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Objective To identify factors affecting adherence to medication, a subjective questionnaire survey was administered to schizophrenia patients regarding the prescribed antipsychotic formulations. Methods We evaluated the patients’ satisfaction and dissatisfaction with prescribed antipsychotic formulations, and patients answered the Drug Attitude Inventory-10 Questionnaire (DAI-10). Inclusion criteria for patients are as follows age between 20 and 75 years and taking antipsychotic agents containing the same ingredients and formulations, for at least 1 month. Results In total, 301 patients answered the questionnaire survey. Tablets were found to be the most commonly used antipsychotic formulations among schizophrenia patients (n = 174, 57.8%), followed by long-acting injections (LAIs, n = 93, 30.9%). No significant differences in the formulation satisfaction level and DAI-10 scores were observed between all formulations. Formulations, except for LAI, were selected by physicians in more than half of the patients. Patients who answered “Decided by consultation with physicians” had significantly higher satisfaction levels and DAI-10 scores compared to those who answered “Decided by physicians” (4.11 ± 0.77 vs. 3.80 ± 1.00, p = 0.0073 and 6.20 ± 3.51 vs. 4.39 ± 4.56, p < 0.001, respectively). Satisfaction levels moderately correlated with DAI-10 scores (r = 0.48, p < 0.001). Conclusion No formulation had a high satisfaction level in all patients, and it is important to be reflect the patients’ individual preferences in pharmacotherapy. Shared decision-making in the selection of the formulations is seen to be useful for improving medication adherence.

Objective To improve poor medication adherence in schizophrenic patients, long-acting injectable (LAI) antipsychotics are used. However, it has not yet become common in Japan. Recently, aripiprazole LAI was approved for alternative injection into the deltoid muscle in addition to the gluteal muscle. The acceptance for the proposal to switch from gluteal to deltoid injections of aripiprazole LAI was investigated. Methods The subjects were 32 outpatients with schizophrenia who had continuously received aripiprazole LAI administration into the gluteal muscle for ≥ 6 months. In the patients who had continued deltoid injection for 3 months after switching, the changes in the pain and shame in comparison with gluteal injections were evaluated. Results Switching to the deltoid injection was chosen by 17 out of 32 patients. Three months later, 9 patients were still receiving deltoid injections with highly rated satisfaction. The main reasons for switching to deltoid injections included the pain and shame associated with gluteal injections. The main reason for returning to the gluteal injection was the pain experienced from the injection in the deltoid. Results The option to select the injected area was based on the amount of pain in the deltoid and gluteal sites, leading to the widespread use of aripiprazole LAI.

In this study, we analyzed coevolution between Staphylococcus aureus strain SA003 and its lytic bacteriophage ΦSA012 to obtain novel insights into S. aureus –its phage interaction. Coevolution was induced in batch co-cultures, repeated 46 times with serial transfer. Although five replicate co-cultures ultimately resulted in bacterial survival and phage extinction, SA003 and ΦSA012 stably coexisted for 260 days (until the end of 45th batch). Strains and phages were periodically isolated from each co-culture replicate until the phage extinction. In the spot testing, isolates showed an antagonistic coevolution with cumulative development of phage resistance and infectivity against the host strain. The center of infection (COI) assays quantitatively revealed that coevolution entailed a gradual reduction of interaction between hosts and phages. The COI value of the isolates from 38th batch was less than 1% of that of the wild-type pair, and this value was still sufficient for their sustained coexistence. Adsorption assays and single-step growth experiments revealed that coevolution involved the changes in both adsorption rate and phage productivity. A fitness cost of phage resistance was observed as a reduction of the specific growth rate. However, it tended to recover during the long-term coevolution.

To introduce phage therapy against multidrug-resistant Staphylococcus aureus in Western medicine, the establishment of phage manufacturing, particularly phage propagation, is indispensable. For the propagation of S. aureus phages, knowledge of the effects of phage types, process parameters, and analytical methodologies should be investigated. In this study, S. aureus phage propagations were studied in a flask with a new class of design of experiments, definitive screening design, using S. aureus phages S13' and S25-3 in different taxonomies. Four process parameters, namely, multiplicity of infection, bacterial density at infection, time of harvest, and temperature, were evaluated with the regression models based on the phage concentration data measured using plaque assay and quantitative polymerase chain reaction. As a result, phage propagations measured using plaque assay and quantitative polymerase chain reaction were overall similar to each other in the case of phage S13', while they differed in the case of phage S25-3. These results suggest that the propagation processes need to be developed according to phage type, and the choice of methodologies for phage concentration measurements should be carefully considered.

Objective The adverse effects of antipsychotic agents can have a marked influence on medication adherence. In this study, we. investigated the adverse events of antipsychotics that are less likely to be reported by patients and the reasons why such symptoms remain latent. Methods Data were collected by interviewing patients using a subjective questionnaire, and the associations between unreported symptoms and background factors were investigated. Results A total of 306 patients with schizophrenia or schizoaffective disorder were examined. Their major symptoms were daytime sleepiness (50.0%), weight gain (42.2%), and sexual dysfunction (38.9%). Sexual dysfunction was nominal significantly more common among the patients that had been treated with antipsychotic agent polypharmacy (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.07 to 4.30), and was nominal significantly more common among outpatients (OR, 1.78; 95% CI, 1.02 to 3.13). Only approximately 30% of the patients had reported their symptoms to their physicians. Conclusion Patients receiving antipsychotic treatment tolerate some symptoms and do not feel able to report them to their physicians. The most common reason for this is an insufficient patient-physician relationship. Sexual dysfunction is especially hard to identify because it is a delicate problem, and our findings demonstrate that subjective questionnaires are helpful for detecting such symptoms.

Objective It is well documented that clozapine treatment causes agranulocytosis, but it can also induce drowsiness, constipation, and hypersalivation; however, these symptoms are usually less severe. It has been reported that clozapine-treated patients with schizophrenia and psychiatric healthcare professionals consider different side effects to be important. The aim of this study was to assess current practice related to the side effects of clozapine in clozapine-treated patients with schizophrenia and psychiatric healthcare professionals in Japan. Methods Data were collected from January 2014 to August 2015 in Okehazama Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated patients with schizophrenia and psychiatric healthcare professionals (psychiatrists and pharmacists) were enrolled in this study. Results Of the 106 patients and 120 psychiatric healthcare professionals screened, 100 patients and 104 healthcare professionals were included in this study. We asked the patients what side effects caused them trouble and we asked psychiatric healthcare professionals what side effects caused them concern. The patients and psychiatrists held similarly positive views regarding the efficacy of clozapine. The healthcare professionals were concerned about agranulocytosis (92.4%), blood routines (61.3%). On the other hand, the patients experienced hypersalivation (76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between patient satisfaction and DAI-10 score. Conclusion Patients experienced more problems than healthcare professionals expected. However, usage experience of clozapine healthcare professionals tended to have similar results to patients. It is necessary that all healthcare professionals fully understand the efficacy and potential side effects of clozapine. This is very important for promoting clozapine treatment in Japan.

We have previously generated strains ofStaphylococcus aureusSA003 resistant to its specific phage ϕSA012 through long-term coevolution experiment. However, the DNA mutations responsible for the phenotypic change of phage resistance are unknown. Whole-genome analysis revealed six genes that acquired unique point mutations: five missense mutations and one nonsense mutation. Moreover, one deletion, 1.779-bp, resulted in the deletion of the genes encoding glycosyltransferase, TarS, and iron-sulfure repair protein, ScdA. The deletion occurred from the second round of coculture (SA003R2) and remained through the last round. The ϕSA012 infection toward SA003R2 had decreased to 79.77±7.50% according to plating efficiency. Complementation of the phage-resistant strain by the wild-type allele showed two mutated host genes were linked to the inhibition of post-adsorption, and five genes were linked to phage adsorption of ϕSA012. Unlike ϕSA012, infection by ϕSA039, a close relative of ϕSA012, onto SA003R2 was impaired drastically. Complementation of SA003R2 by wild-typetarSrestores the infectivity of ϕSA039. Thus, we concluded that ϕSA039 requires β-GlcNAc in Wall Teichoic Acid (WTA) for its binding. In silico analysis of the ϕSA039 genome revealed that several proteins in the tail and baseplate region were different from ϕSA012; notably the partial deletion oforf96of ϕSA039, a homolog oforf99of ϕSA012.Orf100of ϕSA039, a homolog ofOrf103of ϕSA012, a previously reported receptor binding protein (RBP), had low similarity (86%) to that of ϕSA012. The difference in tail and baseplate proteins might be the factor for specificity difference between ϕSA012 and ϕSA039.

OBJECTIVE Long-acting injectable (LAI) aripiprazole is recommended to be combined with oral aripiprazole for 2 weeks after its introduction. However, we often experience patients who require more than 2 weeks of combined use. Therefore, differences in combination periods need to be examined. METHODS This was a case-control study. We surveyed prescription profiles for oral aripiprazole administration in conjunction with LAI aripiprazole introduction and assessed the clinical course during a 12-week follow-up period. RESULTS Among 121 patients, 58 (47.9%) were administered both oral and LAI aripiprazole for more than 2 weeks. Although there was no significant difference in treatment failure (defined as psychiatric hospitalization or discontinuation of LAI aripiprazole from any cause) between the two groups, the group that was administered oral aripiprazole for more than 2 weeks received less additional benzodiazepines compared with that of the 2 weeks group (adjusted odds ratio, 0.055; 95% confidence interval [0.0060, 0.50]; p

Objective This study examined the utility of adenine for preventing clozapine-induced neutropenia. Methods This retrospective study examined the effect of adenine on clozapine-induced neutropenia in patients with treatment-resistant schizophrenia and was conducted at Okehazama Hospital in Japan from July 2010 to June 2013. Adenine was available for use from June 2011 onwards. Twenty-one patients started receiving clozapine treatment from July 2010 to April 2011 (the pre-adenine adoption group), and 47 patients started receiving it from May 2011 to June 2013 (the post-adenine adoption group). The effects of adenine were assessed based on changes in the patients’ leukocyte counts and the frequency of treatment discontinuation due to clozapine-induced neutropenia. Results Sixty-eight patients were treated with clozapine from July 2010 to June 2013. Of the 21 patients in the pre-adenine adoption group, 4 discontinued treatment due to clozapine-induced neutropenia, whereas only 2 of the 47 patients in the post-adenine adoption group discontinued treatment. The frequency of treatment discontinuation due to clozapine-induced neutropenia was significantly lower in post-adenine adoption group than in the pre-adenine adoption group (p=0.047). Conclusion Adenine decreased the frequency of treatment discontinuation due to clozapine-induced neutropenia. Our data suggest that combined treatment with clozapine and adenine is a safe and effective strategy against treatment-resistant schizophrenia.

Blue wavelengths form the portion of the visible electromagnetic spectrum that most potently regulates circadian rhythm. We hypothesized that wearing blue-blocking (BB) glasses in the evening may influence circadian rhythm disturbances in patients with major depressive disorder (MDD), resulting in improved sleep and mood. We used a randomized placebo-controlled double-blinded design. Patients with MDD with sleep onset insomnia were randomly assigned to wearing either BB glasses or clear glasses (placebo). Patients were instructed to wear the glasses from 20:00 hours until bedtime for 2 weeks. We assessed sleep state (sleep quality on a visual analog scale, the Morningness-Eveningness Questionnaire [MEQ], and a sleep diary) and depressive symptoms at baseline and after 2 weeks. Data were analyzed with a full analysis set. In total, 20 patients were randomly assigned to the BB and placebo groups (BB group, n = 10; placebo group, n = 10). There were three dropouts (BB group, n = 1; placebo group, n = 2). At baseline, sleep quality, sleep latency (assessed via a sleep diary), and antipsychotics use differed between the groups. To take account of these differences, the baseline sleep state or depressive symptoms and antipsychotics use were used as covariates in the later analysis. The change scores for sleep quality did not show a significant improvement in the BB group compared with the placebo group (mean [standard deviation, SD] scores for BB versus placebo: 36.1 [31.7] versus 16.2 [15.1], p = 0.43), although half of the BB group showed a clear improvement in sleep quality. The change in MEQ scores did not significantly differ between the groups (p = 0.14), although there was a trend of a shift to morning type in the BB group (3.10 [4.95] points) and to evening type in the placebo group (0.50 [3.89] points). There were no statistically significant changes in depressive symptoms in either group. Across both groups, 40% of the participants reported pain or discomfort from wearing the glasses, which were available in only one size. Thus, the failure to find significant differences may have resulted from the glasses used in this study. Glasses fitted to individual patients may improve efficacy and safety. Replication of the study with a larger sample size and size-adjustable glasses is needed.

A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σB). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σB operon in L. monocytogenes is the TA system mazEF, which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a ΔmazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus, we found that the mazEF locus did not affect transcription of genes within the σB operon, but MazEF effected the expression of the σB-dependent genes opuCA and lmo0880, with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus, suggesting a novel mode of action for MazEF in L. monocytogenes.

This study investigated the efficacy of scopolamine (an anticholinergic agent) ointment against clozapine-induced hypersalivation.The patients enrolled in this study consisted of 10 clozapine-treated schizophrenia patients and 10 healthy adult men. A prospective, randomized, double-blind, crossover, placebo-controlled clinical trial was designed.A total of 10 patients and 10 healthy adult men completed the study. No significant reduction in the saliva production of the clozapine-treated patients was observed; however, that of the healthy adult men decreased significantly.Scopolamine ointment was not effective against clozapine-induced hypersalivation. A further study is necessary for confirming its effect.

In this study, calcium, Ca-, and strontium, Sr-added AZ91 magnesium alloys, which were composed of magnesium, Mg–9 wt.% aluminum, Al–0.8 wt.% zinc, Zn–x wt.% Ca–y wt.% Sr, were formulated and designated as AZXJ91xy alloys. The optimum composition of die-cast AZXJ alloys has been studied by micro-structural analysis and through the application of the constitutive equation of deformation behavior at elevated temperatures that includes the stacking fault energy. The normalized plots of the tensile test results of AZXJ alloys at 448 K by the constitutive equation of deformation behavior indicated that the deformation mechanism of the alloys was climb-controlled dislocation creep. The value of the constant A′ in the constitutive equation differs in the different AZXJ alloys, even though the effect of the solid solution of added elements, which is considered in the stacking fault energy term, was eliminated from A′. Using A′ as an indicator parameter of the creep resistance with the tensile strength at ambient temperature, the optimum composition of the creep-resistant Mg–Al–Zn–Ca–Sr alloy has been determined, and its creep resistance was comparable to those of known heat-resistant magnesium alloys.

The effect of Ca and Sr content on the microstructure and mechanical properties of a cast AZ91 magnesium alloy is investigated. Ca and Sr additions in AZ91 magnesium alloy are expected high creep resistance. The microstructure of the alloy exhibits the dendritic α-matrix and the second-phases forming networks on the grain boundary. Tensile tests at elevated temperatures between 448 and 523K reveal that the creep resistance was improved with increasing the additional amount of Ca, especially more than 1.0wt%. From the perspective of grain refinement effect, it is expected that the additions of Ca and Sr to AZ91 magnesium alloy not only improve creep resistance but also improve mechanical properties at room temperature.

Twin roll casting process combines casting and hot rolling into a single process. In this study, mechanical properties at room temperature and microstructure of the twin roll cast AZ91 magnesium alloy are investigated. The alloy exhibited a good combination of high ultimate strength of 343MPa, yield stress of 224MPa and elongation to failure of 13%. The mechanical property was very excellent compared with AZ91 die-cast alloy. EPMA analysis reveals that the Al concentration in Mg matrix is higher in twin roll cast alloy than that in die-cast alloy. This high Al concentration must be the origin of the good mechanical properties of twin roll cast alloy at room temperature.

Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0- 97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30-60 mg/ day) for 4 weeks. At the baseline and after 4 weeks' treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients' Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.

Introduction This study investigated the efficacy of scopolamine (an anticholinergic agent) ointment against clozapine-induced hypersalivation. Methods The patients enrolled in this study consisted of 10 clozapine-treated schizophrenia patients and 10 healthy adult men. A prospective, randomized, double-blind, crossover, placebo-controlled clinical trial was designed. Results A total of 10 patients and 10 healthy adult men completed the study. No significant reduction in the saliva production of the clozapine-treated patients was observed; however, that of the healthy adult men decreased significantly. Discussion Scopolamine ointment was not effective against clozapine-induced hypersalivation. A further study is necessary for confirming its effect.

An experimental study was conducted on turbulent flow and mixing in a counter-flow type T-junction. We measured the velocity and concentration fields simultaneously by combining PIV and PLIF. Special attention was directed to the concentration fluctuation near the channel wall, which might bring about the high-cycle thermal fatigue in case of mixing of hot and cold flows. The velocity ratio of the counter-channel flow to the main-channel flow was changed from 1.0 to 5.0. The fluorescent dye was mixed in the main-channel flow. The dominant structures of the fluctuating velocity and concentration fields that cause the concentration fluctuation near the channel wall were analyzed by POD. It was found that the concentration fluctuation near the channel wall was caused by the superposition of the spanwise wobbling motion of the mixing interface of two flows and the rotational oscillation of the flows.Copyright © 2007 by ASME

さきに, 郵政省から第2次チャネルプラン修正案が打ち出され, わが国においてもテレビ放送に662Mcから770Mcに至る18チャネル (チャネル名称として45-62チャネル) のUHF帯が使用されることとなった.昭和39年12月現在, NHK総合および教育局は, それぞれ31局に及んでいる.本文ではこれらUHFテレビサテライト局の設備の概要を報告する.