Biophysical foundations underlying TMS: Setting the stage for an effective use of neurostimulation in the cognitive neurosciences

Transcranial Magnetic Stimulation (TMS) induces electrical currents in the brain to stimulate neural tissue. This article reviews our present understanding of TMS methodology, focusing on its biophysical foundations. We concentrate on how the laws of electromagnetic induction apply to TMS; addressing issues such as the location, area (i.e., focality), depth, and mechanism of TMS. We also present a review of the present limitations and future potential of the technique.     

Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.     

Evaluation of plantar hyperhidrosis in patients undergoing video-assisted thoracoscopic sympathectomy

Background Sympathectomy is the treatment of choice for primary hyperhidrosis. One curious occurrence that is difficult to explain from an anatomophysiological point of view in cases of video-assisted thoracoscopic sympathectomy (VATS) for the treatment of palmar hyperhidrosis (PH) is the observed improvement in plantar hyperhidrosis (PLH). Nevertheless, current reports on VATS rarely describe the effect on PLH or just give superficial data. The aim of this study was to prospectively investigate, how surgery affects PLH in patients with PH and PLH over one-year period. Methods From May 2003 to January 2004, 70 consecutive patients with combined PH and PLH underwent VATS at the T2, T3, or T4 ganglion level (47 women and 23 men, with mean age of 23 years). Results Immediately after the operation, all the patients said they were free from PH episodes, except for two patients (2.8%) who suffered from continued PH. Compensatory hyperhidrosis (CH) of various degrees was observed in 58 (90.6%) patients after one year. Only 13 (20.3%) suffered from severe CH. There was a great initial improvement in PLH in 50% of the cases, followed by progressive regression, such that only 23.4% still presented that improvement after one year. The number of cases without overall improvement increased progressively (from 17.1% to 37.5%) and the numbers with slight improvement remained stable (32.9–39.1%). Of the 24 patients with no improvement after one year, 6 patients graded plantar sweating worse. Conclusion Patients with PH and PLH who undergo VATS to treat their PH present a good initial improvement in PLH that reduces to a lower level of improvement after the one-year period.     

Effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on the dopaminergic and cholinergic receptors as evaluated by positron emission tomography in the Rhesus monkey

Summary The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) on the central cholinergic and dopaminergic systems in the Rhesus monkey brain were investigated by positron emission tomography (PET) with the muscarinic cholinergic receptor ligands (N-[¹¹C]methyl-benztropine) and dopaminergic receptor ligands selective for D₁ D₂, and D₃ subtypes ([¹¹C]SCH23390, N-[¹¹C]methyl-spiperone, and (+)[¹¹C]UH232, respectively). None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP used significantly affected the regional cerebral blood flow (rCBF as determined by Raichle's H₂ ¹⁵O method), and 10 mg/kg of R-THBP had little effect on the regional cerebral metabolic rate of glucose (rCMRglc) in the Rhesus monkey brain, as assessed by the graphical [¹⁸F]fluoro-deoxyglucose method. The effect of R-THBP on the muscarinic cholinergic system was dose dependent; while 3 mg/kg of R-THBP did not significantly alter the uptake ratio of N-[¹¹C]methyl-benztropine in several brain regions to that in the cerebellum, 10 and 30 mg/kg of R-THBP significantly reduced the uptake ratio in the thalamus, as well as in the frontal and temporal cortices. None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP tested affected [¹¹C]SCH23390 (dopamine D₁ receptor) binding. However, the k3 value for N-[¹¹C]methyl-spiperone (dopamine D₂ receptor) binding, which represents the association rate × B_max value, was significantly decreased in the striatum. The uptake ratio of (+)[¹¹C]UH232 (dopamine D₃ receptor) in the striatum to that in the cerebellum was also decreased by administration of R-THBP (3 and 30 mg/kg i.v.). These findings suggest that R-THBP acts on dopamine D₂ and D₃ receptors selectively without markedly affecting dopamine D₁ receptor binding. Furthermore, the changes in cholinergic and dopamine D₂ and D₃ receptors in vivo can not be attributed to a change in rCBF but may depend on the action of R-THBP.Abbreviations R-THBP 6R-L-erythro-5,6,7,8-tetrahydrobiopterin - PET positron emission tomography - rCBF regional cerebral blood flow - rCMRglc regional cerebral metabolic rate of glucose     

Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic efficacy.

The frequency-dependent block of cardiac sodium channels by class 1 antiarrhythmic drugs can be described by a periodical ligand binding process between drug molecules and channel binding sites. This predicts a linear relation between onset-rate constant of frequency-dependent block and diastolic interval as well as saturation of block with high stimulation rates. From both relationships, the binding kinetics (time constant, tau on) and saturation level of block (bdinf) can be estimated. This is exemplified for the frequency-dependent block (reduction of the maximal upstroke velocity of action potentials) induced by prajmaline (10(-6) M). In the same way, the frequency-dependent effects of 11 other class 1 drugs reported in the literature were analyzed and compared with each other. When the drugs are ranked with respect to their binding kinetics (tau on), there is a close relationship to the subclasses (1a, 1b, 1c), with 1b drugs exhibiting the fastest and 1c drugs the slowest kinetics. However, differences also exist in the saturation behavior of frequency-dependent block even within the same subclasses (1a and 1c). Thus, the class 1 drugs can also be subdivided in three other groups exhibiting clearly separated bands of block-frequency relations, with half-maximal saturation occurring at different stimulation rates. Our findings may have differential implications for the antiarrhythmic and proarrhythmic efficacy of class 1 drugs.     

Multivariable non-linear controller for a synchronous generator

The problem of multivariable controller synthesis for a turbogenerator is considered. Using the feedback linearization approach for multi-input non-linear systems, the existence of a linearizing state feedback for the improved reduced-order model of a turbogenerator is proved and the simplest form of this feedback is derived. Application of the obtained non-linear controller to the multivariable control of a turbogenerator provides very good results not only for the reduced-order model but also for the ‘exact’ (Park's) model of a turbogenerator. Simulations of fault and post-fault conditions in the obtained nonlinear control system confirm its superiority over a system with a voltage regulator and power system stabilizer.     

Reductions in depressed mood and denial coping during cognitive behavioral stress management with hiv-positive gay men treated with haart

Background: Stress management interventions for HIV-positive persons have been designed to enhance coping skills and encourage health-promoting behaviors with the hope of decreasing distress and slowing disease progression.Purpose: We examined the efficacy of a cognitive behavioral stress management (CBSM) intervention in combination with medication adherence training (MAT) in 130 gay and bisexual men living with HIV infection.Methods: Participants were randomized to either a 10-week CBSM+MAT intervention (n = 76) or a MAT-only condition (n = 54). Measures of self-reported adherence, active cognitive coping (i.e., acceptance and positive reinterpretation), avoidant coping (i.e., denial and behavioral disengagement), and depressed mood were examined over the 10-week intervention period.Results: Men in CBSM+MAT reported reductions in depressed mood and denial coping during the 10-week intervention period, but no changes in active cognitive coping or self-reported adherence were observed. Using path analysis, greater reliance on denial coping at baseline was associated with decreased depressed mood at 10 weeks. We also determined that CBSM+MAT may decrease depressed mood by reducing reliance on denial coping over the 10-week intervention period.Conclusions: Although denial may be an effective means of distress reduction in the short term, reliance on this coping strategy may result in a decreased capacity to effectively manage a variety of disease-related stressors in the long term. CBSM+MAT addresses this potentially detrimental pattern by teaching stress reduction skills that may decrease depressed mood via reduced reliance on denial coping. This research was supported by National Institute of Mental Health Grants P01 MH49548 and T32 MH18917.     

First radiological description of Morgagni's hydatid. Laparoscopic confirmation

The authors explain the clinical case of a female patient suffering from secondary sterility; she was submitted, among other test, to the H.S.G. in order to study the possibility of a among other tests, to the H.S.G. in order to study the possibility of a cervical failure. The radiological findings obtained of Morgagni's Hydatis, not described previously in literature and their laparoscopic confirmation justify, we believe, its publication.