Ten-year stability of EEG biofeedback results for a hyperactive boy who failed fourth grade perceptually impaired class

Ten years ago, the first successful application of a clinical,private-practice based, EEG 14-Hz biofeedback training regimen for the treatment of learning disorders was performed by the author. After the 10-year-old boy, with presenting symptomology including a developmental reading disorder, hyperactivity, and an educational classification of perceptually impaired, continued symptom free for a period oftwo years, his case was submitted for publication. Ten years after his termination from successful treatment, his ongoingly normal social and academic functioning is noted and his EEG brainwave signature examined and compared with a population of 24 used-to-be learning disabled, one-half of which had a pretreatment state including the educational classification of perceptually impaired. This 10-year follow-up confirms the long-term stability of the results of this EEG 14-Hz biofeedback regimen. Current findings on recent medical research identifying a major cerebral locus of dysfunction for hyperkinesis and how it supports the electrode placements of this clinical office setting regimen is also discussed.     

Biofeedback treatments of generalized anxiety disorder: Preliminary results

Forty-five individuals with generalized anxiety (38 with GAD as defined by DSM-III) were randomized to 4 treatment conditions or a waiting list control. Patients received 8 sessions of either frontal EMG biofeedback, biofeedback to increase EEG alpha, biofeedback to decrease EEG alpha, or a pseudomeditation control condition. All treated subjects showed significant reductions in STAI-Trait Anxiety and psychophysiologic symptoms on the Psychosomatic Symptom Checklist. Only alpha-increase biofeedback subjects showed significant reductions in heart rate reactivity to stressors at a separate psychophysiological testing session. Decreased self-report of anxiety was maintained at 6 weeks posttreatment.     

Framework for validation and implementation of in vitro toxicity tests

Summary The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technologic developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial, and regulatory communities, is recommended. Test validation acceptance is contingent on broad buy-in by disparate groups in the scientific community—academics, industry, and government. This is best achieved by early and frequent communication among parties and agreement on common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction, and refinement alternatives in toxicity testing.     

Monitoring growth and acetic acid secretion by a thermotolerantBacillus using conduction microcalorimetry

Summary A method is described to determine power of heat-time curves by conduction microcalorimetry in order to monitor the viability and ability of a thermotolerantBacillus strain to secrete acetic acid both during exponential growth and during stationary-phase. In this system secreted acetic acid is neutralized by an insoluble source of lime (dolime) which results in a poor correlation between optical density and culture dry weight. As an alternative, cells and residual dolime were rapidly resuspended in isothermal fresh medium with glucose in a conduction microcalorimeter. Heat evolution was rapid over a period of 200–800 s. Steady state heat evolution rate decreased as a function of culture time and did not correlate with: 1) specific growth rate: 2) viable cell number: 3) glucose consumption rate; or 4) acetic acid secretion rate. Glucose consumption and acetic acid secretion during the stationary growth phase were correlated with specific heat evolution rate. These initial results indicate that this technique may be useful for further development as an on-line flow or stopped-flow method to monitor the physiology of bacilli in response to nutrient depletion or growth inhibition.     

Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin

Declining nicotinamide adenine dinucleotide (NAD⁺) concentration in the brain during aging contributes to metabolic and cellular dysfunction and is implicated in the pathogenesis of aging-associated neurological disorders. Experimental therapies aimed at boosting brain NAD⁺ levels normalize several neurodegenerative phenotypes in animal models, motivating their clinical translation. Dietary intake of NAD⁺ precursors, such as nicotinamide riboside (NR), is a safe and effective avenue for augmenting NAD⁺ levels in peripheral tissues in humans, yet evidence supporting their ability to raise NAD⁺ levels in the brain or engage neurodegenerative disease pathways is lacking. Here, we studied biomarkers in plasma extracellular vesicles enriched for neuronal origin (NEVs) from 22 healthy older adults who participated in a randomized, placebo-controlled crossover trial (NCT02921659) of oral NR supplementation (500 mg, 2x /day, 6 weeks). We demonstrate that oral NR supplementation increases NAD⁺ levels in NEVs and decreases NEV levels of Aβ42, pJNK, and pERK1/2 (kinases involved in insulin resistance and neuroinflammatory pathways). In addition, changes in NAD(H) correlated with changes in canonical insulin–Akt signaling proteins and changes in pERK1/2 and pJNK. These findings support the ability of orally administered NR to augment neuronal NAD⁺ levels and modify biomarkers related to neurodegenerative pathology in humans. Furthermore, NEVs offer a new blood-based window into monitoring the physiologic response of NR in the brain.     

Loss of DNA repair mechanisms in cardiac myocytes induce dilated cardiomyopathy

Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1^−/D mice). Ckmm-Cre^+/−;Ercc1^−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre^+/−;Ercc1^−/fl mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre^+/-;Ercc1^−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre^+/−;Ercc1^−/fl and Ercc1^−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death.     

Expression of A mating type genes of Coprinus cinereus in a heterologous basidiomycete host

The A mating factor of Coprinus cinereus determines compatibility in mating by regulating part of a developmental sequence that leads to dikaryon formation. The A genes that trigger development encode two different classes of homeodomain proteins, and for a successful mating, a protein of one class, HD 1, must interact with a protein of the other class, HD 2. In this report we show that C. cinereus A genes that encode HD 2 proteins, a2-1 and b2-1, can elicit A-regulated development in the heterologous host C. bilanatus. Transformation rates were very low, suggesting that the genes were poorly transcribed. The fact that the HD 2 genes are functionally expressed implies successful heteromultimeric association of putative DNA-binding proteins coded by the two Coprinus species. This interaction was sufficient to satisfy the need for different A factors in the formation of a fertile C. bilanatus dikaryon, but fertile dikaryons were more readily produced in matings with the a2-1 gene transformants. The C. cinereus A genes, b1-1 and d1-1, which encode HD1 proteins, were either not expressed or their proteins were non-functional in C. bilanatus. These experiments raise some interesting questions regarding HD1–HD2 protein interactions.