Infective Endocarditis: Inflammatory Response, Genetic Susceptibility, Oxidative Stress, and Multiple Organ Failure

Infective endocarditis is defined by a focus of infection within the heart. Despite the optimal care, the mortality approaches 30% at 1 year, so the care for this type of patients represents a challenge to improve the result in your care. The challenges in this clinical entity have several aspects such as the diversity of germs that cause endocarditis, and the most important epidemiologically has generated resistance to antimicrobial treatment along with the possibility of apoptosis in their host-germ interaction. The immunogenetic susceptibility to host infection is discussed, which represents a deep area of research. Inflammation, local and systemic, is complex, with the genesis of reactive oxygen species, which are harmful when the antioxidant defenses are exceeded, causing the break in the mitochondrial electron transport chain with the fall in energy genesis, multiple organ failure, and death. Both at the cellular level and in the mitochondria, possible therapeutic targets are also commented

Detection of non-melanoma skin cancer by in vivo fluorescence imaging with fluorocoxib A.

Non-melanoma skin cancer (NMSC) is the most common form of cancer in the US and its incidence is increasing. The current standard of care is visual inspection by physicians and/or dermatologists, followed by skin biopsy and pathologic confirmation. We have investigated the use of in vivo fluorescence imaging using fluorocoxib A as a molecular probe for early detection and assessment of skin tumors in mouse models of NMSC. Fluorocoxib A targets the cyclooxygenase-2 (COX-2) enzyme that is preferentially expressed by inflamed and tumor tissue, and therefore has potential to be an effective broadly active molecular biomarker for cancer detection. We tested the sensitivity of fluorocoxib A in a BCC allograft SCID hairless mouse model using a wide-field fluorescence imaging system. Subcutaneous allografts comprised of 1000 BCC cells were detectable above background. These BCC allograft mice were imaged over time and a linear correlation (R(2) = 0.8) between tumor volume and fluorocoxib A signal levels was observed. We also tested fluorocoxib A in a genetically engineered spontaneous BCC mouse model (Ptch1(+/-) K14-Cre-ER2 p53(fl/fl)), where sequential imaging of the same animals over time demonstrated that early, microscopic lesions (100 μm size) developed into visible macroscopic tumor masses over 11 to 17 days. Overall, for macroscopic tumors, the sensitivity was 88% and the specificity was 100%. For microscopic tumors, the sensitivity was 85% and specificity was 56%. These results demonstrate the potential of fluorocoxib A as an in vivo imaging agent for early detection, margin delineation and guided biopsies of NMSCs

Local temperature-sensitive mechanisms are important mediators of limb tissue hyperemia in the heat-stressed human at rest and during small muscle mass exercise.

Limb tissue and systemic blood flow increases with heat stress, but the underlying mechanisms remain poorly understood. Here, we tested the hypothesis that heat stress-induced increases in limb tissue perfusion are primarily mediated by local temperature-sensitive mechanisms. Leg and systemic temperatures and hemodynamics were measured at rest and during incremental single-legged knee extensor exercise in 15 males exposed to 1 h of either systemic passive heat-stress with simultaneous cooling of a single leg (n=8) or isolated leg heating or cooling (n=7). Systemic heat-stress increased core, skin and heated leg blood (Tb) temperatures, cardiac output and heated leg blood flow (LBF, 0.6 ± 0.1 l.min(-1); P0.05). Increased heated leg deep tissue BF was closely related to Tb (R(2) = 0.50; P0.05), despite unchanged systemic temperatures and hemodynamics. During incremental exercise, heated LBF was consistently maintained ~ 0.6 l.min(-1) higher than that in the cooled leg (P<0.01), with LBF and vascular conductance in both legs showing a strong correlation with their respective local Tb (R(2) = 0.85 and 0.95, P<0.05). We conclude that local temperature-sensitive mechanisms are important mediators in limb tissue perfusion regulation both at rest and during small-muscle mass exercise in hyperthermic humans.The invasive study was partially funded by Gatorade Sports Science Institute, PepsiCo

Surrogate-based optimization of tidal turbine arrays: a case study for the Faro-Olhão inlet

This paper presents a study for estimating the size of a tidal turbine array for the Faro-Olhão Inlet (Potugal) using a surrogate optimization approach. The method compromises problem formulation, hydro-morphodynamic modelling, surrogate construction and validation, and constraint optimization. A total of 26 surrogates were built using linear RBFs as a function of two design variables: number of rows in the array and Tidal Energy Converters (TECs) per row. Surrogates describe array performance and environmental effects associated with hydrodynamic and morphological aspects of the multi inlet lagoon. After validation, surrogate models were used to formulate a constraint optimization model. Results evidence that the largest array size that satisfies performance and environmental constraints is made of 3 rows and 10 TECs per row.Eduardo González-Gorbeña has received funding for the OpTiCA project (http://msca-optica.eu/) from the Marie Skłodowska-Curie Actions of the European Union's H2020-MSCA-IF-EF-RI-2016 / GA#: 748747. The paper is a contribution to the SCORE pro-ject, funded by the Portuguese Foundation for Science and Technology (FCT–PTDC/AAG-TEC/1710/2014). André Pacheco was supported by the Portuguese Foun-dation for Science and Technology under the Portuguese Researchers’ Programme 2014 entitled “Exploring new concepts for extracting energy from tides” (IF/00286/2014/CP1234).info:eu-repo/semantics/publishedVersio

How to Construct Perfect and Worse-than-Coin-Flip Spoofing Countermeasures: A Word of Warning on Shortcut Learning

Shortcut learning, or `Clever Hans effect` refers to situations where a learning agent (e.g., deep neural networks) learns spurious correlations present in data, resulting in biased models. We focus on finding shortcuts in deep learning based spoofing countermeasures (CMs) that predict whether a given utterance is spoofed or not. While prior work has addressed specific data artifacts, such as silence, no general normative framework has been explored for analyzing shortcut learning in CMs. In this study, we propose a generic approach to identifying shortcuts by introducing systematic interventions on the training and test sides, including the boundary cases of `near-perfect` and `worse than coin flip` (label flip). By using three different models, ranging from classic to state-of-the-art, we demonstrate the presence of shortcut learning in five simulated conditions. We analyze the results using a regression model to understand how biases affect the class-conditional score statistics.Comment: Interspeech 202

Left Atrial Venoarterial Extracorporeal Membrane Oxygenation Strategy in Postcardiotomy Cardiogenic Shock: A Case Series

Postcardiotomy cardiogenic shock is a rare complication with high mortality. When patients do not respond to the placement of an intra-aortic balloon pump or pharmacological treatment, therapy with peripheral venoarterial extracorporeal membrane is a viable option that allows active resuscitation. The adjunct use of Impella® (Abiomed, Danvers, MA, USA) allows active unloading of the dysfunctional left ventricle. However, left atrial venoarterial extracorporeal membrane oxygenation (LAVA-ECMO) is an appealing and effective strategy in cases of aortic dissection, aortic valve replacement, or bioprosthesis of the aorta. Insertion of an extraction cannula that can discharge both atria or only the left atrium allows biventricular discharge or discharge of only the left ventricle, respectively. We present a case series of patients who underwent Bentall–De Bono surgery with severe aortic regurgitation secondary to aortic dissection and/or aneurysm. In one case, the aortic dissection extended before the bifurcation of the iliac arteries, and LAVA-ECMO was a safe treatment option. To our knowledge, this is the first published experience of LAVA-ECMO after cardiac surgery in this population

Attachment and emotion regulation in substance addictions and behavioral addictions

Background Risky behaviors have been related to emotional regulation and attachment, which may constitute risk factors for developing an addictive behavior. However, there may also be differences between substance and non-substance-related addictions. Aims This study aimed to examine the relationship of emotional regulation and attachment, with substance (alcohol and drug abuse), and non-substance-related addictions (gambling disorder, video game addiction, and problematic Internet use) in adolescents and emerging adults. The study also aimed to examine gender differences for such predictors. Methods The sample comprised 472 students aged 13–21 years recruited from high schools and vocational education centers. Results Findings demonstrated that emotion regulation was predictive of all addictive behaviors assessed in this study (alcohol and drug abuse, gambling disorder, video game addiction, and problematic Internet use), whereas attachment predicted non-substance-related addictions (gambling disorder, video game addiction, and problematic Internet use). In addition, gender differences were found, with females scoring significantly higher in maternal and peer attachment, whereas males scored significantly higher in gambling disorder and video game addiction. Conclusion The findings may be useful for preventive and clinical interventions conducted with youth regarding addictive behaviors