A framework for health equity in people living with epilepsy.

Epilepsy is a disease where disparities and inequities in risk and outcomes are complex and multifactorial. While most epilepsy research to date has identified several key areas of disparities, we set out to provide a multilevel life course model of epilepsy development, diagnosis, treatment, and outcomes to highlight how these disparities represent true inequities. Our piece also presents three hypothetical cases that highlight how the solutions to address inequities may vary across the lifespan.

Association between status epilepticus and cardiorespiratory comorbidity in patients with epilepsy: A population-based study.

Purpose: This study aimed to evaluate the relationship between status epilepticus (SE) and cardiorespiratory comorbidity in patients with epilepsy.

Methods: We conducted a population-based study using cloud-based aggregated electronic medical records from >53 million patients in the US (Explorys, IBM Watson; January 1999 to November 2020). During the study period, we identified patients with epilepsy with SE.

A descriptive study of eye and head movements in versive seizures.

Background: Versive seizures, consisting of forced, involuntary, sustained and unnatural turning of eyes and head toward one side, lateralize to the hemisphere contralateral to the direction of the eye and head turn. The characteristics of eye and head movements in version have been rarely and incompletely studied in spontaneous epileptic seizures as opposed to direct cortical stimulation studies.

Methods: We performed a single center retrospective analysis of a cohort of 28 patients with 43 seizures, who had been admitted to the adult epilepsy monitoring unit at University Hospitals Cleveland Medical Center between January 2009 and August 2020.

Stereotactic-EEG-guided radiofrequency multiple hippocampal transection (SEEG-guided-RF-MHT) for the treatment of mesial temporal lobe epilepsy: a minimally invasive method for diagnosis and treatment.

For the treatment of mesial temporal lobe epilepsy on the language-dominant side in patients at high risk of memory decline, we propose a minimally invasive diagnostic and treatment technique, adopting the principles of multiple hippocampal transections (MHT) using stereo-electroencephalography-guided radiofrequency (SEEG-guided-RF-MHT). This new technique allows targeting of the longitudinal fibers in the hippocampus critical for seizure spreading, while sparing the transverse circuits which are considered important for memory processing and avoiding discomfort and longer post-operatory recovery time associated with craniotomies. We report the efficacy and safety of this procedure in a preliminary observational study of cases.

Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception.

Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm.

(Kunth) Govaerts Leaf Extract Influences Cell Proliferation and Angiogenesis on Primary Cultures of Porcine Aortic Endothelial Cells.

(Kunth) Govaerts is an endemic species in Ecuador, where it is used as an anti-inflammatory plant to treat respiratory and digestive affections. In this work, effects of a ethanolic extract (CTEE), prepared from aerial parts of the plant, were investigated on vascular endothelium functions. In particularly, angiogenesis activity was evaluated, using primary cultures of porcine aortic endothelial cells (pAECs).

Therapeutic potential of novel Cell Division Cycle Kinase 7 inhibitors on TDP-43-related pathogenesis such as Frontotemporal Lobar Degeneration (FTLD) and amyotrophic lateral sclerosis (ALS).

TDP-43 has been identified as the major component of protein aggregates found in affected neurons in FTLD-TDP and amyotrophic lateral sclerosis (ALS) patients. TDP-43 is hyperphosphorylated, ubiquitinated, and cleaved in the C-terminus. CDC-7 was reported to phosphorylate TDP-43.

Functional Selectivity and Antinociceptive Effects of a Novel KOPr Agonist.

Kappa opioid receptor (KOPr) agonists represent alternative analgesics for their low abuse potential, although relevant adverse effects have limited their clinical use. Functionally selective KOPr agonists may activate, in a pathway-specific manner, G protein-mediated signaling, that produces antinociception, over β-arrestin 2-dependent induction of p38MAPK, which preferentially contributes to adverse effects. Thus, functionally selective KOPr agonists biased toward G protein-coupled intracellular signaling over β-arrestin-2-mediated pathways may be considered candidate therapeutics possibly devoid of many of the typical adverse effects elicited by classic KOPr agonists.

Stereo-EEG in Tuberous Sclerosis Complex.

A collaborative research team lead by an investigator from the Lyon Neuroscience Research Center and Lyon University Hospital and Lyon 1 University studied epileptogenicity of tuber and its surrounding cortex using stereoelectroencephalography (SEEG) in patients diagnosed with tuberous sclerosis complex (TSC) (genetic or clinical).

Burmese python target reflectivity compared to natural Florida foliage background reflectivity.

The Florida Everglades is infested with Burmese pythons caused by the release of exotic pets in the 1980s. The current estimates are between 30,000 and 300,000 pythons, where the result is a severe decline in Everglade mammals: 90% reductions in raccoon, opossum, bobcats, and foxes. The marsh rabbits are completely gone.

Indazolylketones as new multitarget cannabinoid drugs.

Multitarget cannabinoids could be a promising therapeutic strategic to fight against Alzheimer's disease. In this sense, our group has developed a new family of indazolylketones with multitarget profile including cannabinoids, cholinesterase and BACE-1 activity. A medicinal chemistry program that includes computational design, synthesis and in vitro and cellular evaluation has allowed to us to achieve lead compounds.

Gaucher disease: successful treatment of myoclonic status epilepticus with levetiracetam.

We present the first reported case of a rapid clinical and electroencephalographic response to intravenous levetiracetam infusion of myoclonic status epilepticus in a patient with progressive myoclonus epilepsy due to Gaucher disease. Under continuous video-EEG monitoring, the clinical myoclonic status and the electrographic ictal discharges resolved within 10 minutes after the infusion was initiated. The patient tolerated the treatment well without any reported side effects.

Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia.

The goal of this project was to identify families with autosomal dominant hypercholesterolemia (ADH) to facilitate early detection and treatment and to provide genetic counselling as well as to approximate the mutational diversity of ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five mutations (24 LDLR, 1 APOB) were identified in 38 index cases.

G6PD (AC)n and (CTT)n microsatellites in Mexican Mestizos with common G6PD African variants.

Genotyping for the G6PD (AC)n and (CTT)n microsatellites in a sample of 58 Mexican Mestizos with common G6PD African variants was carried out. The second mutation that defines to the variants G6PD A(-202A/376G), G6PD Santamaria(376G/542T) and G6PD A(-376G/968C) very probably occurred on G6PD A(376G) chromosomes with the compound haplotypes, intragenic silent polymorphisms and microsatellites, Pvu-II/Pst-I/Bcl-I/Nla-III/(AC)n/(CTT)n: +/+/-/+/166 bp/195 bp, -/+/-/+/166 bp/201 bp, and -/+/-/+/166 bp/204 bp respectively. The structure of the repeat sequences for the AC-166 bp allele in the 3 variants was (TA)5(AA)1(TA)9(CA)10 whereas the repeat sequences for the CTT-195 bp, CTT-201 bp and CTT-204 bp alleles were (CTT)11(ATT)6, (CTT)7(ATT)12 and (CTT)7(ATT)13 in the first, second and third variants respectively.

Glucose-6-phosphate dehydrogenase (G-6-PD) mutations in Mexico: four new G-6-PD variants.

Screening for mutations at the G-6-PD gene by PCR-SSCP combined with restriction enzyme analysis and DNA sequencing was performed in nine G-6-PD deficient individuals with negative results for the presence of the most frequent G-6-PD mutations previously observed in Mexican population. The variants G-6-PD Valladolid(406T), G-6-PD Durham(713G), and G-6-PD Viangchan(871A) and four new G-6-PD mutant alleles were identified. The new mutations are located at cDNA nt 376 A --> T (126 Asn --> Tyr), nt 770 G --> T (257 Arg --> Leu), nt 1094 G --> A (365 Arg --> His), and nt 1285 A --> G (429 Lys --> Glu) and they were named G-6-PD San Luis Potosi, G-6-PD Zacatecas, G-6-PD Veracruz, and G-6-PD Yucatán, respectively.

Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Mexico: overall results of a 7-year project.

Several years ago, a project aiming to determine (i) the molecular basis of G-6-PD deficiency, (ii) the distribution of four different mutant alleles previously detected, and (iii) the whole of polymorphic alleles that account for the overall prevalence of G-6-PD deficiency in Mexico was implemented. Nearly 5000 individuals-from the general population and patients with hemolytic anemia-belonging to at least 14 States were screened for G-6-PD deficiency. Seventy-six G-6-PD-deficient subjects were detected and the prevalence of G-6-PD deficiency in 4777 individuals from the general population was 0.

Genotyping by"cold single-strand conformation polymorphism" of the UGT1A1 promoter polymorphism in Mexican mestizos.

Since no data have previously been reported concerning both the (TA) n polymorphism at the promoter of the UGT1A1 gene in the Mexican population and the use of single-strand conformation polymorphism (SSCP) for the detection of such polymorphism, genotyping by SSCP in 375 G-6-PD normal (Group A) and 81 G-6-PD-deficient (Group B) mestizos belonging to 14 states was carried out. Allele frequencies for (TA)6 and (TA)7 repeats were 0.654 and 0.

Glucose-6-phosphate dehydrogenase mutations and haplotypes in Mexican Mestizos.

In a screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 1985 unrelated male subjects from the general population (Groups A and B) belonging to four states of the Pacific coast, 21 G-6-PD-deficient subjects were detected. Screening for mutations at the G-6-PD gene by PCR-restriction enzyme in these 21 G-6-PD-deficient subjects as well as in 14 G-6-PD-deficient patients with hemolytic anemia belonging to several states of Mexico showed two common G-6-PD variants: G-6-PD A-(202A/376G) (19 cases) and G-6-PD A-(376G/968C) (9 cases). In 7 individuals the mutations responsible for the enzyme deficiency remain to be determined.

Molecular genetics of glucose-6-phosphate dehydrogenase deficiency in Mexico.

Several studies carried out between 1965 and 1985 showed that G-6-PD deficiency in Mexico is heterogeneous at the biochemical level and that the G-6-PD A- phenotype is relatively common. We have now investigated the molecular basis of G-6-PD deficiency in Mexico. Up-to-date 60 chromosomes with G6PD mutations have been studied, 16 in previous studies and 44 in the present work.

Structural organization of the human sorbitol dehydrogenase gene (SORD).

The primary structure of human sorbitol dehydrogenase (SORD) was determined by cDNA and genomic cloning. The nucleotide sequence of the mRNA covers 2471 bp including an open reading frame that yields a protein of 356 amino acid residues. The gene structure of SORD spans approximately 30 kb divided into 9 exons and 8 introns.

Molecular heterogeneity of G-6-PD deficiency in Mexico.

DNA samples from seven G-6-PD deficient Mexican mestizo patients were analyzed. Three different G-6-PD genotypes were observed: G-6-PD A-202A/376G (three patients), G-6-PD A-376G/968C (three patients) and G-6-PD Seattle844C. The present results, along with previous reports, suggest not only G-6-PD A-genotypes are relatively common but also G-6-PD deficiency seems to be heterogeneous at DNA level in Mexico.