Search

Tay-Sachs (TS) disease is a neurodegenerative disease resulting from mutations in the gene encoding the α-subunit (HEXA) of lysosomal β-hexosaminidase A (HexA). We report that (1) recombinant HEXA alone increased HexA activity and decreased GM2 content in human TS glial cells and peripheral mononuclear blood cells; 2) a recombinant chimeric protein composed of HEXA linked to two blood-brain barrier (BBB) entry elements, a transferrin receptor binding sequence and granulocyte-colony stimulating factor, associates with HEXB in vitro; reaches human cultured TS cells lysosomes and mouse brain cells, especially neurons, in vivo; lowers GM2 in cultured human TS cells; lowers whole brain GM2 concentration by approximately 40% within 6 weeks, when injected intravenously (IV) to adult TS-mutant mice mimicking the slow course of late-onset TS; and increases forelimbs grip strength. Hence, a chimeric protein equipped with dual BBB entry elements can transport a large protein such as HEXA to the brain, decrease the accumulation of GM2, and improve muscle strength, thereby providing potential treatment for late-onset TS.

Abstract The diagnosis of psychiatric disorders is currently based on a clinical and psychiatric examination (intake). Ancillary tests are used minimally or only to exclude other disorders. Here, we demonstrate a novel mathematical approach based on the field of p-adic numbers and using electroencephalograms (EEGs) to identify and differentiate patients with schizophrenia and depression from healthy controls. This novel approach examines spatio-temporal relations of single EEG electrode signals and characterizes the topological structure of these relations in the individual patient. Our results indicate that the relational topological structures, characterized by either the personal universal dendrographic hologram (DH) signature (PUDHS) or personal block DH signature (PBDHS), form a unique range for each group of patients, with impressive correspondence to the clinical condition. This newly developed approach results in an individual patient signature calculated from the spatio-temporal relations of EEG electrodes signals and might help the clinician with a new objective tool for the diagnosis of a multitude of psychiatric disorders.

No diagnostic or predictive instruments to help with early diagnosis and timely therapeutic intervention are available as yet for most neuro-psychiatric disorders. A quantum potential mean and variability score (qpmvs), to identify neuropsychiatric and neurocognitive disorders with high accuracy, based on routine EEG recordings, was developed. Information processing in the brain is assumed to involve integration of neuronal activity in various areas of the brain. Thus, the presumed quantum-like structure allows quantification of connectivity as a function of space and time (locality) as well as of instantaneous quantum-like effects in information space (non-locality). EEG signals reflect the holistic (nonseparable) function of the brain, including the highly ordered hierarchy of the brain, expressed by the quantum potential according to Bohmian mechanics, combined with dendrogram representation of data and p-adic numbers. Participants consisted of 230 participants including 28 with major depression, 42 with schizophrenia, 65 with cognitive impairment, and 95 controls. Routine EEG recordings were used for the calculation of qpmvs based on ultrametric analyses, closely coupled with p-adic numbers and quantum theory. Based on area under the curve, high accuracy was obtained in separating healthy controls from those diagnosed with schizophrenia (p

No diagnostic or predictive instruments to help with early diagnosis and timely therapeutic intervention are available as yet for most neuro-psychiatric disorders. A quantum potential mean and variability score (qpmvs), to identify neuropsychiatric and neurocognitive disorders with high accuracy, based on routine EEG recordings, was developed. Information processing in the brain is assumed to involve integration of neuronal activity in various areas of the brain. Thus, the presumed quantum-like structure allows quantification of connectivity as a function of space and time (locality) as well as of instantaneous quantum-like effects in information space (non-locality). EEG signals reflect the holistic (nonseparable) function of the brain, including the highly ordered hierarchy of the brain, expressed by the quantum potential according to Bohmian mechanics, combined with dendrogram representation of data and p-adic numbers. Participants consisted of 230 participants including 28 with major depression, 42 with schizophrenia, 65 with cognitive impairment, and 95 controls. Routine EEG recordings were used for the calculation of qpmvs based on ultrametric analyses, closely coupled with p-adic numbers and quantum theory. Based on area under the curve, high accuracy was obtained in separating healthy controls from those diagnosed with schizophrenia (p

Background: While accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. Methods: This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18 weeks and had low levels of vitamin D (70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000 IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. Results: Twenty four patients were randomly assigned to vitamin D (aged 39.4 ± 9.6 years, 75% males) and the other 23 patients to the placebo arm (aged 42.5 ± 11.2 years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs −0.4 nmol/l, p