Possible involvement of zinc transporter ZIP13 in myogenic differentiation.

Ehlers-Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13G64D) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.

Bakuchiol targets mitochondrial proteins, prohibitins and voltage-dependent anion channels: New insights into developing antiviral agents.

We previously reported that bakuchiol, a phenolic isoprenoid anticancer compound, and its analogs exert anti-influenza activity. However, the proteins targeted by bakuchiol remain unclear. Here, we investigated the chemical structures responsible for the anti-influenza activity of bakuchiol and found that all functional groups and C6 chirality of bakuchiol were required for its anti-influenza activity. Based on these results, we synthesized a molecular probe containing a biotin tag bound to the C1 position of bakuchiol. With this probe, we performed a pulldown assay for Madin-Darby canine kidney cell lysates and purified the specific bakuchiol-binding proteins with SDS-PAGE. Using nanoLC-MS/MS analysis, we identified prohibitin (PHB) 2, voltage-dependent anion channel (VDAC) 1, and VDAC2 as binding proteins of bakuchiol. We confirmed the binding of bakuchiol to PHB1, PHB2, and VDAC2 in vitro using Western blot analysis. Immunofluorescence analysis showed that bakuchiol was bound to PHBs and VDAC2 in cells and colocalized in the mitochondria. The knockdown of PHBs or VDAC2 by transfection with specific siRNAs, along with bakuchiol cotreatment, led to significantly reduced influenza nucleoprotein expression levels and viral titers in the conditioned medium of virus-infected Madin-Darby canine kidney cells, compared to the levels observed with transfection or treatment alone. These findings indicate that reducing PHBs or VDAC2 protein, combined with bakuchiol treatment, additively suppressed the growth of influenza virus. Our findings indicate that bakuchiol exerts anti-influenza activity via a novel mechanism involving these mitochondrial proteins, providing new insight for developing anti-influenza agents.

Anti-influenza Activity of Povidone-Iodine-Integrated Materials.

Personal protective equipment (PPE), including medical masks, should be worn for preventing the transmission of respiratory pathogens via infective droplets and aerosols. In medical masks, the key layer is the filter layer, and the melt-blown nonwoven fabric (NWF) is the most used fabric. However, the NWF filter layer cannot kill or inactivate the pathogens spread via droplets and aerosols. Povidone-iodine (PVP-I) has been used as an antiseptic solution given its potent broad-spectrum activity against pathogens. To develop PPE (e.g., medical masks) with anti-pathogenic activity, we integrated PVP-I into nylon-66 NWF. We then evaluated its antiviral activity against influenza A viruses by examining the viability of Madin-Darby canine kidney (MDCK) cells after inoculation with the virus strains exposed to the PVP-I-integrated nylon-66 NWF. The PVP-I nylon-66 NWF protected the MDCK cells from viral infection in a PVP-I concentration-dependent manner. Subsequently, we found to integrate PVP-I into nylon-66 and polyurethane materials among various materials. These PVP-I materials were also effective against influenza virus infection, and treatment with PVP-I nylon-66 NWF showed the highest cell survival among all the tested materials. PVP-I showed anti-influenza A virus activity when used in conjunction with PPE materials. Moreover, nylon-66 NWF integrated with PVP-I was found to be the best material to ensure anti-influenza activity. Therefore, PVP-I-integrated masks could have the potential to inhibit respiratory virus infection. Our results provide new information for developing multi-functional PPEs with anti-viral activity by integrating them with PVP-I to prevent the potential transmission of respiratory viruses.

A non-randomized, controlled, interventional study to investigate the effects of community pharmacists' cognitive behavioral therapy-based interventions on medication adherence and relevant indicators in patients with depression.

BACKGROUND: The prevalence of depression is increasing in Japan. Pharmacists play an important role in helping patients use medicines effectively. Several studies had investigated the impact of community pharmacists on patient adherence to antidepressant therapy, and their results indicated that further study was warranted. METHODS: This study was conducted from June 2019 to May 2020 using a cluster non-randomized, open-label, parallel-group design. Four community pharmacy stores in Osaka and Hyogo Prefectures, Japan, participated in the study, and enrolled patients with unipolar depression. In the intervention group (IG), patients received cognitive behavioral therapy (CBT)-based medication support, and their medication adherence and adverse drug reactions were monitored by telephone. In the control group (CG), the pharmacists engaged in routine interactions with the study participants. Before participating in this study, the intervention-group pharmacists attended a 5-hour training session on CBT-based medication support. The primary outcome of this study was medication adherence, assessed using the Drug Attitude Inventory (DAI)-10. Secondary outcomes included the changes from baseline at 6 months in the following variables: the Patient Health Questionnaire (PHQ)-9 total score, the EQ-5D-5 L (Euro-QOL 5 dimensions 5 levels) score, patient satisfaction, and the Pharmacists' Confidence Scale about Medication Consultation for Depressive Patients (PCMCD) score. RESULTS: Four pharmacies (two in IG and two in CG) completed the intervention period. Results were obtained from 19 patients in the IG and 12 patients in the CG. In the IG, the mean DAI-10 score increased from 4.941 at baseline to 6.105, the mean PHQ-9 score decreased from 9.263 to 8.625, and the mean patient satisfaction score increased from 39.947 to 42.211. In the CG, the mean DAI-10 score decreased from 6.333 to 4.167, the mean PHQ-9 score increased from 9.333 to 12.923, and the mean patient satisfaction score decreased from 38.929 to 38.167. CONCLUSION: CBT-based medication support provided by community pharmacists may improve patient medication adherence to antidepressant therapy and symptoms. Such support can be expected to facilitate better treatment of depressed patients and may also allow the duration of treatment to be shortened. TRIAL REGISTRATION: UMIN000037954, Date of first registration: 17/06/2019.

Imaging Analysis of Neurotrophic Effects by CCN2 Protein in Neuronal Precursor Cells Derived from Human-Induced Pluripotent Stem Cells.

Human-induced pluripotent stem cells (hiPSCs) are useful tools to examine human neuronal maturation processes. In this chapter, we describe the maturation of human neuronal precursor cells derived from hiPSCs by cellular communication network family member 2, also known as connective tissue growth factor. We describe the (1) preparation of feeder cells for undifferentiated culture of hiPSCs, (2) undifferentiated culture of hiPSCs, (3) induction of neuronal precursor cells from hiPSCs, (4) maturation of neuronal precursor cells from hiPSCs, (5) immunofluorescent staining of neuronal cells from hiPSCs, and (6) immunofluorescence analysis.

Communication Management Processes of Dentists Providing Healthcare for Migrants with Limited Japanese Proficiency.

Low health literacy results in health inequity are linked with poor adherence to medical care. In the globalized Japanese context, the number of migrants with Japanese as a second language is increasing year after year. Since limited Japanese proficiency may pose a greater health risk, dentists are expected to manage cross-cultural communication and provide dental care to foreign patients. This study explored dentists' experiences of treating patients with limited Japanese proficiencies. Semi-structured interviews were conducted with 11 community dentists and the qualitative data were analyzed through a thematic analysis approach. Their major challenges were classified into three themes-linguistic aspect (e.g., complicated explanation regarding root canal treatment), sociolinguistic aspect (e.g., communication with foreign residents with limited dental knowledge), and sociocultural aspect (e.g., cultural differences in their dental aesthetics and insurance treatment system). Several management strategies were employed, including linguistic accommodation, avoidance of complexities, use of various communication tools, and getting help from others. However, they were unsatisfied with their practice because they could not understand the patients' psychosocial aspects due to incomplete communication. These findings provided insights into dentists' practice in the globalized context.

Transcriptome Analysis of PC12 Cells Reveals That trans-Banglene Upregulates RT1-CE1 and Downregulates abca1 in the Neurotrophic Pathway.

trans-Banglene and cis(c)-banglene possess neurotrophin-like activity in rat neurons. However, the molecular mechanisms underlying t-banglene-induced neurotrophic activity in rat and human neurons remain unclear. Here, we performed transcriptome analysis in PC12 cells, a rat adrenal gland pheochromocytoma cell line treated with t-banglene, using comprehensive RNA sequencing. The differentially expressed gene analysis of the sequencing data revealed that the expression of RT1 class I, locus CE1 (RT1-CE1) was upregulated, and that of ATP binding cassette subfamily A member 1 (abca1), myosin light chain 6, and hippocampus abundant transcript 1 was downregulated in t-banglene-treated PC12 cells, with statistically significant differences. We also confirmed the RT1-CE1 upregulation and abca1 downregulation in t-banglene-treated PC12 cells by real-time reverse transcription quantitative PCR. RT1-CEl is a major histocompatibility complex class I (MHCI) protein. ABCAl is a major cholesterol transporter that regulates efflux of intracellular cholesterol and phospholipids. Thus, our results suggest an exciting link between MHCI, cholesterol regulation, and neural development.

A pilot study of Pharmacist-Dietician Collaborative support and Advice (PDCA) for patients with type 2 diabetes in community pharmacy: A single-arm, pre-post study.

Background: In Japan, there is a pressing need to improve community health care to cope with the rapid aging of the population. In this context, there have been private-sector-led approaches to enhance community dietary support by employing dietitians in pharmacies. Objectives: To evaluate the effects of collaboration between dietitians and pharmacists working in pharmacies to support patients with type 2 diabetes. Methods: A single group pre- and post-comparative study was conducted on patients with type 2 diabetes mellitus. The intervention period was 6 months. During the intervention period, the dietitians provided dietary support to the patients after first providing them with medication guidance. The contents of these instructions were shared with the pharmacists. The contents of the instructions were recorded, and confirmed in monthly meetings with the principal investigator. The primary endpoint was the Hemoglobin A1c(HbA1c) level, and the secondary endpoints were high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), Triglyceride (TG), degree of dietary self-management, degree of unbalanced diet and satisfaction with pharmacy services. Results: Eight patients completed the intervention period. The first patient's intervention started in March 2021, and all patients' interventions were completed by December 2021. The primary endpoint, the mean (SD) HbA1c, was 7.26 (0.96) at baseline and decreased to 6.63 (0.79) after 6 months (p=0.028, r=0.72). Also, the HDL-c increased from 55.00 (14.81) to 63.14 (10.11) (p=0.110, r=0.51) and the Diabetes Mellitus Dietary Self Efficacy Scale score increased from 51.67 (8.31) to 60.17 (8.45) (p=0.025, r=0.79) and the patient satisfaction score increased 24.0 (4.0) to 26.1 (3.3) (p=0.161, r=0.51). Moderate decreases were also observed in LDL-c (p=0.235, r=0.47) and TG (p=0.368, r=0.37). Conclusions: Collaboration between dietitians and pharmacists working in pharmacies may improve the dietary habits and glycemic control of patients with type 2 diabetes. To verify this hypothesis more reliably, randomized controlled trials need to be conducted.

Self-efficacy of community pharmacists and associated factors in counselling to support self-medication in Japan: A cross-sectional study.

Background: In 2016, the Ministry of Health, Labour and Welfare established the Health Support Pharmacy Certification System. The certification requirements include a track record of counseling regarding the use of over-the-counter drugs (OTC). Therefore, pharmacists must increase their self-efficacy for counseling. Objectives: To determine pharmacists' self-efficacy for OTC counseling and related factors. Methods: A web-based survey was conducted. Multivariate analysis was conducted to test the relationship among the mean scores of self-efficacy for OTC counselling for 25 symptoms, pharmacist attributes, years of work, psychosocial factor, job satisfaction, and level of trust from the community and patients. Results: We received responses from 250 people. The overall self-efficacy was 5.8 (SD= 2.4) but varied depending on the symptoms. Self-efficacy was relatively high for allergic symptoms (6.9), cold/influenza (6.9), and constipation (7.1), but relatively low for contraceptive drugs (3.8), palpitation/shortness of breath (4.6), and abnormal taste/smell (4.2). In bivariate analysis, items related to self-efficacy included "age" (Spearman correlation= 0.276, P<0.001), "academic background" (-0.208, P=0.001), "number of years of work" (0.267, P<0.001), "level of trust from the community" (0.155, P=0.014), "level of trust from patients" (0.271, P<0.001), "job satisfaction" (0.236, P<0.001), "role clarity" (0.181, P=0.004), and "positive challenge at work" (0.271, P<0.001). Multivariate analysis indicated that the number of years of work (Standardizing Coefficient: 0.22), trust from patients (0.13), and positive challenge at work (0.25) had a positive effect on self-efficacy. Conclusions: Years of work, recognition that they are trusted by patients, and positive challenge at work were important for the counseling self-efficacy of pharmacists. These results provide implications for pharmacy management and lifelong education strategies to promote self-efficacy in pharmacist counseling.

Enhancement of Acinetobacter baumannii biofilm growth by cephem antibiotics via enrichment of protein and extracellular DNA in the biofilm matrices.

AIMS: The aims were to determine the effects of subinhibitory concentrations of eight cephem and carbapenem antibiotics on the biofilm formation of Acinetobacter baumannii cells and examine their effects on pre-established biofilms. METHODS AND RESULTS: Effects of antibiotics on biofilm formation were assayed using microtitre plates with polystyrene peg-lids. Cefmetazole, ceftriaxone, ceftazidime and cefpirome increased the biomass of pre-established biofilms on pegs in the range of their sub-minimum inhibitory concentrations (MICs), whereas none increased biofilm formation by planktonic cells. Carbapenems had a negative effect. The constituents of antibiotic-induced biofilms were analysed. Ceftriaxone or ceftazidime treatment markedly increased the matrix constituent amounts in the biofilms (carbohydrate, 2.7-fold; protein, 8.9-12.7-fold; lipid, 3.3-3.6-fold; DNA, 9.1-12.2-fold; outer membrane vesicles, 2.7-3.8-fold and viable cells, 6.8-10.1-fold). The antibiotic-enhanced biofilms had increased outer membrane protein A and were resistant to the anti-biofilm effect of azithromycin. CONCLUSIONS: Some cephems increased the biomass of pre-established biofilms in the ranges of their sub-MICs. The antibiotic-enhanced biofilms possessed more virulent characteristics than normal biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Incomplete administration of certain cephems following biofilm-related Ac. baumannii infections could adversely cause exacerbated and chronic clinical results.

A cross-sectional study of demonstrating expertise and job satisfaction in pharmacists and dietitians working in community pharmacies in Japan.

Background: In Japan, there has been a private-sector initiative to register dietitians in pharmacies. There is not yet an adequate amount of data on the attitudes of dietitians in pharmacies regarding their work. Objectives: To assess the attitudes of pharmacists and dietitians working in community pharmacies in Japan about their work, and particularly about demonstrating expertise and overall job satisfaction. Methods: We administered a web-based questionnaire to pharmacists and dietitians working in pharmacy branches with registered dietitians at two pharmacy chains that agreed to cooperate. We used our own 7-item questionnaire and compared the scores for each item between pharmacists and dietitians. Results: A total of 61 persons (22 pharmacists and 39 dietitians) answered the questionnaire. The item with the highest mean score (standard deviation) for pharmacists was "I feel that I am helpful to patients," at 3.50 (0.74), and for dietitians it was "I have colleagues at my workplace whom I can talk to when I have a problem," at 3.51 (1.00). Conversely, the items with the lowest mean score (standard deviation) were "I am satisfied with my current job" for pharmacists, at 3.14 (0.83), and "I can grow sufficiently as a professional" for dietitians, at 2.41 (0.97). As a result of factor analysis, the seven-item question could be divided into two factors: "demonstrating expertise" and "overall job satisfaction." The factor-score for "demonstrating expertise" was significantly lower for dietitians than for pharmacists (p<0.01), but there was no significant difference in overall job satisfaction between the two professions (p=0.36). Further research is needed to understand why dietitians find "demonstrating expertise" difficult in pharmacies. Conclusions: The attitudes of pharmacists and dietitians working in pharmacies in Japan toward their jobs were shown to consist of "demonstration of expertise" and "overall job satisfaction. Dietitians had significantly lower scores on "demonstration of expertise" than pharmacists.

Acetylation of the influenza A virus polymerase subunit PA in the N-terminal domain positively regulates its endonuclease activity.

The post-translational acetylation of lysine residues is found in many nonhistone proteins and is involved in a wide range of biological processes. Recently, we showed that the nucleoprotein of the influenza A virus is acetylated by histone acetyltransferases (HATs), a phenomenon that affects viral transcription. Here, we report that the PA subunit of influenza A virus RNA-dependent RNA polymerase is acetylated by the HATs, P300/CREB-binding protein-associated factor (PCAF), and general control nonderepressible 5 (GCN5), resulting in accelerated endonuclease activity. Specifically, the full-length PA subunit expressed in cultured 293T cells was found to be strongly acetylated. Moreover, the partial recombinant protein of the PA N-terminal region containing the endonuclease domain was also acetylated by PCAF and GCN5 in vitro, which facilitated its endonuclease activity. Mass spectrometry analyses identified K19 as a candidate acetylation target in the PA N-terminal region. Notably, the substitution of the lysine residue at position 19 with glutamine, a mimic of the acetyl-lysine residue, enhanced its endonuclease activity in vitro; this point mutation also accelerated influenza A virus RNA-dependent RNA polymerase activity in the cell. Our findings suggest that PA acetylation is important for the regulation of the endonuclease and RNA polymerase activities of the influenza A virus.

Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D.

Novel antiviral agents for influenza, which poses a substantial threat to humans, are required. Cyclobakuchiols A and B have been isolated from Psoralea glandulosa, and cyclobakuchiol C has been isolated from P. corylifolia. The structural differences between cyclobakuchiol A and C arise due to the oxidation state of isopropyl group, and these compounds can be derived from (+)-(S)-bakuchiol, a phenolic isoprenoid compound present in P. corylifolia seeds. We previously reported that bakuchiol induces enantiospecific anti-influenza A virus activity involving nuclear factor erythroid 2-related factor 2 (Nrf2) activation. However, it remains unclear whether cyclobakuchiols A-C induce anti-influenza A virus activity. In this study, cyclobakuchiols A, B, and C along with cyclobakuchiol D, a new artificial compound derived from cyclobakuchiol B, were synthesized and examined for their anti-influenza A virus activities using Madin-Darby canine kidney cells. As a result, cyclobakuchiols A-D were found to inhibit influenza A viral infection, growth, and the reduction of expression of viral mRNAs and proteins in influenza A virus-infected cells. Additionally, these compounds markedly reduced the mRNA expression of the host cell influenza A virus-induced immune response genes, interferon-ß and myxovirus-resistant protein 1. In addition, cyclobakuchiols A-D upregulated the mRNA levels of NAD(P)H quinone oxidoreductase 1, an Nrf2-induced gene, in influenza A virus-infected cells. Notably, cyclobakuchiols A, B, and C, but not D, induced the Nrf2 activation pathway. These findings demonstrate that cyclobakuchiols have anti-influenza viral activity involving host cell oxidative stress response. In addition, our results suggest that the suitably spatial configuration between oxidized isopropyl group and phenol moiety in the structure of cyclobakuchiols is required for their effect.

A novel aqueous extract from rice fermented with Aspergillus oryzae and Saccharomyces cerevisiae possesses an anti-influenza A virus activity.

Human influenza virus infections occur annually worldwide and are associated with high morbidity and mortality. Hence, development of novel anti-influenza drugs is urgently required. Rice Power® extract developed by the Yushin Brewer Co. Ltd. is a novel aqueous extract of rice obtained via saccharization and fermentation with various microorganisms, such as Aspergillus oryzae, yeast [such as Saccharomyces cerevisiae], and lactic acid bacteria, possessing various biological and pharmacological properties. In our previous experimental screening with thirty types of Rice Power® extracts, we observed that the 30th Rice Power® (Y30) extract promoted the survival of influenza A virus-infected Madin-Darby canine kidney (MDCK) cells. Therefore, to identify compounds for the development of novel anti-influenza drugs, we aimed to investigate whether the Y30 extract exhibits anti-influenza A virus activity. In the present study, we demonstrated that the Y30 extract strongly promoted the survival of influenza A H1N1 Puerto Rico 8/34 (A/PR/8/34), California 7/09, or H3N2 Aichi 2/68 (A/Aichi/2/68) viruses-infected MDCK cells and inhibited A/PR/8/34 or A/Aichi/2/68 viruses infection and growth in the co-treatment and pre-infection experiments. The pre-treatment of Y30 extract on MDCK cells did not induce anti-influenza activity in the cell. The Y30 extract did not significantly affect influenza A virus hemagglutination, and neuraminidase and RNA-dependent RNA polymerase activities. Interestingly, the electron microscopy experiment revealed that the Y30 extract disrupts the integrity of influenza A virus particles by permeabilizing the viral membrane envelope, suggesting that Y30 extract has a direct virucidal effect against influenza A virus. Furthermore, we observed that compared to the ethyl acetate (EtOAc) extract, the water extract of Y30 extract considerably promoted the survival of cells infected with A/PR/8/34 virus. These results indicated that more anti-influenza components were present in the water extract of Y30 extract than in the EtOAc extract. Our results highlight the potential of a rice extract fermented with A. oryzae and S. cerevisiae as an anti-influenza medicine and a drug source for the development of anti-influenza compounds.

Direct anti-biofilm effects of macrolides on Acinetobacter baumannii: comprehensive and comparative demonstration by a simple assay using microtiter plate combined with peg-lid.

Recently, opportunistic nosocomial infections caused by Acinetobacter baumannii have become increasingly prevalent worldwide. The pathogen often establishes biofilms that adhere to medical devices, causing chronic infections refractory to antimicrobial therapy. Clinical reports have indicated that some macrolide antibiotics are effective against chronic biofilm-related infections. In this study, we examined the direct anti-biofilm effects of seven macrolides (azithromycin, clarithromycin, erythromycin, josamycin, spiramycin, fidaxomicin, and ivermectin) on A. baumannii using a simple and newly established in vitro assay system for the swift and serial spectrophotometric determinations of two biofilm-amount indexes of viability and biomass. These macrolides were found to possess direct anti-biofilm effects exerting specific anti-biofilm effects not exclusively depending on their bacteriostatic/bactericidal effects. The anti-biofilm effect of azithromycin was found to be the strongest, while those of fidaxomicin and ivermectin were weak and limited. These results provide insights into possible adjunctive chemotherapy with macrolides for A. baumannii infection. Common five macrolides also interfered with the Agrobacterium tumefaciens NTL(pCF218) (pCF372) bioassay system of N-acyl homoserine lactones, providing insights into sample preparation for the bioassay, and putatively suggesting the actions of macrolides as remote signals in bacterial quorum sensing systems.

The relationship between community pharmacists' social distance from and their confidence in interacting with patients with depression in Japan.

Background Prejudice and stigma against patients with depression may lead to adverse clinical consequences, such as delayed initiation and premature termination of therapy. However, available survey results on pharmacists' awareness showed a lack of confidence in dealing with patients with depression. Until recently, few studies addressed the relationship between pharmacists' perceptions of their social distance from and confidence in interacting with patients with depression. Objectives To determine pharmacists' social distance from patients with depression, and investigate the factors that influence and are influenced by it. Methods The target population of this survey study included 161 pharmacists employed at a drug chain who had participated in the Effects of Community Pharmacists' Medication Assistance for the Patients Taking Antidepressant study. The questionnaire included six questions on social distance, which were adopted from a previous nation-wide survey of mental illness stigma in Japan. Other questions related to the respondents' attributes, personal experience (living with depression, abusive behaviors inflicted by patients with depression), and confidence in interacting with patients with depression. Results Valid responses were obtained from 77 study participants. The mean total social distance score was 12.49. Greater total social distance scores were associated with greater difficulty in relationship building, information provision, and comprehension of condition. Pharmacists' personal experience of living with depression decreased their social distance from patients with depression, whereas their experience of being verbally or physically abused by patients with depression increased their social distance. Conclusion This study showed that community pharmacists in Japan had less social distance from patients with depression than the general population. A significant negative correlation was observed between community pharmacists' social distance from and their confidence in interacting with patients with depression.

[Introduction of Team-based Learning to Evidence-based Medicine Educational Course for Pharmacy Students].

In Japanese pharmaceutical education, the Model Core Curriculum was revised in 2013 to train pharmacists who can appropriately evaluate literature and use evidence-based medicine (EBM). However, in the investigation of EBM education at pharmaceutical universities in 2015, it was found that literature evaluation was hardly performed in the education of undergraduate students. One of the reason is the lack of EBM lecturers at each universities. Therefore, we adopted team-based learning (TBL) to educate more than 50 undergraduate students on the practical evaluation of literatures and the understanding of EBM concepts. The learning outcomes of this strategy were evaluated using the scores of individual tests before and after the class. As a result, the mean scores on the post-test significantly improved from 4.34 to 6.42 out of 10 total points (p<0.001). We further administered a questionnaire survey regarding the understanding of EBM (the mean score was 4.12). In conclusion, it was suggested that TBL for a large number was effective in EBM education for providing knowledge of literature evaluation and the understanding of fundamental concepts.

Jiadifenolide induces the expression of cellular communication network factor (CCN) genes, and CCN2 exhibits neurotrophic activity in neuronal precursor cells derived from human induced pluripotent stem cells.

Jiadifenolide has been reported to have neurotrophin-like activity in primary rat cortical neurons, and also possesses neurotrophic effects in neuronal precursor cells derived from human induced pluripotent stem cells (hiPSCs), as we have previously reported. However, the molecular mechanisms by which jiadifenolide exerts its neurotrophic effects in rat and human neurons are unknown. Thus, we aimed to investigate the molecular mechanisms and pathways by which jiadifenolide promotes neurotrophic effects. Here, we found that jiadifenolide activated cellular communication network factor (CCN) signaling pathways by up-regulating mRNA level expression of CCN genes in human neuronal cells. We also found that CCN2 (also known as connective tissue growth factor, CTGF) protein promotes neurotrophic effects through activation of the p44/42 mitogen-activated protein kinase signaling pathway. This is the first discovery which links neurotrophic activity with CCN signaling.

The change in pharmacists' attitude, confidence and job satisfaction following participation in a novel hypertension support service.

OBJECTIVES: To demonstrate how the confidence, attitude and job satisfaction of pharmacists who provide interventions and lifestyle support services to patients with hypertension are altered. METHODS: This study was a before-and-after study that used data from 50 pharmacists who participated in the Community Pharmacists Assist for Blood Pressure (COMPASS-BP) study, which was an interventional study that was conducted in Japan to evaluate the effects of lifestyle support services provided to hypertension patients. The pharmacists received 4 h of training before the study was initiated to learn how to quickly provide patients with guidance about diet and exercise and tobacco and alcohol consumption. During the interventional period, each pharmacist provided concise lifestyle guidance to 1-3 hypertension patients. The pharmacists met with the patients a total of 5 times. The parameters that were assessed were the pharmacists' attitudes towards and confidence in their lifestyle support services, as well as their level of job satisfaction. We verified the scores of each parameter assessed before and after the study, as well as changes in the relationships among the different parameters. KEY FINDINGS: Significant increases from baseline to the end of the study were observed for Confidence (P < 0.01), Job satisfaction, including 'Knowledge' (P < 0.01), 'Patient counselling management' (P = 0.04) and 'Sense of personal growth' (P < 0.01). Additionally, path analysis results revealed that after the study, the causal relationship between 'Knowledge' and 'Attitude' disappeared, and a new causal relationship appeared between 'Patient counselling and management' and 'Attitude'. CONCLUSIONS: Providing lifestyle guidance improved pharmacists' confidence and attitude. Also, 'Attitude' tended to improve as the 'Patient counselling and management' score increased.

Creation and validation of a semi-quantitative instrument to assess the confidence of pharmacists in medication consultation for patients with depression: The pharmacists' confidence scale about medication consultation for depressive patients (PCMCD).

OBJECTIVES: To develop a semi-quantitative instrument to assess pharmacists' confidence in medication counseling for patients with depression, The Pharmacists' Confidence scale about Medication Consultation for Depressive patients (PCMCD), and investigated its validity. METHODS: Following discussions with practicing pharmacists, we developed a 12-item questionnaire to assess pharmacists' confidence in medication counseling for patients with depression. We launched web-based cross-sectional survey during November and December 2018 to 77 pharmacists employed at drug chain stores in Kansai area. Factor analysis was performed to evaluate the configuration concept validity. The least-squares method was used for factor extraction, and the resulting factors were subjected to direct oblimin rotation, with a factor loading cut-off of 0.4. To assess internal consistency, Cronbach's alpha values were calculated for each of the extracted factors (subscales). A multiple regression analysis was performed using simultaneous forced entry, with the scores obtained for each subscale as dependent variables and responder attributes as independent variables in order to investigate the factors associated with each subscale. RESULTS: During the factor analysis procedure, four questions were excluded by the cut-off rule. Eventually, a model with three subscales was identified, with a cumulative sum of squared loadings being 61.9%. The subscales were termed "relationship building," "comprehension of condition," and "information provision" based on the nature of the questions relevant for each of them. The Cronbach's alpha values for these subscales were 0.92, 0.73, and 0.72, respectively. The average inter-item correlation was 0.378. In addition, multiple regression analysis revealed that there were significant correlations between pharmacist career and both relationship building and information provision. CONCLUSIONS: The PCMCD model demonstrated a satisfactory construct validity and internal consistency. This model will provide an excellent tool for assessing pharmacists' confidence in depression care.