The Effectiveness of Neurofeedback and Stimulant Drugs in Treating AD/HD: Part I. Review of Methodological Issues

The paper examines major criticisms of AD/HD (Attention Deficit/Hyperactivity Disorder) neurofeedback research using T. R. Rossiter and T. J. La Vaque (1995) as an exemplar and discusses relevant aspects of research methodology. J. Lohr, S. Meunier, L. Parker, and J. P. Kline (2001), D. A. Waschbusch and G. P. Hill (2001), and J. P. Kline, C. N. Brann, and B. R. Loney (2002) criticized Rossiter and La Vaque for (1) using an active treatment control; (2) nonrandom assignment of patients; (3) provision of collateral treatments; (4) using nonstandardized and invalid assessment instruments; (5) providing artifact contaminated EEG feedback; and (6) conducting multiple non-alpha protected t tests. The criticisms, except those related to statistical analysis, are invalid or are not supported as presented by the authors. They are based on the critics' unsubstantiated opinions; require redefining Rossiter and La Vaque as an efficacy rather than an effectiveness study; or reflect a lack of familiarity with the research literature. However, there are broader issues to be considered. Specifically, what research methodology is appropriate for studies evaluating the effectiveness of neurofeedback and who should make that determination? The uncritical acceptance and implementation of models developed for psychotherapy, pharmacology, or medical research is premature and ill-advised. Neurofeedback researchers should develop models that are appropriate to the technology, treatment paradigms, and goals of neurofeedback outcome studies. They need to explain the rationale for their research methodology and defend their choices.     

营养性缺铁性贫血与注意缺陷多动障碍的临床关系研究——258例病例分析

目的:通过对营养性缺铁性贫血与注意缺陷多动障碍的病例研究,探讨两者之间的关系。方法:对258例NIDA的病因、临床表现和治疗进行临床分析,包括其中的31例中重度ADHD。结果:本组NIDA患儿病因主要为未及时添加富铁辅食、饮食结构不合理、消化道疾病、鼻衄等,临床主要表现为头晕、乏力、注意力不集中、记忆力减退等,对患者进行病因治疗以及服用生血宁片;ADHD的病因不明,临床表现为注意力不集中、活动过度、行为冲动等,通过综合治疗可以改善症状。NIDA的患儿ADHD的发病率较正常儿童为高。结论:NIDA与ADHD的关系密切。     

Functional Magnetic Resonance Imaging Investigation of the Effects of Neurofeedback Training on the Neural Bases of Selective Attention and Response Inhibition in Children with Attention-Deficit/Hyperactivity Disorder

Two functional magnetic resonance imaging (fMRI) experiments were undertaken to measure the effect of neurofeedback training (NFT), in AD/HD children, on the neural substrates of selective attention and response inhibition. Twenty unmedicated AD/HD children participated to these experiments. Fifteen children were randomly assigned to the Experimental (EXP) group whereas the other five children were randomly assigned to the Control (CON) group. Only subjects in the EXP group underwent NFT. EXP subjects were trained to enhance the amplitude of the SMR (12–15 Hz) and beta 1 activity (15–18 Hz), and decrease the amplitude of theta activity (4–7 Hz). Subjects from both groups were scanned one week before the beginning of NFT (Time 1) and 1 week after the end of NFT (Time 2), while they performed a “Counting Stroop” task (Experiment 1) and a Go/No-Go task (Experiment 2). At Time 1, in both groups, the Counting Stroop task was associated with significant activation in the left superior parietal lobule. For the Go/No-Go task, no significant activity was detected in the EXP and CON groups. At Time 2, in both groups, the Counting Stroop task was associated with significant activation of the left superior parietal lobule. This time, however, there were significant loci of activation, in the EXP group, in the right ACC, left caudate nucleus, and left substantia nigra. No such activation loci were seen in CON subjects. For the Go/No-Go task, significant loci of activation were noted, in the EXP group, in the right ventrolateral prefrontal cortex, right ACcd, left thalamus, left caudate nucleus, and left substantia nigra. No significant activation of these brain regions was measured in CON subjects. These results suggest that NFT has the capacity to functionally normalize the brain systems mediating selective attention and response inhibition in AD/HD children.     

The Ethical Use of Placebo Controls in Clinical Research: The Declaration of Helsinki

Medical ethicists have questioned the use of no-treatment (placebo and sham procedure) controlled studies of new therapies when safe and effective standard therapies are available for use as an active or equivalence control. Current ethical principles of conduct for biomedical research specifically prohibit designs that withhold or deny the best proven diagnostic and therapeutic treatment to any participant in a clinical study, including those individuals who consent to randomization into a control group. Studies of psychophysiological therapies are often criticized on the grounds they lack a placebo or sham treatment control group. This paper briefly reviews the history of the problem and discusses the ethical standards that govern human research as derived from the Nuremberg Code and the Declaration of Helsinki. An examination of the problem with regard to research involving EEG biofeedback therapy for Attention-Deficit/Hyperactivity Disorder, Traumatic Brain Injury, and depression serves to highlight the issues. It is concluded that the active treatment control (treatment equivalence) design is most appropriate for those clinical studies examining disorders for which there is a known, effective treatment. Sham- or placebo-controlled studies are ethically acceptable for those disorders for which no effective treatment is available.     

Integrating music in breathing training and relaxation: II. Applications

Psychophysiological observations, especially PETCO2 and EEG, during relaxation training with deep-diaphragmatic breathing and mental imagery, suggest that the addition of certain types of music deepens breathing and quickens relaxation: PETCO2 normalizes with decreased respiration rate, and EEG shows decreased average theta and increased alpha. The combined psychophysiological indices suggest that music potentiates the hypometabolic counterarousal state. And clients unanimously report that they enjoy it.     

The Reaction of Pt-Antitumor Drugs with Selected Nucleophiles.: II. Preparation and Characterization of Coordination Compounds of Pt(II) andl-Histidine

Various His-Pt(II) coordination compounds were prepared by reaction of K₂PtCl₄ or cis-[Pt(NH₃)₂Cl₂](cis-DDP) with His and analyzed by ¹H and ¹³C NMR spectroscopy, electrophoresis, and ion-exchange chromatography. His may be coordinated to Pt by the imidazol iminogroup and/or the α-aminogroup; the carboxy group remains always free. Both bidentate as well as monodentate ligands were identified. Cis-DDP reacts with His to give a mixture of compounds where all these possibilities are present: cis-diamine-(histidine-N,N-)Pt(II) and three different types of cis-diammine-bis(histidine). HCl trans cleavage of compounds with bidentate His ligands leads to a mixture of two compounds having His ligated to Pt by an amino or imin group. The methods applied are suitable for analyzing reactions of His with cis-DDP under model conditions similar to physiological conditions.     

The influence of electrostatic interactions on partition in aqueous polyethylene glycol/dextran biphasic systems: Part II

In aqueous polyethylene glycol/dextran two-phase systems, the hydrophobicity, free volume, surface tension, and interfacial tension of the phases in equilibrium were measured as a function of pH and ionic strength. These parameters were found to change with pH, but the pattern and magnitude cannot explain the unusual partition of charged macromolecules, observed previously. The electrostatic potential difference was determined by a new experimental approach based on the measurement of the pH difference between the phases at equilibrium. In polyethylene glycol/dextran systems containing sodium chloride as ionized species, the electrostatic potential is not constant in the pH range 2 to 11. The partition behavior of charged macromolecules and its dependence on pH can be explained by the combined action of charge and phase potential. This conclusion was tested with poly-L-glutamate, which partitioned as predicted and in a pattern opposite to positively charged macro- molecules. (c) 1995 John Wiley & Sons, Inc.     

Alkali modification of carrageenans. Part V. The iota–nu hybrid carrageenan from Eucheuma denticulatum and its cyclization to iota-carrageenan

A homogeneous iota/nu-hybrid carrageenan (71% iota- and 21% nu-) isolated from Eucheuma denticulatum was used as a model compound to study the cyclization reaction of -D-galactose 2,6-disulfate units to 3,6-anhydro--D-galactose 2-sulfate. The rate of cyclization, at 70 °C, of this carrageenan is about 50 times faster than that of a porphyran (non-sulfated β-D-galactose linked to -L-galactose 6-sulfate) and 210 times faster when compared with a lambda-carrageenan (2-sulfated β-D-units linked to -D-galactose 2,6-disulfate). The use of this model compound confirms the previous hypothesis of the accelerating effect of the β-D-4-sulfate group as well as suggests the influence of the 2-sulfate of the -D-galactose units on the ⁴C₁→¹C₄ chair forms interchange. The easy of cyclization indicates that to produce commercial iota-carrageenans milder alkaline treatments could be used, avoiding degradation and increasing the gel strength.     

Assessment of the biocontrol potential of a Trichoderma viride isolate: Part II: Protection against soft rot and basidiomycete decay

A previous paper reported on the establishment of a field and fungal cellar trial set up to determine the biocontrol potential of a specific Trichoderma isolate against wood decay fungi. This paper reports on the analyses used to examine the protective effect of the selected isolate, and presents results indicating an initial protective effect against both basidiomycetes and soft rot fungi. The parameters assessed in the field and fungal cellar trials were soft rot decay, basidiomycete decay, Trichoderma colonisation, moisture content and nitrogen content. The results of these analyses show that the introduction of a biological control agent has had a significant effect on moisture content, decay and nitrogen content. A protective effect has been observed against soft rot and basidiomycete decay fungi in field samples.     

Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H1 antagonists. Part II: Optimising in vivo clearance

The second part of this communication focuses on the resolution of issues surrounding the series of hydroxyamide phenoxypiperidine CCR3/H₁ dual antagonists described in Part I. This involved further structural exploration directed at reducing metabolism and leading to the identification of compound 60 with a greatly improved in vivo pharmacokinetic profile.     

'Steady/equilibrium approximation' in relaxation and fluctuation. II. Mathematical theory of approximations in first-order reaction

A mathematical theory of the steady/equilibrium approximation for first-order reactions is presented. This gives the theoretical basis for the methods of simplifying the complex first-order reactions described in the preceding work The steady/equilibrium relation holds on every fast component after a proper inducation period T degrees T degrees is either of O(1) or less, or nearly of O(1/epsilon) depending on the reaction scheme and on the initial condition but is always less than O(1/epsilon) (as in the preceding paper [1], we use the symbol O(1) to denote a positive number of the order of unity). In the open group, the determinant of the submatrix M(p), representing the interconversion between the fast components in the group and their dissipation, is of O(1). The concentration of the fast components in the open group can thus be expressed as a linear combination of those components neighboring the group after the establishment of a steady/equilibrium relation, and can be eliminated from the reaction scheme leaving the pathway through them. On the other hand, in the closed group the determinant of Mp is of O(epsilon) or less and the components in the group are in quasi equilibrium with each other after T degrees . They are eliminated from the reaction scheme leaving the sum of the components in the closed group as a slow component.     

Enantio- and regioselectivity in the epoxide-hydrolase-catalyzed ring opening of aliphatic oxiranes: Part II: Dialkyl- and trialkylsubstituted oxiranes.

The extent of substrate enantioselectivity and regioselectivity of a series of aliphatic 2,3-dialkyl- and trialkylsubstituted oxiranes in their in vitro epoxide-hydrolase-catalyzed hydrolysis depends on the size of the alkyl residues and on the substitution pattern of the oxirane ring. The enzyme-catalyzed hydrolysis of cis-oxiranes, containing at least one methyl substituent, shows complete or nearly complete substrate enantioselectivity and regioselectivity with nucleophilic attack by water occurring with inversion of configuration at the methylsubstituted ring carbon atom of (S)-configuration. In the hydrolysis of the isomeric trans-oxiranes, both enantiomers are metabolized with a higher rate for the (2S;3S)-enantiomer. The conversion of trimethyloxirane occurs with high substrate enantioselectivity in favor of the (S)-enantiomer and with complete regioselectivity at the monomethylsubstituted ring carbon atom. The differentiation of the enantiotopic ring carbon atoms (product enantioselectivity) in the smallest aliphatic meso-oxirane, cis-2,3-dimethyloxirane, leads to (2R;3R)-butane-2,3-diol with ee = 86%. cis-2-Ethyl-3-propyloxirane, possessing alkyl residues larger than methyl, represents an extremely poor substrate in the epoxide-hydrolase-catalyzed hydrolysis process.     

Effect of viscoelastic relaxation on moisture transport in foods. Part II: Sorption and drying of soybeans

The general fluid transport equation presented in Part-I of this paper is used for predicting moisture transport and viscoelastic stresses during sorption and drying of soybeans. Predicted drying curves were validated using experimental data obtained from literature (average absolute difference 6-13%). For drying temperatures used in the soybean processing industry (70–93 °C), smooth moisture profiles were obtained, which indicated Fickian (Darcian) transport. As the drying temperature approached the glass transition temperature (25 °C at 10% moisture content), the moisture profiles became sharper, which indicated non-Fickian (non-Darcian) transport. The viscoelastic stress profiles clearly exhibited the role of the force terms during imbibition and drying. Increase in drying temperature tends to decrease the stress relaxation function but reduction in moisture content during drying tends to increase it. The increase in stress due to the reduction in moisture content below 10% was not compensated by an increase in drying temperature. Drying of soybeans below 10% moisture content should be avoided in the industry because this will lead to thicker flakes that reduce the amount of oil recovery. During imbibition of soybeans, a high magnitude of stresses was obtained in the rubbery regions, which may cause critical regions prone to fissuring. The role of glass transition on stress development and critical region development was clearly observed during drying and imbibition of soybeans.Revised version: 5 October 2003     

Determination of sensory bristles and pattern formation in Drosophila: II. The achaete-scute locus

In the first paper of this series, we developed a model of bristle determination in which a key role is played by a freely diffusible inducer, the chaetogen. In this paper we show that the complex properties of the achaete-scute locus of Drosophila, including the generalized effect of deficiencies, the peculiar phenotypes of some alleles, the existence of bristle-overproducing variants, and the local nonautonomy, correspond exactly to the properties expected for the locus that controls the synthesis of chaetogen. The correspondence between expectations derived from the model and observations made on a genetic locus of the fly is taken as experimental support for the model.     

The oxidation of D-glucose and D-fructose with oxygen in aqueous,alkaline solutions : Part II. The overall kinetics

Based on a previously reported, integral reaction-scheme, a very simple, kinetic model for the homogeneous oxidation of D-glucose and D-fructose in aqueous, alkaline solutions has been developed. It involves the influence of the type and concentration of the hexose, the hydroxyl-ion concentration, the oxygen concentration in the liquid phase, and the temperature on the rate of formation of the acidic reaction products. No attention is paid to the product distribution.     

Physiology of Geobacter metallireducens under excess and limitation of electron donors. Part II. Mimicking environmental conditions during cultivation in retentostats

The strict anaerobe Geobacter metallireducens was cultivated in retentostats under acetate and acetate plus benzoate limitation in the presence of Fe(III) citrate in order to investigate its physiology under close to natural conditions. Growth rates below 0.003 h⁻¹ were achieved in the course of cultivation. A nano-liquid chromatography–tandem mass spectrometry-based proteomic approach (nano-LC–MS/MS) with subsequent label-free quantification was performed on proteins extracted from cells sampled at different time points during retentostat cultivation. Proteins detected at low (0.002 h⁻¹) and high (0.06 h⁻¹) growth rates were compared between corresponding growth conditions (acetate or acetate plus benzoate). Carbon limitation significantly increased the abundances of several catabolic proteins involved in the degradation of substrates not present in the medium (ethanol, butyrate, fatty acids, and aromatic compounds). Growth rate-specific physiology was reflected in the changed abundances of energy-, chemotaxis-, oxidative stress-, and transport-related proteins. Mimicking natural conditions by extremely slow bacterial growth allowed to show how G. metallireducens optimized its physiology in order to survive in its natural habitats, since it was prepared to consume several carbon sources simultaneously and to withstand various environmental stresses.     

The action of lipase on chloroplast membranes: II. Polypeptide patterns of bean galactolipase- and phospholipase A2-treated thylakoid membranes

Thylakoid membranes obtained from bean chloroplasts treated with bean galactolipase or phospholipase A₂ (from Crotalus terr. terr.) showed marked changes in their polypeptide patterns when separated on SDS-PAGE. The obtained results have been discussed with regard to the relationship between chloroplast lipids and polypeptides originating from chlorophyll-protein complexes of bean thylakoids. A coexistence between galactolipids and the peripheral antennae in PS I complex and LHCP³ as well as a conspicuous role of phospholipids in PSI and PSII centre chlorophyll-protein complexes has to be underlined.Abbreviations CP1 chlorophyll a-protein complex of PSI - CPa chlorophyll a-protein complex of PSII - D₁₀ digitonin subchloroplast particles enriched in PSII - D₁₄₄ digitonin subchloroplast particles enriched in PSI - DCMU 3-(3,4-dichlorophenyl)-1,1-dimethylurea - LHCP^1–3 light harvesting chlorophyll a/b protein complexes - PAGE polyacrylamide gel electrophoresis - PSI photosystem I - PSII photosystem II - SDS sodium dodecyl sulphate - TCA trichloroacetic acid - Tricine N-Tris-(hydroxymethyl)-methylglycine - Tris Tris-(hydroxymethyl)-aminomethan     

The ability of mineral dusts and fibres to initiate lipid peroxidation. Part II: relationship to different particle-induced pathological effects

Abstract

Exposure to pathogenic mineral dusts and fibres is associated with pulmonary changes including fibrosis and cancer. Investigations into aetiological mechanisms of these diseases have identified modifications in specific macromolecules as well as changes in certain early processes, which have preceded fibrosis and cancer. Peroxidation of lipids is one such modification, which is observed following exposure to mineral dusts and fibres. Their ability to initiate lipid peroxidation and the parameters that determine this ability have recently been reviewed.¹ Part II of this review examines the relationship between the capacity of mineral dusts and fibres to initiate lipid peroxidation and a number of pathological changes they produce.

The oxidative modification of polyunsaturated fatty acids is a major contributor to membrane damage in cells and has been implicated in a great variety of pathological processes. In most pathological conditions where an induction of lipid peroxidation is observed it is assumed to be the consequence of disease, without further establishing if the induction of lipid peroxidation may have preceded or accompanied the disease. In the great majority of instances, however, despite the difficulty in proving this association, a causal relationship between lipid peroxidation and disease cannot be ruled out.