Search

Keiji Yoshikawa,1 Shiro Mizoue,2,3 Koji Nitta,4 Hiroshi Onishi,5 Masaharu Ikeda,5 Akemi Mizuno,5 Kaori Kawazoe,5 Yoshiyuki Tamada,5 Ryuji Takeda,6 Shun Matsumoto7 1Yoshikawa Eye Clinic, Tokyo, Japan; 2Ehime University Hospital, Toon, Ehime, Japan; 3Minami-Matsuyama Hospital, Matsuyama, Ehime, Japan; 4Fukui-ken Saiseikai Hospital, Fukui, Japan; 5Senju Pharmaceutical Co. Ltd., Hyogo, Japan; 6Kansai University of Welfare Sciences, Osaka, Japan; 7Ideta Eye Hospital, Kumamoto, JapanCorrespondence: Keiji YoshikawaYoshikawa Eye Clinic, 1-3-1 Nakamachi, Machida, Tokyo, 194-0021, JapanTel +81-42-739-0781Fax +81-42-739-0782Email mayokasyg51@galaxy.ocn.ne.jpPurpose: We previously investigated the efficacy and safety of adding 0.1% brimonidine (Brim) or 0.5% timolol (Tim) to prostaglandin analogue (PGA) monotherapy to treat patients with normal-tension glaucoma (NTG) with intraocular pressure (IOP) of ≤ 16 mmHg. Herein, we describe an additional post-hoc stratifying analysis of the possible differences in the effect of IOP-lowering and pulse rate (PR) after adjunctive Brim or Tim to PGA.Patients and Methods: This study included 128 subjects. Patients with NTG treated with PGA were stratified based on their baseline IOP. The changes in IOP from baseline and the effect of patient factors on IOP changes were investigated. Patients were stratified by age for investigation of their PR and blood pressure (BP). The change and the effect of patient factors on PR and BP were investigated.Results: After stratification analysis, in 52 eyes treated with Brim and 61 eyes with Tim with baseline IOP 12 ≤ IOP ≤ 16 mmHg, both eye drops lowered IOP significantly (P < 0.0001), and the IOP-lowering efficacy of Brim was non-inferior to that of Tim. However, in 9 Brim- and 6 Tim-treated eyes with baseline IOP of < 12 mmHg, no statistically significant decrease in IOP was evident with either eye drop. In the Tim group, PR decreased significantly (P < 0.05) after stratification by age.Conclusion: The IOP-lowering efficacy of Brim was non-inferior to that of Tim after stratification by baseline IOP (12 ≤ IOP ≤ 16 mmHg). The discrepancy in the IOP-lowering effects of Brim and Tim observed in the previous study was thought to be related to enrolled subjects with low baseline IOP. PR decreased significantly in the Tim group even after age stratification. PR should be considered when selecting β-blockers for glaucoma treatment.Keywords: adjunctive therapy, brimonidine, intraocular pressure reduction, post-hoc analysis, pulse rate, timolol

Yu Tamada,1– 3 Takeshi Inoue,2 Atsushi Sekine,4 Hiroyuki Toda,5 Minoru Takeshima,2,6 Masaaki Sasaki,3 Keisuke Shindome,5 Wataru Morita,5 Nagisa Kuyama,3 Susumu Ohmae3 1Department of Psychiatry, Toranomon Hospital Kajigaya, Kawasaki, Kanagawa, Japan; 2Department of Psychiatry, Tokyo Medical University, Tokyo, Japan; 3Department of Psychiatry, Toranomon Hospital, Tokyo, Japan; 4The Medical Foundation of Keishin-Kai, Kei Mental Clinic, Daisen, Akita, Japan; 5Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan; 6Shibata Hospital, Takaoka, Toyama, JapanCorrespondence: Yu TamadaDepartment of Psychiatry, Toranomon Hospital Kajigaya, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki, Kanagawa, 213-8587, JapanTel +81 44 877 5111Fax +81 44 877 5333Email y-tmd@umin.ac.jpPurpose: Melancholia has recently been re-evaluated, because patients with major depressive disorder (MDD) were found to be heterogeneous. However, the DSM-5 criteria for melancholia (DSM-MEL) have been criticized, because of the difficulty in clearly distinguishing between melancholic and non-melancholic depression using DSM-MEL. Psychomotor disturbance (PMD) is one of the most important, as well as one of the only measurable symptoms of melancholia. Parker et al developed the CORE measure, which assesses PMD as a behavioral characteristic. The aim of our study was to objectively identify the subjective symptoms of melancholia by analyzing the symptoms associated with PMD.Patients and Methods: A total of 106 participants with MDD were examined by psychiatrists. Multiple regression analysis was performed in which the total CORE score was the dependent variable, and items of the DSM-MEL and historically suggested melancholic features were independent variables.Results: The following five independent variables were able to predict the total CORE score: 1) feelings of having lost feeling, 2) depressive delusions, 3) perplexity, 4) indecisiveness, and 5) no aggression against others. These five variables were more strongly associated with the total CORE score than the DSM-MEL.Limitation: The major limitation of this study was that when choosing non-DSM melancholic signs and symptoms, we did not comprehensively evaluate and select the symptoms but chose items that are clinically important.Conclusion: We identified five subjective symptoms that were associated with PMD. These five symptoms may be clinically useful as diagnostic criteria for melancholia.Keywords: major depressive disorder, melancholic features, CORE measure, endogenous depression, diagnosis, psychomotor retardation

We consider the Cauchy problem for the damped wave equations with variable coefficients a(x) having power type nonlinearity |u|^p. We discuss the global existence of solutions for small initial data and investigate the relation between the range of a(x) and the order p., Comment: Describes the wrong facts in the text

We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96–1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19–2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and β-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11–1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01–2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24–2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and β-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

This work establishes a method of controlling the c-axis-oriented structure of α-Fe (soft magnetic)/L1_0-FePd (hard magnetic) thin films in the dual-phase compositional region in thermal equilibrium. Two types of thin films were prepared; one is a single-layered thin film, and the other is a multilayered film, [FePd(x nm)/Fe(5 nm)]_n (x: thickness, n: the number of multilayers), both of which are deposited on silica glass substrates. For single-layered films, the ordering process is retarded by phase separation that requires long-range diffusion. In this case, the 〈111〉 oriented domains preferentially grow from the film surface, and the c-axis-oriented structure is not obtained. On the contrary, for multilayered films, each FePd layer can undergo ordering without phase separation subject to the constraint of strong biaxial tensile stress resulting from the difference in the thermal contractions between Fe/FePd film and the silica glass substrate. Consequently, the L1_0 domains with c-axis orientation in the normal direction of the film surface are preferentially formed in the initial amorphouslike structure, eventually leading to the desired c-axis-oriented structure.

Vernalization, the promotion of flowering in response to low temperatures, is one of the best characterized examples of epigenetic regulation in plants. The promotion of flowering is proportional to the duration of the cold period, but the mechanism by which plants measure time at low temperatures has been a long-standing mystery. We show that the quantitative induction of the first gene in the Arabidopsis vernalization pathway, VERNALIZATION INSENSITIVE 3 (VIN3), is regulated by the components of Polycomb Response Complex 2, which trimethylates histone H3 lysine 27 (H3K27me3). In differentiated animal cells, H3K27me3 is mostly associated with long-term gene repression, whereas, in pluripotent embyonic stem cells, many cell lineage-specific genes are inactive but exist in bivalent chromatin that carries both active (H3K4me3) and repressive (H3K27me3) marks on the same molecule. During differentiation, bivalent domains are generally resolved to an active or silent state. We found that H3K27me3 maintains VIN3 in a repressed state prior to cold exposure; this mark is not removed during VIN3 induction. Instead, active VIN3 is associated with bivalently marked chromatin. The continued presence of H3K27me3 ensures that induction of VIN3 is proportional to the duration of the cold, and that plants require prolonged cold to promote the transition to flowering. The observation that Polycomb proteins control VIN3 activity defines a new role for Polycomb proteins in regulating the rate of gene induction. © 2010 Blackwell Publishing Ltd.

This letter reports the control of the c-axis orientation and the magnetic properties of L10 FePd in the well-annealed FePd/Fe thin films Fe(20 nm)/FePd(10 nm)/Fe(5 nm)/SiO2-substrate and Fe(20 nm)/FePd(5 nm)/Fe(5 nm)/SiO2-substrate, with the compositions of dual phase region in phase equilibrium. After annealing at 550 °C for 24 h, the c-axis of L1[sub 0]FePd is controlled to be oriented in the normal direction in the soft Fe matrix. These thin films exhibit the exchange-coupling of hard FePd with soft Fe, and a characteristic spring-magnet behavior showed up reversibly as a significant jump from positive to negative in the magnetization reversal.

The purpose of this study is to evaluate the significance of serum antithrombin ILE (AT III) in acute cerebrovascular stroke. AT III levies were determined by means of single radial immunodiffusion method in 73 serum specimens of 19 patients with cerebral hemorrhage (CH.), 129 of 24 patients with cerebral infarction (C.I.) and 82 of 82 healthy controls. AT III levels of patients with C.H. and with C.I. on the 1st day of the attacks were significantly higher than the value of controls. The high levels maintained from the 1st to the 25th day exculding 7th and 8th days in hemorrhagic patients. In patients with C.I., the levels from the 6th to the 25 day were significantly higher than that from the 1st to the 5th day. No difference was found in the types of the diseases. In 150 serum specimens obtained from the 1st to the 7th day, AT III levels were significantly lower in the patients with high fever, disturbance of consciousness and abnormal ECG findings than those in patients without these clinical findings. In serum specimens obtained from the 5th to the 7th day, AT III level of survivals were significantly higher than that of the dead.AT III levels in patients with high FDP levels were higher than those in patients with normal FDP levels. In C.I., AT III levels were directly proportional to prothormbin and plasminogen levels, and were inversely proportional to α1-antitrypsin levels. It is supposed that high AT III levels in acute stroke patients are caused by the protective effects on excess thrombus formation occurring parimarily in C.I. and secondarily in C.H. The high levels in both types of strokes and the close relation to outcome of patients indicate usefulness in the clinical evaluation of patient’s prognosis.