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There are several psychosocial and ethical issues surrounding the decision making of living kidney transplant donors. This study aimed to determine what health care professionals (HPs) consider in their clinical practice and their attitudes toward donors' decision-making processes.Face-to-face semistructured interviews were conducted with 15 HPs. A thematic analysis was performed to categorize the thematic elements of the transcripts. All procedures were approved by the relevant review board and conducted in accordance with the Declaration of Helsinki.Six main categories-maintaining family relationships, improving donor understanding, supporting voluntary decision making, setting the environment for the examination, having different attitudes toward the donor's intentions, and resisting confirmation of intent-were identified. The HPs provided diverse considerations to respect the donors' autonomy.In clinical practice, there is a lack of practical methods to confirm living donors' levels of understanding and spontaneity, suggesting that these methods need to be established. Factors related to family functioning may reflect the unique culture of Japan, and this may be indicative of the need to consider treatment based on cultural values.

Objective: Physical frailty has been considered a risk factor for certification of long-term care needs (hereafter referred to as Certification) under Japan’s long-term care insurance (LTCI). Therefore, assessment of frailty in elders should be studied from multiple perspectives. The Kihon Checklist (KCL) is widely used to identify need for support/care among Japanese older adults. This study aims to examine the relationship between changes in KCL items and Certification among Japan’s young-old and old-old. Material and Methods: The KCL responses of 7,092 participants were assessed in April 2012 and March 2016, along with gender, age, and living environment. Deaths, Certifications, and relocations were tracked until March 2018. Changes in KCL items were categorized as bad, worse, improved, or good. Results: Between March 2016 and March 2018, about 7.3% of respondents obtained Certifications. KCL item changes increased the risk of new Certification for bad and worse groups, while improved cognitive function among the old-old possibly reduced the risk of new Certification. Conclusion: Therefore, rather than administering the KCL once, identifying KCL changes among people at risk could help prevent or delay their need for long-term care.

MR spectroscopy in a patient with hyponatremic encephalopathy due to the syndrome of inappropriate secretion of antidiuretic hormone revealed decreased N-acetyl-aspartate, creatine plus phosphocreatine, choline-containing compounds, and myo-inositol, with normal glutamate and increased glutamine, which normalized after Na normalization. The decreased concentrations of creatine plus phosphocreatine, choline-containing compounds and myo-inositol are explained by their release as osmolytes from brain cells to adapt to hypo-osmolality induced cerebral edema. Increased glutamine, which not only acts as an osmolyte but also protects neurons under excitotoxic conditions, may suggest that a disrupted glutamate-glutamine cycle may play an important role in the pathogenesis of hyponatremic encephalopathy.

Objective:Although early identification and management services for dementia have become more widespread, their efficacy and the clinical characteristics of service have yet to be fully evaluated. Therefore, the objective of this study is to clarify these issues.Measurements:The subjects were 164 Japanese users of an early identification and management program for dementia, known as the Initial-phase Intensive Support Team (IPIST), between 2013 and 2015. Nonhierarchical cluster analysis was used to derive subgroups based on cognitive status and ability in activities of daily living (ADL) and behavioral and psychological symptoms of dementia (BPSD). One-way analysis of variance was performed to evaluate differences among the groups derived by the cluster analysis. A paired t test was used to assess how the clinical status of the groups changed between baseline and follow-up.Results:Four groups were identified by cluster analysis, i.e. a mild group, a moderate group, a BPSD group with moderate cognitive impairment and severe BPSD, and a severe group with severe cognitive impairment and severe BPSD. Although there were no significant improvements in cognitive impairment or ADL in any group, significant improvements were found in BPSD in the BPSD and severe BPSD groups. Caregiver burden was significantly lessened in all groups. Clinical diagnosis and long-term care insurance service utilization rates were significantly improved overall.Conclusion:The users of IPIST were classified into four subgroups based on their clinical characteristics. The IPIST program could improve the quality of life of people with dementia and their caregivers.

Objective: The rates of care-needs certification were mainly compared between two cohorts: 7,820 specific health checkup examinees/basic checklist respondents and 29,234 non-examinees/non-respondents. Subjects and Methods: Among approximately 37,000 elderly citizens of X City, the number of individuals newly certified as requiring long-term care were observed from the date of the first specific health checkup in 2008 to March 31, 2013. The aggregated totals of these individuals and associated factors were evaluated. Results: 1. Support Required 1, Support Required 2, and Long-term Care Required (level 1) certified individuals accounted for approximately 80% of newly certified individuals aged 65-74 years. Newly certified individuals aged 75 years and over had similar results with 37.2% of them being certified Support Required 1, 19.4% certified Support Required 2, and 22.9% certified Long-term Care Required (level 1). 2. The primary factors for care-needs certification in individuals aged 65-74 years were arthritic disorder in 27.6%, falls and bone fractures in 11.3%, and malignant neoplasm and cerebrovascular disease, among others. This was similar for individuals aged 75 years or over. 3. Of the 7,820 specific health checkup examinees/basic checklist respondents, 1,280 were newly certified as requiring long-term care (16.4%) compared to 7,878 (26.9%) of the 29,234 non-examinees/non-respondents. Therefore, the latter cohort had a significantly higher rate of individuals who were newly certified as requiring long-term care. Conclusion: Both specific health checkups and basic checklists are effective health policies to protect frailty in community elderlies.

Background Human parechovirus (HPeV) and human non-polio enterovirus (EV) are important causes of fever without sources (FWS) in young infants. Their prevalence and clinical characteristics are largely unknown in Asian countries. This study was conducted to elucidate the epidemiology and clinical characteristics of HPeV and EV infections in febrile young infants in Japan. Methods During February 2010 – August 2015, we obtained 53 stool, 44 throat swab, and 20 cerebrospinal fluid (CSF) samples from 56 infants (

This study aimed to verify whether the incidence of frailty in elderly individuals is higher among those who are housebound than those who are not. This study found no correlation between elderly people's houseboundedeness and physical, mental, social, and overall frailty. However, the Tilburg Frailty Indicator (TFI) frailty score and grip strength value were higher in non-housebound elderly persons than in housebound elderly ones. This suggests that being housebound may lead to frailty. On the other hand, it is thought that individual interaction with family and friends, and lack of anxiety about falls correlates with the prevention of frailty in housebound elderly persons. The results of the study also suggest that the basic checklist may be effective for ascertaining the actual situation of housebound elderly people who may be manifesting frailty.

Objective: This study aimed to examine the factors influencing the requirement of a certificate of long-term care using a basic checklist and items listed in the Special Health Checkup. Method: This study included 7,820 individuals living in Uji city, who were selected from among 8,000 elderly individuals who, in 2008, underwent a specific health checkup (hereafter referred to as the 'specific health checkup for the old-old elderly individuals') for those aged 75 years and above. They answered questions from basic checklists at the time, and 180 individuals were excluded as they had already qualified for requiring the certificate of long-term care at the time of the checkup. The follow-up period extended from the day of the specific health checkup for the old-old elderly individuals to March 31, 2013. The data were analyzed using the certificate of needing long-term care as the response variable. The explanatory variables were the basic attributes, items listed in the specific health checkup for the old-old elderly individuals, interview sheets, and basic checklists. Cox proportional hazards regression analysis was conducted. Results: In total, 1,280 elderly individuals qualified for requiring the certificate of needing long-term care. The risk factors for the young-old elderly individuals aged 65 to 74 years were as follows: hepatic dysfunction (hazard ratio {HR}=1.69), the presence of subjective symptoms (HR=1.41), an above-normal abdominal circumference (HR=1.36), old age (HR=1.13), a reduced frequency of going out since the previous year (HR=1.87), the use of support for standing up after being seated on a chair (HR=1.86), no deposit or withdrawals made (HR=1.84), the anxiety of falling down (HR=1.50), an inability to climb stairs without holding a railing or wall (HR=1.49), as well as an increased difficulty in eating tough food items compared with 6 months prior (HR=1.44). The risk factors for the old-old elderly individuals were as follows: a positive reaction on proteinuria (HR=1.27), anemia (HR=1.18), old age (HR=1.10), inability to travel on a bus or train by themselves (HR=1.53), the inability to climb stairs without holding a railing or wall (HR=1.48), weight loss (HR=1.36), a reduced sense of appreciation of the activities they had previously participated in, over a span of 2 weeks (HR=1.30), the use of support for standing up after being seated on a chair (HR=1.23), and the anxiety of falling down (HR=1.20). Conclusion: The items listed in the specific medical checkup as well as the basic checklists were found to be risk factors for both the young-old elderly individuals and the old-old elderly individuals, indicating the need to utilize these lists for the prevention of nursing even in the late stages of life. Moreover, these results suggest the importance of screening elderly individuals suffering from hyperkinesis using the basic checklist and conducting preventive interventions in order to maintain and improve their physical functions.

Tipepidine hibenzate (Asverin) is commonly used as an antitussive drug for acute and chronic cough in various age groups and is generally safe and well-tolerated. However, we experienced a case of tipepidine hibenzate-induced anaphylactic shock in a 1-year-old boy. After ingesting cold medication including tipepidine hibenzate, the patient presented with generalized erythema and urticaria, swollen face, coughing, wheezing and vomiting, together with hypotension and a decreased level of consciousness. To identify the culprit drug, we performed skin prick tests (SPTs) and oral drug provocation tests (DPTs). SPTs revealed a negative reaction for all drugs, but DPTs caused a positive reaction only for a full therapeutic dose of tipepidine hibenzate. Physicians need to consider tipepidine hibezate as a culprit drug when anaphylaxis occurs after taking anticough or common cold medication.

Background: Acetaminophen, an analgesic and antipyretic drug, has been used clinically for more than a century. Previous studies showed that acetaminophen undergoes metabolic transformations to form an analgesic compound, N-(4-hydroxyphenyl) arachidonamide (AM404), in the rodent brain. However, these studies were performed with higher concentrations of acetaminophen than are used in humans. Objectives: The aim of the present study was to examine the metabolism of AM404 from acetaminophen in the rat brain at a concentration of 20 mg/kg, which is used in therapeutic practice in humans, and to compare the pharmacokinetics between them. Materials and Methods: We used rat brains to investigate the metabolism of AM404 from acetaminophen at concentrations (20 mg/kg) used in humans. In addition, we determined the mean pharmacokinetic parameters for acetaminophen and its metabolites, including AM404. Results: The maximum plasma concentrations of acetaminophen and AM404 in the rat brain were 15.8 µg/g and 150 pg/g, respectively, with corresponding AUC 0-2h values of 8.96 μg hour/g and 117 pg hour/g. The t max for both acetaminophen and AM404 was 0.25 hour. Conclusions: These data suggest that AM404’s concentration-time profile in the brain is similar to those of acetaminophen and its other metabolites. Measurement of blood acetaminophen concentration seems to reflect the concentration of the prospective bioactive substance, AM404.

Mesenchymal stromal cells (MSCs) derived from bone marrow have the capacity for self-renewal and differentiation, and can give rise to cells of a muscle, bone, fat or cartilage lineage. Based on this potential and feasibility, MSCs are expected to be used in cell therapy for human diseases. Intriguingly, MSCs migrate to various in vivo locations, including injury and tumor sites. However, their cellular fate and distribution remain unclear. In this review, we first describe the potential of a photogenic transgenic rat that expresses fluorescent and/or luminescent proteins (e.g., green fluorescent protein and luciferase), and then focus on the characteristic migration of MSCs to injury and tumor sites. In addition, we will discuss an efficient delivery method for targeting the injured site. Synergized with modern advances in optical imaging, the photogenic rat system provides innovative preclinical tools and a new platform on which to further our understanding of matters concerning stem cell biology.

Thrombomodulin (TM) is a thrombin receptor on the surface of endothelial cells that converts thrombin from a procoagulant to an anticoagulant. Thrombin promotes invasion by various tumor cells, and positive or negative correlations are found between the expression of TM and tumorigenesis in some patients. In this study, we used an invasion assay to investigate the effect of TM on the invasive activity of a mouse mammary tumor cell line, MMT cells, and the effects of TM were compared with those of thrombin as a positive control. In the presence of 1% fetal calf serum (FCS), TM significantly stimulated MMT cell invasion in a dose-dependent manner, resulting in an approximately 3-fold increase at 1-10 pg/ml over the untreated control. Thrombin also caused a similar degree of stimulation at 50 ng/ml. Since thrombin activity was detected in the components of the assay system, an invasion assay was also performed in a thrombin-activity-depleted assay system constructed to eliminate the effect of thrombin activity; TM (10 pg/ml) plus thrombin (1 pg/ml) stimulated invasion by approximately 3.5-fold in this assay system. Hirudin, a specific thrombin inhibitor, inhibited stimulation by TM as well as by thrombin in both the presence and absence of 1% FCS. Investigations of the effects of TM on proliferation, adhesion and chemotaxis to clarify the mechanism of stimulation by TM revealed that TM does not affect proliferation or adhesion in the presence of 1% FCS, but stimulates chemotaxis by approximately 2.3-fold. Similar results were obtained in experiments using thrombin. TM (10 pg/ml) plus thrombin (1 pg/ml), on the other hand, stimulated chemotaxis by approximately 2.3-fold in the thrombin-activity-depleted assay system. Binding studies using [ 1 2 5 I]-thrombin revealed that the cells have specific saturable binding sites for thrombin. These results show that TM stimulates the invasive activity of MMT cells, probably by acting as a cofactor for the thrombin-stimulated invasion of the cells via its receptor and lowering the effective concentration of thrombin. The findings also indicate that the stimulation of invasive activity in the presence of 1% FCS and in the thrombin-activity-depleted assay system may mainly be mediated by the stimulation of chemotaxis.

Motor neurons (MNs) are designated as alpha/gamma and fast/slow based on their target sites and the types of muscle fibers innervated; however, few molecular markers that distinguish between these subtypes are available. Here we report that osteopontin (OPN) is a selective marker of alpha MNs in the mouse spinal cord. OPN was detected in approximately 70% of postnatal choline acetyltransferase (ChAT)-positive MNs with relatively large somas, but not in those with smaller somas. OPN+/ChAT+ MNs were also positive for NeuN, an alpha MN marker, but were negative for Err3, a gamma MN marker. The size distribution of OPN+/ChAT+ cells was nearly identical to that of NeuN+/ChAT+ alpha MNs. Group Ia proprioceptive terminals immunoreactive for vesicular glutamate transporter-1 were selectively detected on the OPN+/ChAT+ cells. OPN staining was also detected at motor axon terminals at neuromuscular junctions, where the OPN+ terminals were positive or negative for SV2A, a marker distinguishing fast/slow motor endplates. Finally, retrograde labeling following intramuscular injection of fast blue indicated that OPN is expressed in both fast and slow MNs. Collectively, our findings show that OPN is an alpha MN marker present in both the soma and the endplates of alpha MNs in the postnatal mouse spinal cord.

N-Bis(methylthio)methylene-p-toluenesulfonamide (1) reacted with active methylene compounds such as malononitrile (2a) and, cyanoacetamide (2b) to give the corresponding 3-methylthio-3-p-toluenesulfonylami-nopropenenitrile derivatives 3a,b which were found to be convenient starting materials for the synthesis of 3,5-diaminopyrazole derivatives. Reaction of 3a and 3b with hydrazines gave the corresponding 3,5-diaminopyrazoles 4a-e, key intermediates for the synthesis of 3-aminopyrazolo[3,4-d]pyrimidine derivatives 5a-d.

International audience; Two new bisindole alkaloids, bisnicalaterines B and C (1 and 2) consisting of an eburnane and a corynanthe type of skeletons, were isolated from the bark of Hunteria zeylanica. Their absolute structures were determined by combination of NMR, CD, and computational methods, and each of them was shown to be in an atropisomeric relationship. Bisnicalaterines B and C (1 and 2) showed potent vasorelaxant activity on isolated rat aorta.

With melanoma, as with many other malignancies, aberrant transcriptional repression is a hallmark of refractory cancer. To restore gene expression, use of a histone deacetylase inhibitor (HDACi) is expected to be effective. Our recent DNA micro-array analysis showed that the HDACi depsipeptide (FK228) significantly enhances gp100 antigen expression. Herein, we demonstrate that depsipeptide promotes tumor-specific T-cell-mediated killing of B16/F10 murine melanoma cells. First, by a quantitative assay of caspase-3/7 activity, a sublethal dose of depsipeptide was determined (ED50: 5 nM), in which p21(Waf1/Cip1) and Fas were sufficiently evoked concomitantly with histone H3 acetylation. Second, the sublethal dose of depsipeptide treatment with either a recombinant Fas ligand or tumor-specific T cells synergistically enhanced apoptotic cell death in B16/F10 cells in vitro. Furthermore, we found that depsipeptide increased levels of perforin in T cells. Finally, in vivo metastatic growth of B16/F10 in the lung was significantly inhibited by a combination of depsipeptide treatment and immune cell adoptive transfer from immunized mice using irradiated B16 cells and gp100-specific (Pmel-1) TCR transgenic mice (P

N-Bis(methylthio)methylene-p-toluenesulfonamide (1) reacted with active methylene compounds such as malononitrile (2a) and, cyanoacetamide (2b) to give the corresponding 3-methylthio-3-p-toluenesulfonylami-nopropenenitrile derivatives 3a,b which were found to be convenient starting materials for the synthesis of 3,5-diaminopyrazole derivatives. Reaction of 3a and 3b with hydrazines gave the corresponding 3,5-diaminopyrazoles 4a-e, key intermediates for the synthesis of 3-aminopyrazolo[3,4-d]pyrimidine derivatives 5a-d.

The cyclization of 5-amino-3-methylthiopyrazole-4-carbonitriles or 4-carboxamides 3a-j, which were prepared by the reaction of ketene dithioacetals 1a,b [1a: bis(methylthiomethylenemalononitrile; 1b: bis(methylthio)methylenecyanoacetamide] with hydrazines (hydrazine hydrate, phenylhydrazine, p-chlorophenylhydrazine, p-nitrophenylhydrazine), with formamide or carbon disulfide proceeded to give the corresponding 4-amino- or 4-hydroxy-3-methylthiopyrazolo[3,4-d]pyrimidines 6a-h in good yields. 3-Aminopyrazolo[3,4-d]pyrimidine derivatives 6i-1 were also obtained by the application of the cyclization reaction of 3,5-diaminopyrazoles with formamide.

We investigate the relationship between the fate and healing effect of transplanted mesenchymal stromal cells (MSCs) in a rat diabetic skin wound model. Rats are treated with streptozotocin to induce diabetic conditions. A full-thickness skin defect is surgically made on the head of diabetic rats, and covered with an artificial dermis impregnated with either bone marrow cells (BMCs) or bone-marrow-derived MSCs from firefly luciferase (luc) transgenic (Tg) rats. Wound healing is evaluated using planimetry and immunohistochemistry, and the fate of transplanted MSCs is determined using in-vivo luminescent imaging. The diabetic wound treated with MSCs-impregnated artificial dermis is significantly smaller than that treated with artificial dermis alone at 1 week postoperation. Photons of luc+ MSCs are detected at the transplanted site during healing (3 weeks), whereas those of luc+ MSCs are depleted only after 1 week postimplantation. Immunohistochemistry at the healing site treated with MSCs demonstrates that CD31+ vessels increase with expression of vascular endothelial growth factor, suggesting that MSCs accelerate angiogenesis. These findings suggest that transplanted MSCs could be retained at wound sites during the healing process in a diabetic rat model, and subsequently promote wound healing through angiogenesis.

The cyclization of 5-amino-3-methylthiopyrazole-4-carbonitriles or 4-carboxamides 3a-j, which were prepared by the reaction of ketene dithioacetals 1a,b [1a: bis(methylthiomethylenemalononitrile; 1b: bis(methylthio)methylenecyanoacetamide] with hydrazines (hydrazine hydrate, phenylhydrazine, p-chlorophenylhydrazine, p-nitrophenylhydrazine), with formamide or carbon disulfide proceeded to give the corresponding 4-amino- or 4-hydroxy-3-methylthiopyrazolo[3,4-d]pyrimidines 6a-h in good yields. 3-Aminopyrazolo[3,4-d]pyrimidine derivatives 6i-1 were also obtained by the application of the cyclization reaction of 3,5-diaminopyrazoles with formamide.

The porphyrin portion of cylodextrin(CD)-linked porphyrin derivatives (1)-(3) has been anchored onto a lipid bilayer and a light-induced intramolecular electron transfer between the porphyrin on (1) and (2) and the acceptor, α-naphthoquinone held in the CD cavity in aqueous solution, has been examined.