A Circuit for Safe Diagnostic Electrical Stimulation of the Human Brain

Abstract

An electronic circuit for controlled electrical stimulation of the human brain has been designed to optimize safety in charge transfer from electrodes to brain and to eliminate the likelihood of unwanted currents from the neurostimulator resulting from component failure. The circuit schematics feature the following designs: (1) a highly accurate and versatile rate generator 0.5 p.p.s. to 99 in increments of 0.5 p.p.s., (2) symmetrically-biphasic lead and lag pulses of 100 μsec duration, (3) photo-isolated driver amplifiers with accurate waveform, reproduction, (4) true biphasic passive-current regulators driven by an isolated battery supply voltage for switch-selectable currents of 0.25 to 5 ma or variable current regulation, (5) accurate current and voltage waveform monitors that isolate the stimulating electrodes from the monitors, and (6) capacity-coupled outputs to guarantee no net D.C. component at the end of each biphasic pulse. Relay-switching circuits are also shown that allow sequential stimulation and recording from one or several electrodes. This neurostimulator has been in use for over two years without evidence of electrolytic damage at identifiable electrode tips. The utility of simultaneous stimulation of several different electrodes at safe charge levels is described.     

Linguistic measures of the referential process in psychodynamic treatment: The English and Italian versions

Abstract

The referential process is defined in the context of Bucci's multiple code theory as the process by which nonverbal experience is connected to language. The English computerized measures of the referential process, which have been applied in psychotherapy research, include the Weighted Referential Activity Dictionary (WRAD), and measures of Reflection, Affect and Disfluency. This paper presents the development of the Italian version of the IWRAD by modeling Italian texts scored by judges, and shows the application of the IWRAD and other Italian measures in three psychodynamic treatments evaluated for personality change using the Shedler-Westen Assessment Procedure (SWAP-200). Clinical predictions based on applications of the English measures were supported.     

Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation

Journal of Autism and Developmental Disorders - Behavioural phenotype and autism-related traits of 38 patients affected by Cornelia de Lange syndrome (CdLS) were assessed using a specific...     

Circulating SIRT1 Increases After Intragastric Balloon Fat Loss in Obese Patients

Background

Sirtuins (SIRTs), ubiquitous deacetylases, are main regulators of energy homeostasis and metabolism. SIRT1 has a positive impact on obesity, diabetes mellitus, liver steatosis, and other metabolic disorders. Lean subjects have higher expression of SIRT1 in the adipose tissue compared to obese. However, it is not known whether weight loss associates with changes in blood SIRT1. We evaluated the effect of weight loss on circulating SIRT1, metabolic parameters, and body composition.

Methods

Thirty-two obese subjects were studied before and 6 months after BioEnterics® Intragastric Balloon (BIB®) [22 patients, BMI 41.82?±?6.28 kg/m²] or hypocaloric diet [10 patients, BMI 38.95?±?6.90 kg/m²]. Plasma SIRT1, body composition, measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL cholesterol, triglycerides), and inflammation markers (ESR, CRP, fibrinogen) were recorded.

Results

SIRT1 levels showed a significant increase, together with a significant reduction of BMI, excess body weight, and total fat mass either after BIB or diet intervention. The percent excess body weight loss was 33.73?±?19.06 and 22.08?±?11.62 % after BIB and diet, respectively, a trend toward a metabolic and inflammatory amelioration was observed with both treatments. Negative correlation between SIRT1 and % fat mass (BIB, ρ?=??0.537, p?=?0.017; diet, ρ?=??0.638, p?=?0.047) was also seen.

Conclusions

The reduction of fat mass associates with increased plasma SIRT1 indicating that, besides tissue levels, circulating SIRT1 is stimulated by a negative caloric balance. The rise of plasma SIRT1 may represent a parameter associating with fat loss rather than weight lowering regardless of the weight reduction system method used.

     

Expanding the clinical spectrum of the ‘HDAC8‐phenotype’ – implications for molecular diagnostics,counseling and risk prediction

Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin‐related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS‐overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X‐inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction.     

Lymphocyte subset patterns and cytokine production in Alzheimer's disease patients

To investigate the signs of inflammatory processes in Alzheimer's disease (AD), we examined peripheral blood mononuclear cells (PBMC) from 51 AD patients (29 with mild and 22 with moderately severe dementia) and 51 age-matched healthy controls (HC), using flow cytometry to analyse the absolute number and the percentage of T, B and NK cells. We also studied the surface expression of CD25, CD28, CD57, CD71, CD45RA and CD45RO markers on cells CD4+ and CD8+. In 30 AD patients and 20 HC the production of IL-2, IFN-gamma, IL-10 and TNF-alpha by PBMC after stimulation with [25-35], [1-40] and [1-16] beta-amyloid (betaA) fragments was also evaluated. A significant decrease in circulating B and CD8+CD28- cells, as well as an increase in CD8+ cells expressing CD71+ and CD28+, was observed in AD patients. A significant decrease in IL-10 production was also found after stimulation of PMBC with betaA [1-40]. The decreased IL-10 production was not related to disease severity. The observed imbalance of immune peripheral cell subpopulations and decreased IL-10 production point to a reduction of suppressor cell function in AD patients.     

Cell loss in the inferior olive of the staggerer mutant mouse is an indirect effect of the gene

Staggerer (sg) is an autosomal recessive mutation in mouse that causes severe cerebellar atrophy. In this mutant, the Purkinje cell (PC) number is reduced by about 75% and the remaining Purkinje cells have a reduced dendritic arbor and an ectopic location. Previous analysis of staggerer chimeras has demonstrated that the Purkinje cell phenotypes are all direct consequences of the cell-autonomous action of the staggerer gene. The two major afferents to the Purkinje cell are also affected. Virtually all of the granule cells die by the end of the first postnatal month. This death, however has been shown to be an indirect consequence of mutant gene action. The second major afferent system is from the cells of the inferior olive that projects to the main trunks of the Purkinje cell dendrite via the climbing fiber system. Quantitative studies of cell number in the inferior olive have shown that the number of cells is reduced by about 62% in adult sg/sg mutants. We report here the results of our quantitative analysis of three staggerer chimeras. beta-glucuronidase activity was used as an independent cell marker. Our findings demonstrate that inferior olive cell death in staggerer mutant mice is an indirect effect of staggerer gene action. Thus as for the granule cells, the loss of olivary neurons most likely results from a target related cell death.