Precision therapy for a medically actionable ATP1A3 variant from a genomic medicine program in an underserved population.

Background: Genomic medicine is revolutionizing the diagnosis of rare diseases, but the implementation has not benefited underrepresented populations to the same degree. Here, we report the case of a 7-year-old boy with hypotonia, global developmental delay, strabismus, seizures, and previously suspected mitochondrial myopathy. This proband comes from an underrepresented minority and was denied exome sequencing by his public insurance.

Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers.

Pain is a complex experience that involves physical, emotional, and cognitive aspects. This review focuses specifically on the physiological processes underlying pain perception, with a particular emphasis on the various types of sensory neurons involved in transmitting pain signals to the central nervous system. Recent advances in techniques like optogenetics and chemogenetics have allowed researchers to selectively activate or inactivate specific neuronal circuits, offering a promising avenue for developing more effective pain management strategies.

Autologous CXCR4+ Hematopoietic Stem Cells Injected into the Scar Tissue of Chronic Myocardial Infarction Patients Normalizes Tissue Contractility and Perfusion.

Background: Chronic myocardial infarction (CMI), represents a public health and a financial burden. Since stem cell transplant is used to regenerate cardiac tissue after acute myocardial infarction.

Aim Of The Study: To determine if autologous CXCR4 stem cells could restore damaged myocardial tissue in patients with CMI lesions.

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism.

Dopamine (DA) depletion modifies the firing pattern of neurons in the substantia nigra pars reticulata (SNr), shifting their mostly tonic firing toward irregularity and bursting, traits of pathological firing underlying rigidity and postural instability in Parkinson's disease (PD) patients and animal models of Parkinsonism (PS). Drug-induced Parkinsonism (DIP) represents 20-40% of clinical cases of PS, becoming a problem for differential diagnosis, and is still not well studied with physiological tools. It may co-occur with tardive dyskinesia.

Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat.

The external globus pallidus (GPe) is central for basal ganglia processing. It expresses muscarinic cholinergic receptors and receives cholinergic afferents from the pedunculopontine nuclei (PPN) and other regions. The role of these receptors and afferents is unknown.

Sporadic Hemiplegic Migraine with ATP1A2 and Prothrombin Gene Mutations.

Background. Hemiplegic migraine is a rare type of migraine that may present in children and adolescents. Both familial and sporadic hemiplegic migraines have similar prevalence and clinical characteristics.

Clinical pharmacology and pharmacokinetics of levetiracetam.

Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam (IV LEV), a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available.

The role of levetiracetam in treatment of seizures in brain tumor patients.

Levetiracetam, trade name Keppra, is a new second generation antiepileptic drug that is being increasingly used in brain tumor patients. In patients suffering with brain tumors, seizures are one of the leading neurologic complications being seen in more than 30% of patients. Unlike other antiepileptic drugs, levetiracetam is proposed to bind to a synaptic vesicle protein inhibiting calcium release.

Efficacy and tolerability of intravenous levetiracetam in childrens.

Intractable epilepsy in children poses a serious medical challenge. Acute repetitive seizures and status epilepticus leads to frequent emergency room visits and hospital admissions. Delay of treatment may lead to resistance to the first-line anticonvulsant therapies.

Neurobehavioral effects of levetiracetam in brain tumor related epilepsy.

The neurobehavioral profile of anti-epileptic drugs (AEDs) has been a recurrent research topic in the scientific literature. As pharmacological treatments for epilepsy continue to evolve, there is a general consensus that newer AEDs have less detrimental side effects in comparison to their older counterparts. Among newer AEDs and epilepsy patients, potential risk for neurobehavioral changes has been reported with levetiracetam (LEV).

Bidirectional plasticity in striatonigral synapses: a switch to balance direct and indirect basal ganglia pathways.

There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral (direct pathway) synapses are not known.

Diversity in long-term synaptic plasticity at inhibitory synapses of striatal spiny neurons.

Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term potentiation (LTP) at synapses among spiny neurons (intrinsic striatal circuitry); a postsynaptically dependent long-term depression (LTD) at synapses between spiny and pallidal neurons (indirect pathway); and a presynaptically dependent LTP at strionigral synapses (direct pathway).

[Correction of the perpendicular positioning of the Amplatzer device during closure of an ostium secundum atrial septal defect].

Introduction And Objectives: Ostium secundum atrial septal defects require closure. Echocardiographic studies have reported that, in 7% of cases, the Amplatzer occluder is orientated perpendicular to the rim of the defect. This article describes the use of an ancillary technique involving a balloon catheter that enables the Amplatzer device to be positioned transversely.

[Stem cell perspectives in myocardial infarctions].

Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue.

Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction.

Autologous transplant of bone marrow stem cells (BMSC), although extremely useful after acute myocardial events, has not been evaluated in patients with old (>one-year-old) myocardial infarction. Our aim was to determine if CD34(+)-enriched peripheral-blood cells, obtained by apheresis, injected directly into the severely damaged myocardium of five patients with old myocardial infarction could restore depressed myocardial function. We found that 28 weeks after revascularization and peri-infarction injection of the enriched CD34(+) peripheral mononuclear cells, ventricular hemodynamic parameters that included left ventricular ejection fraction, left ventricular diastolic volume, ventricular systolic volume and left ventricular diastolic diameter approximated normal values and there was no restenosis; two patients have been followed for >52 weeks and their parameters are within normal values.

A subpopulation of large granular von Willebrand Ag negative and CD105 positive endothelial cells, isolated from abdominal aortic aneurysms, overexpress ICAM-1 and Fas antigen.

The aim of this work was to determine whether there is a pre-established basal condition of the endothelial cells isolated from aortic abdominal aneurysm that might augment immune effector mechanisms and thus provide us an insight into the possible causes of aneurysm rupture. Endothelial cells isolated from saccular aortic aneurysm fragments were analyzed by cytofluorometry for the expression of different immune response-related molecules. Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected.