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Infantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations.

Children (Basel)

December 2024

Division of Pediatric Neurology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Infantile spasms are common in Down Syndrome (DS), but the mechanisms by which DS predisposes to this devastating epilepsy syndrome are unclear. In general, neuronal excitability and therefore seizure predisposition results from an imbalance of excitation over inhibition in neurons and neural networks of the brain. Animal models provide clues to mechanisms and thereby provide potential therapeutic approaches.

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Inhibitory Effects of Cenobamate on Multiple Human Cardiac Ion Channels and Possible Arrhythmogenic Consequences.

Biomolecules

December 2024

Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.

Cenobamate is a novel third-generation antiepileptic drug used for the treatment of focal onset seizures and particularly for multi-drug-resistant epilepsy; it acts on multiple targets: GABA receptors (EC 42-194 µM) and persistent neuronal Na currents (IC 59 µM). Side effects include QT interval shortening with >20 ms, but not <300 ms. Our in vitro cardiac safety pharmacology study was performed via whole-cell patch-clamp on HEK293T cells with persistent/inducible expression of human cardiac ion channel isoforms hNav1.

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Background Numerous risk factors have been identified for developing severe COVID-19, including sociodemographic variables and concomitant diseases. Individuals with underlying comorbidities such as diabetes, hypertension, asthma, and coronary artery disease are at a greater risk of severe illness and death. This study aimed to observe the association between risk factors and the severity of COVID-19.

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Allopregnanolone (Allo) is a positive allosteric modulator of the GABA receptor, and amiloride (Ami) is a competitive antagonist of the GABA receptor. The purpose of this work was to study the combined effect of Allo and Ami on functional activity of GABA receptor. The GABA-induced chloride current (I) was measured in isolated Purkinje cells of rat cerebellum using the patch-clamp technique and a system of fast application.

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Variability in HIV-1 transmitted/founder virus susceptibility to combined APOBEC3F and APOBEC3G host restriction.

J Virol

December 2024

Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Several APOBEC3 enzymes restrict HIV-1 by deaminating cytosine to form uracil in single-stranded proviral (-)DNA. However, HIV-1 Vif counteracts their activity by inducing their proteasomal degradation. This counteraction by Vif is incomplete, as evidenced by footprints of APOBEC3-mediated mutations within integrated proviral genomes of people living with HIV-1.

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