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Publication Open Access The Effects of Acute Multisession Bifrontal Transcranial Direct Current Stimulation on Intractable Tinnitus and comorbid depression and anxiety: A Study Protocol for Randomized Controlled Trial(International Tinnitus Journal, 2019-01-20) Rashidi, Samaneh; Ali, Yadollahpour; Alkahtani, Saad Ahmed; Kunwar, Pramod Singh; Robles-Camarillo, Daniel; Meneses-Flores, Arturo; Trejo-Macotela, FranciscoTranscranial Direct Current Stimulation (tDCS) may exert therapeutic effects on tinnitus. This Randomized Control Trial (RCT) with double blind and placebo design investigates the potential therapeutic effects of Transcranial Direct Current Stimulation on chronic and intractable tinnitus using a new protocol. Acute repeated sessions of bifrontal Transcranial Direct Current Stimulation with two months follow up will be used for treatment of tinnitus symptoms and comorbid anxiety and depression. To best of our knowledge, this is the first randomized control trial investigating the effects of acute Transcranial Direct Current Stimulation exposure in intractable tinnitus.Methods: This randomized control trial is conducted as double blinded placebo controlled with parallel group in patients with chronic intractable tinnitus. The patients will be randomly divided into two real or intervention and sham or placebo Transcranial Direct Current Stimulation. The real Transcranial Direct Current Stimulation group will receive two sessions per day with intersession interval of 6 hours for 5 consecutive days per week for one week (total 10 sessions). The Transcranial Direct Current Stimulation parameters include bifrontal (anode/cathode over right/left dorsolateral prefrontal cortex (DLPFC) 2 mA current (current density 57.1 μA/cm2), each session 20 min through 35 cm2 electrodes. The sham group will receive the same Transcranial Direct Current Stimulation parameters and electrode montage and after 30 seconds, the device will be turned off without informing the patient. The primary outcome is the score of Tinnitus Handicap Inventory (THI) measured at baseline (pre-intervention) and post-intervention at immediately, one, and two months after last session. The secondary outcomes are tinnitus loudness, tinnitus distress, depression, and anxiety scores. The tinnitus loudness and distress are measured with a 0-10 Numerical Rating Scale (NRS) pre-intervention and post-intervention at immediately, one hour, one week, one, and two months after the last Transcranial Direct Current Stimulation session. Beck Depression (BDI-II) and Anxiety Inventories (BAI) is respectively used for measuring depression and anxiety score pre- and post-intervention. Finally, the adverse effects of and tolerability to Transcranial Direct Current Stimulation will be assessed in both real and sham groups using customized questionnaire.Discussion: To the best of our knowledge this is the first RCT investigating the effects of daily two sessions of Transcranial Direct Current Stimulation in repeated regime on chronic intractable tinnitus symptoms, depression, anxiety, and adverse effects in a long term study of two months follow-up.Publication Open Access Transcranial Direct Current Stimulation for Treatment of ADHD: A Review of the Mechanisms of Action(Bentham Science, 2018-09-11) Mirzaiyan, Maryam; Kunwar, Pramod Singh; Uzayisenga, Rosette; Rashidi, SamanehAttention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder. The current pharmaceutical treatments are associated with side effects and with low efficacy so that about one third of the adults do not respond to these treatments. Transcranial direct current stimulation (tDCS) is a non-invasive and safe brain modulation technique with promising therapeutic effects on ADHD symptoms. This paper aims to comprehensively review the clinical trials of tDCS conducted in humans for the treatment of ADHD. We aim to review the clinical efficacy and mechanisms of action of the technique in ADHD treatment. Method: The databases of PubMed (1990-2017), Web of Sciences (1990-2017), Google Scholar (1990-2017) and Scopus (1990-2017) were searched using the keywords “Attention deficit hyperactivity disorder” OR “ADHD” AND “Transcranial direct current stimulation” OR “tDCS” AND "treatment" AND "mechanism". The title and abstract of the papers were reviewed by at least two authors and the relevant papers were selected for in depth review. We selected the preclinical and clinical trials that studied the effects of tDCS on ADHD patients through measuring behavioral, hemodynamic, or neurophysiological features. Results: The current evidence supports the therapeutic efficacy of tDCS in the improvement of ADHD, but, the findings are controversial. Anodal tDCS seems to be more effective than cathodal in ADHD. In addition, the appropriate sites of stimulation are frontal cortex in particular left dorsolateral prefrontal cortex and right inferior frontal gyrus. The tDCS can improve inhibitory control and interference control in ADHD patients. Conclusion: tDCS has shown promising but limited clinical efficacy for ADHD treatment. However, the current evidence supports continuing the preclinical and clinical studies to determine physiological mechanisms and dose response of tDCS in ADHD to establish a clinical protocol.Publication Open Access Vascular activity of protopanaxadiol and protopanaxatriol, the major saponin fractions isolated from roots of Panax notoginseng(Drug Invention Today; Vol 10 Issue 6, 2018, 2018-04-29) Uzayisenga, Rosette; Wang, Yi; Ren, Yu; Ayeka, Peter Amwoga; Kunwar, Pramod Singh; Twahirwa, EpaphroditePanax notoginseng (PN) (Burk) F. H. Chen (Araliacea) is a Chinese herb commonly known in Asia for its medicinal potentials, antihypertensive included. The aim of this study was to investigate the vasorelaxant activity of protopanaxadiol (PDS) and protopanaxatriol (PTS), the major saponin fractions isolated from roots of PN, and identify the underlying mechanisms on isolated rat aortic rings. Methods: Radnoti Tissue-Organ bath instrument (ADInstruments) was used to perform Tissue-Organ bath experiments, and tensions produced on isolated rat aortic rings were recorded by the help of ADInstruments PowerLab 8/30 system (Model ML 870, Australia). Results: Both PDS and PTS (10−6−10−3 μg/ ml) induced concentration-dependent relaxations in intact rat aortic rings pre-contracted with norepinephrine (1 μM).This activity was considerably reduced after removal of the endothelium and in intact rings pre-treated with NG-nitro-L-arginine methyl ester (L-NAME, 100 μM), 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxaline-1-one (ODQ, 10 μM), and combination of L-NAME and ODQ. However, pre-treatment with indomethacin (10 μM) did not affect either PDS- or PTS-induced relaxations. Furthermore, both PDS and PTS (10−4 and 10−3 μg/ml) decreased CaCl2- and potassium chloride (KCL)-induced vasoconstrictions in a dose-dependent manner. Our findings suggest that both PDS and PTS produced vasorelaxant effect that was mediated by NO-cyclic guanosine monophosphate in intact rings and by blockade of calcium influx in vascular smooth muscle. Cyclooxygenase pathway, on the other hand, had no apparent role. Among these fractions, PDS showed better effect with a slight difference. Conclusion: Findings from this study showed that both PDS and PTS fractions possess vasorelaxant activity. This supports the potential use of PN in management of cardiovascular diseases, especially hypertension.