Public Knowledge and Attitude of Caregivers Regarding Leftover Medications for Children under 6 Years of Age in Japan: A Descriptive Study on a Nationwide Exploratory Questionnaire Survey to Caregivers.

Leftover medications are a global concern for harm to health and inadequate medical care costs. However, information on leftover medicines and their inappropriate use in children in Japan is lacking. We aimed to clarify the proportion of leftover and re-use of children's medications in Japan.

Investigation of Glucose Metabolism by Continuous Glucose Monitoring and Validation of Dipeptidyl Peptidase 4 Inhibitor Use in Patients with Myotonic Dystrophy Type 1.

We characterized blood glucose fluctuations in patients with myotonic dystrophy type 1 (DM1). After confirming the incretin secretion capacity of patients with DM1, we intended to clarify whether dipeptidyl peptidase 4 (DPP-4) inhibitor administration was appropriate in cases of DM1 with diabetes mellitus. A 48 h continuous glucose monitoring (CGM) was performed in 29 Japanese patients with DM1.

Charge block-driven liquid-liquid phase separation: A mechanism of how phosphorylation regulates phase behavior of disordered proteins.

Phosphorylation regulates protein function by modulating stereospecific interactions between protein-protein or enzyme-ligand. On the other hand, many bioinformatics studies have demonstrated that phosphorylation preferably occurs in intrinsically disordered regions (IDRs), which do not have any secondary and tertiary structures. Although studies have demonstrated that phosphorylation changes the phase behavior of IDRs, the mechanism, which is distinct from the "stereospecific" effect, had not been elucidated.

Requirement of Rab5 GTPase during heat stress-induced endocytosis in yeast.

The plasma membrane (PM) is constantly exposed to various stresses from the extracellular environment, such as heat and oxidative stress. These stresses often cause the denaturation of membrane proteins and destabilize PM integrity, which is essential for normal cell viability and function. For maintenance of PM integrity, most eukaryotic cells have the PM quality control (PMQC) system, which removes damaged membrane proteins by endocytosis.

Laparoscopic Resection Combined with a Transsacral Approach for a Recurrent Tailgut Cyst with a Refractory Fistula.

Tailgut cyst is a rare cystic disease of the anterior sacral surface and the remains of an embryonic tail gut. Tailgut cysts have a potential for malignancy, and complete resection with an adequate surgical margin is necessary. Even if incomplete resection does not result in recurrence of malignant disease, there is a risk of local infection leading to refractory fistulas.

Topical Application of a PDE4 Inhibitor Ameliorates Atopic Dermatitis through Inhibition of Basophil IL-4 Production.

Phosphodiesterase 4 inhibitors have been approved for the treatment of atopic dermatitis. However, the cellular and molecular mechanisms underlying their therapeutic effect remain to be fully elucidated. In this study, we addressed this unsolved issue by analyzing the action of difamilast, a novel phosphodiesterase 4 inhibitor, on an oxazolone-induced skin allergic inflammation commonly used as a mouse model of atopic dermatitis.

Distinct role of TGN-resident clathrin adaptors for Vps21p activation in the TGN-endosome trafficking pathway.

Clathrin-mediated vesicle trafficking plays central roles in post-Golgi transport. In yeast (Saccharomyces cerevisiae), the AP-1 complex and GGA adaptors are predicted to generate distinct transport vesicles at the trans-Golgi network (TGN), and the epsin-related proteins Ent3p and Ent5p (collectively Ent3p/5p) act as accessories for these adaptors. Recently, we showed that vesicle transport from the TGN is crucial for yeast Rab5 (Vps21p)-mediated endosome formation, and that Ent3p/5p are crucial for this process, whereas AP-1 and GGA adaptors are dispensable.

Universal Design of Luciferase Fusion Proteins for Epigenetic Modifications Detection Based on Bioluminescence Resonance Energy Transfer.

Global hypomethylation and promoter hypermethylation of tumor-suppressor genes are the hallmarks of cancer. We previously reported a global DNA methylation level sensing system based on dual-color bioluminescence resonance energy transfer (BRET) using methyl-CpG binding domain (MBD)-fused firefly luciferase (Fluc) and unmethyl-CpG binding domain (CXXC)-fused luciferase (Oluc). Moreover, BRET-based hydroxymethylation and hemi-methylation level sensing systems have been developed using hydroxymethyl-CpG and hemi-methyl-CpG binding domain-fused Fluc.

Determinants of Outdoor Time in Children and Youth: A Systematic Review of Longitudinal and Intervention Studies.

Spending more time outdoors can improve children's social and cognitive development, physical activity, and vision. Our systematic review summarized the determinants of outdoor time (OT) based on the social-ecological model. We searched nine databases: MEDLINE, APA PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, SPORTDiscus, ERIC, SocINDEX, and ProQuest Dissertations and Theses.

Role of phosphatidylserine in the localization of cell surface membrane proteins in yeast.

Phosphatidylserine (PS) is a constituent of the cell membrane, being especially abundant in the cytoplasmic leaflet, and plays important roles in a number of cellular functions, including the formation of cell polarity and intracellular vesicle transport. Several studies in mammalian cells have suggested the role of PS in retrograde membrane traffic through endosomes, but in yeast, where PS is localized primarily at the plasma membrane (PM), the role in intracellular organelles remains unclear. Additionally, it is reported that polarized endocytic site formation is defective in PS-depleted yeast cells, but the role in the endocytic machinery has not been well understood.

Development of medication regimen complexity index: Japanese version and application in elderly patients.

Background Medication regimen complexity includes various aspects of a regimen, including the dosage form, number of medications and need for additional information for use. Complicated medication regimens cause non-adherence to prescribed medications, making it essential to evaluate medication regimen complexity in older adults to improve adherence to prescribed medications and clinical outcomes. The medication regimen complexity index is currently the most widely used scale for quantifying regimen complexity; however, it has yet to be adopted in Japan.

Functional complementation reveals that 9 of the 13 human V-ATPase subunits can functionally substitute for their yeast orthologs.

Vacuolar-type H-ATPase (V-ATPase) is a highly conserved proton pump responsible for acidification of intracellular organelles and potential drug target. It is a multisubunit complex comprising a cytoplasmic V domain responsible for ATP hydrolysis and a membrane-embedded V domain that contributes to proton translocation across the membrane. V-ATPase is composed of 14 subunits, deletion of any one of which results in well-defined growth defects.

Rab5-independent activation and function of yeast Rab7-like protein, Ypt7p, in the AP-3 pathway.

The small GTPases, Rab5 and Rab7, are key regulators at multiple stages of the endocytic/endolysosomal pathway, including fusion and maturation of endosomes. In yeast, Vps21p (Rab5 homolog) recruits a GEF for Rab7 and activates the downstream Ypt7p (Rab7 homolog) on endosomal membrane. Although the model of this sequential activation from Vps21p to Ypt7p in the endocytic pathway has been established, activation mechanism of Ypt7p in the Vps21p-independent pathway has not been completely clarified.

Expression of Epithelial-Mesenchymal Transition Proteins in Pancreatic Anaplastic (Undifferentiated) Carcinoma.

Objectives: The aim of this study was to identify an association of pancreatic anaplastic carcinoma (APC) with the epithelial-mesenchymal transition (EMT).

Methods: Resected APCs (n = 24) were examined to assess components of APCs, including carcinomatous, transitional, and sarcomatous regions. Analysis was performed based on the immunoreactivity of E-cadherin and 3 EMT-related proteins: Slug (zinc finger protein SNAI2), Twist (Twist-related protein 1), and Zeb1 (zinc finger E-box-binding homeobox 1).

A Standard Intervention Practice to Promote Appropriate Lamotrigine Therapy by Pharmacists.

The dosage and frequency of lamotrigine administration for each patient must be prescribed carefully according to the disease, age, concomitant medications, and administration period. According to Pharmaceuticals and Medical Devices Agency (PMDA) reports, either the number of patients with adverse events caused by the inappropriate use of lamotrigine or the ratio of the patients who have benefited from the Relief System for Adverse Drug Reactions did not change even after the revision of the package insert in 2015. The procedure for auditing lamotrigine prescriptions was standardized to improve patient safety in our hospitals.

Synthesis and Evaluation of Antibacterial Activity of Bottromycins.

Total synthesis of bottromycin A can be accomplished through a diastereoselective Mannich reaction of a chiral sulfinamide, mercury-mediated intermolecular amidination, and cyclization of a constrained tetracyclic peptide. Exploitation of this process allowed the synthesis of several novel bottromycin analogs. The antimicrobial activity of these analogs was evaluated in vitro against Gram-positive bacteria, such as methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE).

[A case of non-invasive IPMC with fibrotic lesion-like "tubular complex"].

A 73-year-old man was incidentally diagnosed with a cystic lesion in the pancreatic body. Ultrasonography, abdominal computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasound were performed, and a nodule was detected in the cystic lesion along with an irregularity of the main pancreatic duct. An initial diagnosis of a mixed-type intraductal papillary mucinous neoplasm was made, and a central pancreatectomy was performed.

Ameliorative effect of chlorpromazine hydrochloride on visceral hypersensitivity in rats: possible involvement of 5-HT receptor.

Background And Purpose: Visceral hypersensitivity is responsible for pathogenesis of irritable bowel syndrome (IBS). Therefore, its prevention can help avoid abdominal pain and discomfort in IBS. To find candidate drugs for visceral hypersensitivity, we screened existing medicines for their ability to prevent visceral sensitivity induced by colorectal distension (CRD) in rats and identified chlorpromazine, a typical antipsychotic drug, as a candidate compound.

Membrane vesicle-mediated bacterial communication.

The classical quorum-sensing (QS) model is based on the assumption that diffusible signaling molecules accumulate in the culture medium until they reach a critical concentration upon which expression of target genes is triggered. Here we demonstrate that the hydrophobic signal N-hexadecanoyl-L-homoserine lactone, which is produced by Paracoccus sp., is released from cells by the aid of membrane vesicles (MVs).

Aminophylline suppresses stress-induced visceral hypersensitivity and defecation in irritable bowel syndrome.

Pharmacological therapy for irritable bowel syndrome (IBS) has not been established. In order to find candidate drugs for IBS with diarrhea (IBS-D), we screened a compound library of drugs clinically used for their ability to prevent stress-induced defecation and visceral hypersensitivity in rats. We selected the bronchodilator aminophylline from this library.

Feasibility Assessment of Modified FOLFOX-6 as adjuvant treatment after resection of liver metastases from colorectal cancer: analyses of a multicenter phase II clinical trial (Miyagi-HBPCOG Trial-001).

Background/aims: This multicenter and single arm phase II clinical trial was performed to examine the safety and efficacy of modified FOLFOX6 (mFOLFOX6) as adjuvant treatment after resection of liver metastases from colorectal cancer.

Methodology: Patients who had undergone R0-1 resection of liver metastases were assigned to 12 cycles of mFOLFOX6. The primary end point was disease-free survival (DFS).

Twelve weeks of smoking cessation therapy with varenicline increases the serum levels of apolipoprotein A-I only in the success group.

Background: Cigarette smoking adversely affects lipid profiles, and smoking cessation should improve lipid profiles in the long term. However, it remains unclear whether intensive, medication-based smoking cessation therapy can affect lipid profiles in the short term. Thus, we evaluated the short-term effects of smoking cessation therapy with varenicline on lipid profiles.

The establishment and validation of efficient assays for anti-IIa and anti-Xa activities of heparin sodium and heparin calcium.

Heparin is used as an anticoagulant drug. The anticoagulation process is mainly caused by the interaction of heparin with antithrombin followed by inhibition of anticoagulant factor IIa and factor Xa. The anti-factor IIa and anti-factor Xa activities of heparin are critical for its anticoagulant effect; however, physicochemical methods that can reflect these activities have not been established.

Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial.

Background: Surgical resection is the only curative strategy for pancreatic ductal adenocarcinoma (PDAC), but recurrence rates are high even after purported curative resection. First-line treatment with gemcitabine and S-1 (GS) is associated with promising antitumor activity with a high response rate. The aim of this study was to assess the feasibility and efficacy of GS in the neoadjuvant setting.

Total synthesis of complestatin: development of a Pd(0)-mediated indole annulation for macrocyclization.

Full details of the initial development and continued examination of a powerful intramolecular palladium(0)-mediated indole annulation for macrocyclization closure of the strained 16-membered biaryl ring system found in complestatin (1, chloropeptin II) and the definition of factors impacting its intrinsic atropodiastereoselectivity are described. Its examination and use in an alternative, second-generation total synthesis of complestatin are detailed in which the order of the macrocyclization reactions was reversed from our first-generation total synthesis. In this approach and with the ABCD biaryl ether ring system in place, the key Larock cyclization was conducted with substrate 36 (containing four phenols, five secondary amides, one carbamate, and four labile aryl chlorides) and provided the product 37 (56%) exclusively as a single atropisomer (>20:1, detection limits) possessing the natural (R)-configuration.