First unprovoked seizures among soldiers recruited to the Israeli Defense Forces during 10 consecutive years: A population-based study.

OBJECTIVE: The management of patients after a first unprovoked seizure (FUS) can benefit from stratification of the average 50% risk for further seizures. We characterized subjects with FUSs, out of a large generally healthy homogenous population of soldiers recruited by law to the Israeli Defense Forces, to investigate the role of the type of service, as a trigger burden surrogate, in the risk for additional seizures. METHODS: Soldiers recruited between 2005 and 2014, who experienced an FUS during their service, were identified from military records. Subjects with a history of epilepsy or lack of documentation of FUS characteristics were excluded from the study. Data on demographics and military service and medical details were extracted for the eligible soldiers. RESULTS: Of 816 252 newly recruited soldiers, representing 2 138 000 person-years, 346 had an FUS, indicating an incidence rate of 16.2 per 100 000 person-years. The FUS incidence rate was higher in combat versus noncombat male and female soldiers (p < .0001). Most subjects (75.7%) were prescribed antiseizure medications (ASMs), and 29.2% had additional seizures after the FUS. Service in combat units, abnormal magnetic resonance imaging, and being prescribed ASMs were correlated with a lower risk of having multiple seizures (95% confidence interval [CI] = .48-.97, .09-.86, .15-.28, respectively). On multivariate analysis, service in combat units (odds ratio [OR] = .48 for seizure recurrence, 95% CI = .26-.88) and taking medications (OR = .46, 95% CI = .24-.9) independently predicted not having additional seizures. SIGNIFICANCE: FUS incidence rate was higher in combat soldiers, but they had a twofold lower risk of additional seizures than noncombat soldiers, emphasizing the value of strenuous triggers as negative predictors for developing epilepsy. This suggests a shift in the perception of epilepsy from a "yes or no" condition to a continuous trend of predisposition to seizures, warranting changes in the ways etiologies of epilepsy are weighted and treatments are delivered.

Translational longevity medicine: a Swiss perspective in an ageing country.

Breakthroughs in medical research in the last century have led to a significant extension of the human lifespan, resulting in a shift towards an elderly population worldwide. Due to the ongoing progress of global development towards elevated standards of living, this study specifically examines Switzerland as a representative nation to explore the socioeconomic and healthcare ramifications associated with an ageing population, thereby highlighting the tangible impact experienced in this context. Beyond the exhaustion of pension funds and medical budgets, by reviewing the literature and analysing publicly available data, we observe a "Swiss Japanification". Old age is associated with late-life comorbidities and an increasing proportion of time spent in poor health. To address these problems, a paradigm shift in medical practice is needed to improve health rather than respond to existing diseases. Basic ageing research is gaining momentum to be translated into therapeutic interventions and provides machine learning tools driving longevity medicine. We propose that research focus on closing the translational gap between the molecular mechanisms of ageing and a more prevention-based medicine, which would help people age better and prevent late-life chronic diseases.

Abundance of P-glycoprotein and Breast Cancer Resistance Protein Measured by Targeted Proteomics in Human Epileptogenic Brain Tissue.

Our goal was to measure the absolute differential abundance of key drug transporters in human epileptogenic brain tissue and to compare them between patients and at various distances from the epileptogenic zone within the same patient. Transporter protein abundance was quantified in brain tissue homogenates from patients who underwent epilepsy surgery, using targeted proteomics, and correlations with clinical and tissue characteristics were assessed. Fourteen brain samples (including four epileptogenic hippocampal samples) were collected from nine patients. Among the quantifiable drug transporters, the abundance (median, range) ranked: breast cancer resistance protein (ABCG2/BCRP; 0.55, 0.01-3.26 pmol/g tissue) > P-glycoprotein (ABCB1/MDR1; 0.30, 0.02-1.15 pmol/g tissue) > equilibrative nucleoside transporter 1 (SLC29A1/ENT1; 0.06, 0.001-0.35 pmol/g tissue). The ABCB1/ABCG2 ratio (mean 0.27, range 0.08-0.47) was comparable with literature values from nonepileptogenic brain tissue (mean 0.5-0.8). Transporter abundance was lower in the hippocampi than in the less epileptogenic neocortex of the same patients. ABCG2/BCRP and ABCB1/MDR1 expression strongly correlated with that of glucose transporter 1 (SLC2A1/GLUT1) (r = 0.97, p < 0.001; r = 0.90, p < 0.01, respectively). Low transporter abundance was found in patients with overt vascular pathology, whereas the highest abundance was seen in a sample with normally appearing blood vessels. In conclusion, drug transporter abundance highly varies across patients and between epileptogenic and less epileptogenic brain tissue of the same patient. The strong correlation in abundance of ABCB1/MDR1, ABCG2/BCRP, and SLC2A1/GLUT1 suggests variation in the content of the functional vasculature within the tissue samples. The epileptogenic tissue can be depleted of key drug transport mechanisms, warranting consideration when selecting treatments for patients with drug-resistant epilepsy.

Folate homeostasis in epileptic rats.

Folate is involved in metabolic processes and it has been implicated in both aggravation and amelioration of seizures. The aim of the current work was to study the effect of chronic temporal lobe epilepsy (TLE) on the plasma and brain concentrations of folate and on its uptake carriers in the brain - the reduced folate carrier (RFC), folate receptor α (FRα) and proton coupled folate transporter (PCFT). We utilized the rat lithium pilocarpine model for TLE. Approximately two months following status epilepticus, rats with spontaneous recurrent seizures (SRS) were sacrificed for brain and plasma folate concentration analyses and folate uptake carrier expression studies. RT-PCR and western blot analyses were utilized for quantification of folate carriers' mRNAs and proteins, respectively. The distribution of folate carriers in the brain was studied using immunohistochemistry. In the SRS rats we found lower plasma concentrations (10 ±â€¯0.9 in control vs. 6.6 ±â€¯1.6 ng/ml in SRS, P < 0.05), but preserved cortical and increased hippocampal levels of folate (0.5 ±â€¯0.1 in control vs. 0.9 ±â€¯0.2 ng/mg in SRS, P = 0.055). Hippocampus - to - plasma ratio of folate concentration was 3-fold higher in the SRS group, compared with the controls (0.13 ±â€¯0.03 vs. 0.04 ±â€¯0.02, respectively; P < 0.01). mRNA and protein levels of the folate uptake carriers did not differ between SRS rats and controls. However, immunofluorescent staining quantification revealed that the emission intensity of both RFC and FRα was elevated 8-fold and 4-fold, respectively, in hippocampal CA1 neurons of SRS rats, compared to controls (P < 0.01). PCFT was unquantifiable. If corroborated by complementary research in humans, the findings of this study may be utilized clinically for supplemental therapy planning, in imaging the epileptic focus, and for drug delivery into the epileptic brain. Further studies are required for better elucidating the clinical and mechanistic significance of altered folate balances in the epileptic brain.