Functional brain connectomes reflect acute and chronic cannabis use.

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.

Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington's disease.

Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.

An independent SSVEP-based brain-computer interface in locked-in syndrome.

OBJECTIVE: Steady-state visually evoked potential (SSVEP)-based brain-computer interfaces (BCIs) allow healthy subjects to communicate. However, their dependence on gaze control prevents their use with severely disabled patients. Gaze-independent SSVEP-BCIs have been designed but have shown a drop in accuracy and have not been tested in brain-injured patients. In the present paper, we propose a novel independent SSVEP-BCI based on covert attention with an improved classification rate. We study the influence of feature extraction algorithms and the number of harmonics. Finally, we test online communication on healthy volunteers and patients with locked-in syndrome (LIS). APPROACH: Twenty-four healthy subjects and six LIS patients participated in this study. An independent covert two-class SSVEP paradigm was used with a newly developed portable light emitting diode-based 'interlaced squares' stimulation pattern. MAIN RESULTS: Mean offline and online accuracies on healthy subjects were respectively 85 ± 2% and 74 ± 13%, with eight out of twelve subjects succeeding to communicate efficiently with 80 ± 9% accuracy. Two out of six LIS patients reached an offline accuracy above the chance level, illustrating a response to a command. One out of four LIS patients could communicate online. SIGNIFICANCE: We have demonstrated the feasibility of online communication with a covert SSVEP paradigm that is truly independent of all neuromuscular functions. The potential clinical use of the presented BCI system as a diagnostic (i.e., detecting command-following) and communication tool for severely brain-injured patients will need to be further explored.

New insights into the biodegradation of thiodiglycol, the hydrolysis product of Yperite (sulfur mustard gas).

AIMS: To isolate thiodiglycol (TDG)-degrading bacteria, the mustard gas hydrolysis product, and to characterize the metabolites formed and the enzymes involved in the degradation. METHODS AND RESULTS: Two strains, identified as Achromobacter xylosoxydans G5 and Paracoccus denitrificans E4, isolated from a petroleum-contaminated soil, utilized TDG as sole carbon and sulfur source. During the degradation of TDG by strain E4 [(2-hydroxyethyl)thio] acetic acid (HETA), thiodiglycolic acid (TDGA) and bis-(2-hydroxyethyl)disulfide (BHEDS) were identified by gas chromatography-mass spectrometry analysis, while HETA and TDGA were identified for strain G5. Two-dimensional isoelectric focussing-gel electrophoresis (2-D IEF/SDS-PAGE) maps of protein extracts of P. denitrificans E4 grown on TDG showed a spot identified as a methanol dehydrogenase. Increased expression of a putative iscS gene, involved in sulfur assimilation, was observed in TDG-grown cells of A. xylosoxydans G5. CONCLUSIONS: TDG degradation by P. denitrificans E4 occurred through two pathways: one involved cleavage of the C-S bond of HETA, yielding BHEDS and the other, oxidation of the alcoholic groups of TDG, yielding TDGA. The cleavage of the C-S bond of TDGA gave mercaptoacetic acid, further oxidized to acetate and sulfate. SIGNIFICANCE AND IMPACT OF THE STUDY: Increased knowledge of TDG-degrading bacteria and the possibility of using them in a tailored-two-stage mustard gas destruction process.

Avaliação do alinhamento postural e do desempenho em atividades funcionais de crianças hemofílicas em idade inferior a sete anos, com e sem sinovite crônica: correlação com a incidência de hemartroses / Evaluation of postural alignment and performance in functional activities among hemophilic children under 7 years old with and without chronic synovitis: correlation with hemarthrosis incidence

INTRODUÇÃO: A sinovite na hemofilia pode induzir às alterações nos receptores sensitivos e proprioceptivos articulares. Tal efeito favorece a redução de estabilidade e um desalinhamento corporal, podendo comprometer a funcionalidade das crianças acometidas. OBJETIVO: Avaliar o alinhamento postural dos membros inferiores e o desempenho funcional de crianças hemofílicas, relacionando-os com a incidência de hemartroses. MÉTODO: Foi avaliado um grupo experimental (GE) de 28 crianças hemofílicas e um grupo controle (GC) de 20 crianças sem hemofilia. O GE foi dividido de acordo com o grau de comprometimento articular: 16 crianças no grupo sem sinovite crônica (GSS) e 12 no grupo com sinovite crônica (GCS). Cada grupo foi subdividido por faixa etária: 3-4 anos, 5-6 anos, 7 anos. A avaliação consistiu da análise do alinhamento dos ângulos do joelho e do tornozelo através do programa Geometer Sketchpad. O desempenho das atividades funcionais foi avaliado através de testes modificados a partir do Exame Neurológico Evolutivo de Lefévre. RESULTADOS: Foi constatado que a média dos sangramentos dos hemofílicos aumenta com a idade (p< 0,001) e parece ser relacionada com o grau de comprometimento articular (GCS>GSS), (p< 0,059); o ângulo do joelho do GCS tende a um menor valor (semiflexão) quando comparado aos outros grupos; e há diferença significativa no percentual de desempenho nos testes entre grupos na faixa etária de 7 anos (GSS>GC e GSS>GCS), (p< 0,087). DISCUSSÃO E CONCLUSÃO: Crianças hemofílicas de 7 anos apresentaram menor desempenho funcional quando comparadas aos outros grupos. Este resultado ressalta a importância da fisioterapia precoce associada à terapêutica médica para evitar comprometimentos articulares severos.

Four-year outcomes from adolescent alcohol and drug treatment.

OBJECTIVE: Knowledge of treatment response for alcohol and drug problems among adults is mounting; less is known about long-term outcome for adolescents who receive treatment for alcohol and drug problems. The current study examined youth substance involvement over 4 years (using five waves of data collection) following treatment for alcohol and drug abuse. METHOD: A cohort of youth (N = 162, 60% male) treated during adolescence (mean age = 16 years) was followed into young adulthood, a period associated with stabilization of alcohol use patterns and elevated risk for life problems secondary to both alcohol and drug use. Participants (14-18 years old) were consecutive admissions to inpatient adolescent alcohol and drug treatment centers in San Diego that were abstinence focused and based on the 12-step approach. RESULTS: Alcohol and other drug use were reduced during the 4 years posttreatment, with the exception of nicotine. The greatest prevalence reduction occurred for stimulants; modest changes were evident in alcohol and marijuana use. Nicotine was the most commonly used substance throughout the 4 years after treatment. Several distinct substance involvement trajectories were evident during the 4 years following treatment. CONCLUSIONS: Alcohol and drug use patterns during the 4 years following treatment highlight both changes and diversity in substance involvement as youth make the transitions from middle to late adolescence and into young adulthood. Findings demonstrate the importance of identifying transitional periods and the need for alternative intervention strategies that may help the progression of this population into young adulthood.

Effects of catechins on human blood platelet aggregation and lipid peroxidation.

The activity of catechins was studied for inhibitory activity in human blood platelets. Platelet aggregation and peroxidation were evaluated in platelet rich plasma (PRP) obtained from samples of healthy volunteers. Human blood platelets were submitted to stimulation with 300 microM arachidonic acid, 3 microM adenosine diphospate (ADP) and 6 microM epinephrine. Treatment with (200 microg/mL) catechin or epicatechin was sufficient to exhibit a potent inhibitory effect of the three agents. The inhibitory effect was dose dependent at concentrations of 20-200 microg/mL. Using malondialdehyde (MDA) as an index of total lipid peroxidation capacity, decreased production of MDA of the platelets treated with catechin or epicatechin after stimulation by arachidonic acid was observed. These findings suggest that catechins protect platelets from peroxidative stress and their aggregation.

Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects.

OBJECTIVE: The authors' goal was to study the relationship between smoking status and clinical characteristics in schizophrenic patients. METHOD: Seventy-eight schizophrenic outpatients were assessed by a single rater using the Brief Psychiatric Rating Scale (BPRS), the Abnormal Involuntary Movement Scale, and the Simpson-Angus Scale for extrapyramidal symptoms. Current smokers (N = 58) were compared with nonsmokers (N = 20) on clinical variables by independent t tests and chi-square tests. Differences in outcome variables were tested by multiple analysis of covariance (ANCOVA) with smoking status and gender as factors and age, neuroleptic dose, and caffeine consumption as covariates. RESULTS: Seventy-four percent of patients were current smokers and reported a mean of 19 cigarettes smoked per day. Compared to nonsmokers, current smokers were significantly more likely to be men, to be younger, and to have had an earlier age at onset and a greater number of previous hospitalizations. Current smokers and nonsmokers received mean neuroleptic doses of 1160 and 542 mg/day (chlorpromazine equivalents); the difference was significant. Current smokers also displayed significantly less parkinsonism and more akathisia and had higher total scores on the BPRS. Overall multiple ANCOVA demonstrated a significant main effect for smoking status but not gender or the interaction between gender and smoking status. Univariate ANCOVAs demonstrated a significant main effect of smoking status only for the Simpson-Angus Scale score. CONCLUSIONS: Cigarette smokers receive significantly higher neuroleptic doses, in part because of a smoking-induced increase in neuroleptic metabolism. Smoking is also associated with significant reduction in levels of parkinsonism. Smoking status is a significant factor that should be considered in assessment of neuroleptic dose requirements and neuroleptic side effects.

The delusion of possession in chronically psychotic patients.

Sixty-one chronically psychotic outpatients were grouped according to the presence or absence of a history of delusional possession. Compared with patients without a history of delusional possession (N = 36), possessed patients (N = 25) had significantly more self-reported childhood sexual abuse, higher dissociation scores, more cannabis abuse, more experiences of thought control, and more voices heard inside their heads. These findings support the hypothesis that in some psychotic patients, possession beliefs may reflect childhood trauma and dissociation.

An aqueous extract of guaraná (Paullinia cupana) decreases platelet thromboxane synthesis.

The effects of an aqueous extract of guaraná (Paullinia cupana) on rabbit platelet aggregation and thromboxane synthesis were examined. The guaraná extract (100 mg/ml) and fractions separated by TLC (origin and xanthines) decreased platelet aggregation (37, 27 and 31% of control values, respectively) and platelet thromboxane formation from [14C]-arachidonic acid (78, 70 and 50% of control values, respectively). The decreased thromboxane synthesis could be responsible, at least in part, for the antiaggregatory action of guaraná.

An aqueous extract of guaraná (Paullinia cupana) decreases platelet thromboxane synthesis

The effects of an aqueous extract of guaraná (Paullinia cupana) on rabbit platelet aggregation and thromboxane synthesis were examined. The guaraná extract (100 mg/ml) and fractions separated by TLC (origin and xanthines) decreased platelet aggregation (37.27 and 31% of control values, respectively) and platelet thromboxane formation from [14C]-arachidonic acid (78, 70 and 50% of control values respectively). The decreased thromboxane synthesis could be responsible, at least in part, for the antiaggregatory action of guaraná

Epidural spinal cord stimulation for the treatment of neurogenic bladder.

The effect of percutaneous epidural spinal cord stimulation on neurogenic bladder has been evaluated on the basis of objective clinical and urodynamic criteria. Seven patients suffering from stable bladder and sphincter dysfunction due to spinal cord diseases of different causes of non-evolutive nature were examined. In some of them chronic pain or substantially improved micturition in six of our seven patients. Complete or almost complete relief of bladder spasticity, marked increase of bladder capacity, and reduction or abolition of residual urine were recorded. The beneficial effect on bladder and sphincter function is strictly dependent on the stimulation, though it can outlast it. It requires some weeks to reach its maximum. It is still obtained after 22 months of treatment (longest present follow-up). No changes of straital activity and detrusor reflex were produced by spinal cord stimulation in two additional patients, treated for chronic pain but having intact bladder function.