Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study.

Objective: Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult.

Methods: Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis.

Cancer cell stiffening via CoQ and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer.

CoQ (Coenzyme Q) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment.

Gene therapy for epilepsy targeting neuropeptide Y and its Y2 receptor to dentate gyrus granule cells.

Gene therapy is emerging as an alternative option for individuals with drug-resistant focal epilepsy. Here, we explore the potential of a novel gene therapy based on Neuropeptide Y (NPY), a well-known endogenous anticonvulsant. We develop a lentiviral vector co-expressing NPY with its inhibitory receptor Y2 in which, for the first time, both transgenes are placed under the control of the minimal CamKIIa(0.

Local Tetanus Begins with a Neuromuscular Junction Paralysis around the Site of Tetanus Neurotoxin Release due to Cleavage of the Vesicle-Associated Membrane Protein.

Local tetanus develops when limited amounts of tetanus neurotoxin (TeNT) are released by Clostridium tetani generated from spores inside a necrotic wound. Within days, a spastic paralysis restricted to the muscles of the affected anatomical area develops. This paralysis follows the retrograde transport of TeNT inside the axons of motoneurons and its uptake by inhibitory interneurons with cleavage of a vesicle-associated membrane protein required for neurotransmitter release.

Cognitive comorbidities in the rat pilocarpine model of epilepsy.

Patients with epilepsy are prone to cognitive decline, depression, anxiety and other behavioral disorders. Cognitive comorbidities are particularly common and well-characterized in people with temporal lobe epilepsy, while inconsistently addressed in epileptic animals. Therefore, the aim of this study was to ascertain whether there is good evidence of cognitive comorbidities in animal models of epilepsy, in particular in the rat pilocarpine model of temporal lobe epilepsy.

A schedule for tapering glucocorticoid treatment in patients with severe SARS-CoV 2 infection can prevent acute adrenal insufficiency in the geriatric population.

Objective And Design: Glucocorticoids (GCs) have been widely used in symptomatic patients for the treatment of COVID-19. The risk for adrenal insufficiency must be considered after GC withdrawal given that it is a life-threatening condition if left unrecognized and untreated. Our study aimed to diagnose adrenal insufficiency early on through a GC reduction schedule in patients with COVID-19 infection.

Lack of Direct Effects of Neurotrophic Factors in an In Vitro Model of Neuroinflammation.

Neuroinflammation is associated with several neurological disorders including temporal lobe epilepsy. Seizures themselves can induce neuroinflammation. In an in vivo model of epilepsy, the supplementation of brain-derived neurotropic factor (BDNF) and fibroblast growth factor-2 (FGF-2) using a Herpes-based vector reduced epileptogenesis-associated neuroinflammation.

Agonists of melatonin receptors strongly promote the functional recovery from the neuroparalysis induced by neurotoxic snakes.

Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause a potentially lethal peripheral neuroparalysis with respiratory deficit in a large number of people each year. In order to prevent the development of a deadly respiratory paralysis, hospitalization with pulmonary ventilation and use of antivenoms are the primary therapies currently employed.

Viral Vector-Based Gene Therapy for Epilepsy: What Does the Future Hold?

In recent years, many pre-clinical studies have tested gene therapy approaches as possible treatments for epilepsy, following the idea that they may provide an alternative to conventional pharmacological and surgical options. Multiple gene therapy approaches have been developed, including those based on anti-sense oligonucleotides, RNA interference, and viral vectors. In this opinion article, we focus on translational issues related to viral vector-mediated gene therapy for epilepsy.

Late Survival After Valve-in-Valve Transcatheter Aortic Valve Implantation With Balloon- Versus Self-Expandable Valves: Meta-Analysis of Reconstructed Time-to-Event Data.

Valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) in patients with failed bioprostheses arose as an alternative to redo surgical aortic valve replacement. There is an increasing interest in exploring the differences between self-expanding valves (SEVs) and balloon-expandable valves (BEVs). Our study aimed to evaluate the all-cause mortality in ViV-TAVI with SEV versus BEV in patients with failed bioprostheses.

Sampling Cerebrospinal Fluid and Blood from Lateral Tail Vein in Rats during EEG Recordings.

Because the composition of body fluids reflects many physiological and pathological dynamics, biological liquid samples are commonly obtained in many experimental contexts to measure molecules of interest, such as hormones, growth factors, proteins, or small non-coding RNAs. A specific example is the sampling of biological liquids in the research of biomarkers for epilepsy. In these studies, it is desirable to compare the levels of molecules in cerebrospinal fluid (CSF) and in plasma, by withdrawing CSF and plasma in parallel and considering the time distance of the sampling from and to seizures.

Insight Into the Optimal Timing of Percutaneous Coronary Intervention and Transcatheter Aortic Valve Replacement.

Patients being considered for transcatheter aortic valve replacement (TAVR) are frequently diagnosed with coronary artery disease. In patients requiring revascularization, there is a paucity of data informing when to perform percutaneous coronary artery intervention (PCI). We evaluated the impact of PCI timing on clinical outcomes and readmissions after TAVR.

Guideline-Directed Medical Therapy Tolerability in Patients With Heart Failure and Mitral Regurgitation: The COAPT Trial.

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.

Objectives: The authors sought to assess the rates, reasons, and predictors of GDMT intolerance in the COAPT trial.

Methods: Baseline use, dose, and intolerances of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were analyzed in patients with left ventricular ejection fraction (LVEF) ≤40%, in whom maximally tolerated doses of these agents as assessed by an independent HF specialist were required before enrollment.

Effect of preoperative pulmonary hemodynamic and cardiopulmonary bypass on lung function in children with congenital heart disease.

In children with congenital heart disease (CHD), pulmonary blood flow (Qp) contributes to alterations of pulmonary mechanics and gas exchange, while cardiopulmonary bypass (CPB) induces lung edema. We aimed to determine the effect of hemodynamics on lung function and lung epithelial lining fluid (ELF) biomarkers in biventricular CHD children undergoing CPB. CHD children were classified as high Qp (n = 43) and low Qp (n = 17), according to preoperative cardiac morphology and arterial oxygen saturation.

Early postnatal weight loss does not affect the 2-year neurodevelopment in preterm infants of less than 32 weeks.

Aim: It is still unclear if the magnitude of early postnatal weight loss (PWL) could be associated with neurodevelopmental outcomes in preterm infants. We studied the association between PWL and neurodevelopment at 2-year corrected age in preterm infants.

Methods: We retrospectively reviewed data of preterm infants with a gestational age between 24 + 0 and 31 + 6 weeks/days, admitted at the G.

Shaping the future of European epilepsy research: Final meeting report from EPICLUSTER.

Collaboration is essential to the conduct of basic, applied and clinical research and its translation into the technologies and treatments urgently needed to improve the lives of people living with brain diseases and the health professionals who care for them. EPICLUSTER was formed in 2019 by the European Brain Research Area (EBRA) to support the coordination of epilepsy research in Europe. A key objective was to provide a platform to discuss shared research priorities by bringing together scientists and clinicians with multiple stakeholders including patient organisations and industry and the networks and infrastructures that provide healthcare and support research.

Late outcomes of valve-in-valve transcatheter aortic valve implantation versus re-replacement: Meta-analysis of reconstructed time-to-event data.

Aims: To evaluate all-cause mortality in ViV-TAVI versus redo SAVR in patients with failed bioprostheses.

Methods: Study-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of non-randomized studies published by September 30, 2021.

Results: Ten studies met our eligibility criteria and included a total of 3345 patients (1676 patients underwent ViV-TAVI and 1669 patients underwent redo SAVR).

Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development.

Temporal lobe epilepsy often manifests months or even years after an initial epileptogenic insult (e.g., stroke, trauma, status epilepticus) and, therefore, may be preventable.

A novel deuterium-based model for measurement of exogenous surfactant using deuterium-depleted water.

Stable isotope tracers, like C, can be used for the measurement of the partition between the endogenous and exogenous pulmonary disaturated-phosphatidylcholine (DSPC). Deuterium labeling methods are still not fully explored. Our aim was to investigate the feasibility of using deuterium-depleted water (DDW) and deuterium-enriched water (DEW) to measure endogenous and exogenous pulmonary DSPC in a rabbit model of surfactant depletion.

Tuning lower dimensional superconductivity with hybridization at a superconducting-semiconducting interface.

The influence of interface electronic structure is vital to control lower dimensional superconductivity and its applications to gated superconducting electronics, and superconducting layered heterostructures. Lower dimensional superconductors are typically synthesized on insulating substrates to reduce interfacial driven effects that destroy superconductivity and delocalize the confined wavefunction. Here, we demonstrate that the hybrid electronic structure formed at the interface between a lead film and a semiconducting and highly anisotropic black phosphorus substrate significantly renormalizes the superconductivity in the lead film.