Pigmented acuminated condylomas seborrhoeic keratosis-like: a new entity?

BACKGROUND: Condyloma acuminatum is caused by human papillomavirus (HPV), which typically presents as excrescent, pedunculated, papillomatous lesions which may be of a pale colour. On rare occasions, we have observed pigmented genital lesions that are similar to seborrhoeic keratoses, but with histological findings of condyloma acuminatum and positive genotyping for HPV. We have termed these 'seborrhoeic keratosis-like' type condylomas. METHODS: This is an observational retrospective study. The following clinical data were collected: age, sex, time of evolution, location, isolated or multiple lesions, monomorphous or polymorphous/mixed lesions. HPV genotyping was performed in all cases, and excision for histological study in eight cases. RESULTS: A total of 31 patients were diagnosed with this type of pigmented condylomata acuminata. Of these, 16 had isolated lesions (less than five lesions) and 15 had multiple lesions. 67% of the lesions exhibited slow growth, with an evolution period of greater than 1 year. The most frequent location was the base of the penis and pubis. HPV genotyping of the lesions was positive in all cases, with the HPV-6 genotype predominating (28 cases, 90.3%). The lesions exhibited dermoscopic differences from other pigmented lesions and histological findings attributable to HPV infection (pseudoparakeratosis, koilocytosis, etc) and others similar to those observed in seborrhoeic keratoses. CONCLUSIONS: A total of 31 patients were diagnosed with pigmented verrucous lesions, excrescents, isolated or multiple, in the genital region. These lesions exhibited clinical characteristics similar to seborrhoeic keratoses, with positive genotyping for HPV. In the majority of cases, the genotype was HPV-6. These lesions have been named 'pigmented condylomata acuminata seborrhoeic keratosis-like'. Only 10 cases of these lesions have been described in the literature.

Aloe vera mucilage loaded gelatin electrospun fibers contained in polylactic acid coaxial system and polylactic acid and poly(e-caprolactone) tri-layer membranes for tissue engineering.

BACKGROUND: Polymeric electrospun mats have been used as scaffolds in tissue engineering for the development of novel materials due to its characteristics. The usage of synthetic materials has gone in decline due to environmental problems associated with their synthesis and waste disposal. Biomaterials such as biopolymers have been used recently due to good compatibility on biological applications and sustainability. OBJECTIVE: The purpose of this work is to obtain novel materials based on synthetic and natural polymers for applications on tissue engineering. METHODS: Aloe vera mucilage was obtained, chemically characterized, and used as an active compound contained in electrospun mats. Polymeric scaffolds were obtained in single, coaxial and tri-layer structures, characterized and evaluated in cell culture. RESULTS: Mucilage loaded electrospun fibers showed good compatibility due to formation of hydrogen bonds between polymers and biomolecules from its structure, evidenced by FTIR spectra and thermal properties. Cell viability test showed that most of the obtained mats result on viability higher than 75%, resulting in nontoxic materials, ready to be used on scaffolding applications. CONCLUSION: Mucilage containing fibers resulted on materials with potential use on scaffolding applications due to their mechanical performance and cell viability results.

GIS mapping of agricultural plastic waste in southern Europe.

The escalating use of plastics in agriculture, driven by global population growth and increasing food demand, has concurrently led to a rise in Agricultural Plastic Waste (APW) production. Effective waste management is imperative, prompting this study to address the initial step of management, that is the quantification and localization of waste generated from different production systems in diverse regions. Focused on four Southern European countries (Italy, Spain, Greece, and Portugal) at the regional level, the study uses Geographic Information System (GIS), land use maps, indices tailored to each specific agricultural application and each crop type for plastic waste mapping. Furthermore, after the data was employed, it was validated by relevant stakeholders of the mentioned countries. The study revealed Spain, particularly the Andalusia region, as the highest contributor to APW equal to 324,000 tons per year, while Portugal's Azores region had the lowest estimate equal to 428 tons per year. Significantly, this research stands out as one of the first to comprehensively consider various plastic applications and detailed crop cultivations within the production systems, representing a pioneering effort in addressing plastic waste management in Southern Europe. This can lead further on to the management of waste in this area and the transfer of the scientific proposition to other countries.

Synthesis and Characterization of Triticale Starch-Based Hydrogel for pH Responsive Controlled Diffusion.

Considering the FAO perspectives for agriculture toward 2030, many natural sources will be no longer profitable for the synthesis of many biomaterials. Triticale (X Triticosecale Wittmack) is a cereal crop synthesized to withstand those marginal conditions; however, it is primarily used as fodder worldwide. We reported for the first time the synthesis of a natural anionic hydrogel with gastrointestinal pH stimulus-response as a new alternative of smart material, based on Eronga triticale starch as sustainable biomass, using citrate (pK a ∼3.1, 4.7, and 6.4) as cross-linking agent. The scanning electron microscopy and X-ray diffraction exhibited A and B-type starch granules, and semicrystallinity A-type. The presence of the anionic sensing group (COOH) was verified by infrared spectroscopy, the interactions by hydrogen bonds between starch and glycerol and esterification between starch and citric acid were identified by 1H NMR spectra, and through thermal analysis hydrogels exhibited four endothermic curves (179-319 °C, ∼0.711-39 kJ/mol E a). The results showed that the slight addition of glycerol increases the thermal stability, but a higher amount of glycerol decreases the intermolecular forces affecting the thermal stability contrary, the mechanical properties could be benefited. The rheological analyses showed viscoelastic tendency (G' > G″) with high stability (Tanδ < 1) in frequency, time, and strain sweeps. Gastrointestinal pH sensitivity (∼2-7.8) was verified (α ≤ 0.01) following Fick's diffusive parameters, which resulted in a tendency to gradually release BSA with increasing pH ∼3-7 by anomalous and case-II diffusion, showing greater release at pH ∼7.8/3.5 h (80-96%). We aim to expand the biomaterials area focusing on triticale starch due to its limited reported investigations, low-cost, green modification, and its rheological performance as plastic.

Clinical Outcomes and Management Strategies for Capitellum and Trochlea Fractures: A Systematic Review.

Purpose: Capitellum and trochlea fractures, also referred to as coronal shear fractures of the distal humerus, are infrequent yet challenging intra-articular fractures of the elbow. There are a variety of surgical approaches and fixation methods with often variable outcomes. This systematic review investigates interventions, outcomes and complications of capitellum and trochlea fractures. Methods: A systematic review of studies published in MEDLINE, EMBASE, Web of Science and Cumulative Index to Nursing and Allied Health literature (CINAHL) was conducted to assess the clinical outcomes of capitellum and trochlea fractures managed surgically. Data on patient demographics, surgical approach, implant usage, postoperative outcomes and complications were compiled. Results: Forty-one studies met the inclusion criteria with a total of 700 patients. Surgical interventions primarily utilized either the lateral (79%) or antero-lateral (15%) approaches with headless compression screws as the most common fixation method (68%). Clinical outcomes were measured using the Mayo Elbow Performance Index (MEPI) with a mean score of 89.9 (±2.6) and the DASH score with a mean of 16.9 (±7.3). Elbow range of motion showed a mean flexion of 126.3° (±19.4), extension of 5.71° (±11.8), pronation of 75.23° (±12.2), and supination of 76.6° (±9.8). The mean flexion-extension arc was 113.7° (±16.9), and the mean pronation-supination arc was 165.31° (±9.41). Complications occurred in 19.8% of cases, with re-interventions required in 8.3% of cases, mainly due to symptomatic implants and elbow stiffness requiring surgical release. Other complications included implant removal (10.4%), overall reported stiff elbows (6%), nerve palsies (2%), non-union (1.5%), and infection (1.2%). Conclusion: The treatment of capitellum and trochlea fractures yields satisfactory outcomes but has a considerable rate of complications and reoperations primarily due to symptomatic implants and elbow stiffness. There is noteworthy variability in the achieved range of motion, suggesting unpredictable outcomes. Deficits in functionality and range of motion are common after surgery, especially with more complex injury patterns.

In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.

Natural killer (NK) cells play a crucial role in antitumoral and antiviral responses. Yet, cancer cells can alter themselves or the microenvironment through the secretion of cytokines or other factors, hindering NK cell activation and promoting a less cytotoxic phenotype. These resistance mechanisms, often referred to as the "hallmarks of cancer" are significantly influenced by the activation of oncogenes, impacting most, if not all, of the described hallmarks. Along with oncogenes, other types of genes, the tumor suppressor genes are frequently mutated or modified during cancer. Traditionally, these genes have been associated with uncontrollable tumor growth and apoptosis resistance. Recent evidence suggests oncogenic mutations extend beyond modulating cell death/proliferation programs, influencing cancer immunosurveillance. While T cells have been more studied, the results obtained highlight NK cells as emerging key protagonists for enhancing tumor cell elimination by modulating oncogenic activity. A few recent studies highlight the crucial role of oncogenic mutations in NK cell-mediated cancer recognition, impacting angiogenesis, stress ligands, and signaling balance within the tumor microenvironment. This review will critically examine recent discoveries correlating oncogenic mutations to NK cell-mediated cancer immunosurveillance, a relatively underexplored area, particularly in the era dominated by immune checkpoint inhibitors and CAR-T cells. Building on these insights, we will explore opportunities to improve NK cell-based immunotherapies, which are increasingly recognized as promising alternatives for treating low-antigenic tumors, offering significant advantages in terms of safety and manufacturing suitability.

Known pathogenic gene variants and new candidates detected in sudden unexpected infant death using whole genome sequencing.

The purpose of this study is to gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID). Whole Genome Sequencing (WGS) was performed on 144 infants that succumbed to SUID, and 573 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences. Variants of interest were identified in 88 genes, in 64.6% of our cohort. Seventy-three of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders and in two genes associated with immunological function. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria. Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID.

Stealth and Biocompatible Gold Nanoparticles through Surface Coating with a Zwitterionic Derivative of Glutathione.

Gold nanoparticles (AuNPs) hold promise in biomedicine, but challenges like aggregation, protein corona formation, and insufficient biocompatibility must be thoroughly addressed before advancing their clinical applications. Designing AuNPs with specific protein corona compositions is challenging, and strategies for corona elimination, such as coating with polyethylene glycol (PEG), have limitations. In this study, we introduce a commercially available zwitterionic derivative of glutathione, glutathione monoethyl ester (GSHzwt), for the surface coating of colloidal AuNPs. Particles coated with GSHzwt were investigated alongside four other AuNPs coated with various ligands, including citrate ions, tiopronin, glutathione, cysteine, and PEG. We then undertook a head-to-head comparison of these AuNPs to assess their behavior in biological fluid. GSHzwt-coated AuNPs exhibited exceptional resistance to aggregation and protein adsorption. The particles could also be readily functionalized with biotin and interact with streptavidin receptors in human plasma. Additionally, they exhibited significant blood compatibility and noncytotoxicity. In conclusion, GSHzwt provides a practical and easy method for the surface passivation of AuNPs, creating "stealth" particles for potential clinical applications.

Simulation of daily soft multifocal contact lenses using SimVis Gekko: from in-vitro and computational characterization to clinical validation.

Multifocal contact lenses (MCLs) are one of the solutions to correct presbyopia, but their adoption is not widespread. To address this situation, visual simulators can be used to refine the adaptation process. This study aims to obtain accurate simulations for a visual simulator (SimVis Gekko; 2EyesVision) of daily soft MCL designs from four manufacturers. In-vitro characterization of these MCLs-several powers and additions- was obtained using NIMO TR-1504. From the averaged relative power profiles across powers, phase maps were reconstructed and the Through-Focus Visual Strehl metric was calculated for each MCL design. The SimVis Gekko simulation corresponding to each MCL design was obtained computationally and bench-validated. Finally, the MCL simulations were clinically validated involving presbyopic patients. The clinical validation results show a good agreement between the SimVis Gekko simulations and the real MCLs for through-focus visual acuity (TF-VA) curves and VA at three real distances. All MCL designs showed a partial correlation higher than 0.90 and a Root Mean Square Error below 0.07 logMAR between the TF-VA of simulations and Real MCLs across subjects. The validity of the simulation approach using SimVis Gekko and in-vitro measurements was confirmed in this study, opening the possibility to accelerate the adaptation of MCLs.

Improving outcomes for patients with hard-to-heal wounds following adoption of the Wound Hygiene Protocol: real-world evidence.

OBJECTIVE: To evaluate the impact of a four-step biofilm-based wound care strategy, Wound Hygiene Protocol (WHP: cleanse, debride, refashion, and dress), on hard-to-heal wounds. METHOD: This was a prospective, real-world analysis of hard-to-heal wounds managed with the WHP that incorporated Aquacel Ag+ (Convatec Ltd., UK) dressings. Data were captured electronically between April 2021 and December 2022. The primary endpoint was change in wound volume from baseline to final assessment. RESULTS: A total of 693 wounds in 669 patients (median patient age: 74 years) were included in the analysis with a median treatment time of 31 days. Most health professionals were general nurses (50%) or nurse practitioners (38%). Patient homes (27%) and community clinics (27%) were the most common clinical settings. Venous leg ulcers (26%) and pressure ulcers/injuries (17%) were the most common wound type. Duration was >12 months in 21% of wounds. At baseline, the mean wound volume was 57.8cm3. At the final assessment, mean wound volume was 17.2cm3, corresponding to an 80% reduction from baseline; p<0.001). At baseline, 66% of wounds were static or deteriorating. At final assessment, this had decreased to 5%, and 94% had improved or healed. Exudate levels were moderate or high in 69% of wounds at baseline which decreased to 25% at final assessment (p<0.001). Suspected biofilm and local wound infection decreased from 79% and 43%, respectively, at baseline, to 18% and 3%, respectively, at final assessment (p<0.001 for both). CONCLUSION: The WHP is a new proposed standard of care that successfully treated hard-to-heal wounds by addressing the key local barriers to wound healing.

Effects of intraocular scatter on near peripheral vision.

Both cataracts and age-related macular degeneration (AMD) may occur with aging and are often developed simultaneously. We performed a study to better characterize the impact of induced scatter on the quality of vision in the near periphery, a region where individuals with AMD typically maintain their functional vision. We used an optical instrument as a cataract simulator based on projecting at the eye's pupil plane phase masks with controlled spatial properties generated with a spatial light modulator. The phase wavefronts were designed to accurately replicate the angular distribution of light intensity in the retina found in cataractous eyes with different severities. The induced amount of scatter ranged from values of straylight (S) from 10 to 85 degree2/sr, which corresponds from normal aging eye to advanced cataract stages. Mesopic visual acuity (VA) and contrast sensitivity (CS) at 3 cycles per degree were measured at the fovea and two retinal eccentricities (5 and 10 degrees in nasal visual field). We observed a consistent linear decline in VA (expressed in LogMAR) as the amount of induced scatter (quantified by the straylight parameter S) increased, both at the fovea and in the periphery. The effect of induced scattering on mesopic VA and CS at the fovea and the near periphery was evaluated. We found a relatively lower impact of scatter in the near periphery. This may explain the modest improvement in vision often found after cataract surgery in patients with AMD.

Current trends and prospects in quinoa research: An approach for strategic knowledge areas.

Currently, the demand for healthy consumption and the use of alternatives to dairy proteins for the development of foods with good nutritional value are growing. Quinoa has received much attention because it contains a high content of proteins, essential amino acids, essential fatty acids, minerals, vitamins, dietary fibers, and bioactive compounds. Nevertheless, this content and the bioavailability of specific compounds of interest are related to the genotype, the agri-environmental conditions, and management practices where quinoa is grown and postharvest management. This article aimed to analyze the research trends for three knowledge areas: quinoa plant breeding for nutraceutical properties, plant-soil relations focused on abiotic stresses, and postharvest and value-added transformation activities. To this end, a specific methodological design based on bibliometrics and scientometrics methods was used. Through these analyses based on publications' keywords, titles, abstracts, and conclusions sections, for each knowledge area, the key research trends (scope and main topics), the classification of trends based on their development and relevance degree, and the core of knowledge were established. The trends comprise the current state of research. Finally, analyzing the conclusions, recommendations, and future research sections of key publications, a strong correlation among plant breeding research to obtain varieties with tolerance to biotic and abiotic stresses, nutritional and functional compounds of interest for food safety, and the development of products with higher added value established interest in further research on the potential bioactivity of quinoa and the verification of health benefits to humans.

Inverse-Vaccines for Rheumatoid Arthritis Re-establish Metabolic and Immunological Homeostasis in Joint Tissues.

Rheumatoid arthritis (RA) causes immunological and metabolic imbalances in tissue, exacerbating inflammation in affected joints. Changes in immunological and metabolic tissue homeostasis at different stages of RA are not well understood. Herein, the changes in the immunological and metabolic profiles in different stages in collagen induced arthritis (CIA), namely, early, intermediate, and late stage is examined. Moreover, the efficacy of the inverse-vaccine, paKG(PFK15+bc2) microparticle, to restore tissue homeostasis at different stages is also investigated. Immunological analyses of inverse-vaccine-treated group revealed a significant decrease in the activation of pro-inflammatory immune cells and remarkable increase in regulatory T-cell populations in the intermediate and late stages compared to no treatment. Also, glycolysis in the spleen is normalized in the late stages of CIA in inverse-vaccine-treated mice, which is similar to no-disease tissues. Metabolomics analyses revealed that metabolites UDP-glucuronic acid and L-Glutathione oxidized are significantly altered between treatment groups, and thus might provide new druggable targets for RA treatment. Flux metabolic modeling identified amino acid and carnitine pathways as the central pathways affected in arthritic tissue with CIA progression. Overall, this study shows that the inverse-vaccines initiate early re-establishment of homeostasis, which persists through the disease span.

CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells.

ABSTRACT: Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155/pulmonary vascular resistance (PVR), CD112/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell-based clinical trials.

Magnetic graphene derivates for efficient herbicide removal from aqueous solution through adsorption.

2,4-Dichlorophenoxyacetic acid (2,4-D) is an herbicide and is among the most widely distributed pollutant in the environment and wastewater. Herein is presented a complete comparison of adsorption performance between two different magnetic carbon nanomaterials: graphene oxide (GO) and its reduced form (rGO). Magnetic functionalization was performed employing a coprecipitation method, using only one source of Fe2+, requiring low energy, and potentially allowing the control of the amount of incorporated magnetite. For the first time in literature, a green reduction approach for GO with and without Fe3O4, maintaining the magnetic behavior after the reaction, and an adsorption performance comparison between both carbon nanomaterials are demonstrated. The nanoadsorbents were characterized by FTIR, XRD, Raman, VSM, XPS, and SEM analyses, which demonstrates the successful synthesis of graphene derivate, with different amounts of incorporate magnetite, resulting in distinct magnetization values. The reduction was confirmed by XPS and FTIR techniques. The type of adsorbent reveals that the amount of magnetite on nanomaterial surfaces has significant influence on adsorption capacity and removal efficiency. The procedure demonstrated that the best performance, for magnetic nanocomposites, was obtained by GO∙Fe3O4 1:1 and rGO∙Fe3O4 1:1, presenting values of removal percentage of 70.49 and 91.19%, respectively. The highest adsorption capacity was reached at pH 2.0 for GO∙Fe3O4 1:1 (69.98 mg g-1) and rGO∙Fe3O4 1:1 (89.27 mg g-1), through different interactions: π-π, cation-π, and hydrogen bonds. The adsorption phenomenon exhibited a high dependence on pH, initial concentration of adsorbate, and coexisting ions. Sips and PSO models demonstrate the best adjustment for experimental data, suggesting a heterogeneous surface and different energy sites, respectively. The thermodynamic parameters showed that the process was spontaneous and exothermic. Finally, the nanoadsorbents demonstrated a high efficiency in 2,4-D adsorption even after five adsorption/desorption cycles.

Exploring the chemical diversity of Capsicum chinense cultivars using NMR-based metabolomics and machine learning methods.

The habanero pepper (Capsicum chinense) is a prominent spicy fruit integral to the historical, social, cultural, and economic fabric of the Yucatan peninsula in Mexico. This study leverages the power of 1H NMR spectroscopy coupled with machine learning algorithms to dissect the metabolomic profile of eleven C. chinense cultivars, including those grown by INIFAP (Habanero-Jaguar, Antillano-HRA 1-1, Antillano-HRA 7-1, Habanero-HAm-18A, Habanero-HC-23C, and Jolokia-NJolokia-22) and commercial hybrids (Habanero-Rey Votán, Habanero-Kabal, Balam, USAPR10117, and Rey Pakal). A total of fifty metabolites, encompassing sugars, amino acids, short-chain organic acids, and nucleosides, were identified from the 1H NMR spectra. The optimized machine learning model proficiently predicted the similarity percentage between the INIFAP-grown cultivars and commercial hybrids, thereby facilitating a comprehensive comparison. Biomarkers unique to each cultivar were delineated, revealing that the Habanero-Rey Votán cultivar is characterized by the highest concentration of sugars. In contrast, the Balam cultivar is rich in amino acids and short-chain organic acids, sharing a similar metabolomic profile with the Jolokia-NJolokia-22 cultivar. The findings of this study underscore the efficacy and reliability of NMR-based metabolomics as a robust tool for differentiating C. chinense cultivars based on their intricate chemical profiles. This approach not only contributes to the scientific understanding of the metabolomic diversity among habanero peppers but also holds potential implications for food science, agriculture, and the culinary arts.

Unraveling motor imagery brain patterns using explainable artificial intelligence based on Shapley values.

BACKGROUND AND OBJECTIVE: Motor imagery (MI) based brain-computer interfaces (BCIs) are widely used in rehabilitation due to the close relationship that exists between MI and motor execution (ME). However, the underlying brain mechanisms of MI remain not well understood. Most MI-BCIs use the sensorimotor rhythms elicited in the primary motor cortex (M1) and somatosensory cortex (S1), which consist of an event-related desynchronization followed by an event-related synchronization. Consequently, this has resulted in systems that only record signals around M1 and S1. However, MI could involve a more complex network including sensory, association, and motor areas. In this study, we hypothesize that the superior accuracies achieved by new deep learning (DL) models applied to MI decoding rely on focusing on a broader MI activation of the brain. Parallel to the success of DL, the field of explainable artificial intelligence (XAI) has seen continuous development to provide explanations for DL networks success. The goal of this study is to use XAI in combination with DL to extract information about MI brain activation patterns from non-invasive electroencephalography (EEG) signals. METHODS: We applied an adaptation of Shapley additive explanations (SHAP) to EEGSym, a state-of-the-art DL network with exceptional transfer learning capabilities for inter-subject MI classification. We obtained the SHAP values from two public databases comprising 171 users generating left and right hand MI instances with and without real-time feedback. RESULTS: We found that EEGSym based most of its prediction on the signal of the frontal electrodes, i.e. F7 and F8, and on the first 1500 ms of the analyzed imagination period. We also found that MI involves a broad network not only based on M1 and S1, but also on the prefrontal cortex (PFC) and the posterior parietal cortex (PPC). We further applied this knowledge to select a 8-electrode configuration that reached inter-subject accuracies of 86.5% ± 10.6% on the Physionet dataset and 88.7% ± 7.0% on the Carnegie Mellon University's dataset. CONCLUSION: Our results demonstrate the potential of combining DL and SHAP-based XAI to unravel the brain network involved in producing MI. Furthermore, SHAP values can optimize the requirements for out-of-laboratory BCI applications involving real users.

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of women's mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. METHODS: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and (5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-ß estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson's staining. RESULTS: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) -dP/dt was decreased in Ovx groups without ERT (-750 vs -1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. CONCLUSIONS: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.