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Introduction: The risk of complications associated with transvenous ICDs make the subcutaneous implantable cardiac defibrillator (S-ICD) a valuable alternative in patients with adult congenital heart disease (ACHD). However, higher S-ICD ineligibility and higher inappropriate shock rates-mostly caused by T wave oversensing (TWO)- are observed in this population. We report a novel application of deep learning methods to screen patients for S-ICD eligibility over a longer period than conventional screening., Methods: Adult patients with ACHD and a control group of normal subjects were fitted with a 24-h Holters to record their S-ICD vectors. Their T:R ratio was analysed utilising phase space reconstruction matrices and a deep learning-based model to provide an in-depth description of the T: R variation plot for each vector. T: R variation was compared statistically using t-test., Results: 13 patients (age 37.4 ± 7.89 years, 61.5 % male, 6 ACHD and 7 control subjects) were enrolled. A significant difference was observed in the mean and median T: R values between the two groups (p < 0.001). There was also a significant difference in the standard deviation of T: R between both groups (p = 0.04)., Conclusions: T:R ratio, a main determinant for S-ICD eligibility, is significantly higher with more tendency to fluctuate in ACHD patients when compared to a population with normal hearts. We hypothesise that our novel model could be used to select S-ICD eligible patients by better characterisation of T:R ratio, reducing the risk of TWO and inappropriate shocks in the ACHD patient cohort., Competing Interests: Declaration of competing interest x The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: -Dr. Mohamed ElRefai has received an unrestricted grant from Boston Scientific. -Dr. Benedict Wiles has received unrestricted research funding and consultancy payments from Boston Scientific. -Dr. Paul Roberts receives consultancy fees from Boston Scientific and Medtronic. -Professor John Morgan is a medical director at Boston Scientific. - None of the other authors of this study has conflict of interest to declare., (Copyright © 2024 Indian Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.)

Background: Machine learning methods are used in the classification of various cardiovascular diseases through ECG data analysis. The concept of varying subcutaneous implantable cardiac defibrillator (S-ICD) eligibility, owing to the dynamicity of ECG signals, has been introduced before. There are practical limitations to acquiring longer durations of ECG signals for S-ICD screening. This study explored the potential use of deep learning methods in S-ICD screening., Methods: This was a retrospective study. A deep learning tool was used to provide descriptive analysis of the T:R ratios over 24 h recordings of S-ICD vectors. Spearman's rank correlation test was used to compare the results statistically to those of a "gold standard" S-ICD simulator., Results: A total of 14 patients (mean age: 63.7 ± 5.2 years, 71.4% male) were recruited and 28 vectors were analyzed. Mean T:R, standard deviation of T:R, and favorable ratio time (FVR)-a new concept introduced in this study-for all vectors combined were 0.21 ± 0.11, 0.08 ± 0.04, and 79 ± 30%, respectively. There were statistically significant strong correlations between the outcomes of our novel tool and the S-ICD simulator (p < .001)., Conclusion: Deep learning methods could provide a practical software solution to analyze data acquired for longer durations than current S-ICD screening practices. This could help select patients better suited for S-ICD therapy as well as guide vector selection in S-ICD eligible patients. Further work is needed before this could be translated into clinical practice., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Oils are an essential part of the human diet and are primarily derived from plant (or sometimes fish) sources. Several of them exhibit anti-inflammatory properties. Specific diets, such as Mediterranean diet, that are high in ω-3 polyunsaturated fatty acids (PUFAs) and ω-9 monounsaturated fatty acids (MUFAs) have even been shown to exert an overall positive impact on human health. One of the most widely used supplements in the developed world is fish oil, which contains high amounts of PUFAs docosahexaenoic and eicosapentaenoic acid. This review is focused on the natural sources of various polyunsaturated and monounsaturated fatty acids in the human diet, and their role as precursor molecules in immune signaling pathways. Consideration is also given to their role in CNS immunity. Recent findings from clinical trials utilizing various fatty acids or diets high in specific fatty acids are reviewed, along with the mechanisms through which fatty acids exert their anti-inflammatory properties. An overall understanding of diversity of polyunsaturated fatty acids and their role in several molecular signaling pathways is useful in formulating diets that reduce inflammation and increase longevity.

Introduction: S-ICD eligibility is assessed at pre-implant screening where surface ECG traces are used as surrogates for S-ICD vectors. In heart failure (HF) patients undergoing diuresis, electrolytes and fluid shifts can cause changes in R and T waves. Subsequently, T:R ratio, a major predictor of S-ICD eligibility, can be dynamic., Methods: This is a prospective study of patients with structurally normal hearts and HF patients undergoing diuresis. All patients were fitted with Holters® to record their S-ICD vectors. Our deep learning model was used to analyze the T:R ratios across the recordings. Welch two sample t-test and Mann-Whitney U were used to compare the data between the two groups., Results: Twenty-one patients (age 58.43 ± 18.92, 62% male, 14 HF, 7 normal hearts) were enrolled. There was a significant difference in the T:R ratios between both groups. Mean T: R was higher in the HF group (0.18 ± 0.08 vs 0.10 ± 0.05, p < .001). Standard deviation of T: R was also higher in the HF group (0.09 ± 0.05 vs 0.07 ± 0.04, p = .024). There was no difference between leads within the same group., Conclusions: T:R ratio, a main determinant for S-ICD eligibility, is higher and has more tendency to fluctuate in HF patients undergoing diuresis. We hypothesize that our novel neural network model could be used to select HF patients eligible for S-ICD by better characterization of T:R ratio reducing the risk of T-wave over-sensing (TWO) and inappropriate shocks. Further work is required to consolidate our findings before applying to clinical practice., (© 2022 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Some aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H 2 O 2 ), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H 2 O 2 , and thus ROS scavenging, appears particularly important for controlling the redox state of cells in physiological and pathophysiological conditions. Several compounds have been screened and characterized for this purpose. This study aimed to analyze the effect of cerium oxide nanoparticles (CNPs) presenting antioxidant activity on AQP functioning. HeLa cells express AQP3, 6, 8, and 11, able to facilitate H 2 O 2 . AQP3, 6, and 8 are expressed in the plasma membrane and intracellularly, while AQP11 resides only in intracellular structures. CNPs but not cerium ions treatment significantly increased the water and H 2 O 2 permeability by interacting with AQP3, 6, and especially with AQP8. CNPs increased considerably the AQP-mediated water diffusion in cells with oxidative stress. Functional experiments with silenced HeLa cells revealed that CNPs increased the H 2 O 2 diffusion mainly by modulating the AQP8 permeability but also the AQP3 and AQP6, even if to a lesser extent. Current findings suggest that CNPs represent a promising pharmaceutical agent that might potentially be used in numerous pathologies involving oxidative stress as tumors and neurodegenerative diseases.

Subcutaneous Implantable Cardioverter-Defibrillators (S-ICDs) are used for prevention of sudden cardiac death triggered by ventricular arrhythmias. T Wave Over Sensing (TWOS) is an inherent risk with S-ICDs which can lead to inappropriate shocks. A major predictor of TWOS is a high T:R ratio (the ratio between the amplitudes of the T and R waves). Currently, patients' Electrocardiograms (ECGs) are screened over 10 s to measure the T:R ratio to determine the patients' eligibility for S-ICD implantation. Due to temporal variations in the T:R ratio, 10 s is not a long enough window to reliably determine the normal values of a patient's T:R ratio. In this paper, we develop a convolutional neural network (CNN) based model utilising phase space reconstruction matrices to predict T:R ratios from 10-second ECG segments without explicitly locating the R or T waves, thus avoiding the issue of TWOS. This tool can be used to automatically screen patients over a much longer period and provide an in-depth description of the behavior of the T:R ratio over that period. The tool can also enable much more reliable and descriptive screenings to better assess patients' eligibility for S-ICD implantation., (Copyright © 2021 University of Southampton. Published by Elsevier B.V. All rights reserved.)

BACKGROUND Patients with HIV infection tend to have poor intensive care unit (ICU) outcomes; however, survival in the modern combination antiretroviral therapy (cART) era has markedly improved, but Pneumocystis jirovecii pneumonia (PJP) still remains a preeminent cause of respiratory failure in AIDS patients. Extracorporeal membrane oxygenation (ECMO) is an adapted cardiopulmonary bypass circuit for temporary life support for patients not responding to conventional treatment. CASE REPORT A 43-year-old male HIV "late presenter" was admitted to our hospital for fever and dyspnea. A chest CT scan revealed bilateral ground-glass opacities. Empiric antibiotic treatment and cART were started. The emergence of ARDS due to PJP dictated urgent veno-venous (VV) ECMO placement. One week later, radiologic findings and respiratory function had improved and the patient was started on a weaning trial from ECMO and removed 12 days after placement. CONCLUSIONS Acute respiratory distress syndrome (ARDS) is a potentially reversible clinical syndrome with a high mortality rate. ECMO is a rescue therapy allowing lung recovery during acute processes and should be considered an adequate treatment option in HIV+ patients with respiratory failure. ECMO should be considered a useful and adequate treatment option in AIDS patients who have a high risk of dying from respiratory failure.

Introduction: Altered expression of Septin 9 (SEPT9), a septin coding for multiple isoform variants, has been observed in several carcinomas, including colorectal, head and neck, ovarian and breast, compared to normal tissues. The mechanisms regulating its expression during tumor initiation and progression in vivo and the oncogenic function of its different isoforms remain elusive., Methods: Using an integrative approach, we investigated SEPT9 at the genetic, epigenetic, mRNA and protein levels in breast cancer. We analyzed a panel of breast cancer cell lines, human primary tumors and corresponding tumor-free areas, normal breast tissues from reduction mammoplasty patients, as well as primary mammary gland adenocarcinomas derived from the polyoma virus middle T antigen, or PyMT, mouse model. MCF7 clones expressing individual GFP-tagged SEPT9 isoforms were used to determine their respective intracellular distributions and effects on cell migration., Results: An overall increase in gene amplification and altered expression of SEPT9 were observed during breast tumorigenesis. We identified an intragenic alternative promoter at which methylation regulates SEPT9&#95;v3 expression. Transfection of specific GFP-SEPT9 isoforms in MCF7 cells indicates that these isoforms exhibit differential localization and affect migration rates. Additionally, the loss of an uncharacterized SEPT9 nucleolar localization is observed during tumorigenesis., Conclusions: In this study, we found conserved in vivo changes of SEPT9 gene amplification and overexpression during human and mouse breast tumorigenesis. We show that DNA methylation is a prominent mechanism responsible for regulating differential SEPT9 isoform expression and that breast tumor samples exhibit distinctive SEPT9 intracellular localization. Together, these findings support the significance of SEPT9 as a promising tool in breast cancer detection and further emphasize the importance of analyzing and targeting SEPT9 isoform-specific expression and function.

The cytokine scatter factor/hepatocyte growth factor (HGF/SF) protects epithelial, carcinoma, and other cell types against cytotoxicity and apoptosis induced by DNA-damaging agents such as ionizing radiation and adriamycin (ADR, a topoisomerase IIalpha inhibitor). We investigated the role of nuclear factor kappa B (NF-kappaB) signaling in HGF/SF-mediated protection of human prostate cancer (DU-145) and Madin-Darby canine kidney (MDCK) epithelial cells against ADR. HGF/SF caused the rapid nuclear translocation of the p65 (RelA) subunit of NF-kappaB associated with the transient loss of the inhibitory subunit IkappaB-alpha. Exposure to HGF/SF caused the activation of an NF-kappaB luciferase reporter that was blocked or attenuated by the expression of a mutant 'super-repressor' IkappaB-alpha. Electrophoretic mobility shift assay supershift assays revealed that HGF/SF treatment induced the transient binding of various NF-kappaB family proteins (p65, p50, c-Rel, and RelB) with radiolabeled NF-kappaB-binding oligonucleotides. The HGF/SF-mediated protection of DU-145 and MDCK cells against ADR (demonstrated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays) was abrogated by the IkappaB-alpha super-repressor. The ability of HGF/SF to activate NF-kappaB signaling was dependent on c-Akt --> Pak1 (p21-associated kinase-1) signaling (with Pak1 downstream of c-Akt) and was inhibited by the tumor suppressor PTEN (phosphatase and tensin homolog). Inhibitors of phosphatidylinositol-3'-kinase and Src family kinases significantly inhibited HGF/SF-mediated activation of NF-kappaB, while inhibitors of MEK, protein kinase C, and p70 S6 kinase had a modest effect or no effect on NF-kappaB activity. HGF/SF induced the expression of several known NF-kappaB target genes (cIAP-1 (cellular inhibitor of apoptosis-1), cIAP-2, and TRAF-2 (TNF receptor-associated factor-2)) in an NF-kappaB-dependent manner; HGF/SF blocked the inhibition of expression of these genes by ADR. Experimental manipulation of expression of these genes suggests that they (particularly TRAF-2 and cIAP-2) contribute to the protection against ADR by HGF/SF. These findings suggest that HGF/SF activates NF-kappaB through a c-Akt --> Pak1 signaling pathway that is also dependent on Src, and that NF-kappaB contributes to HGF/SF-mediated protection against ADR.

Invadopodia are actin-rich membrane protrusions with a matrix degradation activity formed by invasive cancer cells. We have studied the molecular mechanisms of invadopodium formation in metastatic carcinoma cells. Epidermal growth factor (EGF) receptor kinase inhibitors blocked invadopodium formation in the presence of serum, and EGF stimulation of serum-starved cells induced invadopodium formation. RNA interference and dominant-negative mutant expression analyses revealed that neural WASP (N-WASP), Arp2/3 complex, and their upstream regulators, Nck1, Cdc42, and WIP, are necessary for invadopodium formation. Time-lapse analysis revealed that invadopodia are formed de novo at the cell periphery and their lifetime varies from minutes to several hours. Invadopodia with short lifetimes are motile, whereas long-lived invadopodia tend to be stationary. Interestingly, suppression of cofilin expression by RNA interference inhibited the formation of long-lived invadopodia, resulting in formation of only short-lived invadopodia with less matrix degradation activity. These results indicate that EGF receptor signaling regulates invadopodium formation through the N-WASP-Arp2/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia.

The unusual reactivity of 1-phenyl-1-ethanesulfonic acid in thionyl chloride was investigated. Mechanistic considerations led us to set up a new and efficient synthesis of E-arylethenesulfonamides starting from 1-hydroxy-1-arylalkanes. The easy availability of the starting materials and the straightforward, one-pot procedure make this process an attractive method for the preparation of these compounds currently largely employed in chemical and pharmaceutical fields.

The rates of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), progression to AIDS following HIV-1 infection, and AIDS-associated mortality are all inversely correlated with serum vitamin A levels (R. D. Semba, W. T. Caiaffa, N. M. H. Graham, S. Cohn, and D. Vlahov, J. Infect. Dis. 171:1196-1202, 1995; R. D. Semba, N. M. H. Graham, W. T. Caiaffa, J. B. Margolik, L. Clement, and D. Vlahov, Arch. Intern. Med. 153:2149-2154, 1993; R. D. Semba, P. G. Miotti, J. D. Chiphangwi, A. J. Saah, J. K. Canner, G. A. Dallabetta, and D. R. Hoover, Lancet 343:1593-1596, 1994). Here we show that physiological concentrations of vitamin A, as retinol or as its metabolite, all-trans retinoic acid, repressed HIV-1Ba-L replication in monocyte-derived macrophages (MDMs). Repression required retinoid treatment of peripheral monocytes during their in vitro differentiation into MDMs. Retinoids had no repressive effect if they were added after virus infection. Retinol, as well as all-trans retinoic acid and 9-cis retinoic acid, also repressed HIV-1 long terminal repeat (LTR)-directed expression up to 200-fold in transfected THP-1 monocytes. Analysis of HIV-1 LTR deletion mutants demonstrated that retinoids were able to repress activation of HIV-1 expression by both NF-kappaB and Tat. A cis-acting sequence required for retinoid-mediated repression of HIV-1 transcription was localized between nucleotides -51 and +12 of the HIV-1 LTR within the core promoter. Protein-DNA cross-linking experiments identified four proteins specific to retinoid-treated cells that bound to the core promoter. We conclude that retinoids render macrophages resistant to virus replication by modulating the interaction of cellular transcription factors with the viral core promoter.