A discrete time relativistic Toda lattice

Four integrable symplectic maps approximating two Hamiltonian flows from the relativistic Toda hierarchy are introduced. They are demostrated to belong to the same hierarchy and to examplify the general scheme for symplectic maps on groups equiped with quadratic Poisson brackets. The initial value problem for the difference equations is solved in terms of a factorization problem in a group. Interpolating Hamiltonian flows are found for all the maps.Comment: 32 pages, LaTe

Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency

In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134-147 ms; normal <118 ms. We hypothesize that elevated GABA in ocular tissue of SSADH patients leads to a use-dependent downregulation of the major GABAergic receptor in eye, GABA(C), and that the VEP recordings' abnormalities, as evidenced by P100 latency and/or amplitude measurements, may be reflective of abnormalities within visual systems. This is a preliminary finding that may suggest the utility of performing VEP analysis in a larger sample of SSADH-deficient patients, and encourage a neurophysiological assessment of GABA(C) receptor function in Aldh5a1(-/-) mice to reveal new pathophysiological mechanisms of this rare disorder of GABA degradation

The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a major prevalence in Canada, Italy and Japan. Acute clinical signs include intermittent episodes of vomiting, confusion or coma and hepatitis-like attacks. Alternatively, patients show a chronic course with aversion for protein rich foods, developmental delay/intellectual disability, myoclonic seizures, ataxia and pyramidal dysfunction. HHH syndrome is caused by impaired ornithine transport across the inner mitochondrial membrane due to mutations in SLC25A15 gene, which encodes for the mitochondrial ornithine carrier ORC1. The diagnosis relies on clinical signs and the peculiar metabolic triad of hyperammonemia, hyperornithinemia, and urinary excretion of homocitrulline. HHH syndrome enters in the differential diagnosis with other inherited or acquired conditions presenting with hyperammonemia

CUGC for hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome

From 1999 to date, 50 affecting function variants have been identified and associated to HHH syndrome [1–5]. As it is not available in the literature a complete up-to-date list of disease-causing variants for SLC25A15 gene, we included this information as a Supplementary Excel sheet (See Supplementary Material File #1): this list was created by using LOVD and ClinVar databases and liked to the relevant literature reference. Reported variants consist of: 29 missense variants, 4 frameshift, 11 nonsense, 2 splicing, 2 small deletion, 1 in frame insertion, 1 gross deletion

The ketogenic diet increases in vivo glutathione levels in patients with epilepsy

The Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that has been utilized as the first line treatment for contrasting intractable epilepsy. It is responsible for the presence of ketone bodies in blood, whose neuroprotective effect has been widely shown in recent years but remains unclear. Since glutathione (GSH) is implicated in oxidation-reduction reactions, our aim was to monitor the effects of KD on GSH brain levels by means of magnetic resonance spectroscopy (MRS). MRS was acquired from 16 KD patients and seven age-matched Healthy Controls (HC). We estimated metabolite concentrations with linear combination model (LCModel), assessing differences between KD and HC with t-test. Pearson was used to investigate GHS correlations with blood serum 3-B-Hydroxybutyrate (3HB) concentrations and with number of weekly epileptic seizures. The results have shown higher levels of brain GSH for KD patients (2.5 ± 0.5 mM) compared to HC (2.0 ± 0.5 mM). Both blood serum 3HB and number of seizures did not correlate with GSH concentration. The present study showed a significant increase in GSH in the brain of epileptic children treated with KD, reproducing for the first time in humans what was previously observed in animal studies. Our results may suggest a pivotal role of GSH in the antioxidant neuroprotective effect of KD in the human brain

Employment among Childhood Cancer Survivors: A Systematic Review and Meta-Analysis

To date, there are heterogeneous studies related to childhood cancer survivors&rsquo; (CCS) employment rates. Given the importance of this topic, we aimed to perform a systematic review and meta-analysis to investigate the prevalence of employment among CCS and to examine its association with socio-demographic and clinical factors. We followed the PRISMA guidelines to search for pertinent articles in relevant electronic databases. Eighty-nine articles comprising 93 cohorts were included. The overall prevalence of employment was 66% (CI: 95% 0.63&ndash;0.69). Subgroup meta-analyses showed that lower rates were found for central nervous system tumor survivors (51%, CI: 95% 0.43&ndash;0.59), and for CCS treated with cranial-radiotherapy (53%, CI: 95% 0.42&ndash;0.64) or haematopoietic stem-cell transplantation (56%, CI: 95% 0.46&ndash;0.65). The studies conducted in Asia highlighted employment rates of 47% (CI: 95%, 0.34&ndash;0.60). Univariate meta-regressions identified the following socio-demographic factors associated with higher rates of employment: a female gender (p = 0.046), a higher mean age at the time of investigation (p = 0.00), a longer time since diagnosis (p = 0.00), a higher educational level (p = 0.03), and a married status (p = 0.00). In conclusion, this systematic review and meta-analysis provides evidence that two-thirds of CCS are employed worldwide. Identifying vulnerable groups of CCS may allow for the design of multidisciplinary support strategies and interventions to promote employment in this population

Novel large-range mitochondrial dna deletions and fatal multisystemic disorder with prominent hepatopathy

Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies