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Fibroblast growth factor 23 (FGF23), a phosphaturic factor, is involved in the regulation of renal inorganic phosphate (Pi) reabsorption. Proteolysis-resistant FGF23 mutants expressed in rodents reduce Pi uptake in both intestine and kidney, independent of parathyroid hormone action. In the present study, we investigated whether FGF23 affects dietary regulation of Na+-dependent Pi (Na/Pi) cotransport in the rat kidney using wild-type FGF23 and an R179Q mutant, which disrupts a consensus proteolytic cleavage motif. Rats injected with naked human FGF23 DNA (wild-type or R179Q mutant) expressed the human FGF23 transcript in the liver. In those animals, plasma calcium and parathyroid hormone levels were not affected by FGF23 (either wild-type or R179Q mutant). FGF23-R179Q did, however, significantly decrease plasma Pi and renal Na/Pi cotransport activity and also the level of type-IIc Na/Pi cotransporter protein in brush-border membrane vesicles (BBMVs) from normal rat kidney. Western blot and immunohistochemical analyses in rats fed a low-Pi diet showed the levels of types-IIa and -IIc Na/Pi cotransporters to be markedly increased. After injection of FGF23-R179Q DNA into the rats fed a low-Pi diet, the levels of the types-IIa and -IIc transporter proteins were decreased. The FGF23 mutant thus blunts the signalling of Pi deprivation to the renal type-II Na/Pi cotransporter, suggesting that the FGF23 pathway could be involved in the signalling of dietary Pi. [ABSTRACT FROM AUTHOR]

(1) Background: Small Animal Fast Insert for MRI detector I (SAFIR-I) is a preclinical Positron Emission Tomography (PET) insert for the Bruker BioSpec 70/30 Ultra Shield Refrigerated (USR) preclinical 7 T Magnetic Resonance Imaging (MRI) system. It is designed explicitly for high-rate kinetic studies in mice and rats with injected activities reaching 500 M Bq , enabling truly simultaneous quantitative PET and Magnetic Resonance (MR) imaging with time frames of a few seconds in length. (2) Methods: SAFIR-I has an axial field of view of 54.2 m m and an inner diameter of 114 m m. It employs Lutetium Yttrium OxyorthoSilicate (LYSO) crystals and Multi Pixel Photon Counter (MPPC) arrays. The Position-Energy-Timing Application Specific Integrated Circuit, version 6, Single Ended (PETA6SE) digitizes the MPPC signals and provides time stamps and energy information. (3) Results: SAFIR-I is MR-compatible. The system's Coincidence Resolving Time (CRT) and energy resolution are between (209.0 ± 0.3) p s and (12.41 ± 0.02) % Full Width at Half Maximum (FWHM) at low activity and (326.89 ± 0.12) p s and (20.630 ± 0.011) % FWHM at 550 M Bq , respectively. The peak sensitivity is ∼ 1.6 % . The excellent performance facilitated the successful execution of first in vivo rat studies beyond 300 M Bq. Based on features visible in the acquired images, we estimate the spatial resolution to be ∼2 m m in the center of the Field Of View (FOV). (4) Conclusion: The SAFIR-I PET insert provides excellent performance, permitting simultaneous in vivo small animal PET/MR image acquisitions with time frames of a few seconds in length at activities of up to 500 M Bq. [ABSTRACT FROM AUTHOR]

Objective: Burning mouth syndrome (BMS) and atypical odontalgia (AO) are examples of somatic symptom disorders with predominant pain around the orofacial region. Neuroinflammation is thought to play a role in the mechanisms, but few studies have been conducted. We aimed to better understand the role of neuroinflammation in the pathophysiology and treatment of BMS/AO. Methods: Plasma levels of 28 neuroinflammation‐related molecules were determined in 44 controls and 48 BMS/AO patients both pretreatment and 12‐week post‐treatment with duloxetine. Results: Baseline plasma levels of interleukin (IL)‐1β (p < .0001), IL‐1 receptor antagonist (p < .001), IL‐6 (p < .0001), macrophage inflammatory protein‐1β (p < .0001), and platelet‐derived growth factor‐bb (.04) were significantly higher in patients than in controls. Plasma levels of granulocyte macrophage colony stimulating factor were significantly higher in patients than in controls (p < .001) and decreased with treatment (.009). Plasma levels of eotaxin, monocyte chemoattractant protein‐1, and vascular endothelial growth factor decreased significantly with treatment (p < .001,.022, and.029, respectively). Conclusions: Inflammatory mechanisms may be involved in the pathophysiology and/or treatment response of somatic symptom disorders with predominant pain around the orofacial region. [ABSTRACT FROM AUTHOR]

Objective　We conducted an ecological analysis of the structures and processes of municipalities implementing countermeasure-type colorectal cancer screening services, which are associated with high mortality and morbidity rates. We analyzed the populations' demographic characteristics, number of public health nurses (PHNs), and human base for such services. The process was evaluated using the screening uptake rates for countermeasure-type cancer screening and detection indices.Methods　The data included municipal population figures, areas, and national health insurance enrolments, all sourced from a government statistics portal (e-Stat). We obtained the number of PHNs per 100,000 population from PHN activity area surveys, information on municipal colorectal cancer screening from public health centers (PHCs) and health promotion project reports, and cancer detection indices from the National Cancer Registry data. The analysis covered 1,234 municipalities with populations of ≥10,000 and ≥50,000, categorized into three groups based on the presence of PHCs. The internal structures were compared using multiple regression analysis.Results　The number of PHNs per 100,000 population was categorized as follows; <50,000 population group (42.9), ≥50,000 population group (24.3), and PHC-present city group (16.4).Among these groups, the mass and individual screening rates were 96.2% and 47.7%, 69.1% and 91.5%, and 83.7% and 69.9%, respectively. The average uptake rates of countermeasure-type screenings and detailed examinations were 10.6-13.7% and 68.4-75.3%, respectively. In both cases, the <50,000 population and PHC-present city groups exhibited high and low values, respectively. However, the proportion of patients with "early cancer" detection was approximately 42% in all groups.Multiple regression analysis, using the countermeasure-type screening uptake rate and colorectal cancer detection indices as dependent variables, revealed that in the <50,000 population group, in which mass screening was prevalent, the number of PHNs was significantly positively correlated with the countermeasure-type screening uptake rate and proportion of "new cancers" detected by screening.Contrastingly, the PHC-present city group showed no correlation between the number of PHNs and countermeasure-type screening uptake rate, but a highly detailed examination uptake rate was significantly positively correlated with the proportion of "early cancer" detection.Conclusion　In municipalities without PHCs, countermeasure-type screening uptake rates, particularly mass screening rates, were positively correlated with the number of PHNs and cancer detection indices. In cities with PHCs, in which individual screening was prevalent, the detailed examination uptake rate through countermeasure-type screening was correlated with detection indices.

Objectives　In Japan, efforts to provide "end-of-life care" in nursing homes are increasing and its introduction through long-term care insurance in 2006 is a major step forward. However, previous studies have shown that relocating older adults to their end-of-life care affects their burden. This study examined individuals' end-of-life care use under long-term care insurance in older care facilities and investigated the relocation frequency among terminally ill older residents of nursing facilities using receipt data.Methods　The research targeted individuals aged ≥ 65 years under long-term care insurance who used formal end-of-life care services and were passed into residential facilities between April 1, 2018 and March 31, 2021. Data were obtained from anonymous long-term care certification information provided by the Ministry of Health, Labor, and Welfare. Six facilities providing end-of-life care were considered; older care facilities, geriatric health service facilities, designated establishments, and dementia group homes. A total of 233,735 individuals with service use records in the month of service cessation were aggregated according to facility, individual factors, and prefecture. Additionally, we defined end-of-life relocation as occurring if three categories of end-of-life care fees (day of death, 1-2 days before death, and 4-30 days before death) did not continue until the day of death.Results　The participants were individuals aged ≥ 85 years (83.35%), 25.29% were men, and 93.53% required a care level of ≥ 3. Older nursing care facilities recorded the highest number (114,356) of end-of-life care users. The proportion of individuals with moderate-to-severe dementia (level ≥ IIIa; approximately 80%) was higher in nursing homes for older adults, community-based nursing homes for older adults, and dementia group homes than in other facilities. Relocation during the terminal phase was less prevalent in facilities with higher doctor and nurse staffing levels. At the individual level, relocation is more frequent among men, younger individuals, those with lower care levels, and those with intact decision-making and communication abilities. Conclusion　Terminally ill residents aged ≥ 80 years with severe levels of care were the most likely to use end-of-life care. Moreover, 0.2-2% relocated across all facilities within 30 days before death. The relocation frequency increased based on individual factors and was mitigated by a thorough system of medical staff deployment.

Abstract: Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients., (Copyright © 2023 International Association for the Study of Pain.)

Background and purpose Given that chronic pain has become a major problem in recent years, affecting approximately 30% of the general population, this study used the Japanese version of the Short Form-8 (SF-8) to investigate (1) the quality of life (QOL) of patients with burning mouth syndrome (BMS) or persistent idiopathic facial pain (PIFP) (compared with a Japanese control group) and (2) whether therapeutic intervention improves the QOL and reduces pain (comparison between 0 and 12 weeks) of patients with BMS or PIFP. Materials and methods A total of 63 patients diagnosed with either BMS (n=45) or PIFP (n=18) were included in this study. The diagnostic criteria for BMS and PIFP were established based on the third edition of the International Classification of Headache Disorders. Results Our study results showed that while Physical Component Summary (PCS) in patients with BMS or PIFP improved with treatment, it did not improve to the national standard value (NSV) after 12 weeks of intervention. In contrast, the Mental Component Summary (MCS) improved to the same level as the NSV after 12 weeks of intervention. Conclusions We found that therapeutic intervention improves MCS and reduces pain; however, improving PCS requires time., Competing Interests: This article was previously posted to the medRxiv preprint server on May 22, 2023., (Copyright © 2023, Sato-Boku et al.)

Brachytherapy is a type of radiation therapy in which the radioactive source is directly delivered to the tumor and is used to treat a variety of malignancies. Although the local control effect of brachytherapy is higher than that of external beam radiation therapy (EBRT), it is often the case that brachytherapy is more invasive than conventional EBRT. As a result, patients receiving head and neck brachytherapy confront several physical, nutritional, and pain management issues. The nurses caring for patients with head and neck cancer receiving high-dose rate interstitial brachytherapy (ISBT) should have a thorough understanding of radiation therapy principles, technology, applicator management, and the acute and chronic side effects of ISBT. However, there are no appropriate textbooks or review articles regarding nursing care for head and neck patients undergoing ISBT. The purpose of this article is to provide radiation oncologists and nurses who want to start head and neck ISBT with a comprehensive guide regarding nursing care and to help the wide spread of this treatment strategy., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Refeeding syndrome is a major clinical problem that leads to fatal complications in patients suffering from malnutrition. Hypophosphatemia inevitably is observed at the onset of refeeding syndrome and therefore is monitored during refeeding; however, the causes of metabolic changes in phosphate concentration during refeeding remain poorly understood. In a previous study, we established a refeeding syndrome model employing total parenteral nutrition with insulin-induced hypophosphatemia, but the symptoms were severe and the metabolic mechanisms in this model may not have been representative of clinical conditions. Therefore, we established a new animal model of mild refeeding syndrome by using a shorter fasting period followed by a single refeeding. These mild refeeding syndrome-model rats exhibited hypophosphatemia without increases in urinary phosphate excretion. Interestingly, administration of the combination of phosphate and insulin during refeeding promoted insulin secretion during refeeding. This model implies that Pi may directly promote insulin secretion in pancreatic cells. These results clarify the interaction between phosphate and glucose metabolism pancreatic cells during refeeding syndrome in a mild refeeding syndrome model., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2023 JCBN.)

Background: Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail., Purpose: The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system., Methods: In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived., Results: The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p = 0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p = 0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities., Conclusions: This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively., (© 2022 American Association of Physicists in Medicine.)

Objective: The aim of this study was evaluation of the association between severity of pain and expression of total or ubiquitinated serotonin transporter (SERT) protein in patients with burning mouth syndrome and atypical odontalgia (BMS/AO), who were treated by duloxetine., Methods: Patients with BMS/AO were assessed for severity of pain using the visual analog scale (VAS), and expression of total and ubiquitinated SERT protein in platelets before (baseline) and 12 weeks after duloxetine-treatment., Results: The expression of total and ubiquitinated SERT protein at baseline in all patients (n = 33) were higher and lower, respectively, compared to those in healthy controls. 12 weeks after duloxetine-treatment, there was no difference in the total SERT protein levels between patients (n = 21) and healthy controls. In the 16 patients who could be measured, mean VAS scores and total SERT protein levels were significantly decreased after the treatment, compared to those at baseline. There was tendency for a positive correlation between total SERT protein levels and VAS scores in these patients., Conclusions: Our findings indicate that duloxetine relieves pain in association with downregulation of platelet SERT expression in patients with BMS/AO., (© 2021 John Wiley & Sons Ltd.)

A 24-year-old woman diagnosed with 22 q 11.2 deletion syndrome was referred for multiple extractions. Due to the syndrome, the patient had schizophrenia, cardiac anomalies, and maxillofacial complications. This case report suggested that a multidisciplinary team approach is important for perioperative management of patients with 22 q 11.2 deletion syndrome., Competing Interests: There were no conflict of interest related to this publication., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Objectives　By targeting the public health nurses (PHNs) who are expected to be actively involved in the implementation of community DOTS practices, we evaluated the quality of the regional DOTS practices based on the three aspects of "enhancing tuberculosis (TB) treatment adherence," "patient-centered support other than treatment," and "coordination with related organizations." We examined the individual and organizational factors that affect the quality of these practices. Further, we clarified the challenges related to the abilities of PHNs.Methods　A self-report questionnaire survey of 958 PHNs from local governments with a TB incidence rate of 15 or more was administered in 2015. This resulted in there being 410 valid responses with a valid response rate of 42.8%.　The quality of the community DOTS practices was evaluated based on the three aspects by reviewing the literature on expert PHNs for TB patient support. After a preliminary survey, each was evaluated based on a scale of 10 points. A multiple regression analysis was conducted to understand the relationship between these and the TB control implementation system (organizational factors), the experience and motivation of PHNs to support tuberculosis patients, and the learning situation (individual factors).Results　The quality of the community DOTS practices was 7.54±1.69 for "enhancing TB treatment adherence," was 6.91±1.63 for "coordination with related organizations," and was 6.68±1.53 for "patient-centered support." The scores for the first factor were higher than those for the latter two factors (P<0.05). With regard to "patient-centered support," one-fourth of the surveyed PHNs rated their practices as low. Each predictor showed a strong relationship with the quality of community DOTS practices, especially "coordination with related organizations" and "patient-centered support" (r=0.787). The significant organizational factors associated with the quality of the community DOTS practices in terms of each aspect were "making an individual support plan for TB patients" (β=0.112-0.270), "reporting own practices at the DOTS conference as a responsible PHN" (β=0.113-0.173), "attending cohort study meetings" (β=0.129-0.167), and the individual factor of "many years of experience as a PHN" (β=0.210-0.316). Additionally, in the model of "coordination with related organizations," "reading specialized books and journals" (β=0.108) was found to be significant and positively related.Conclusion　To improve the quality of the community DOTS practices based on the self-evaluation of PHNs, "patient-centered support" with a low score and high relevance to other aspects is a priority. It was also suggested that it would be useful if the PHNs participated in DOTS evaluations, developed individual patient support plans, presented support plans, and participated in performance evaluations to improve the quality of DOTS practices.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are chronic inflammatory disorders associated with oxidative stress. The intestines produce 5-hydroxytryptamine that may negatively affect disease state under inflammatory conditions when overproduced. 5-Hydroxytryptamine is a substrate for myeloperoxidase and is converted into reactive tryptamine-4,5-dione. Here, an experimental colitis model was established through oral administration of 5% dextran sulfate sodium to ICR mice for 7 days. Furthermore, the formation of tryptamine-4,5-dione in the colorectal mucosa/submucosa and colorectal tissue was analyzed by chemical and immunochemical methodologies. First, free tryptamine-4,5-dione in the homogenate was chemically trapped by o -phenylenediamine and analyzed as the stable phenazine derivative. Tryptamine-4,5-dione localization as adducted proteins in the colorectal tissue was immunohistochemically confirmed, and as demonstrated by both methods, this resulted in the significant increase of tryptamine-4,5-dione in dextran sulfate sodium-challenged mice compared with control mice. Immunohistochemical staining confirmed tryptamine-4,5-dione-positive staining at the myeloperoxidase accumulation site in dextran sulfate sodium-challenged mice colorectal tissue. The tryptamine-4,5-dione locus in the mice was partly matched with that of a specific marker for myeloperoxidase, halogenated tyrosine. Overall, the results possibly indicate that tryptamine-4,5-dione is generated by neutrophil myeloperoxidase in inflammatory tissue and may contribute to the development of inflammatory bowel disease., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2021 JCBN.)

Vascular calcification is major source of cardiovascular disease in patients with chronic kidney disease. Hyperphosphatemia leads to increased intracellular phosphorus influx, which leads to an increase in osteoblast-like cells in vascular smooth muscle cell. PiT-1 transports phosphate in vascular smooth muscle cell. However, the mechanism of vascular calcification is not completely understood. This study investigated candidate phosphorus-related molecules other than PiT-1. We hypothesized that phosphorus-related molecules belonging to the solute-carrier (SLC) superfamily would be involved in vascular calcification. As a result of DNA microarray analysis, we focused on SLC37A2 and showed that mRNA expression of these cells increased on calcified aotic smooth muscle cells (AoSMC). SLC37A2 has been reported to transport both glucose-6-phosphate/phosphate and phosphate/phosphate exchanges. In vitro analysis showed that SLC37A2 expression was not affected by inflammation on AoSMC. The expression of SLC37A2 mRNA and protein increased in calcified AoSMC. In vivo analysis showed that SLC37A2 mRNA expression in the aorta of chronic kidney disease rats was correlated with osteogenic marker genes. Furthermore, SLC37A2 was expressed at the vascular calcification area in chronic kidney disease rats. As a result, we showed that SLC37A2 is one of the molecules that increase with vascular calcification in vitro and in vivo ., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2021 JCBN.)

Background/purpose: Various questionnaires have been validated as methods for screening of neuropathic pain, but none have been established for the orofacial region. Although chronic pain and depression are likely to comorbid, few studies have examined the relationship between orofacial chronic pain and depression. Therefore, we evaluated the potential of the Japanese Version of PainDETECT as an assessment tool for neuropathic pain associated with burning mouth syndrome (BMS) and persistent idiopathic facial pain (PIFP). We also evaluated the depression scale such as Beck's Depression Inventory (BDI: a subjective index) and Hamilton Depression Rating Scale (HDRS: an objective index) with BMS or PIFP., Materials and Methods: As a target, we administered the Japanese version of the PainDETECT questionnaire to the BMS (29 patients) and PIFP (17 patients). As a control, patients with post-extraction pain (typical nociceptive pain, (EXT) 16 patients) were also participated. We performed BDI and HDRS with BMS or PIFP., Results: Although PainDETECT final score was significantly higher in BMS [median: 10] compared with PIFP [6] and EXT [5] (p < 0.05), PainDETECT final scores for all groups were lower than the cutoff value for the possibility of neuropathic pain. HDRS was significantly higher in the BMS than the PIFP. There were no significant differences between the BMS and PIFP in BDI., Conclusion: Under the limitations of current research design, the Japanese version of the PainDETECT questionnaire does not show sufficient potential as pain assessment tool for patients with BMS and PIFP. BMS is comorbid with depression objectively when compared with PIFP., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2020 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Vascular calcification progresses under hyperphosphatemia, and represents a risk factor for cardiovascular disease in chronic kidney disease (CKD) patients. We recently indicated that phosphorus (P) fluctuations also exacerbated vascular calcification in early-stage CKD rats. Dietary fiber intake is reportedly associated with cardiovascular risk. This study investigated the effects of dietary fiber on vascular calcification by repeated P fluctuations in early-stage CKD rats. Unilateral nephrectomy rats were used as an early-stage CKD model. For 36 days, a P fluctuation (LH) group was fed low-P (0.02% P) and high-P (1.2% P) diets alternating every 2 days, and a P fluctuation with dietary fiber intake (LH + F) group was fed low-P and high-P diets containing dietary fiber alternating every 2 days. The effect on vascular calcification was measured calcium content. Effects on uremic toxin were measured levels of indoxyl sulfate (IS) and investigated gut microbiota. The LH + F group showed significantly reduced vessel calcium content compared to the LH group. Further, dietary fiber inhibited increases in blood levels of IS after intake of high-P diet, and decreased uremic toxin-producing intestinal bacteria. Dietary fiber may help suppress progression of vascular calcification due to repeated P fluctuations in early-stage CKD rats by decreasing uremic toxin-producing intestinal bacteria., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2020 JCBN.)

Background: Despite increasing opportunities for acquiring health information online, discussion of the specific words used in searches has been limited., Objective: The aim of this study was to clarify the medical information gap between medical professionals and the general public in Japan through health information-seeking activities on the internet., Methods: Search and posting data were analyzed from one of the most popular domestic search engines in Japan (Yahoo! JAPAN Search) and the most popular Japanese community question answering service (Yahoo! Chiebukuro). We compared the frequency of 100 clinical words appearing in the clinical case reports of medical professionals (clinical frequency) with their frequency in Yahoo! JAPAN Search (search frequency) logs and questions posted to Yahoo! Chiebukuro (question frequency). The Spearman correlation coefficient was used to quantify association patterns among the three information sources. Additionally, user information (gender and age) in the search frequency associated with each registered user was extracted., Results: Significant correlations were observed between clinical and search frequencies (r=0.29, P=.003), clinical and question frequencies (r=0.34, P=.001), and search and question frequencies (r=0.57, P<.001). Low-frequency words in clinical frequency (eg, "hypothyroidism," "ulcerative colitis") highly ranked in search frequency. Similarly, "pain," "slight fever," and "numbness" were highly ranked only in question frequency. The weighted average of ages was 34.5 (SD 2.7) years, and the weighted average of gender (man -1, woman +1) was 0.1 (SD 0.1) in search frequency. Some words were specifically extracted from the search frequency of certain age groups, including "abdominal pain" (10-20 years), "plasma cells" and "inflammatory findings" (20-30 years), "DM" (diabetes mellitus; 30-40 years), "abnormal shadow" and "inflammatory findings" (40-50 years), "hypertension" and "abnormal shadow" (50-60 years), and "lung cancer" and "gastric cancer" (60-70 years)., Conclusions: Search and question frequencies showed similar tendencies, whereas search and clinical frequencies showed discrepancy. Low-clinical frequency words related to diseases such as "hypothyroidism" and "ulcerative colitis" had high search frequencies, whereas those related to symptoms such as "pain," "slight fever," and "numbness" had high question frequencies. Moreover, high search frequency words included designated intractable diseases such as "ulcerative colitis," which has an incidence of less than 0.1% in the Japanese population. Therefore, it is generally worthwhile to pay attention not only to major diseases but also to minor diseases that users frequently seek information on, and more words will need to be analyzed in the future. Some characteristic words for certain age groups were observed (eg, 20-40 years: "cancer"; 40-60 years: diagnoses and diseases identified in health examinations; 60-70 years: diseases with late adulthood onset and "death"). Overall, this analysis demonstrates that medical professionals as information providers should be aware of clinical frequency, and medical information gaps between professionals and the general public should be bridged., (©Kazuya Taira, Taichi Murayama, Sumio Fujita, Mikiko Ito, Kei Kamide, Eiji Aramaki. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 13.04.2020.)

Objective: The ratio of dietary carbohydrate to fat may affect phosphorus metabolism because both calcium and phosphorus are regulated by similar metabolic mechanisms, and a high-fat diet (HFD) induces deleterious effects on the absorption of dietary calcium. We hypothesized that an HFD induces an increase in phosphorus absorption. The aim of this study was to evaluate the effects of differences in the quantity and quality of dietary fat on phosphorus metabolism over the short- and long-term., Methods: Eighteen 8-wk-old Sprague-Dawley male rats were fed an isocaloric diet containing varied ratios of carbohydrates to fat energy and sources of fat (control diet, HFD, and high- saturated fat diet [HF-SFA]). At 3 d and 7 wk after the allocation and initiation of the test diets, feces and urine were collected and used for phosphorus and calcium measurement., Results: The fecal phosphorous concentration (F-Pi) was lower in the HF-SFA group than in the other two groups; however, the urine phosphorus concentration (U-Pi) was significantly higher in the HF-SFA group than the other two groups when the rats were fed over the short- (P < 0.01) and long -term (P < 0.01 versus control, P < 0.05 versus HFD group). There were no significant differences in type-IIa sodium-phosphate cotransporter (NaPi-2 a) and type-IIc sodium-phosphate cotransporter (NaPi-2 c) mRNA expression, which are renal phosphate transport-related genes; however, the expression of type-IIb sodium-phosphate cotransporter (NaPi-2 b) and type-III sodium-phosphate cotransporter (Pit-1) mRNA in the duodenum was higher in the HFD and HF-SFA groups than in the control group (P < 0.05), although there were no significant differences in these in the jejunum., Conclusions: The present results indicated that an HFD, particularly HF-SFA, increases intestinal phosphate absorption compared with control., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cardiovascular disease is a major cause of death among hemodialysis patients. Hyperphosphatemia induces cardiovascular disease through vascular endothelial dysfunction and calcification. Repetition of a short-term excessive-phosphorus (P) diet causes transient elevations in plasma P and subsequent vascular endothelial dysfunction in normal rats. The purpose of this study was to investigate the effects of the P fluctuation on vascular calcification and inflammation in rats after unilateral nephrectomy as an early-stage chronic kidney disease (CKD) model. Rats were bred for 36 days; CP group, fed a control P (0.6%) diet; HP group, fed a high-P (1.2%) diet; and P fluctuation group, fed low-P (0.02%) and high-P diets alternately every 2 days. Influences on vascular calcification were analyzed using Von Kossa staining and measurement of vessel Ca content. The influence on inflammation was measured as urinary levels of 8-hydroxy-2'-deoxyguanosine. We demonstrated that the P fluctuation group showed similar vascular calcification and inflammation to the HP group, despite having the same total P intake as the CP group. A diet avoiding P fluctuations may be important for patients with early-stage CKD., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2020 JCBNCopyright © 2020 JCBN.)

Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA 2nd /AA 1st ratio in subjects who progressed from a health. y state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD.

Purpose : This study aimed to clarify the experiences of caregivers desiring to refuse life-prolonging treatment for their elderly parents at the end of life. Methods : A semi-structured interview was performed for four family caregivers who wanted to refuse life-prolonging treatment suggested by the physicians. Results : In this study, four caregivers who refused life-prolonging treatment suggested by the physicians for their elderly parents completed semi-structured interviews. The obtained data were analyzed in relation to the theme "Experiences of caregivers who desire to refuse life-prolonging treatment for their elderly parents at the end of life." As a result, 38 subcategories and 12 categories were extracted. Conclusions : Participants in this study initially had a negative view of life-prolonging treatment. However, they agonized over the decision when they received conflicting advice from the physicians. The participants indicated that physicians' advice and attitudes complicated their decisions to reject life-prolonging treatment for their elderly parents.

Background: Injection of parathyroid hormone (PTH) rapidly stimulates renal Pi excretion, in part by downregulating NaPi-IIa (Npt2a/SLC34A1) and NaPi-IIc (Npt2c/SLC34A3) transporters. The mechanisms underlying the effects of PTH on NaPi-IIc are not fully elucidated., Methods: We analyzed the effect of PTH on inorganic phosphate (Pi) reabsorption in Npt2a -/- mice to eliminate the influence of Npt2a on renal Pi reabsorption. In opossum kidney (OK) cells and Xenopus oocytes, we investigated the effect of NaPi-IIc transporter phosphorylation. Studies of mice with mutations of NaPi-IIc protein in which serine and threonine were replaced with either alanine (A), which prevents phosphorylation, or aspartic acid (D), which mimics the charged state of phosphorylated NaPi-IIc, were also performed to evaluate the involvement of phosphorylation in the regulation of transport function., Results: The Npt2a -/- experiments showed that PTH administration rapidly inactivated NaPi-IIc function in the apical membrane of proximal tubular cells. Analysis of mutant proteins (S71, S138, T151, S174, T583) at putative protein kinase C sites, revealed that S138 markedly suppressed the function and cellular expression of mouse NaPi-IIc in Xenopus oocytes and OK cells. In addition, 138D had a short half-life compared with wild-type protein., Conclusions: The present study suggests that acute regulation of NaPi-IIc protein by PTH is involved in the inactivation of Na + -dependent Pi cotransporter activity and that phosphorylation of the transporter is involved in the rapid modification.

Rugosin G, an ellagitannin trimer, was isolated from the water-soluble fraction of red rose petals, and its inhibitory activity against recombinant human histidine decarboxylase was investigated. Rugosin G showed potent inhibition compared to ellagitannin monomers and a dimer with macrocyclic structure (oenothein B), suggesting the potent inhibition of rugosin G was attributed to its linear oligomeric conformation. Abbreviations: HDC, histidine decarboxylase; Me 2 CO, acetone; EtOAc, ethyl acetate.

Background: The role of Na + -dependent inorganic phosphate (Pi) transporters in the human kidney is not fully clarified. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by loss-of-function mutations in the IIc Na + -dependent Pi transporter (NPT2c/Npt2c/NaPi-IIc) gene. Another Na + -dependent type II transporter, (NPT2A/Npt2a/NaPi-IIa), is also important for renal Pi reabsorption in humans. In mice, Npt2c deletion does not lead to hypophosphatemia and rickets because Npt2a compensates for the impaired Pi reabsorption. To clarify the differences between mouse and human, we investigated the relation between NaPi-IIa and NaPi-IIc functions in opossum kidney (OK) cells., Methods: We cloned NaPi-IIc from OK cells and created opossum NaPi-IIc (oNaPi-IIc) antibodies. We used oNaPi-IIc small interference (si)RNA and investigated the role of NaPi-IIc in Pi transport in OK cells., Results: We cloned opossum kidney NaPi-IIc cDNAs encoding 622 amino acid proteins (variant1) and examined their pH- and sodium-dependency. The antibodies reacted specifically with 75-kDa and 150-kDa protein bands, and the siRNA of NaPi-IIc markedly suppressed endogenous oNaPi-IIc in OK cells. Treatment with siRNA significantly suppressed the expression of NaPi-4 (NaPi-IIa) protein and mRNA. oNaPi-IIc siRNA also suppressed Na + /H + exchanger regulatory factor 1 expression in OK cells., Conclusion: These findings suggest that NaPi-IIc is important for the expression of NaPi-IIa (NaPi-4) protein in OK cells. Suppression of Npt2c may downregulate Npt2a function in HHRH patients.

Aim: In home-visiting bathing services (HVBs), a nurse's role is to evaluate the vital signs, judge bathing possibilities and provide treatment before/after bathing. There are no guidelines regarding specific physical criteria for judging the bathing possibility. However, the body condition of HVB users during bathing has not been investigated. Thus, the present study aimed to clarify users' actual conditions and the factors related to the judgment of the possibility of bathing., Methods: An anonymous self-administered questionnaire survey of HVBs users was conducted by Company-A, which provides HVBs. Six hundred sixty responses were collected (response rate: 40.1%).We described the conditions of HVB users and used chi-squared tests and logistic regression analyses to confirm the factors, including the certified Long-term Care Insurance (LTCI) care rank, past medical history and physical conditions that were associated with aborted HVB experiences., Results: The mean age of the care-recipients was 82.1±12.1 and 93.3% of the recipients had severe conditions, including conditions necessitation the use of medical equipment, pressure ulcers, and contracture. The logistic regression analysis showed that the LTCI-certified-care-rank, the presence of pain, and the need for treatment before bathing were significant factors., Conclusions: This study showed that users of HVBs not only had high LTCI-certified-care ranks, but that they also required pain management and pre-bathing treatment.

Phosphorus management through dietetic therapy is vital for the prevention of cardiovascular disease in chronic kidney disease patients. There are two main sources of phosphorus in the diet, organic phosphorus from protein and inorganic phosphorus from food additives. The adverse effects of high phosphorus intake on vascular-endothelium function have been reported; however, the differences in the effects of organic phosphorus versus inorganic phosphorus are not clear. In this study, we examined an acute effect of these high phosphorus meals intake on vascular-endothelium function. This was a randomized, double-blind, cross-over test study design targeting healthy young men. We conducted a food intake test using two test meals, one high in organic phosphorus from organic food sources, and one high in inorganic phosphorus from food additives. Endothelium-dependent vasodilation, phosphorus and calcium in the urine and blood, and phosphorus-related hormones were measured preprandial to 120 min postprandial. The results showed higher serum and urine phosphorus values after the high inorganic phosphorus meal, and a significant reduction in endothelium-dependent vasodilation at 30 min postprandial. These findings are evidence that inorganic phosphorus has a stronger influence on vascular-endothelium function than organic phosphorus., Competing Interests: No potential conflicts of interest were disclosed.

Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes that occur following aggressive nutritional supplementation in malnourished patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment in clinical practice. However, the mechanism of hypophosphatemia during RFS is unclear because of the lack of an animal model. In this study, we developed a rat RFS model as a first step to clarifying the molecular mechanism. After establishing the parenteral route, rats were fasted for 5 days and refeeding was started using total parenteral nutrition. The animals were infused with a high calorie solution with or without insulin administration. Results showed that plasma phosphate levels did not decrease in rats infused with the high calorie solution alone;in contrast, a 20% reduction compared to baseline was observed in rats administered insulin. In addition, rats infused with the high calorie solution containing added phosphate did not present with hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by tube feeding and insulin administration, and demonstrated the importance of phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55, February, 2018.

Purpose: In Japan, about 80% of deaths occur in hospitals, especially long-term care beds. The purpose of this study was to clarify the nursing practices used for such older patients at the end-of-life stage in long-termcare wards via the modified grounded theory approach (M-GTA)., Methods: Data were obtained through semi-structured interviews of nineteen nurses working in cooperating long-term care wards, acute care wards, or hospice services (to allow for constant comparison between these types of wards) in western Japan in 2014. We analyzed the transcribed data using M-GTA., Results: The core category that emerged from the analysis was "Balancing enhancement of patients' daily life quality and life-sustaining care in the face of uncertainty about the patients' character." Eleven categories emerged, such as Seeking older patients' character with their family, Supporting families' decision making, Rebuilding patients' daily life in the ward, and Sustaining patients' life span through medical care., Conclusions: Nurses experienced uncertainty about the care needs of older patients, the ethical problems of Enhancing the patients' QOL by using risky care, and the evaluation criteria used to judge their own nursing care after the patients' death. All nurses had the goal of ensuring a natural death for all patients. Nurses' acceptance and evaluation of their own care was critically influenced by the patient's family's responses to their care after patients' death. Further research is necessary to develop evaluation criteria and educational programs for end-of-life nursing care of older adults., (Copyright © 2017. Published by Elsevier B.V.)

Objective: The purpose of this study was to examine the relationship between the pain-relieving effects of duloxetine and its plasma concentrations in patients with burning mouth syndrome and atypical odontalgia characterized by chronic nonorganic pain in the orofacial region., Methods: We administered duloxetine to 77 patients diagnosed as having burning mouth syndrome or atypical odontalgia for 12 weeks. The initial dose of duloxetine was established as 20 mg/d and was increased to 40 mg/d after week 2. We evaluated pain using the visual analog scale and depressive symptoms using the Structured Interview Guide for the Hamilton Depression Rating Scale at weeks 0, 2, 4, 6, 8, 10, and 12 and measured plasma concentrations of duloxetine 12 weeks after the start of its administration., Results: Visual analog scale scores were significantly lower 12 weeks after than at the start of the administration of duloxetine (paired t test, t = 6.65, P < 0.0001). We examined the relationship between the rate of decreases in visual analog scale scores and plasma concentrations of duloxetine. There was no significant linear regression or quadratic regression., Conclusions: Duloxetine significantly relieved pain in patients with chronic nonorganic pain in the orofacial region. However, no relationship was observed between its pain-relieving effects and plasma concentrations.

Serotonin (5-hydroxytryptamine) is a putative substrate for myeloperoxidase, which may convert it into the reactive quinone tryptamine-4,5-dione (TD). In this study, we found that the viability of human SH-SY5Y neuroblastoma cells treated with 25 μM TD was increased to approximately 117%. On the other hand, the cell viability was significantly decreased by exposure to TD (150-200 μM), with an increase in intracellular reactive oxygen species (ROS). Interestingly, pre-treatment of SH-SY5Y cells with 100 μM TD prevented cell death and suppressed intracellular ROS generation evoked by the addition of hydrogen peroxide (H 2 O 2 ). Expression of the phase-II antioxidant enzyme NAD(P)H: quinone oxidoreductase 1 and haem oxygenase 1 were upregulated by TD at a concentration of 50-100 μM. Nuclear factor erythroid 2-related factor 2 (Nrf2), the regulator of these enzyme, was translocated from the cytosol to the nucleus by 100 μM TD. In summary, moderate concentrations of TD may increase the self-defence capacity of neuronal cells against oxidative stress.

It is necessary to include a nurse as staff in"Home Visit Bathing Long-Term Care"because nurses provide medical care such as vital sign measurement. However, the shortage of nurses is serious. A questionnaire survey was administered to nurses of E company, and findings showed that more than 50% of nurses felt physical fatigue. Correlation analysis showed that there was a significant correlation between"the intentions to continue working"and"good relationship between nurses and staff" (r=0.398, p<0.001), and there was a negative correlation with"low payment"(r=-0.232, p<0.01)and"physical fatigue" (r=-0.272, p<0.01). Although physical fatigue and low payment are factors that inhibit the intentions to continue working, the most important factor is human relationships. It was suggested that maintaining good human relationships enhances the intentions of nurses to continue working.

The nutrition is important for prevention and improvement in bone disorder. Especially osteoporosis associated with nutrition. It has entered the super-aged society in 2007, a further increase in osteoporosis patients are concerned in Japan. Many studies have shown that associated with calcium, vitamin D, vitamin K intake and bone density and fracture. Relationship of osteoporosis and nutrition, despite the general awareness is high, calcium intake is not at all reached the achievement to recommend dietary allowance. In addition, vitamin D deficiency rickets in children, which has been considered in the past of the disorder, there is an increasing trend from such exposure shortage to the infancy of sunlight, vitamin D deficiency in pregnant women, the recommended breastfeeding. Improvement of lifestyle and diet from young age is important for bone disorder prevention.

Renal osteodystrophy is the damage of bone morphology by CKD and treatment and occurred abnormal bone metabolism through renal dysfunction. It demonstrated that the control of P and Ca improves to normalization of mineral metabolism. Protein energy wasting and malnutrition are common in patients with CKD stage 5 and has been associated with life prognosis. In CKD patients, nutritional management is a critical role of treatment. Also it may be important of nutritional management that control P and Ca and improve nutritional status in renal osteodystrophy patients.

Objective: Burning mouth syndrome (BMS) is a chronic disease in which patients feel a burning sensation and pain in the oral cavity. Although personality traits have been suggested to influence the development and course of BMS, they have not yet been examined in detail. We therefore investigated the personality traits of BMS patients., Methods: Sample consisted of 65 BMS patients presenting to the Aichi-Gakuin Dental School Hospital between May 2005 and April 2009. They were also diagnosed as having pain disorder by a psychiatrist. The control group consisted of 116 healthy subjects. The Temperament and Character Inventory (TCI) was used to evaluate personality traits, while the Beck Depression Inventory (BDI) was used to evaluate the depression rate in both groups., Results: In TCI, we found that, in comparison to the control group, the novelty seeking score was significantly lower (p = 0.009), the harm avoidance score was significantly higher (p < 0.001), and the self-directedness score was significantly lower (p = 0.039) in the BMS group. To remove the influence of depression, we performed an analysis of covariance of each TCI item using the BDI score as a covariate. No significant differences were observed in harm avoidance or self-directedness, whereas the differences noted in novelty seeking were significant (p = 0.008)., Conclusion: The novelty seeking score was low in BMS patients in comparison to the control group. They also had high harm avoidance and low self-directedness tendencies, but these were attributed to the influence of depression., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na(+)-dependent phosphate (Pi) uptake decreased by 50%-60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na(+)-dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells.

Aims: The objectives of this study were to understand the experiences of people with cleft lip and cleft palate (CLCP) and to describe the processes and factors leading to the acquisition of high self-esteem., Methods: Semi-structured interviews were conducted of 19 subjects with CLCP recruited via hospitals and through snowball sampling, and the results were analyzed qualitatively, comparing high and low self-esteem groups., Results: Participants with high self-esteem had gone through the phases of "noticing their difference from others", "knowing about and deepening their understanding of CLCP", "no denial of their life with CLCP" and "affirmation of life with CLCP". Seven factor categories including "received sufficient explanation of CLCP condition (from parents) in the early stage", "have not received negative messages about CLCP" and "feeling the presence of someone who accepts their feelings and supports them" were extracted as factors promoting these processes., Conclusions: Knowing about and understanding CLCP enables individuals to acquire a sense of coherence in their lives, which may be related to gaining a feeling of control over their cleft condition, acquiring a sense of autonomy, and finding a meaning for their lives. Thus, medical professionals should provide explanations that enable patients to understand CLCP, and also facilitate interaction between patients with the same condition., (© 2011 The Authors. Japan Journal of Nursing Science © 2011 Japan Academy of Nursing Science.)

Mutations in the apically located Na(+)-dependent phosphate (NaPi) cotransporter, SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We have characterized the impact of several HHRH mutations on the processing and stability of human NaPi-IIc. Mutations S138F, G196R, R468W, R564C, and c.228delC in human NaPi-IIc significantly decreased the levels of NaPi cotransport activities in Xenopus oocytes. In S138F and R564C mutant proteins, this reduction is a result of a decrease in the V(max) for P(i), but not the K(m). G196R, R468W, and c.228delC mutants were not localized to oocyte membranes. In opossum kidney (OK) cells, cell surface labeling, microscopic confocal imaging, and pulse-chase experiments showed that G196R and R468W mutations resulted in an absence of cell surface expression owing to endoplasmic reticulum (ER) retention. G196R and R468W mutants could be partially stabilized by low temperature. In blue native-polyacrylamide gel electrophoresis analysis, G196R and R468W mutants were either denatured or present in an aggregation complex. In contrast, S138F and R564C mutants were trafficked to the cell surface, but more rapidly degraded than WT protein. The c.228delC mutant did not affect endogenous NaPi uptake in OK cells. Thus, G196R and R468W mutations cause ER retention, while S138F and R564C mutations stimulate degradation of human NaPi-IIc in renal epithelial cells. Together, these data suggest that the NaPi-IIc mutants in HHRH show defective processing and stability.

Objectives: This study was performed to assess the relationship between plasma levels of milnacipran and its analgesic/antidepressive effect in patients with chronic orofacial pain treated with this drug., Methods: A total of 44 patients took milnacipran for 12 weeks. Patients were assessed for their pain and depressive symptoms using the visual analog scale (VAS) and Hamilton Depression Rating Scale, respectively. The plasma milnacipran level was also assessed at week 12., Results: Forty patients completed study treatment and were included in the analysis. In these patients, the VAS score at week 12 significantly decreased from the baseline score (t = 5.15, p < 0.0001). The dose of milnacipran was positively correlated in a linear manner with the plasma level of the drug (Y = 44.86 + 0.33X, r = 0.54, R(2)  = 0.29, p = 0.0004). A quadratic regression curve was plotted between the percentage of decrease in the VAS score and plasma milnacipran level (Y = 27.39 + 0.76X - 0.008X(2) , p = 0.048, r = 0.40, R(2)  = 0.16). On the other hand, no significant relationship was noted between the percentage of decrease in the Hamilton Depression Rating Scale score and plasma milnacipran level., Conclusion: The analgesic effect of milnacipran was suppressed in the presence of the plasma level of the drug outside the therapeutic range, whereas its antidepressant effect was not affected by its plasma level., (Copyright © 2012 John Wiley & Sons, Ltd.)

The position-sensitive multi-anode photomultiplier tube (MA-PMT) is widely used in high-resolution scintillation detectors. However, the anode gain nonuniformity of this device is a limiting factor that degrades the intrinsic performance of the detector module. The aim of this work was to develop a gain compensation method for the MA-PMT and evaluate the resulting enhancement in the performance of the detector. The method employs a circuit that is composed only of resistors and is placed between the MA-PMT and a resistive charge division network (RCN) used for position encoding. The goal of the circuit is to divide the output current from each anode, so the same current flows into the RCN regardless of the anode gain. The current division is controlled by the combination of a fixed-value series resistor with an output impedance that is much larger than the input impedance of the RCN, and a parallel resistor, which detours part of the current to ground. PSpice simulations of the compensation circuit and the RCN were performed to determine optimal values for the compensation resistors when used with Hamamatsu H8500 MAPMTs. The intrinsic characteristics of a detector module consisting of this MA-PMT and a lutetium-gadolinium-oxyorthosilicate (LGSO) crystal array were tested with and without the gain compensation method. In simulation, the average coefficient of variation and max/min ratio decreased from 15.7% to 2.7% and 2.0 to 1.2, respectively. In the flood map of the LGSO-H8500 detector, the uniformity of the photopeak position for individual crystals and the energy resolution were much improved. The feasibility of the method was shown by applying it to an octagonal prototype positron emission tomography scanner.

Purpose: We examined spousal gender differences in change of caregiving experience over 2-years, focusing on care-recipient's physical and mental conditions, living arrangements, financial status, utilization of long-term care insurance (LTCI), availability of secondary caregivers, caregiver's coping strategies and psychological well-being. We also investigated causal associations between caregiving experiences and psychological well-being of the spousal caregivers., Method: We conducted a 2-wave survey, in Oct. 2003 and 2005. The subjects were a stratified random sample of 5,000 users of LTCI in Higashi-osaka city in Japan. Data were collected through mailed, anonymous self-report questionnaires. Totals of 212 wives and 356 husbands were longitudinally analyzed. A cross-lagged effect model by simultaneous analysis of multiple populations was made to analyze a causal association between caregiving experiences and caregivers' psychological well-being., Results: There were no significant changes in care-recipient's physical and mental conditions. Over the 2 years, husbands increased the amount of ADL assistance and availability as secondary caregivers, and wives increased utilization of LTCI services. We also found gender differences in the priority of coping strategies. Husbands' preferred coping strategy over 2 years was more on 'willing commitment caregiver's role 'while for wives' it was 'instrumental support seeking'. Wives demonstrated a significantly reduced positive appraisal of caregiving. Though the amount of ADL assistance and 'instrumental support seeking' reduced husband's depression, husband's positive appraisal of caregiving significantly increased strategies of 'emotional support seeking' and 'willing commitment of care role'. Wives & depression decreased with 'valuing own leisure and refreshing' strategies. Furthermore, wives' positive caregiving appraisal increased both strategies of 'keeping own pace of caregiving' and willing acceptance of care role'., Conclusion: The husband's results support an interpretation of adaptation to the caregiving role over two years. Therefore husbands who do not experience increase in ADL assistance might be at risk of caregiver's depression. We should monitor their situation of caregiving continually. Though wives increased utilization of LTCI services, this service use did not improve their psychological wellbeing, and they exhibited decreased positive appraisal of caregiving.

Background: An increasing number of old people, and their medical requirements, cannot be managed by their families in their homes, which has been the traditional and prevalent practice in Japan. The number of people with dementia is increasing and behavioral and psychological symptoms of dementia (BPSD) make care difficult. In the present study, we investigated management techniques for BPSD in long-term care facilities in Japan by using the data mining method, which looks at the reported behaviors of care providers., Methods: First, interviews were conducted with 15 care providers to develop items for a questionnaire. These data were analyzed qualitatively and synthesized with criteria from the professional literature. The resulting self-report questionnaire on techniques used to manage different symptoms of dementia was completed by 275 care providers. We applied the association rule as a data mining method examining 15 management techniques related to 13 BPSD., Results: Analysis identified four types of management techniques: (i) emotional and behavior-concordance techniques; (ii) acceptance and supportive techniques; (iii) restraining techniques; and (iv) avoidance techniques. Different management techniques, and combinations of techniques, were found to vary in use and effectiveness with different BPSD., Conclusions: Good management techniques for many BPSD have been developed and are being implemented by care providers. The present study has the potential to inform researchers and care providers in Japan about the types of management techniques in current use, as well as areas of potential need for staff training.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessively inherited disorder, characterized by hypophosphatemia, short stature, rickets and/or osteomalacia, and secondary absorptive hypercalciuria. HHRH is caused by a defect in the sodium-dependent phosphate transporter (NaPi-IIc/Npt2c/NPT2c), which was thought to have only a minor role in renal phosphate (P(i)) reabsorption in adult mice. In fact, mice that are null for Npt2c (Npt2c(-/-)) show no evidence for renal phosphate wasting when maintained on a diet with a normal phosphate content. To obtain insights and the relative importance of Npt2a and Npt2c, we now studied Npt2a(-/-)Npt2c(+/+), Npt2a(+/-)Npt2c(-/-), and Npt2a(-/-)Npt2c(-/-) double-knockout (DKO). DKO mice exhibited severe hypophosphatemia, hypercalciuria, and rickets. These findings are different from those in Npt2a KO mice that show only a mild phosphate and bone phenotype that improve over time and from the findings in Npt2c KO mice that show no apparent abnormality in the regulation of phosphate homeostasis. Because of the nonredundant roles of Npt2a and Npt2c, DKO animals showed a more pronounced reduction in P(i) transport activity in the brush-border membrane of renal tubular cells than that in the mice with the single-gene ablations. A high-P(i) diet after weaning rescued plasma phosphate levels and the bone phenotype in DKO mice. Our findings thus showed in mice that Npt2a and Npt2c have independent roles in the regulation of plasma P(i) and bone mineralization.

In 2003, the NKF K/DOQI released new clinical practice guidelines for bone metabolism and disease in chronic kidney disease, respectively. Target level of phosphate and Ca x Pi products are set at relative low levels in the new guidelines. Prescription of a new phosphate binder, severamer hydrochloride, a widely recommended in this quideline. Other approaches that could prove fruitful include inhibition of intestinal and renal phosphate transporters. Inhibition of the sodium-dependent phosphate transporter by a small molecule would be a desirable method to control serum phosphate levels in patients with chronic renal disease or undergoning dialysis. In this review the progress in the identification of such an agent is discussed.

Background: Gender differences in spousal caregivers and their relationship to care experiences, social demographics, and caregivers' depression were examined., Methods: A stratified random sample of 2,020 users of public long-term care insurance in a city of Osaka prefecture, Japan, participated in this study. Responses from 308 spouses (56.2% wives, 43.8% husbands) were analyzed. Variables relating to care experiences, social demographics, and caregivers' depression were compared by conducting simultaneous analyses of multiple populations., Results: Wives caring for husbands had higher depression scores than husbands caring for wives. Wives tended to adopt "emotional support seeking" and "willing commitment" as coping strategies for their caregiving experience. Husband caregivers used more home-care services; however, increased service use had no effect on husbands' depression. The availability of secondary caregivers reduced depression for caregivers, regardless of gender., Conclusions: The effects on depression differed related to the caregiver's gender. Husbands relied more on family or home-care services when caring for their wives, whereas wives provided higher levels of care, positively accepted their role, and did not seek to share caregiving, but sought emotional support.

Abnormalities of the inorganic phosphate (Pi) reabsorption in the kidney result in various disorders. Na(+)-dependent Pi (NaPi) transporters (NaPi- II a and NaPi- II c) in the brush border membrane of proximal tubular cells mediate the rate-limiting step in the overall Pi-reabsorptive process. The PTH (parathyroid hormone) -induced inhibition of Pi reabsorption is mediated by endocytosis of the NaPi- II a transporter from brush border membrane. NaPi- II a is part of the heteromeric protein complexes organized by PDZ ( [PSD-95/Disc-large/ZO-1] -binding proteins) proteins. The NaPi- II c transporter is also regulated by PTH via internalization, but by a vesicular transport pathway distinct from that used by the NaPi- II a transporter. In addition, the importance of the fibrobalst growth factor 23 (FGF23) -klotho axis in regulating mineral ion homeostasis. We will summarize how the FGF23-klotho might regulate renal Pi reabsorption.

Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. Urakawa et al demonstrated that the concerted action of klotho and fibroblast growth factor receptor 1 reconstitutes the fibroblast growth factor 23 (FGF23) receptor (Nature 444,770,2006). We investigated the correlation between hyperphosphatemia and Pi transport activity in klotho mutant mice (kl/kl mice). kl/kl mice displayed hyperphosphatemia, high plasma 1,25 (OH) (2)D(3) levels, increased activity of the renal and intestinal sodium-dependent P (i) cotransporters, and increased levels of the type II a, type II b, and type II c transporter proteins compared with wild-type mice. Interestingly, transcript levels of the type II a/type II c transporter mRNA abundance, but not transcripts levels of type II b transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type mice. Furthermore, plasma FGF23 levels were 150-fold higher in kl/kl mice than in wild-type mice. Feeding of a low-P (i) diet induced the expression of klotho protein and decreased plasma FGF23 levels in kl/kl mice, whereas colchicine treatment experiments revealed evidence of abnormal membrane trafficking of the type IIa transporter in kl/kl mice. These results indicate that hyperphosphatemia in klotho mice is due to dysregulation of expression and trafficking of the renal type II a/ II c transporters rather than to intestinal P (i) uptake.

During bone resorption, a large amount of inorganic phosphate (P(i)) is generated within the osteoclast hemivacuole. The mechanisms involved in the disposal of this P(i) are not clear. In the present study, we investigated the efflux of P(i) from osteoclast-like cells. P(i) efflux was activated by acidic conditions in osteoclast-like cells derived by the treatment of RAW264.7 cells with receptor activator of nuclear factor-kappaB ligand. Acid-induced P(i) influx was not observed in renal proximal tubule-like opossum kidney cells, osteoblast-like MC3T3-E1 cells, or untreated RAW264.7 cells. Furthermore, P(i) efflux was stimulated by extracellular P(i) and several P(i) analogs [phosphonoformic acid (PFA), phosphonoacetic acid, arsenate, and pyrophosphate]. P(i) efflux was time dependent, with 50% released into the medium after 10 min. The efflux of P(i) was increased by various inhibitors that block P(i) uptake, and extracellular P(i) did not affect the transport of [(14)C]PFA into the osteoclast-like cells. Preloading of cells with P(i) did not stimulate P(i) efflux by PFA, indicating that the effect of P(i) was not due to transstimulation of P(i) transport. P(i) uptake was also enhanced under acidic conditions. Agents that prevent increases in cytosolic free Ca(2+) concentration, including acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 2-aminoethoxydiphenyl borate, and bongkrekic acid, significantly inhibited P(i) uptake in the osteoclast-like cells, suggesting that P(i) uptake is regulated by Ca(2+) signaling in the endoplasmic reticulum and mitochondria of osteoclast-like cells. These results suggest that osteoclast-like cells have a unique P(i) uptake/efflux system and can prevent P(i) accumulation within osteoclast hemivacuoles.

In general, twins have delayed language development early in childhood compared with singletons. The purpose of this study was to clarify the overall linguistic features of twins. A Japanese version of the Illinois Test of Psycholinguistic Abilities (ITPA) was administered in 24 twin pairs (aged 3 to 4 years) at their own homes. The overall language abilities of the twins were in the normal range (based on ITPA normative data: mean scale score 36.0 +/- 6.0 points), and for the ITPA subtests only, Auditory Reception fell within the range of language disorder (mean scale score 24.9 +/- 5.1 points). The findings suggest that in 3- to 4-year-old Japanese twins, overall language abilities are not delayed. However, there may be specific difficulties with auditory reception skills.