Treating late-onset Tay Sachs disease: Brain delivery with a dual trojan horse protein.

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 ; reaches human cultured TS cells lysosomes and mouse brain cells, especially neurons, ; 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.

EEG-based spatio-temporal relation signatures for the diagnosis of depression and schizophrenia.

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.

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antidepressant Treatment.

The aim of this study was to characterize the clinical profiles, tolerability, and efficacy of two groups of antidepressants, selective serotonin reuptake inhibitors (SSRIs), and the atypical antidepressant, mirtazapine, in children and adolescents treated in a large pediatric Hematology-Oncology center. A review of computerized medical charts of 32 pediatric patients with cancer, from December 2011 to April 2020, was conducted. Efficacy and tolerability of antidepressant medications were retrospectively analyzed.

EEG p-adic quantum potential accurately identifies depression, schizophrenia and cognitive decline.

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.

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antipsychotic Medications Palliate Symptoms in Children with Cancer.

The present study characterized the psychiatric diagnoses and symptoms that led to the administration of antipsychotic medications in children and adolescents with cancer, and to evaluate the benefits and tolerability of these drugs in a large hospital-based pediatric hematology-oncology practice. Efficacy and adverse effects of two second-generation antipsychotics were retrospectively analyzed in 43 patients 2.9-19.

Comorbid personality disorders in manic bipolar I disorder patients is associated with increased use of long-acting injectable antipsychotic treatment and higher rates of rehospitalization.

Personality disorder comorbidity is considered a poor prognostic factor among bipolar disorder patients. However, an evidence-based pharmacological treatment for this sub-population is lacking, and only few studies investigated the impact of personality disorder on bipolar disorder-I course. Here, we studied the effect of comorbid personality disorder on the administrated psychopharmacotherapy and rehospitalization risk among manic bipolar disorder-I patients.

Aggressive symptoms in children with tic disorders.

Episodes of explosive anger and aggression are reported in patients with tic disorders and probably contribute to psychosocial stress and low quality of life. The source of these symptoms is controversial. The objective of the study was to study the relationship between tic disorders, their associated comorbidities, and aggressive behavior.

Differences in demographic and clinical characteristics between cannabis users and non-drug users: A retrospective study of patients at first hospitalization due to psychotic symptoms.

This retrospective, chart review, cohort study compared demographic and clinical characteristics of cannabis -users and non-drug users at first admission due to psychotic symptoms at Geha Mental Health Center, Israel, between August 2002 and December 2013. We assessed the role of current cannabis use as a risk for re-hospitalization during this period as well as the stability of psychotic diagnoses at re-hospitalization. A total of 318 patients were included in the study, of which 106 (33.

Adjunctive antidepressants in bipolar depression: A cohort study of six- and twelve-months rehospitalization rates.

Although antidepressants (ADs) are widely used in bipolar depression, there is weak evidence for their effectiveness and safety in this condition. Furthermore, there is a paucity of studies on the risk-benefit ratio of AD maintenance treatment in bipolar disorder (BD). We compared rehospitalization rates of patients with BD-I depressive episode who were discharged with mood stabilizers (MSs) and/or atypical antipsychotics (AAPs) with or without adjunctive AD.

Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

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 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS scores >70 (to ascertain the presence of residual symptoms).

Antipsychotic adjunctive therapy to mood stabilizers and 1-year rehospitalization rates in bipolar disorder: A cohort study.

Objectives: Antipsychotic adjunctive therapy to mood stabilizers (MSs) may improve relapse prevention; however, only a few naturalistic studies, reflecting more generalizable bipolar disorder (BD) samples, support this notion. We compared the 1-year rehospitalization rates of manic patients with bipolar I disorder (BD-I) who were discharged with MS (lithium or valproate) monotherapy or with adjunctive atypical or typical antipsychotic therapy.

Methods: A total of 201 patients with BD-I who were hospitalized with manic episodes between 2005 and 2013 were retrospectively followed for 1-year rehospitalization rates according to treatment at discharge: MS monotherapy, MS with atypical antipsychotics, and MS with typical antipsychotics.

Emotional Reactivity and Regulation Following Citalopram Therapy in Children and Adolescents with Anxiety Disorders.

Objective: Emotional dysregulation is an important element in the pathophysiology of childhood anxiety disorders and can distinguish anxious subjects from controls. Treatment with selective serotonin inhibitors (SSRIs) has been found to lessen anxiety, but its effects on emotional reactivity and regulation are less documented. The aim of the study was to prospectively assess changes in emotional reactivity and regulation in response to citalopram in children and adolescents with anxiety disorders, with special focus on the mechanism of reappraisal.

Seasonal pattern of manic episode admissions among bipolar I disorder patients is associated with male gender and presence of psychotic features.

Background: Bipolar I disorder (BD-I) patients demonstrate disrupted chronobiology expressed as seasonal variation in mood symptoms. The seasonal pattern (SP) specifier of mood disorders was recently extended by the DSM-5, to be applied to manic episodes. However, the significance of seasonality of manic episodes for the course of BD-I is unknown.

Effect of cyclic, low dose pyrimethamine treatment in patients with Late Onset Tay Sachs: an open label, extended pilot study.

Background: Late Onset Tay- Sachs disease (LOTS) is a rare neurodegenerative lysosomal storage disease which results from mutations in the gene encoding the α subunit (HEXA) of β-hexosaminidase enzyme (HexA). At the present time, no effective treatment exists for LOTS and other neurodegenerative diseases involving the central nerve system (CNS). Pyrimethamine (PMT) was previously shown to act as a HexA chaperone in human fibroblasts in vitro carrying some (e.

Association between bipolar episodes and fluid and electrolyte homeostasis: a retrospective longitudinal study.

Objectives: Imbalance of fluid and electrolyte homeostasis has been suggested to be associated with the neuropathological processes underlying bipolar disorder. However, longitudinal data regarding the association of bipolar episodes with fluid balance are still lacking. We hypothesized that mania may be associated with a relative fluid retention and hemodilution, and depression with a relative hemoconcentration.

Neuroimmunological function in parents of children suffering from cancer.

The main aim of this study is to evaluate the relationship between depression and immunological function in parents of children with cancer. Thirty-two parents participated in the study. The parents completed the following assessments: a list of major stressful events in a Hemato-Oncology ward, beck depression inventory II (BDI-II), posttraumatic diagnostic scale (PDS) and quality of life (QOL) questionnaire.

Acute manic episode is associated with an increased risk of lower limb edema.

Objective: Lower limb edema (LLE) was suggested to be associated with the use of psychotropic drugs among patients suffering from severe mental illnesses; however no direct mechanism was found. Therefore, we examined the association between the occurrence of LLE and acute untreated episode leading to hospitalization.

Methods: A retrospective cross-sectional study was conducted using medical charts of 2529 patients admitted to Geha Mental Health Center between 2002 and 2012.

Gender differences in emotional and behavioral disorders and service use among adolescent smokers: a nationwide Israeli study.

Marked gender differences have been identified in cigarette smoking. In this study, we aimed to identify the gender-specific emotional and behavioral disorders among adolescent smokers and their consequent utilization of mental health services. We performed a nationwide survey study of an Israeli representative sample of 906 adolescents and their mothers.

Outcomes of compulsorily admitted schizophrenia patients who agreed or disagreed to prolong their hospitalization.

Background: Compulsory admission is practiced around the world with legislative variations. The legal status during compulsory hospitalization might be changed to consent or the patient might be discharged against medical advice (AMA), if he no longer poses a risk.

Objective: In the present study, we investigated the outcome of compulsory admitted patients who left the hospital after commitment period despite request by the treating psychiatrist to remain in the hospital (AMA) vs those who agreed to prolong their hospitalization.

Antipsychotic monotherapy and adjuvant psychotropic therapies in schizophrenia patients: effect on time to readmission.

This study assessed the relationship between pharmacological regimens at hospital discharge and hospital readmission among schizophrenia patients. The records reviewed were all consecutive admissions (N=720) from a specific catchment area during the period 1991-2005. Two main groups were selected for analysis: the first group (N=537) included patients discharged with first-generation antipsychotics (FGA), and the second group (N=183) included patients with second-generation antipsychotics (SGA).

Predictors of clozapine discontinuation in patients with schizophrenia.

Clozapine has superior efficacy for treating patients with schizophrenia. Its discontinuation could have detrimental consequences. We attempted to identify the clinical parameters that could predict clozapine discontinuation in patients diagnosed as having schizophrenia by conducting a retrospective analysis of all of those who started on clozapine treatment during their hospitalization in our institution between 2002 and 2008 (n=100).

Rate of readmission and mortality risks of schizophrenia patients who were discharged against medical advice.

Purpose: To compare the readmission and the mortality rates of schizophrenia patients who were discharged against medical advice (AMA) and patients who were discharged by physician recommendation.

Methods: The records (1984-2005) of all consecutive admissions (n=12,937) of schizophrenia patients (n=8,052) were reviewed. Out of this group, 673 (8.