Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions

<p>Abstract</p> <p>Background</p> <p>Transcranial direct current stimulation (tDCS) is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability. Its safety profile places tDCS in the pole-position for translating in real-world therapeutic application. However, an episode of transient respiratory depression in a subject receiving tDCS with an extracephalic electrode led to the suggestion that such an electrode montage could modulate the brainstem autonomic centres.</p> <p>We investigated whether tDCS applied over the midline frontal cortex in 30 healthy volunteers (sham n = 10, cathodal n = 10, anodal n = 10) with an extracephalic reference electrode would modulate brainstem activity as reflected by the monitoring and stringent analysis of vital parameters: heart rate (variability), respiratory rate, blood pressure and sympatho-vagal balance.</p> <p>We reasoned that this study could lead to two opposite but equally interesting outcomes: 1) If tDCS with an extracephalic electrode modulated vital parameters, it could be used as a new tool to explore the autonomic nervous system and, even, to modulate its activity for therapeutic purposes. 2) On the opposite, if applying tDCS with an extracephalic electrode had no effect, it could thus be used safely in healthy human subjects. This outcome would significantly impact the field of non-invasive brain stimulation with tDCS. Indeed, on the one hand, using an extracephalic electrode as a genuine neutral reference (as opposed to the classical "bi-cephalic" tDCS montages which deliver bi-polar stimulation of the brain) would help to comfort the conclusions of several modern studies regarding the spatial location and polarity of tDCS. On the other hand, using an extracephalic reference electrode may impact differently on a given cortical target due to the change of direct current flow direction; this may enlarge the potential interventions with tDCS.</p> <p>Results</p> <p>Whereas the respiratory frequency decreased mildly over time and the blood pressure increased steadily, there was no differential impact of real (anodal or cathodal) <it>versus </it>sham tDCS. The heart rate remained stable during the monitoring period. The parameters reflecting the sympathovagal balance suggested a progressive shift over time favouring the sympathetic tone, again without differential impact of real <it>versus </it>sham tDCS.</p> <p>Conclusions</p> <p>Applying tDCS with an extracephalic reference electrode in healthy volunteers did not significantly modulate the activity of the brainstem autonomic centres. Therefore, using an extracephalic reference electrode for tDCS appears safe in healthy volunteers, at least under similar experimental conditions.</p

Di-tert-butyl 2-benzoyl­hydrazine-1,1-dicarboxyl­ate

The crystal structure of the title compound, C17H24N2O5, was determined in the course of our studies on the preparation of two families of pseudopeptides, viz. hydrazino- and N-amino- peptides. The most significant inter­action in the crystal structure is a bifurcated inter­molecular N—H⋯O hydrogen bond

Stability of Concentrated Solution of Vancomycin Hydrochloride in Syringes for Intensive Care Units

Abstract Background Vancomycin is increasingly administrated by continuous infusion. But the treatment of patient in intensive care need restricted volume to prevent fluid overload. The aim of the study was to evaluate the physical and chemical stability of solutions of a high concentration of vancomycin hydrochloride in 5 % glucose or 0.9 % NaCl. Methods Eight syringes of 50 mL, containing 41.66 mg/mL of vancomycin hydrochloride four syringes in 5 % glucose and four in 0.9 % NaCl were prepared and stored at ambient temperature during 48 h. Immediately after preparation and during 48 h, vancomycin hydrochloride concentrations were measured by a high-performance liquid chromatography (HPLC). Spectrophotometric absorbance at different wavelengths, pH measurement and microscopic observations were also performed. Results All solutions were physico-chemically stable during the whole period storage at ambient temperature: no color change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable as the lower limit of the 95 % unilateral confidence interval on the mean remained above 90 % of the initial concentration for at least 48 h. Conclusions Solutions of vancomycin hydrochloride 41.66 mg/mL in syringe of 5 % glucose or 0.9 % NaCl are physically and chemically stable for at least 48 h when stored in syringes at ambient temperature. </jats:sec

Enzyme-catalyzed mechanism of isoniazid activation in class I and class III peroxidases.

There is an urgent need to understand the mechanism of activation of the frontline anti-tuberculosis drug isoniazid by the Mycobacterium tuberculosis catalase-peroxidase. To address this, a combination of NMR spectroscopic, biochemical, and computational methods have been used to obtain a model of the frontline anti-tuberculosis drug isoniazid bound to the active site of the class III peroxidase, horseradish peroxidase C. This information has been used in combination with the new crystal structure of the M. tuberculosis catalase-peroxidase to predict the mode of INH binding across the class I heme peroxidase family. An enzyme-catalyzed mechanism for INH activation is proposed that brings together structural, functional, and spectroscopic data from a variety of sources. Collectively, the information not only provides a molecular basis for understanding INH activation by the M. tuberculosis catalase-peroxidase but also establishes a new conceptual framework for testing hypotheses regarding the enzyme-catalyzed turnover of this compound in a number of heme peroxidases

Methicillin-resistant Staphylococcus aureus Toxic Shock Syndrome

Case ReportsLetterSCOPUS: le.jinfo:eu-repo/semantics/publishe

Short-and long-lasting tinnitus relief induced by transcranial direct current stimulation

Abstract A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes

Comparison of five D-dimer reagents and application of an age-adjusted cut-off for the diagnosis of venous thromboembolism in emergency department

There is still a considerable uncertainty concerning D-dimer cut-off values used in exclusion of venous thromboembolic (venous thromboembolism, VTE) disease, especially among the elderly patients. The objectives were to compare five different D-dimer reagents in the daily practice of an emergency department and to test retrospectively the performances of an age-adjusted cut-off. A total of 473 consecutive ambulatory outpatients suspected of VTE (confirmed VTE = 21) were included in this study. Five commercially available tests were assessed: STA-Liatest D-Di (LI), AxSYMD-Dimer (AX), VIDAS D-Dimer (VI), INNOVANCE D-Dimer (IN), and HemosIL D-Dimer HS (HS). When using a cut-off value of 500 ng/ml fibrinogen equivalent units (FEUs), D-dimer reagents differ in their abilities to avoid further testing. Indeed, LI allowed exclusion of VTE diagnosis in statistically more patients than VI, AX, and IN but not HS. The use of an age-adjusted cut-off is cost-effective without increasing significantly the number of false negative results. The interest of such strategy is more or less pronounced, depending on the type of D-dimer reagent. The application of an age-adjusted cut-off may be useful to reduce differences among D-dimer reagents to lower costly imaging studies. Prospective validation studies on large cohorts of patients are required to determine the safety of such strategy

Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation

A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes

Clinical profiles of patients colonized or infected with extended-spectrum beta-lactamase producing Enterobacteriaceae isolates: a 20 month retrospective study at a Belgian University Hospital

<p>Abstract</p> <p>Background</p> <p>Description of the clinical pictures of patients colonized or infected by ESBL-producing <it>Enterobacteriaceae </it>isolates and admitted to hospital are rather scarce in Europe. However, a better delineation of the clinical patterns associated with the carriage of ESBL-producing isolates may allow healthcare providers to identify more rapidly at risk patients. This matter is of particular concern because of the growing proportion of ESBL-producing <it>Enterobacteriaceae </it>species isolates worldwide.</p> <p>Methods</p> <p>We undertook a descriptive analysis of 114 consecutive patients in whom ESBL-producing <it>Enterobacteriaceae </it>isolates were collected from clinical specimens over a 20-month period. Clinical data were obtained through retrospective analysis of medical record charts. Microbiological cultures were carried out by standard laboratory methods.</p> <p>Results</p> <p>The proportion of ESBL-producing <it>Enterobacteriaceae </it>strains after exclusion of duplicate isolates was 4.5% and the incidence rate was 4.3 cases/1000 patients admitted. Healthcare-associated acquisition was important (n = 104) while community-acquisition was less frequently found (n = 10). Among the former group, two-thirds of the patients were aged over 65 years and 24% of these were living in nursing homes. Sixty-eight (65%) of the patients with healthcare-associated ESBL, were considered clinically infected. In this group, the number and severity of co-morbidities was high, particularly including diabetes mellitus and chronic renal insufficiency. Other known risk factors for ESBL colonization or infection such as prior antibiotic exposure, urinary catheter or previous hospitalisation were also often found. The four main diagnostic categories were: urinary tract infections, lower respiratory tract infections, septicaemia and intra-abdominal infections. For hospitalized patients, the median hospital length of stay was 23 days and the average mortality rate during hospitalization was 13% (Confidence Interval 95%: 7-19). <it>Escherichia coli</it>, by far, accounted as the most common ESBL-producing <it>Enterobacteriaceae </it>species (77/114; [68%]) while CTX-M-1 group was by far the most prevalent ESBL enzyme (n = 56).</p> <p>Conclusion</p> <p>In this retrospective study, the clinical profiles of patients carrying healthcare-associated ESBL-producing <it>Enterobacteriacae </it>is characterized by a high prevalence rate of several major co-morbidities and potential known risk factors. Both, the length of hospital stay and overall hospital mortality rates were particularly high. A prospective case-control matched study should be designed and performed in order to control for possible inclusion bias.</p