Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes

BackgroundMost children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early identification of at-risk children is of utmost importance.AimTo develop a predictive model of encephalopathic transformation using data-driven approaches, reveal complex interactions to identify potential risk factors.MethodsData were collected from a cohort of 91 patients diagnosed with BECTS treated between the years 2005–2017 at a pediatric neurology institute. Data on the initial presentation was collected based on a novel BECTS ontology and used to discover potential risk factors and to build a predictive model. Statistical and machine learning methods were compared.ResultsA subgroup of 18 children had encephalopathic transformation. The least absolute shrinkage and selection operator (LASSO) regression Model with Elastic Net was able to successfully detect children with ECSWS or LKS. Sensitivity and specificity were 0.83 and 0.44. The most notable risk factors were fronto-temporal and temporo-parietal localization of epileptic foci, semiology of seizure involving dysarthria or somatosensory auras.ConclusionNovel prediction model for early identification of patients with BECTS at risk for ECSWS or LKS. This model can be used as a screening tool and assist physicians to consider special management for children predicted at high-risk. Clinical application of machine learning methods opens new frontiers of personalized patient care and treatment.     

Can Achilles and patellar tendon structures predict musculoskeletal injuries in combat soldiers?

Aiming to investigate whether Achilles tendon (AT) structure and patellar tendon (PT) structure are risk factors for musculoskeletal injuries in combat soldiers, 168 participants were recruited from an infantry commander's course. The AT and PT were examined pre‐course using UTC to capture the structure of four echo‐type fibers (I–IV). All injuries were assessed by military physicians pre‐course and throughout the 14‐week course. Soldiers who were injured during the course had a significantly higher pre‐course prevalence of AT and PT echo‐type III and echo‐type IV compared to soldiers that were not injured during the course. Variables that were found to be associated with injured/non‐injured participants were echo‐type III + IV of the PT (OR = 1.44, 95% CI = 1.24‐1.68) and echo‐type III of the AT (OR = 1.69, 95% CI = 1.35‐2.12). ROC analyses showed that the best model, exhibiting both high sensitivity and low specificity, was that participants with PT echo‐type III + IV > 10% or AT echo‐type III >8.5% had the highest risk of being injured during the course. In conclusions, the tendon structure at the beginning of high‐intensity activity or physical training program might be a risk factor for subsequent injury during the course. Soldiers and high‐level athletes should be aware of the cutoff points for fiber types in tendon structure that might put them at high risk for future injury. At‐risk soldiers/athletes should be provided with an intervention program before they start their training program, with the aim of improving the tendon structure and preventing subsequent injury.     

Immunoglobulin-Mediated Neuro-Cognitive Impairment: New Data and a Comprehensive Review

Excessive influx of immunoglobulin (IgG) into the brain has been reported to induce central nervous system (CNS) dysfunction. Depressed patients may exhibit immune activation manifested by elevated inflammatory markers and pro-inflammatory cytokines. The brain and especially the limbic system contain high concentrations of high affinity Fc receptors. We reviewed the literature on this phenomena and present data on the behavioral effects of pooled normal IgG on the brain. Many disease states are associated with depression and we examined whether this may be linked to high IgG influx. Female Balb/C mice were injected intra-cerbroventricularly with human immunoglobulin whole molecule, or human IgG F(ab′)₂ or Fc fragments. Control mice were injected with saline. The four groups were subjected to behavioral (staircase, forced swimming test, and elevated plus maze) and cognitive tests (passive avoidance test). IgG-injected mice exhibited depression-like behavior as reflected by significantly higher immobility time in the forced swimming test (p?<?0.05) and hyperactive behavior as reflected by higher number of stairs climbed in the staircase test compared to controls (p?<?0.01). Fc-fragments-injected mice showed hyperactive behavior as reflected by both higher number of stairs climbed and rearing events in the staircase test compared to controls. The results indicate that high levels of normal IgG in the cerebrospinal fluid can cause hyperactivity and depression-like behavior. The mechanism involved in these CNS manifestations include possibly Fc receptor binding.     

Paraoxonase1 deficiency in mice is associated with hypotension and increased levels of 5,6-epoxyeicosatrienoic acid

AimSerum paraoxonase 1 (PON1) is an HDL-associated lipolactonase and its association with hypertension is controversial. We studied the possible role of PON1 in blood pressure (BP) regulation, by using PON1 knockout (PON1KO) mice.Methods and resultsBoth, systolic and diastolic BPs were lower in PON1KO compared to WT mice. Hypotension detected in PON1KO is probably neither related to nitric oxide/guanylate cyclase-mediated vasodilation nor to angiotensin II or aldosterone-mediated vasoconstriction. Surprisingly, when challenged by high-salt diet, BP was further reduced in PON1KO mice. The later, pointed to a possible involvement of transient receptor potential vanilloid 4 (TRPV4), and indeed, administration of ruthenium red, a TRPV4 blocker, resulted in a sharp rise in BP. The protein levels of TRPV4 in kidneys of PON1KO were not higher than in WT. However, the renal level of 5,6-epoxyeicosatrienoic acid (5,6-EET), a TRPV4 specific agonist, was significantly higher in PON1KO compared with WT mice. 5,6-EET levels were further elevated under high-salt diet or administration of arachidonic acid. Injection of inhibitor of CYP450 epoxygenase resulted in increased BP in PON1KO mice. Injection of recombinant human PON1 resulted in elevation of BP and a concomitant reduction in renal content of 5,6-EET. PON1, in vitro, metabolized 5,6-EET, but not other EETs, to its corresponding diol. Vasodilation, blocked by excess of dietary K⁺ but not reversed by depletion of cellular Ca²⁺ stores, point to endothelial-derived hyperpolarization-like response.ConclusionThe present study shows causal, direct relationship between PON1 and blood pressure which is mediated, at least in part, by the regulation of 5,6-EET.     

Endothelial progenitor cells are suppressed in anemic patients with acute coronary syndrome

ObjectiveAnemia is an independent predictor of poor prognosis in acute coronary syndrome. Endothelial progenitor cells are bone marrow-derived cells that are mobilized into the circulation in response to ischemia. The number of circulating endothelial progenitor cells increases within days of acute coronary syndrome. There is no confirmation regarding the correlation between the occurrence of anemia and the deficiency in endothelial progenitor cells in patients with acute coronary syndrome. The correlation between chronic anemia and endothelial progenitor cells in patients with acute coronary syndrome was investigated.MethodsEndothelial progenitor cells were examined in 26 patients with acute coronary syndrome. Fifteen patients had chronic nonprogressive anemia, and 11 patients had a normal blood count. Blood samples were drawn on the first day of admission and 4 to 7 days later. Mononuclear cells were separated and cultured on fibronectin-coated plates with EndoCult medium (StemCell Technologies, Vancouver, BC, Canada) for 5 days. Colony forming unit count and a migration assay were performed at each time point.ResultsBaseline colony forming unit in the non-anemic group was higher than in the anemic group (P < .0001). There was a highly significant correlation between admission hemoglobin and colony forming unit count (R = 0.83, P < .0001). Colony forming units increased in both groups on the second measurement but to a lower extent in the anemic group (P = .0004). The migration assay in the non-anemic group was higher than in the anemic group at baseline (P = .017) and 4 to 7 days later (P = .0054).ConclusionPatients with acute coronary syndrome with anemia demonstrate a reduced number of peripheral endothelial progenitor cells with impaired function, possibly representing a lower capacity for vascular healing. These phenomena may partly explain the poor prognosis observed in patients with acute coronary syndrome and anemia.