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Yoshihisa Ohashi,1 Kensuke Fukushima,1 Kentaro Uchida,1 Tomohisa Koyama,1 Maho Tsuchiya,1 Hiroki Saito,1 Katsufumi Uchiyama,2 Naonobu Takahira,3 Gen Inoue,1 Masashi Takaso1 1Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan; 2Department of Patient Safety and Healthcare Administration, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan; 3Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara City, Kanagawa, 252-0374, JapanCorrespondence: Kensuke FukushimaDepartment of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara City, Kanagawa, 252-0374, JapanTel +81-42-778-9343Fax +81-42-778-5850Email kenfu@r4.dion.ne.jpBackground: In patients with hip osteoarthritis (OA), pain at rest, unlike pain on activity, is due to pain mechanisms that cannot be explained by nociceptive pain. However, it remains unclear whether central sensitization (CS) is one of the causes of exacerbated pain at rest in patients with hip OA. Therefore, we investigated the differences in causative factors and postoperative course of total hip arthroplasty (THA) between preoperative pain at rest and on activity in patients with hip OA.Methods: In total, 120 patients (125 hips, 22 men and 98 women, aged 64.5± 1.0 years) with hip OA were included. Preoperative pain at rest and on activity and CS were assessed using the visual analog scale (VAS) and CS Inventory (CSI), respectively. Postoperative assessments were evaluated using the Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ); pain, satisfaction, function, and mental scores were evaluated 6 and 12 months after THA.Results: Multivariate regression analysis indicated the CSI score as affecting VAS for pain at rest (β=0.067, P=0.002) but not VAS for pain on activity (β=0.036, P=0.073). VAS for pain at rest had a weak negative correlation with satisfaction and pain scores at both 6 and 12 months after THA (satisfaction, r=− 0.309, − 0.278; pain, r=− 0.202, − 0.22). VAS for pain on activity was not correlated with JHEQ. The CSI score had a weak or moderate negative correlation with three scores other than the function score at both 6 and 12 months after THA (satisfaction, r=− 0.266, − 0.213; pain, r=− 0.332, − 0.203, mental, r=− 0.427, − 0.370). The function score was weakly correlated with the CSI score only 6 months after THA (function, r=− 0.231, − 0.190).Conclusion: A higher level of preoperative pain at rest, a CS-related symptom, may affect postoperative pain persistence and dissatisfaction in patients with hip OA.Keywords: central sensitization, pain at rest, postoperative pain, hip osteoarthritis, total hip arthroplasty

PurposeUrologists have been criticized for overtreating men with low risk prostate cancer and for passively observing older men with higher risk disease. Proponents of active surveillance for low risk disease and critics of watchful waiting for higher risk disease have advocated for more judicious use of observation. Thus, we compared 2 population based cohorts to determine how expectant management has evolved during the last 2 decades.Materials and methodsA total of 5,871 men with localized prostate cancer were enrolled in the PCOS (Prostate Cancer Outcomes Study) or the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study. We compared the use of definitive treatment vs expectant management (watchful waiting or active surveillance) across cohorts, focusing on the influence of disease risk, age and comorbidities.ResultsUse of watchful waiting or active surveillance was similar in PCOS and CEASAR (14% in each). Compared to the PCOS, more men in the CEASAR study with low risk disease selected watchful waiting or active surveillance (25% vs 15%, respectively), whereas fewer men with intermediate (7% vs 14%) and high risk (3% vs 10%) disease chose watchful waiting or active surveillance (p

Purpose Robotic assisted radical prostatectomy has largely replaced open radical prostatectomy for the surgical management of prostate cancer despite conflicting evidence of superiority with respect to disease control or functional sequelae. Using population cohort data, in this study we examined sexual and urinary function in men undergoing open radical prostatectomy vs those undergoing robotic assisted radical prostatectomy. Materials and Methods Subjects surgically treated for prostate cancer were selected from 2 large population based prospective cohort studies, the Prostate Cancer Outcomes Study (enrolled 1994 to 1995) and the Comparative Effectiveness Analysis of Surgery and Radiation (enrolled 2011 to 2012). Subjects completed baseline, 6-month and 12-month standardized patient reported outcome measures. Main outcomes were between-group differences in functional outcome scores at 6 and 12 months using linear regression, and adjusting for baseline function, sociodemographic and clinical characteristics. Sensitivity analyses were used to evaluate outcomes between patients undergoing open radical prostatectomy and robotic assisted radical prostatectomy within and across CEASAR and PCOS. Results The combined cohort consisted of 2,438 men, 1,505 of whom underwent open radical prostatectomy and 933 of whom underwent robotic assisted radical prostatectomy. Men treated with robotic assisted radical prostatectomy reported better urinary function at 6 months (mean difference 3.77 points, 95% CI 1.09-6.44) but not at 12 months (1.19, -1.32-3.71). Subjects treated with robotic assisted radical prostatectomy also reported superior sexual function at 6 months (8.31, 6.02-10.56) and at 12 months (7.64, 5.25-10.03). Sensitivity analyses largely supported the sexual function findings with inconsistent support for urinary function results. Conclusions This population based study reveals that men undergoing robotic assisted radical prostatectomy likely experience less decline in early urinary continence and sexual function than those undergoing open radical prostatectomy. The clinical meaning of these differences is uncertain and longer followup will be required to establish whether these benefits are durable.

We have carried out nuclear magnetic resonance (NMR) and nuclear quadrupole resonance (NQR) measurements on ThRu2Si2 and LaRu2Si2, which are the nonmagnetic references of the intriguing heavy fermion URu2Si2. The comparisons of URu2Si2 with the reference materials allow us to analyze the already known NMR and NQR data on URu2Si2 phenomenologically and semiquantitatively. The study of 101Ru-NQR frequency suggests the relatively close electronic configuration of URu2Si2, including the valence of the actinide ion, to that of the tetravalent ThRu2Si2 at high temperatures, as well as the delocalization of 5 f electrons at low temperatures. Ising-like spin fluctuations along the c-axis were brought to light by 29Si-NMR data in the so-called hidden order phase of URu2Si2. The unique magnetic property is plausibly associated with the mechanism of the unconventional superconductivity.

Background Despite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time. Objective To evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart. Design, setting, and participants Patients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter. Outcome measurements and statistical analysis We performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies. Results and limitations The study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding. Conclusions Reporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations. Patient summary Patient reporting of urinary and sexual function has evolved and is likely contingent on continually changing societal norms. Recognizing the evolving nature of patient reporting is essential in efforts to conduct high-quality, impactful comparative effectiveness research.

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n¼260) and placebo (n¼246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p¼0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p¼0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p

Introduction: Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker pane

Prospective equivalent internal quantum efficiency (eta(int)) of approximately 34% at 300 K was demonstrated for the blue emission peak of nonpolar m-plane (1 (1) over bar 00) InxGa1-xN/GaN multiple quantum well light emitting diodes (LEDs) fabricated on freestanding m-plane GaN substrates. Although the eta(int) value is yet lower than that of conventional c-plane blue LEDs (> 70%), the results encourage one to realize high performance green, amber, and red LEDs by reducing the concentration of nonradiative defects, according to the absence of the quantum-confined Stark effects due to the polarization fields parallel to the quantum well normal. The electric field component of the blue surface emission was polarized perpendicular to the c axis with the in-plane polarization ratio of 0.58 at 300 K. (c) 2006 American Institute of Physics.

An international, multiple-code benchmark test (BMT) study is being conducted within the international DECOVALEX project to analyse coupled thermal, hydrological, mechanical and chemical (THMC) processes in the excavation disturbed zone (EDZ) around emplacement drifts of a nuclear waste repository. This BMT focuses on mechanical responses and long-term chemo-mechanical effects that may lead to changes in mechanical and hydrological properties in the EDZ. This includes time-de-pendent processes such as creep, and subcritical crack, or healing of fractures that might cause "weakening" or "hardening" of the rock over the long term. Five research teams are studying this BMT using a wide range of model approaches, including boundary element, finite element, and finite difference, particle mechanics, and elasto-plastic cellular automata methods. This paper describes the definition of the problem and preliminary simulation results for the initial model inception part, in which time dependent effects are not yet included.

The ultrafast relaxation dynamics of photoexcited electrons in six transition metals, Au, Ag, Cu, Pt, Pd, and Ni, were investigated using femtosecond luminescence spectroscopy in the infrared region between 0.4 and 1.05 eV. The behaviors of the time-resolved spectra are significantly different between group 11 noble metals (Au, Ag, and Cu) and group 10 transition metals (Pt, Pd, and Ni), which are neighbors in the periodic table of elements. In the latter group, the instantaneous luminescence intensities are one order of magnitude lower and the lifetimes (around 200 fs) are far shorter than those of the group 11 metals (typically 700 fs). The time-resolved spectra, decay profiles, and excitation power dependence were analyzed using a phenomenological model that considers both the nonthermal and thermal electrons. It was found that the nonthermal component is remarkably small in the group 10 transition metals. These systematic differences between group 10 and 11 metals are ascribed to the differences in their electron band structures and/or electron–phonon coupling strengths. [ABSTRACT FROM AUTHOR]

Satoshi Asakura,1 Taiji Hayano,2 Atsushi Hagino,2 Tsukasa Koyama3 1Health Care Center and Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 2Clinical Development Planning and Management, Mochida Pharmaceutical Co., Ltd, Tokyo, 3Clinical Research Center, Oyachi Hospital, Sapporo, Hokkaido, Japan Purpose: To investigate the safety, tolerability, and effectiveness of escitalopram in patients with social anxiety disorder in Japan.Methods: A 52-week, open-label study was conducted in Japanese patients with social anxiety disorder with a total score ≥60 on the Liebowitz Social Anxiety Scale – Japanese Version (LSAS-J) and ≥4 on the Clinical Global Impression – Severity Scale. Escitalopram 10 mg/day was administered for the first week and could be increased to 20 mg/day.Results: The study included 158 patients: 81.0% (128/158) completed 52 weeks of escitalopram treatment, 68.4% (108/158) increased their dose to 20 mg/day, and 56.3% (89/158) remained on 20 mg/day. Adverse drug reactions were reported by 57.6% (91/158) of patients. The most common (incidence ≥10%) were somnolence and nausea. The incidence of adverse drug reactions was similar in extensive and poor metabolizers of cytochrome P450 2C19. No adverse drug reactions increased in incidence by >5% after week 12. The incidence of serious adverse events was 1.3% (2/158). No deaths occurred. The LSAS-J total scores improved until week 52. The LSAS-J response rate (≥30% improvement in LSAS-J) was 69.0%, the Clinical Global Impression – Improvement Scale response rate (≤2) was 73.0%, and the LSAS-J remission rate (≤30) was 27.0%.Conclusion: In this first 52-week clinical study of social anxiety disorder, escitalopram 10–20 mg/day was safe, well tolerated, and effective in Japanese patients. Keywords: escitalopram, Japanese, long-term study, social anxiety disorder, selective serotonin reuptake inhibitors

The effect of emissivity on the ultrafast luminescence spectrum was studied for bulk silver having surfaces with varying grades of roughnesses by using the femtosecond upconversion technique in the infrared region of 0.3-1.0 eV under excitation by 130 fs pulses at 1.19 eV. In addition, the absorptivity spectra were measured by the calorimetric method in the same energy range. As the roughnesses increase, the intensity of the time-resolved luminescence at 0.9 eV at 0 ps increases for three orders of magnitude proportional to the square of the absorptivity, indicating that the luminescence intensity is proportional to the product of absorptivity and emissivity. Although the spectral shapes are very different for the surfaces with different roughnesses, we successfully retrieved internal luminescence spectra after correcting for the emissivity spectrum. It is shown that the retrieval process does not require precise knowledge of microscopic surface morphology. [ABSTRACT FROM AUTHOR]

Eiji Harada,1 Alexander Schacht,2 Tsukasa Koyama,3 Lauren Marangell,4,5 Toshinaga Tsuji,6 Rodrigo Escobar41Medical Science, Eli Lilly Japan K.K, Kobe, Japan; 2Global Statistical Sciences, Eli Lilly and Company, Bad Homburg, Germany; 3Clinical Research Center, Ohyachi Hospital, Sapporo, Japan; 4Eli Lilly and Company, Indianapolis, IN, 5The University of Texas Health Science Center, Houston, TX, USA; 6Medical Affairs, Shionogi & Co Ltd, Osaka, JapanBackground: Approved doses of antidepressants in Japan are usually lower than those in the USA and European Union, but to date meta-analyses comparing antidepressants have all used the higher doses approved in the USA and European Union and often have used indirect comparisons. The purpose of this study was to conduct an integrated database analysis of patient level data to compare the effects of duloxetine with those of selective serotonin reuptake inhibitors (SSRIs) at the doses approved in Japan.Methods: Pooled data were analyzed from four randomized, double-blind, placebo-controlled studies that compared duloxetine at the dose range approved in Japan (40–60 mg/day) with other SSRIs (paroxetine 20 mg/day or escitalopram 10 mg/day) and placebo in patients with major depressive disorder. In total, 1,694 patients were included in the analysis (duloxetine, n=688; selective serotonin reuptake inhibitors, n=690; placebo, n=316). The primary outcome measure was the mean change from baseline at week 8 in 17-item Hamilton Rating Scale for Depression (HAMD17) total and subscale scores.Results: Duloxetine and both selective serotonin reuptake inhibitors were superior to placebo in HAMD17 total score at week 8 in both the all-randomized group and the more severe subgroup (HAMD17 total scores ≥19). Duloxetine was superior to SSRIs in improving the HAMD17 Retardation subscale score (least squares mean difference [95% confidence interval]): all-randomized group, −0.33 [−0.60, −0.07], P=0.015; severe subgroup, −0.45 [−0.83, −0.07], P=0.020).Conclusion: Within the dose range approved in Japan for patients with major depressive disorder, duloxetine and selective serotonin reuptake inhibitors demonstrated comparable overall efficacy, with a possible advantage for duloxetine in improving loss of energy and interest. To the best of our knowledge, this analysis is unique not only in evaluating dosages specific to Japan, but also in using individual patient data and the same endpoint across studies to allow for strictly direct head-to-head data comparisons as opposed to pooling direct and indirect comparisons.Keywords: duloxetine, selective serotonin reuptake inhibitors, Japan, approved dosage, meta-analysis, major depressive disorder

Recently, to enlarge spin-current-induced phenomena, such as spin–orbit torque (SOT) in a ferromagnet (FM)/heavy-metal (HM) bilayer, enhancement of spin-current transmittance by inserting an antiferromagnetic insulator at the FM/HM interface has been extensively studied. In this study, we have investigated the SOT modulation in a Pt/NiO/Co structure in which the NiO layer was deposited using Ar and Xe process gases. Consequently, the quality of the NiO layer could be regulated. An increase in the damping-like SOT efficiency was observed by inserting the 1 nm NiO layer in the Ar type while it monotonically decreased with an increase in the NiO thickness in the Xe type. Significant temperature dependence of the SOT efficiency in the Ar type indicates that thermal magnon largely contributes to the spin-current propagation. X-ray diffraction measurement result suggests that the difference in crystallinity of the NiO layer between the Ar and Xe types attributes to the different SOT modulations. [ABSTRACT FROM AUTHOR]

Yuji Kitaichi,1 Takeshi Inoue,1 Nobuyuki Mitsui,1 Shin Nakagawa,1 Rie Kameyama,1 Yoshiyuki Hayashishita,1 Tohru Shiga,2 Ichiro Kusumi,1 Tsukasa Koyama1 1Department of Psychiatry, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan Abstract: We report a case in which selegiline, an irreversible monoamine oxidase B (MAO-B) inhibitor, greatly improved depressive symptoms in an adult with stage 5 treatment-resistant major depressive disorder. Four antidepressants and four augmentation therapies had previously been ineffective or intolerable, and electroconvulsive therapy had only a temporary effect. After 20 weeks of treatment with selegiline (10 mg/day), the patient's score on the 17-item Hamilton Depression Rating Scale (HDRS) had decreased from 19 to 4 points. [18F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased glucose metabolism in the bilateral basal ganglia after initiating selegiline treatment; blood dopamine levels were also increased after selegiline treatment. These results raise the possibility that selegiline enhances dopaminergic neural transmission in treatment-resistant depression, thus leading to an improvement in depressive symptoms. Keywords: treatment-resistant depression, FDG-PET, glucose metabolism, basal ganglia

Hiromi Kimura, Akemi Osaki, Rui Kawashima, Takeshi Inoue, Shin Nakagawa, Katsuji Suzuki, Satoshi Asakura, Teruaki Tanaka, Yuji Kitaichi, Takuya Masui, Nobuki Kitagawa, Yuki Kako, Tomohiro Abekawa, Ichiro Kusumi, Hiroyoshi Yamanaka, Kenzo Denda, Tsukasa KoyamaDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, JapanBackground: The bipolar-unipolar distinction in patients with a major depressive episode is the most important issue related to the diagnosis and treatment of mood disorders, but remains unresolved. This study was undertaken to compare bipolar and unipolar depression on Rorschach testing using the Comprehensive System with reference to healthy Japanese controls.Methods: Patients with bipolar or unipolar depression who had undergone the Rorschach test for routine clinical purposes were followed up naturalistically for a long period. Based on diagnostic confirmation after long-term follow-up, scores on this test for patients with bipolar and unipolar depression were compared with those published elsewhere for healthy Japanese controls.Results: The bipolar depression group showed significantly higher scores or positive findings in five variables of the Rorschach test, ie, WSum6, DR2 > 0, (CF + C) > FC + 2, PureC > 1, and Populars > 7, as assessed using the Comprehensive System, than did the unipolar depression group and healthy controls. These scores did not differ between the unipolar depression and control groups.Conclusion: The results of this study show thought disorder or cognitive slippage and marked laxness in modulating emotion in bipolar depression, indicating the psychopathological characteristics of bipolar disorder.Keywords: bipolar depression, bipolar disorder, Rorschach test, thought disorder, unipolar depression

Kunitoshi Kamijima,1 Shinji Hashimoto,2 Eiichi Nagayoshi,2 Tsukasa Koyama3 1International University of Health and Welfare, Tochigi, 2Asahi-kasei Pharma Corporation, Tokyo, 3Ohyachi Hospital, Sapporo, Japan Background and methods: A double-blind, parallel-group, controlled study was performed to investigate if milnacipran was noninferior to paroxetine in terms of improvement in symptoms of depression in Japanese patients with major depressive disorders in a fixed-dose design. The efficacy and safety of milnacipran 200 mg/day were also assessed in comparison with those at the standard dose of 100 mg/day. Results: Changes in 17-item Hamilton depression rating scale (HAM-D) total score (mean ± standard deviation) for group M1 (milnacipran 100 mg/day), group M2 (milnacipran 200 mg/day), and group PX (paroxetine 30 or 40 mg/day) were -12.9 ± 5.8, -12.8 ± 6.1, and -13.1 ± 6.2, respectively, and the estimated differences in total score for group PX (Dunnett's 95% simultaneous confidence interval) were 0.1 (-1.1 to 1.3) for group M1 and 0.3 (-0.9 to 1.5) for group M2. The noninferiority of groups M1 and M2 to group PX was thus confirmed, because the upper confidence limit of differences between groups M1 and PX and between groups M2 and PX was less than 2.0. The estimated mean difference of change in HAM-D total score (95% confidence interval) between groups M2 and M1 was 0.2 (-0.9 to 1.2), indicating a comparable change in total score for both groups. The incidence of treatment-related adverse events was 71.7% for group M1, 68.8% for group M2, and 69.3% for group PX, indicating no significant difference between the three groups. Conclusion: These results demonstrate that milnacipran 100 mg/day and 200 mg/day is not inferior to paroxetine in terms of efficacy and safety. Keywords: milnacipran, paroxetine, depression, noninferiority, Japan

Yuji Kitaichi, Takeshi Inoue, Shin Nakagawa, Shuken Boku, Akiko Kato, Ichiro Kusumi, Tsukasa KoyamaDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, JapanBackground: Up to 30% of depressed patients are partially or totally resistant to antidepressant therapy. The administration of triiodothyronine (T3) to antidepressant nonresponders can be an effective augmentation strategy, although the mechanism is not fully understood.Methods: In vivo microdialysis was used to examine the effect of T3 augmentation of the antidepressant, milnacipran. Basal extracellular serotonin, norepinephrine, and dopamine levels were measured before and after acute milnacipran administration in the medial prefrontal cortex and amygdala of rats which had received subchronic (7 days) T3 treatment or control saline.Results: Subchronic administration of T3 at 0.1 mg/kg significantly increased basal extracellular levels of serotonin in the medial prefrontal cortex, but not in the amygdala. In contrast, subchronic administration of T3 at 0.2 mg/kg did not alter basal extracellular serotonin levels in the medial prefrontal cortex. Basal extracellular levels of norepinephrine and dopamine were not modified by either dose of T3 in either region. Acute administration of milnacipran, a serotonin-norepinephrine reuptake inhibitor, to control animals resulted in a significant increase of extracellular levels of serotonin, norepinephrine, and dopamine. When administered to animals treated subchronically with T3 at 0.1 mg/kg, milnacipran produced an additional increase in extracellular serotonin levels but not in levels of norepinephrine or dopamine in the medial prefrontal cortex of rats.Conclusion: These results suggest that the mechanism of the augmentation effect of milnacipran by T3 administration occurs via enhancement of serotonergic neurotransmission, but not through noradrenergic or dopaminergic neurotransmission.Keywords: depression, in vivo microdialysis, milnacipran, monoamines, triiodothyronine