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We previously reported that the intake of heat-killed Lacticaseibacillus paracasei MCC1849 suppressed the onset of cold-like symptoms in healthy young women who were susceptible to colds. This study aimed to investigate the effects of MCC1849 on subjective symptoms of physical condition in healthy adults of a wide age range. In this randomized, double-blind, placebo-controlled, parallel-group study, 200 healthy adults were randomly divided into the MCC1849 group or placebo group. The participants received test powder with 50 billion MCC1849 cells or placebo powder without MCC1849 for 24 weeks. Subjective symptoms were assessed by diary scores. Analysis was performed on 183 participants (MCC1849 group; n = 91, placebo group; n = 92) in the per-protocol set. The number of days of stuffy nose and cold-like symptoms was significantly reduced in the MCC1849 group compared with the placebo group. In addition, the duration of stuffy nose, sore throat and cold-like symptoms was significantly lower in the MCC1849 group. No side effects were observed. Therefore, oral intake of MCC1849 suppressed subjective symptoms in healthy adults of a wide age range. These data suggest that MCC1849 may help maintain physical condition.

The present study examines the role of Pyk2 in acid regulation of sodium/hydrogen exchanger 3 (NHE3) activity in OKP cells, a kidney proximal tubule epithelial cell line. Incubation of OKP cells in acid media caused a transient increase in Pyk2 phosphorylation that peaked at 30 seconds and increased Pyk2/c-Src binding at 90 seconds. Pyk2 isolated by immunoprecipitation and studied in a cell-free system was activated and phosphorylated at acidic pH. Acid activation of Pyk2 (a) was specific for Pyk2 in that acid did not activate focal adhesion kinase, (b) required calcium, and (c) was associated with increased affinity for ATP. Transfection of OKP cells with dominant-negative pyk2(K457A) or small interfering pyk2 duplex RNA blocked acid activation of NHE3, while neither had an effect on glucocorticoid activation of NHE3. In addition, pyk2(K457A) blocked acid activation of c-Src kinase, which is also required for acid regulation of NHE3. The present results demonstrate that Pyk2 is directly activated by acidic pH and that Pyk2 activation is required for acid activation of c-Src kinase and NHE3. Given that partially purified Pyk2 can be activated by acid in a cell-free system, Pyk2 may serve as the pH sensor that initiates the acid-regulated signaling cascade involved in NHE3 regulation.

Major depressive disorder (MDD) is frequently unrecognized and underdiagnosed by clinicians and thus remains untreated or inappropriately treated in routine clinical practice. Although the symptoms of MDD are widely acknowledged and recognized by clinicians, numerous epidemiological studies have reported that this disorder is more prevalent than had previously been thought, and that it is challenging to diagnose and treat, particularly because somatic symptoms and comorbid conditions are common in real clinical situations. MDD is associated with increased morbidity and mortality as well as with higher healthcare costs and more severe functional impairment. Therefore, optimal treatment for MDD should include collaboration focussed on comorbid physical diseases, rehabilitation aimed at restoring social functioning, and pharmacotherapy designed to ensure complete remission including psychological and physical symptoms, as well as functional recovery.

Visceral fat accumulation is considered to be associated with a higher risk of chronic diseases. We investigated the effects of Bifidobacterium longum subsp. longum (B. longum) BB536 and Bifidobacterium breve (B. breve) MCC1274 on body composition, including visceral fat, in a randomized, parallel-group, placebo-controlled study. Participants were between 29 and 64 years of age and had a body mass index (BMI) of greater than 23 and less than 30. One hundred participants were randomly assigned to the probiotics group or placebo group. Participants were administered probiotic capsules containing 1 × 10[sup.10] colony-forming units (CFUs) of B. longum BB536 and 5 × 10[sup.9] CFU of B. breve MCC1274 or placebo capsules without bifidobacteria for 16 weeks. In the probiotics group, abdominal visceral fat area, total abdominal fat area, and serum triglyceride levels were significantly decreased compared to those in the placebo group. Additionally, the increase in BMI observed in the placebo group was significantly suppressed in the probiotics group. This study showed that B. longum BB536 and B. breve MCC1274 reduced abdominal visceral fat and total fat levels in healthy normal and overweight adults, suggesting their beneficial effects on body composition.

Previous clinical studies have shown that heat-killed Lacticaseibacillus paracasei MCC1849 suppresses subjective symptoms among healthy adults. However, the mechanism underlying this beneficial effect remains unclear. This clinical study aimed to investigate the effects of MCC1849 on immune functions in humans. In this randomized, double-blind, placebo-controlled, parallel-group study, 100 healthy adults were randomly divided into MCC1849 or placebo groups. Participants ingested test powder with 5 × 10[sup.10] MCC1849 cells or placebo powder for 4 weeks. Immune functions were evaluated using expression levels of CD86 and HLA-DR on dendritic cells (DCs), neutrophils, and natural killer cells. The expression levels of interferon (IFN)-α, -β, and -γ in peripheral blood mononuclear cells incubated with Cpg2216 in vitro were quantified. Efficacy analysis was performed on participants in the per-protocol set (placebo group; n = 47, MCC1849 group; n = 49). The expression level of CD86 on pDCs and the gene expression levels of IFN-α, -β, and -γ upon TLR9 agonist stimulation were significantly higher in the MCC1849 group at 4 weeks. No side effects were observed. This is the first report to show the positive effects of MCC1849 on human immune cells. These findings reveal one possible mechanism of how MCC1849 suppresses subjective symptoms.

We previously reported that the intake of heat-killed Lacticaseibacillus paracasei MCC1849 suppressed the onset of cold-like symptoms in healthy young women who were susceptible to colds. This study aimed to investigate the effects of MCC1849 on subjective symptoms of physical condition in healthy adults of a wide age range. In this randomized, double-blind, placebo-controlled, parallel-group study, 200 healthy adults were randomly divided into the MCC1849 group or placebo group. The participants received test powder with 50 billion MCC1849 cells or placebo powder without MCC1849 for 24 weeks. Subjective symptoms were assessed by diary scores. Analysis was performed on 183 participants (MCC1849 group; n = 91, placebo group; n = 92) in the per-protocol set. The number of days of stuffy nose and cold-like symptoms was significantly reduced in the MCC1849 group compared with the placebo group. In addition, the duration of stuffy nose, sore throat and cold-like symptoms was significantly lower in the MCC1849 group. No side effects were observed. Therefore, oral intake of MCC1849 suppressed subjective symptoms in healthy adults of a wide age range. These data suggest that MCC1849 may help maintain physical condition.

Heat‐killed Lacticaseibacillus paracasei MCC1849 (MCC1849) is a postbiotic used as a functional food ingredient. It has been shown to affect immune regulation both in vivo and in several clinical trials. Based on a previous safety evaluation, the intake of MCC1849 by healthy adults did not raise safety concerns. However, the effects of high‐dose intake have not been investigated. In this study, the safety associated with a high‐dose MCC1849 was evaluated in 20 healthy adults for 4 weeks. The participants received 250 billion cells of MCC1849 per day. Safety evaluations included anthropometric and blood pressure measurements, hematological and biochemical tests, urinalysis, and adverse event monitoring. No clinical differences were detected in anthropometric measurements, blood pressure, or blood and urine parameters between the baseline and post‐intervention measurements. No adverse events associated with MCC1849 intake were observed. In conclusion, an intake of 250 billion cells of MCC1849 per day for 4 weeks was found to be safe in healthy adults. These results suggest that the intake of MCC1849 is safe for use as functional foods, such as for immune‐enhancing effects. This study evaluated the safety of a high‐dose intake of heat‐killed Lacticaseibacillus paracasei MCC1849, a type of postbiotic. No adverse events related to the test food were observed in anthropometric and blood pressure measurements, blood and urine analysis, or medical interviews. These results suggest that the intake of MCC1849 is safe.

Heat-killed Lacticaseibacillus paracasei MCC1849 (MCC1849) is a postbiotic used as a functional food ingredient. It has been shown to affect immune regulation both in vivo and in several clinical trials. Based on a previous safety evaluation, the intake of MCC1849 by healthy adults did not raise safety concerns. However, the effects of high-dose intake have not been investigated. In this study, the safety associated with a high-dose MCC1849 was evaluated in 20 healthy adults for 4 weeks. The participants received 250 billion cells of MCC1849 per day. Safety evaluations included anthropometric and blood pressure measurements, hematological and biochemical tests, urinalysis, and adverse event monitoring. No clinical differences were detected in anthropometric measurements, blood pressure, or blood and urine parameters between the baseline and post-intervention measurements. No adverse events associated with MCC1849 intake were observed. In conclusion, an intake of 250 billion cells of MCC1849 per day for 4 weeks was found to be safe in healthy adults. These results suggest that the intake of MCC1849 is safe for use as functional foods, such as for immune-enhancing effects.Heat-killed Lacticaseibacillus paracasei MCC1849 (MCC1849) is a postbiotic used as a functional food ingredient. It has been shown to affect immune regulation both in vivo and in several clinical trials. Based on a previous safety evaluation, the intake of MCC1849 by healthy adults did not raise safety concerns. However, the effects of high-dose intake have not been investigated. In this study, the safety associated with a high-dose MCC1849 was evaluated in 20 healthy adults for 4 weeks. The participants received 250 billion cells of MCC1849 per day. Safety evaluations included anthropometric and blood pressure measurements, hematological and biochemical tests, urinalysis, and adverse event monitoring. No clinical differences were detected in anthropometric measurements, blood pressure, or blood and urine parameters between the baseline and post-intervention measurements. No adverse events associated with MCC1849 intake were observed. In conclusion, an intake of 250 billion cells of MCC1849 per day for 4 weeks was found to be safe in healthy adults. These results suggest that the intake of MCC1849 is safe for use as functional foods, such as for immune-enhancing effects.

English translation team: (affiliation as of May 2021) Ryota Hashimoto, Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry Junichi Iga, Department of Neuropsychiatry, Ehime University Graduate School of Medicine Ken Inada, Department of Psychiatry, Tokyo Women’s Medical University Taro Kishi, Department of Psychiatry, Fujita Health University School of Medicine Hiroshi Kimura, Department of Psychiatry, International University of Health and Welfare/Gakuji-kai Kimura Hospital Yuki Matsuda, Department of Psychiatry, Jikei University School of Medicine Nobumi Miyake, Department of Neuropsychiatry, St. Marianna University School of Medicine Kiyotaka Nemoto, Department of Psychiatry, Faculty of Medicine, University of Tsukuba Shusuke Numata, Department of Psychiatry, Graduate School of Biomedical Science, Tokushima University Shinichiro Ochi, Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine Hideki Sato, National Center Hospital, National Center of Neurology and Psychiatry Seiichiro Tarutani, Department of Psychiatry, Shin-Abuyama Hospital, Osaka Institute of Clinical Psychiatry Hiroyuki Uchida, Department of Neuropsychiatry, Keio University School of Medicine English translation team: (COI as of 2018-2020) Ryota Hashimoto: Received research grants from Otsuka Pharmaceutical Co., Ltd., Japan Tobacco Inc., and Takeda Pharmaceutical Company Ltd.; rewards for lectures from Takeda Pharmaceutical Company Ltd., Lundbeck Japan K.K., Dainippon Sumitomo Pharma Co., Ltd., and Mochida Pharmaceutical.Co., Ltd.; manuscript fees for writing from Dainippon Sumitomo Pharma Co., Ltd. Junchi Iga: Received rewards for lectures from Otsuka Pharmaceutical Co. Ltd., Meiji Seika Pharma Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Kyowa Pharmaceutical Industry Co. Ltd., Shionogi & Co. Ltd., Mochida Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mylan Inc., Sawai Pharmaceutical Co. Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Sanofi K.K., Viatris Inc., and Yoshitomiyakuhin Co. Ken Inada: Received research grants, rewards for lectures, manuscript fees for writing, and donations from Astellas Pharma Inc., Eisai Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., Shionogi & Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Pfizer Inc., Meiji Seika Pharma Co. Ltd., Mochida Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., and Yoshitomiyakuhin Co. Taro Kishi: Received speaker’s honoraria from Sumitomo Dainippon, Otsuka, Eisai, Daiichi Sankyo, Janssen, Takeda, Kyowa, Kissei, Meiji, Pfizer, Mochida, Eli Lilly, MSD, Janssen, and Tanabe-Mitsubishi (Yoshitomi); as well as research grants from Eisai, the Japanese Ministry of Health, Labour and Welfare, Grant-in-Aid for Scientific Research, and Fujita Health University School of Medicine. Before reading this guideline (For experts, patients, families, and supporters) This guideline was written for specialists in the treatment of schizophrenia, but patients, as well as their families and supporters, may also use this guideline. [...]a very simple explanation will first be given on the aims of this guideline. [...]one may have the impression from reading the individual texts that it is recommended to treat schizophrenia with pharmacological therapy alone, or that pharmacological therapy has a larger effect than other therapies. [...]the available drugs and their administration and the medical system can vary between Japan and other countries. [...]a clinical guideline that is aligned with the medical circumstances in Japan was needed.

Background Every psychiatrist must pay careful attention to avoid violating human rights when initiating coercive treatments such as seclusion and restraint. However, these interventions are indispensable in clinical psychiatry, and they are often used as strategies to treat agitated patients. In this study, we investigated young psychiatrists' attitudes toward psychiatric coercive measures. Methods A total of 183 young psychiatrists participated as subjects in our study. A questionnaire with a case vignette describing a patient with acute psychosis was sent to the study subjects via the Internet or by mail. This questionnaire included scoring the necessity for hospitalization, and the likelihood of prescribing seclusion and/or restraint, on a 9-point Likert scale (with 9 indicating strong agreement). Results There was general agreement among the study subjects that the case should be admitted to a hospital (8.91 ± 0.3) and secluded (8.43 ± 1.0). The estimated length of hospitalization was 13.53 ± 6.4 weeks. Regarding the likelihood of prescribing restraint, results showed great diversity (5.14 ± 2.5 on 9-point scale); psychiatrists working at general hospitals scored significantly higher (6.25 ± 2.5) than those working at university hospitals (5.02 ± 2.3) or psychiatric hospitals (4.15 ± 2.6). A two-group comparison of the length of inpatient care revealed a significant difference between those psychiatrists who scored 1-3 (n = 55, 14.22 ± 7.4 wks) and those who scored 7-9 (n = 62, 12.22 ± 4.0) regarding the need to use restraint. Conclusion Our results may reflect the current dilemma in Japanese psychiatry wherein psychiatrists must initiate coercive measures to shorten hospitalization stays. This study prompted its subject psychiatrists to consider coercive psychiatric treatments.