide good clinical and hemodynamic results, but may be difficult to implant. Their use is also contraindicated in the presence of a severely calcified aortic root. The study aim was to assess the mid-term results of a simplified implant technique of the Sorin Pericarbon Freedom stentless bioprosthesis (SPF), that allows its use in the presence of severe aortic root calcification., Methods: Between 2001 and 2007, a total of 51 patients underwent aortic valve replacement (AVR) with the SPF, using a new technique which consisted of standard annular fixation and the fixation of each strut with a single 'U' stitch. The perioperative characteristics, early and late mortality and occurrence of valve-related events were evaluated. The overall mean cross-clamp and cardiopulmonary bypass times were 91.5 +/- 30.2 and 125.3 +/- 44.9 min, respectively, and 77.8 +/- 17.7 and 105.6 +/- 22.8 min, respectively, for AVR (these times were comparable to those required in patients receiving stented valve bioprostheses). The mean follow up period was 40.5 months (range: 3-75 months), and was 100% complete., Results: Hospital mortality was 4% and survival 76.5 +/- 14.5% at six years. Late deaths occurred in eight patients; in four cases this was valve-related (1.9%/patient-year). Freedom from valve-related death and reoperation was 91 +/- 9% and 98 +/- 2% respectively, at six years. The mean transprosthetic gradients were 12.0 +/- 3.4, 9.9 +/- 2.6, 8.7 +/- 4.2, 5.2 +/- 3.9, 4.5 +/- 3.0 and 3.2 +/- 2.7 mmHg for the 19, 21, 23, 25, 27 and 29 mm valve sizes, respectively. No valvular or paravalvular regurgitation was recorded., Conclusion: This new implantation technique for the aortic SPF stentless bioprosthesis is simple, effective and versatile, and showed good early results. It may be applicable to other stentless bioprostheses, and also be particularly useful in patients with small aortic annulus and in those with a calcified aortic root.

In this educational presentation, we offer an overview of acquired anomalies of the portal venous system explored by biphasic helical CT and MRI. Portosystemic collateral vessels, cavernous transformation of the portal vein, intrahepatic vascular shunts, aneurysms of the portal venous system, thrombosis of the portal venous system, and gas in the portal venous system will be discussed. For liver surgery and interventional procedures it is necessary to have a correct mapping of normal anatomy, variants, and different pathologies involving the portal venous system.