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Y Soeroso,1,2 T Akase,3 H Sunarto,1,2 Y Kemal,1 R Salim,1 M Octavia,1 A Viandita,1 J Setiawan,1 BM Bachtiar2,4 1Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia; 2Oral Sciences Research Center, Universitas Indonesia, Jakarta, Indonesia; 3R&D, Oral Care Company, Sunstar Group, Takatsuki City, Japan; 4Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia Background: The aim of this study was to evaluate the clinical and microbiological effects of local application minocycline HCl 2% gel, used as an adjunct to scaling and root planing (SRP) for treatment of chronic periodontitis (CP). CP is an inflammation of periodontal tissue that is caused mainly by bacterial infection, where periodontal destruction such as loss of attachment and bone destruction occurred. Methods: A total of 81 subjects with moderate to severe periodontitis whose baseline clinical attachment loss (CAL) was ≥4 mm were randomly assigned to receive SRP alone (control group, N=39) or SRP followed by four times of local application of minocycline HCl gel (Periocline) once a week (test group, N=42). Pocket depth, CAL, and papilla bleeding index were examined at baseline, 21 days, 2, 3, and 6 months. Subgingival plaque samples were collected with sterile curettes and were analyzed by real-time polymerase chain reaction for the presence of three periodontal pathogens (Porphyromonas gingivalis [P.g.], Tannerella forsythia [T.f.], and Treponema denticola [T.d.]) at baseline, 2, 3, and 6 months. Results: The number of bacteria was reduced in both groups at 2 months after baseline (SRP treatment). The changes (2–6 months) in T.d. and T.f. counts in the test group were significantly lower than those in the control group. In the control group, a significant regrowth of P.g., T.f., and T.d. was observed from 2 to 6 months and of P.g. and T.f. from 3 to 6 months. On the other hand, in the test group, the number of the three bacteria did not significantly increase during the 6-month period. Conclusion: The results showed that local application of minocycline, used as an adjunct to SRP, was effective for suppressing regrowth of periodontal pathogens, suggesting its risk reduction of recurrent periodontal pathogens in CP. Keywords: chronic periodontitis, minocycline, scaling and root planing, real-time PCR, periodontal pathogen

A new general route for large area, submicron thick ceramic thin films (crystalline metal oxide thin films) on plastic substrates is presented, where the crystallization of films is guaranteed by a firing process. Gel films are deposited on silicon substrates with a release layer and fired to be ceramic films, followed by transferring onto plastic substrates using adhesives. The ceramic films thus fabricated on plastics exhibit a certain degree of flexibility, implying the possibility of the technique to be applied to high-throughput roll-to-roll processes. Using this technique, we successfully realized transparent anatase thin films that provide high optical reflectance and transparent indium tin oxide thin films that exhibit electrical conductivity on polycarbonate and acrylic resin substrates, respectively. Crystallographically oriented zinc oxide films and patterned zinc oxide films are also demonstrated to be realized on acrylic resin substrates. [ABSTRACT FROM AUTHOR]

Background: Randomized, controlled trials (RCTs) in 220 patients with advanced colorectal cancer reported no significant differences in survival periods between folinic acid/5-fluorouracil/irinotecan (FOLFIRI) and folinic acid/5-fluorouracil/oxaliplatin (FOLFOX6) therapies, irrespective of the treatment sequence. Based on a literature search, an economic assessment of both treatments given in 1 of 2 sequences (FOLFIRI and FOLFOX6, or FOLFOX6 and FOLFIRI) has not been conducted in Japan. Objective: The present cost-minimization analysis used a mathematical Markov model to assess health care costs of these 2 treatment sequences from the perspective of National Health Insurance (NHI) in Japan. Methods: The analysis simulated the expected costs resulting from the influence of treatment sequence in a hypothetical cohort of 10,000 patients with nonresectable advanced colorectal cancer over a period of 100 months using a hypothetical Markov model. Clinical parameters were obtained from the RCTs. Cost parameters included those for physical examination, medication, and personnel. Medication and physical examination costs were based on 2008 NHI drug prices and medical service fees, respectively. Costs were discounted at a monthly rate of 0.4575% (equivalent to an annual rate of 3%). The influence of each parameter (clinical and cost parameters) was assessed using a probabilistic sensitivity analysis by the 10,000-time Monte Carlo simulation. Results: When FOLFIRI was used as the initial treatment in this analysis, costs to the NHI were reduced. On analysis of the influence of each parameter, the expected reduction in costs, compared with FOLFOX administered as the initial treatment, was significant (¥7,787,828 [95% CI, ¥6,098,517-¥9,499,952]). Conclusions: The findings of this cost-minimization analysis suggest that using FOLFIRI followed by FOLFOX versus the reverse strategy produced cost savings from the perspective of the NHI in Japan. However, differences in adverse-events profiles may warrant treatment adjustments in individual patients. [ABSTRACT FROM AUTHOR]

This study aimed to identify risk factors and combinations thereof that are associated with severe skin injuries due to the extravasation of injectable drugs. A cross-sectional study using the Japanese Adverse Drug Event Report database was conducted according to the RECORD-PE checklist. Adverse event reports related to necrosis, ulcers, or erosions due to extravasation were considered "with severe skin injury," and others were considered "without severe skin injury." Approximately 255 cases "with" and 260 cases "without" severe skin injury were identified. The relationship between the incidence of severe skin injury and age, sex, drugs, and primary disease was evaluated using the χ2 test. Association rule mining was used to evaluate the correlation between each combination of factors and skin injury. Nine factors were identified as independent risk factors for severe skin injury, including age (<10 or ≥70 years), peripheral parenteral nutrition use, and mental disorders. The association rule mining results suggested that a combination of specific patient backgrounds and drug use was associated with the incidence of necrosis or ulcers. The findings of this study reiterate that nurses might consider closely observing patients with the risk factors identified in this study for the prevention and early detection of extravasation-related skin injuries., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Infusion Nurses Society.)

Objective: Obesity is not only a risk factor for lifestyle-related diseases but also causes skin barrier dysfunction, which leads to a reduced quality of life due to dryness, itching, and scratching, and thus requires appropriate treatment. However, there are no studies on this issue. Therefore, this study aimed to examine whether oral intake of linseed oil is effective for skin barrier function in obesity and to confirm how the effect is demonstrated., Methods: TSOD mice received either sterile distilled water (Control group) or linseed oil (Omega group), containing a high level of omega-3 fatty acids, including α-linolenic acid, orally for eight weeks. Mice were then irradiated with ultraviolet B (UVB) and three days later, transepidermal water loss (TEWL), which is the primary outcome of skin barrier function, was measured and gross skin appearance was observed. Hematoxylin and eosin (HE) staining and Ki-67 immunostaining were performed on skin samples. mRNA expression levels of the inflammatory markers Tnfα , Cox2 , Mcp1 , and Hmox1 were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). We also performed fatty acid analysis of skin and erythrocytes by gas chromatography. Statistical analysis was performed using unpaired Student's t-test and Pearson's correlation analysis., Results: Compared with the Control group, the Omega group exhibited lower TEWL values and little skin erythema. Histological analysis revealed thinner epidermis and fewer Ki-67 positive cells. Additionally, in the Omega group, mRNA levels of four inflammation-related genes were lower, α-linolenic acid levels in both skin and erythrocytes were higher, and a lower n-6/n-3 ratio was observed. And α-linolenic acid levels in the skin were negatively correlated with the expression levels of inflammation-related genes., Conclusion: Oral intake of linseed oil was found to inhibit skin barrier dysfunction in obesity. This effect was mediated by α-linolenic acid, a major component of linseed oil with anti-inflammatory properties, which was taken up by erythrocytes and supplied to the skin. Therefore, oral intake of linseed oil is expected to be a useful therapeutic method for skin barrier dysfunction in obesity., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: Yokohama City University Animal Experiment Committee Issued protocol number F-A-23-051. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was supported by the Japan Academy of Nursing Science (JANS) and the Association for Fordays Self-Reliance Support in Japan. Financial relationships: Yoshiko Horie declare(s) a grant from Japan Academy of Nursing Science (JANS) . Yoshiko Horie declare(s) a grant from Association for Fordays Self-Reliance Support in Japan. Toru Moriguchi (Chairman), Akiko Harauma (Director) declare(s) non-financial support from Japan Society for Lipid Nutrition. Toru Moriguchi, Akiko Harauma declare(s) a grant from Ota Oil Co., Ltd. Endowment course. Toru Moriguchi declare(s) non-financial support from Krill Association. Director. Toru Moriguchi declare(s) non-financial support from Society of Preventive Medicine for Animals and Humans. Director. Intellectual property info: Akiko Harauma and Toru Moriguchi have a patent planned, issued, or pending: 095P001JP1; Toru Moriguchi has a patent planned, issued, or pending: TPJ0508AZU. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Horie et al.)

Various cytochrome P450 enzymes (CYPs) that contribute to drug metabolism are expressed in the skin. However, variation among individuals in CYP expression profiles is not well-understood.To investigate CYPs related to the metabolism of transdermal preparations in Japan, multiple skin tissue specimens of individuals of Japanese descent were prepared, and the mRNA expression levels of CYP1A2 , CYP3A4 , and CYP3A5 were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investigated.There were considerable individual differences in epidermal CYP1A2 mRNA expression levels, and CYP1A2 showed a weak positive correlation with CYP3A4 mRNA expression levels. In contrast to previous results for other organs, epidermal CYP3A4 mRNA expression levels showed a weak positive correlation with BMI. CYP3A4 in the epidermis may have been locally enhanced as a defence mechanism against xenobiotics in response to impaired barrier function. These differences in mRNA expression in the skin may affect the transdermal absorption of drugs, such as lidocaine and fentanyl, which are metabolised by multiple overlapping CYPs.Our study provides new insights into drug metabolism in the skin. These results are valuable for predicting drug effects and transdermal drug transfer rates in Japanese patients.

Polyglutamine (polyQ) diseases are rare autosomal-dominant neurodegenerative diseases associated with the expansion of glutamine-encoding triplet repeats in certain genes. To investigate the functional influence of repeat expansion on disease mechanisms, we applied a biallelic genome-engineering platform that we recently established, called Universal Knock-in System or UKiS, to develop a human cell trio, a set of three isogenic cell lines that are homozygous for two different numbers of repeats (first and second lines) or heterozygous for the two repeat numbers (third line). As an example of a polyQ disease, we chose spinocerebellar ataxia type 2 (SCA2). In a pseudodiploid human cell line, both alleles of the glutamine-encoding triplet repeat in the SCA2-causing gene, ataxin 2 or ATXN2, were first knocked in with a donor sequence encoding both thymidine kinase and either puromycin or blasticidin resistance proteins under dual drug selection. The knocked-in donor alleles were then substituted with a payload having either 22 or 76 triplet repeats in ATXN2 by ganciclovir negative selection. The two-step substitution and subsequent SNP typing and genomic sequencing confirmed that the SCA2-modeling isogenic cell trio was obtained: three clones of 22-repeat homozygotes, two clones of 22/76-repeat heterozygotes and two clones of 76-repeat homozygotes. Finally, RT-PCR and immunoblotting using the obtained clones showed that, consistent with previous observations, glutamine tract expansion reduced transcriptional and translational expression of ATXN2. The cell clones with homozygous long-repeat alleles, which are rarely obtained from patients with SCA2, showed more drastic reduction of ATXN2 expression than the heterozygous clones. This study thus demonstrates the potential of UKiS, which is a beneficial platform for the efficient development of cell models not only for polyQ diseases but also for any other genetic diseases, which may accelerate our deeper understanding of disease mechanisms and cell-based screening for therapeutic drugs.

Insulin therapy is one of the central treatments for diabetes mellitus. Insulin-derived localized amyloidosis (IDLA) is a known skin-related complication of insulin injection. This is one of the causes of poor glycemic control in diabetic patients on insulin therapy. The aim of this study was to review and update the findings on the extent and mechanism of reduced insulin absorption in IDLA. A literature search was conducted on decreased insulin absorption and its mechanisms, and nine references were selected, with seven of these on decreased insulin absorption and four on mechanisms. Insulin absorption at IDLA sites was reported to be 27-94% lower compared with normal sites. In addition, a comparison between nonpalpable and palpable IDLA sites revealed a significant decrease in insulin absorption at the palpable IDLA site. The mechanism of insulin malabsorption was found to be a reduction in insulin absorption at the palpable IDLA sites. Four mechanisms of decreased insulin absorption were identified: decreased subcutaneous blood flow, adsorption of administered insulin onto insulin amyloid fibers, impaired diffusion of insulin subcutaneously, and physical factors such as shaking of the insulin preparation. These mechanisms should be investigated in vivo in the future.

Purpose: Perioperative depressive symptoms are associated with poor postoperative quality of life (QOL), leading to prolonged hospital stays, and delayed return to society. Previous studies show that physical and mental states change on the third day after surgery, and there is a correlation between quality of recovery (QoR) on this day and QOL at 3 months after surgery. QoR after surgery is an important indicator of postoperative QOL. However, there are no reports on the association between depressive symptoms, and postoperative QoR. Therefore, the study purpose was to clarify the relationship between depressive symptoms in perioperative cancer patients during the prehospitalization waiting period, and QoR on the third postoperative day., Design: This was a prospective cohort study., Methods: We examined whether depressive symptoms during the prehospitalization waiting period were related to QoR on day 3 after surgery in perioperative cancer patients. Subjects were patients with primary tumors who underwent surgery under general anesthesia. Subjects completed self-administered questionnaires during the prehospitalization waiting period and on postoperative day 3. The presence and/or absence of depressive symptoms was measured using the Hospital Anxiety and Depression Scale. Subjects were divided into two groups: depressive symptoms or non-depressive symptoms. Postoperative QoR was determined using the QoR-40 questionnaire and we calculated the rate of change in QoR-40 global and dimension scores from preoperation to postoperation., Findings: 231 individuals met the inclusion criteria and agreed to participate in the study. Of these, 173 were included in the analysis. Only the rate of change in emotional state differed significantly between groups (P = .022). Both global and dimension QoR-40 scores were lower in the depressive symptoms group than in the non-depressive symptoms group., Conclusions: These findings demonstrate the need to provide both psychological and physical support continuously from the preoperative to early postoperative stage for cancer patients with depressive symptoms in the prehospitalization waiting period., (Copyright © 2021 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Functional annotation of the vast noncoding landscape of the diploid human genome still remains a major challenge of genomic research. An efficient, scarless, biallelic, and gene-wide mutagenesis approach is needed for direct investigation of the functional significance of endogenous long introns in gene regulation. Here we establish a genome substitution platform, the Universal Knock-in System or UKiS, that meets these requirements. For proof of concept, we first used UKiS on the longest intron of TP53 in the pseudo-diploid cell line HCT116. Complete deletion of the intron, its substitution with mouse and zebrafish syntenic introns, and specific removal of retrotransposon-derived elements (retroelements) were all efficiently and accurately achieved in both alleles, revealing a suppressive role of intronic Alu elements in TP53 expression. We also used UKiS for TP53 intron deletion in human induced pluripotent stem cells without losing their stemness. Furthermore, UKiS enabled biallelic removal of all introns from three human gene loci of ~100 kb and longer to demonstrate that intron requirements for transcriptional activities vary among genes. UKiS is a standard platform with which to pursue the design of noncoding regions for genome writing in human cells., (© 2022. The Author(s).)

Background: This study examined the relationship between survival prognosis and alanine aminotransferase (ALT), a critical factor contributing to aging-related health and mortality. The research is based on a follow-up study with 6- and 10-year intervals., Methods: The participants included 1,610 males (63 ± 14 years old) and 2,074 females (65 ± 12 years old) who were part of the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort). The multivariable-adjusted hazard ratios (HRs) of death between the baseline health checkup and the end of the follow-up periods were estimated using a Cox proportional hazards model, controlling for potential confounding factors., Results: The follow-up survey revealed 180 male deaths (11.2% of male participants) and 146 female deaths (7.0% of female participants). The univariate Cox regression analysis showed a significant increase in the HRs of all-cause mortality with decreasing ALT levels (p < 0.001). Furthermore, compared with individuals with ALT levels of 20-29 IU/L, the multivariable-adjusted HRs (95% confidence interval) for all-cause mortality were 2.73 (1.59-4.70) for those with ALT levels <10 IU/L, 1.45 (1.05-2.00) for those with ALT levels of 10-19 IU/L, and 1.63 (1.05-2.53) for those with ALT levels ≥30 IU/L., Conclusions: Our findings show that abnormally low ALT levels and high within the normal range were related to all-cause mortality in Japan's community-dwelling individuals. Especially, ALT activity may be an important biomarker for predicting the long-term survival of older adults., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Purpose: In addition to playing a critical role in cardiovascular health, muscle mass and strength independently impact aging-related health outcomes in adults. There are limited predictive data for all-cause mortality, particularly for community-dwelling persons in Japan. This study examined whether handgrip strength (HGS) and thigh circumference are related to survival prognosis based on a 6-year follow-up period., Methods: Participants were 787 men (aged 69 ± 11 years) and 963 women (aged 69 ± 9 years) who took part in a Nomura cohort study conducted in 2014 and who continued with follow-ups for the subsequent 6 years (follow-up rate: 95.5%). We obtained adjusted relative hazards of all-cause mortality from the basic resident register. The data were subjected to a Cox regression with age as the time variable and gender, age, anthropometric index, smoking habits, drinking habits, exercise habits, cardiovascular history, blood pressure, lipid levels, diabetes, renal function, and serum uric acid as risk factors., Results: Of the 1750 participants, a total of 97 (5.5%) were confirmed to have died, of which 56 were men (7.1% of all male participants), and 41 were women (4.3% of all female participants). The multivariable Cox regression analysis revealed that smaller thigh circumference and lower HGS in men were found to predict 6-year all-cause mortality, but in women only baseline HGS was associated with all-cause mortality., Conclusion: Thigh circumference and HGS are useful predictors of death in Japanese community-dwelling men., (© 2021. European Geriatric Medicine Society.)

Background: Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up., Methods: Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD., Results: Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m 2 , and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58-4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15-2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87-1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This association was particularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015)., Conclusions: There is an inverse relationship between LDL-C levels and the risk of all-cause mortality, and this association is statistically significant., (© 2021. The Author(s).)

Background: Serum uric acid (SUA) is a key risk factor contributing to renal failure, a serious public health problem. However, few studies have examined whether the interactive relationship between alcohol consumption and SUA is independently associated with the estimated glomerular filtration rate (eGFR)., Methods: Our sample comprised 742 men aged 69 ± 11 years (mean ± standard deviation) and 977 women aged 69 ± 10 years from a rural area. We cross-sectionally examined the relationships between the confounding factors of alcohol consumption and SUA with renal function denoted by eGFR estimated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations modified by a Japanese coefficient., Results: In both genders, eGFR increased with a rise in alcohol consumption. This tendency was more pronounced in participants with hyperuricemia, where SUA was greater than 7.0 mg/dL in men and greater than 6.0 mg/dl in women (men: F = 41.98, p < 0.001; women: F = 41.98, p < 0.001). A multiple linear regression analysis showed that alcohol consumption (men: β = 0.112, p < 0.001; women: β = 0.060, p = 0.011) and SUA (men: β = -0.282, p < 0.001; women: β = 0.317, p < 0.001) were significantly and independently related to eGFR. Further, the interactive relationship between alcohol consumption and SUA (men: F = 6.388, p < 0.001; women: F = 5.368, p < 0.001) was a significant and independent indicator of eGFR., Conclusions: These results suggested that alcohol consumption and SUA were synergistically associated with renal dysfunction among community-dwelling persons., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

In nursing degree course education, it is needed to enhance contents of pharmacology education for acquiring nursing practice ability in the nursing education model core curriculum and revision of designation regulations. Therefore, it is intended to consider pharmacology education in nursing degree course in universities in the current study in order to cultivate nurses skilled in drug therapy. We have conducted a survey on knowledge required for students of universities of nursing as well as an analysis on contents of inquiries made by nurses on drugs. As a result, it has been revealed that students have recognized effect and side effects of drugs as basic knowledge required for a nurse. With less recognition required on pharmacokinetics and practical contents, however, the knowledge held by students was dissociated with practical knowledge often required for nurses when administering drugs. A possibility has been also revealed by the current survey that nurses may not be able to make use of pharmacokinetics as pharmacological knowledge for patients' treatment management. From results of the survey and previous study, it is believed to be necessary in university education to extend pharmacological knowledge from its basic to clinical stage and build up adequate basic knowledge and thinking power of pharmacology in nursing degree course as well as to sufficiently learn and understand necessity of pharmacokinetics for conducting evaluation of drug efficacy.

Background: The risk associated with serum uric acid (SUA) levels when within the normal range is unknown. This study aims to examine whether SUA within the normal range is a predictor of hypertension., Methods: The subjects comprised 704 men aged 71 ± 9 (mean ± standard deviation) years and 946 women aged 70 ± 8 years recruited for a survey at the community based annual medical check-up. The main outcome was the presence of hypertension (antihypertensive medication and/or having SBP ≥140 mmHg and/or DBP ≥90 mmHg)., Results: At baseline, 467 (66.3%) men and 608 (64.3%) women had hypertension. Comparing to lowest quartile in women (SUA-1, uric acid < 4.1 mg/dL), the unadjusted odds ratios (ORs) [95% confidence interval (CI)] for hypertension of SUA-2 (4.1 to 4.7 mg/dL), SUA-3 (4.8 to 5.4 mg/dL), and SUA-4 (≥5.5 mg/dL) were 1.11 (0.78-1.59), 1.75 (1.20-2.55), and 1.89 (1.30-2.77), respectively. These associations were apparent even after adjustments for age, but ORs were attenuated after adjusting for all confounding factors. During a follow-up of 3.0 years, there were 35 (24.0%) hypertension cases in men and 51 (20.8%) in women. In women only, a significant association between increased SUA categories and incidence of hypertension was observed, and the multivariate-ORs (95% (CI) for incident hypertension of SUA-3 (4.5-5.2 mg/dL) and SUA-4 (≥5.3 mg/dL) were 2.23 (0.81-6.11) and 3.84 (1.36-10.8), respectively., Conclusions: These results suggest that baseline SUA within the normal range could be an important predictor for incidence of hypertension in Japanese community-dwelling elderly women., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Purpose: Body mass index (BMI) is a simple index of weight-to-height that is commonly used to classify people as underweight, overweight or obesity, and high BMI has been clearly linked to increased risk of illness in adults. However, few studies have examined the significance of upper normal weight as a risk factor for the development of chronic kidney disease (CKD) in the general Japanese population., Methods: We conducted a prospective cohort study designed as part of the Nomura study. We recruited a random sample of 421 men aged 67 ± 10 (mean ± standard deviation; range 24-95) years and 565 women aged 68 ± 9 (22-84) years during their annual health examination in a single community. We examined the relationship between quartiles of baseline BMI and renal dysfunction after a 3-year evaluation based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations modified by the Japanese coefficient. CKD was defined as having dipstick-positive proteinuria (≥ 1 +) or a low eGFR (< 60 mL/min/1.73 m 2 )., Results: Of the 986 participants, a total of 134 (13.6%) participants, including 72 (17.1%) men and 62 (11.0%) women, received a new diagnosis of CKD during the study period, and 25 (9.7%), 19 (8.0%), 47 (19.0%), and 43 (17.8%) diagnoses were received in the BMI-1 (BMI, < 20.7 kg/m 2 ), BMI-2 (BMI, 20.7 to 22.5 kg/m 2 ), BMI-3 (BMI, 22.6 to 24.4 kg/m 2 ), and BMI-4 (BMI ≥ 24.5 kg/m 2 ) groups, respectively. Using BMI-2 as the reference group, the non-adjusted odds ratio (OR) (95% confidence interval) for CKD was 2.70 (1.53-4.75) for BMI-3 and 2.49 (1.40-4.42) for BMI-4, and the multivariable-adjusted OR was 2.52 (1.40-4.56) for BMI-3 and 2.30 (1.26-4.22) for BMI-4., Conclusions: Increased BMI from upper normal weight is strongly associated with the development of CKD in community-dwelling persons.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been widely evaluated as a biomarker in various medical and surgical prognoses, but its usefulness in diabetic kidney disease is not yet known., Methods: This prospective observational study included outpatients, comprised of 184 men aged 73 ± 11 (mean ± standard deviation) years and 174 women aged 76 ± 10 years at baseline, from a rural hospital. We examined the relationship between baseline NLR calculated by analyzing the differential leukocyte counts in the complete blood count and the 2-year estimated glomerular filtration rate (eGFR) decline rate (i.e. 2-year eGFR-baseline eGFR) ∗100/baseline eGFR. Rapid eGFR decline rate was defined as a value < -25%., Results: Multiple linear regression analysis using rapid eGFR decline rates as objective variables, adjusted for confounding factors as explanatory variables, showed that NLR (β = 0.138, p = 0.007) as well as presence of antidyslipidemic medication, hemoglobinA1c, and urinary albumin excretion stage were significantly and independently associated with a rapid eGFR decline rate. The multivariate-adjusted odds ratios (95% confidence interval) of the 2nd and 3rd tertiles of baseline NLR for rapid eGFR decline rate were 3.62 (0.70-18.7) and 8.03 (1.54-41.9), respectively. Multivariate-adjusted mean eGFR (95% confidence interval) values after 2 years categorized by tertile of baseline NLR were: 1st, 63.9 (61.8-66.1); 2nd, 60.8 (58.7-62.9); and 3rd, 58.9 (56.8-61.0)., Conclusions: These results suggest that baseline NLR might be a useful biomarker for renal function decline in outpatients with diabetes., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: The incidence of hypertension is increasing worldwide and obesity is one of the most significant risk factors. Obesity can be defined by various anthropometric indices such as body mass index (BMI), waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR). This study examined a range of anthropometric indices and their relationships with hypertension., Methods: This study included 768 men aged 70 ± 10 years and 959 women aged 70 ± 8 years from a rural village. The relationship between anthropometric indices (BMI, WHpR, and WHtR) and hypertension was examined using cross-sectional (baseline, N  = 1727) and cohort data (follow-up, N  = 419). Receiver operating characteristic (ROC) analysis was used to determine the predictive ability of obesity indices for hypertension in both genders. Logistic regression models were used to evaluate WHtR as a significant predictor of hypertension., Results: In the cross-sectional study, WHtR, BMI, and WHpR showed significant predictive abilities for hypertension in both genders, with WHtR showing the strongest predictive ability. Also, in the cohort study, WHtR showed a significant predictive ability for incident hypertension in both genders, and, for women, BMI as well as WHtR had also predictive ability. In the cross-sectional study, the optimal WHtR cutoff values were 0.53 (sensitivity, 44.3%; specificity, 80.2%) for men and 0.54 (sensitivity, 60.9%; specificity, 68.6%) for women. In the cohort study, the optimal WHtR values were 0.47 (sensitivity, 85.4%; specificity, 39.8%) for men and 0.51 (sensitivity, 66.7%; specificity, 58.2%) for women., Conclusions: The results suggest that WHtR is a useful screening tool for hypertension among Japanese middle-aged and elderly community-dwelling individuals., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Chronic kidney disease (CKD) is a major public health concern. Baseline serum uric acid (SUA) levels were independently associated with incident renal dysfunction, but whether baseline and changes in SUA produce an interactive effect on renal dysfunction remains unclear., Methods: The subjects comprised 460 men aged 68 ± 10 (mean ± standard deviation) years and 635 women aged 68 ± 9 years from a rural village. We have found participants who underwent a similar examination 3 years later, and analyzed the relationship between baseline SUA, changes in SUA, and a 3-year follow-up renal function evaluated by estimated glomerular filtration rate (eGFR)., Results: A total of 93 (20.2%) men and 76 (12.0%) women had hyperuricemia (men: SUA ≥ 7.0 mg/dL and women: SUA ≥ 6.0 mg/dL) at baseline. Multiple regression analysis using changes in eGFR as objective variable, adjusted for risk factors as explanatory variables, showed that the baseline SUA and changes in SUA were linearly associated with changes in eGFR (β = －0.115, P < .001 and β = －0.431, P < .001, respectively). In both normal SUA group and hyperuricemia group, changes in SUA significantly associated with changes in eGFR (β = －0.473, P < .001 and β = －0.197, P = .009, respectively). Participants with increased SUA from normal to hyperuricemia group had greater eGFR decline over the follow-up period, and their multivariate-adjusted 3-year follow-up eGFR was significantly lower than in other groups (P < .001)., Conclusion: Our data demonstrated that baseline and longitudinal changes in SUA were independently and interactively associated with the renal function decline among community-dwelling persons., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Purpose: Metabolic syndrome (MetS) is increasing worldwide with the continuous increase in obesity prevalence. Chronic kidney disease (CKD) is also a major public health problem, but there is controversy over whether baseline MetS is a predictor of decreased renal function among Japanese community-dwelling middle-aged and elderly Japanese., Methods: We conducted a prospective cohort study designed as part of the Nomura study. We recruited a random sample of 410 men aged 68 ± 8 (mean ± standard deviation; range, 50-95) years and 549 women aged 69 ± 7 (50-84) years during their annual health examination in a single community. We examined the relationship between baseline MetS and renal dysfunction after a 3-year evaluation based on estimated glomerular filtration rate (eGFR CKDEPI ) using the CKD-EPI equations modified by the Japan coefficient. CKD was defined as dipstick-positive proteinuria (> or = 1 +) or a low eGFR CKDEPI (< 60 mL/min/1.73 m 2 )., Results: Of the 959 participants, 413 (43.1%) had MetS at baseline. Annual eGFR decline rate was significantly greater in those with MetS than in those without MetS, and the annual eGFR decline rate of < - 1.2 mL/min/1.73 m 2 /year increased significantly in relation to presence of baseline MetS, especially low HDL cholesterol (HDL-C). Moreover, the incidence rate of CKD after 3 years was 13.5% and increased significantly in relation to presence of baseline MetS, especially its components such as elevated HbA1c. The multivariate-adjusted odd ratio (OR) for CKD in participants with MetS versus those without MetS was 1.55 (0.99-2.43). The multivariate-adjusted ORs for rapid annual eGFR decline rate were significantly high in patients aged ≥ 65 years and presence of medication, regardless of gender and eGFR value., Conclusions: Low HDL-C and elevated HbA1c levels correlated significantly with eGFR decline in a short period of 3 years. MetS also showed a significant association with eGFR decline. This study suggests the importance of low HDL-C and elevated HbA1c in the effect of MetS on eGFR decline rather than obesity among Japanese community-dwelling middle-aged and elderly Japanese without CKD.

Competing Interests: None

Background: Serum uric acid (SUA) has been shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized SUA {i.e, SUA/creatinine (Cr) ratio} is a predictor of decreased renal function among diabetic patients., Methods: The subjects comprised 185 men aged 72 ± 11 (mean ± standard deviation) years and 175 women aged 77 ± 10 years from a rural hospital. We examined the relationship between SUA/creatinine (Cr) ratio and renal function evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation., Results: Annual eGFR decline rate was significantly increased with increased tertile of baseline SUA/Cr ratio (p = 0.011), and prevalence of the rapid progression types (≥3.0 ml/min/1.73 m 2 /year) was significantly higher in the second and third tertile (≥7,21) of baseline SUA/Cr ratio than the first tertile (<5.86) (p = 0.032). Pearson's correlation coefficient showed that baseline SUA/Cr ratio (r = 0.136, p = 0.012) as well as systolic blood pressure (SBP) and SUA were significantly correlated with annual eGFR decline rate. Multiple regression analysis using annual eGFR decline rate as an objective variable, adjusted for confounding factors as explanatory variables, showed that baseline SUA/Cr ratio (β = 0.334, p < 0.001) as well as gender and SBP were significantly and independently associated with annual eGFR decline rate. The multivariate-adjusted odds ratios (ORs) (95% confidence interval) of the baseline tertile of the SUA/Cr ratio for rapid progression of annual eGFR decline rate were 1.0, 3.15 (1.66-5.95) and 3.19 (1.57-6.51), respectively., Conclusion: Our data demonstrated that baseline SUA/Cr ratio was independently and significantly associated with future renal function decline among diabetic patients., (Copyright © 2019. Published by Elsevier Ltd.)

This study examined a range of anthropometric indices and their relationships with metabolic syndrome (MetS). Despite recommendations that central obesity assessment should be employed as a marker of metabolic health, there is no consensus regarding the protocol for measurement. The present study included 720 men aged 71 ± 8 years and 919 women aged 71 ± 7 years from a rural village. We examined the relationship between anthropometric indices {e.g., body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHpR)}, and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report in a cross-sectional (N = 1,639) and cohort (N = 377) data. A receiver operating curve (ROC) analysis was performed to determine the optimal cut-off value and best discriminatory value of each of these anthropometric indices to predict MetS. In the cross-sectional study, WHtR as well as BMI and WHpR showed significantly predictive abilities for MetS in both genders; and WHtR showed the strongest predictive ability for the presence of MetS. Also in the cohort study, WHtR as well as BMI and WHpR showed significantly predictive abilities for incident MetS in both genders, and in men WHtR showed the strongest predictive ability for incident MetS, but in women BMI showed the strongest predictive ability. In the cross-sectional study, the optimal WHtR cutoff values were 0.52 (sensitivity, 71.0%; specificity, 77.9%) for men and 0.53 (sensitivity, 79.8%; specificity, 75.7%) for women. In the cohort study, the optimal WHtR values were 0.50 (sensitivity, 60.7%; specificity, 73.2%) for men and 0.50 (sensitivity, 75.0%; specificity, 56.1%) for women. Increased WHtR was significantly and independently associated with prevalence of MetS in both genders. These results suggest that WHtR is a useful screening tool for determining metabolic risk in Japanese elderly community dwelling individuals., Competing Interests: The authors have declared that no competing interests exist.

Background Warfarin has been used in Japan for a long time in patients after cerebral embolism to prevent recurrence. Recently, several novel oral anti-coagulants (NOACs) have been approved for use and are gradually replacing warfarin. However, it remains unclear whether warfarin and other NOACs differ from each other with respect to drug costs and length of stay (LOS) during treatment in Japan. Objective To assess differences in LOS and direct medical cost between patients after cerebral embolism treated with warfarin and those treated with NOACs. Setting Thirteen acute care hospitals in Japan. Method For hospitalized patients with cerebral embolisms who were treated with NOACs and/or warfarin between April 2012 and March 2014, we assessed LOS for patients with warfarin and NOAC using log-rank test, and stratified proportional hazard regression. Also, we assess direct medical cost using paired-t test. Main Outcome measure LOS and medical cost after first treatment with warfarin and NOAC. Results The median LOS for NOACs-treated patients was 12.5 days and that for warfarin treated patients was 19.0 days while the corresponding mean medical costs were USD 7151 ± 6228 [JPY 736,546 ± 641,437] and USD 8950 ± 5891 [JPY 921,830 ± 606,765]. The drug cost for NOACs-treated patients was higher but costs for laboratory-test and hospitalization were lower than those for warfarin-treated patients. Conclusions For NOAC-treated patients, LOS was shorter, and medical cost during hospitalization tended to be lower than those for warfarin-treated patients, whereas NOACs prices were higher than warfarin price.

Background: Metabolic syndrome (MetS) is related to the increased risk of major cardiovascular diseases (CVD). The link between high serum total bilirubin (TBL) is cross-sectionally related to MetS and its components. However, whether serum TBL predicts incidence of MetS and its components remains inconclusive., Methods: The present study included 893 women aged 70 ± 9 years from a rural village. We examined the relationship between serum TBL and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report in a cross-sectional (N = 893) and cohort (N = 288) data., Results: In the cross-sectional study, serum TBL (β = 0.536, p < 0.001) as well as age, alcohol consumption, exercise habits, history of CVD, SUA, GGT, and ALT was significantly and dependently associated with number of MetS components, but in the cohort study serum TBL was not associated with number of MetS components. Compared with the 1st tertile of serum TBL (0.20-0.55 mg/dL), multivariate-adjusted odds ratio (95% confidence interval) for the 2nd -3rd tertiles of serum TBL (0.54-2.00 mg/dL) was 0.70 (0.51-0.95) in the cross-sectional study and 0.41 (0.21-0.81) in the cohort study., Conclusions: Our data demonstrated an independently negative association between serum TBL and MetS in Japanese community-dwelling women., (Copyright © 2019 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Metabolic syndrome (MetS) is related to the increased risk of major cardiovascular disease. The link between high serum uric acid (SUA) and creatinine (Cr) levels is causally related to MetS and its components. However, whether renal function-normalized SUA [i.e., SUA to Cr ratio (SUA/Cr)] predicts incident MetS and its components remains inconclusive., Materials and Methods: We conducted a prospective cohort study designed as part of the Nomura study. The subjects comprised 447 men ages 68 ± 10 years and 625 women ages 68 ± 9 years from a rural village, and 155 (34.7%) men and 310 women (49.6%) had MetS at baseline. We found participants who underwent a similar examination 3 years later and analyzed the relationship between baseline SUA/Cr and incident MetS defined according to the modified criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III)., Results: One hundred forty-nine (33.3%) men and 286 (45.8%) women had MetS after a 3-year follow-up. Multiple linear regression analysis was performed to evaluate the contribution of possible confounding factors for MetS. In women only, baseline SUA/Cr, as well as baseline number of MetS and age, was significantly and independently associated with the number of MetS components at follow-up. The multivariable-adjusted odds ratios (95% confidence interval) for incident MetS across three quartiles of baseline SUA/Cr (1st-2nd, 3rd, and 4th) were 1.00, 1.62 (0.97-2.69), and 2.07 (1.20-3.56), respectively. Furthermore, when subjects were stratified by age, estimated glomerular filtration rate (eGFR), and presence of baseline MetS, baseline SUA/Cr was also a significant and independent determinant for incident MetS in women with age ≥60 years, eGFR ≥70 mL/min/1.73 m 2 , and presence of baseline MetS., Conclusions: Baseline SUA/Cr was significantly associated with incident MetS among community-dwelling women.

Purpose: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in diabetic kidney disease is not yet established., Methods: The subjects comprised 199 men aged 73 ± 11 (mean ± standard deviation) years and 187 women aged 77 ± 10 years from a rural hospital. We examined the relationship between NLR calculated by analyzing differential leukocyte count in complete blood picture and renal function evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation and urinary albumin excretion (UAE)., Results: NLR was negatively related to eGFR and positively related to UAE. Multiple linear regression analysis using eGFR and UAE as an objective variables, adjusted for confounding factors as explanatory variables showed that NLR (β = - 0.101, p = 0.009) as well as age, body mass index, serum uric acid, and presence of uric acid lowing medication were significantly and independently associated with eGFR, and NLR (β = 0.113, p = 0.031) as well as prevalence of cardiovascular disease, systolic blood pressure, presence of antihypertensive medication, presence of antilipidemic medication, and eGFR were significantly and independently associated with UAE. The multivariate-adjusted odds ratios (95% confidence interval) of NLR for stage 3a (eGFR < 60 mL/min/1.73 m 2 ), stage 3b (eGFR < 45 mL/min/1.73 m 2 ), and microalbuminuria (UAE ≥ 30 mg/g Cr) were 1.90 (1.02-3.56) and 2.99 (1.28-6.98), and 1.77 (1.04-3.01), respectively. Next, to examine the consistency of the observed association between NLR and eGFR, we performed subgroup analyses. There was a significant interaction (p = 0.006) only between the two groups regarding antihypertensive medication (absence: β = - 0.272, p < 0.001 and presence: β = - 0.029, p = 0.564)., Conclusions: Our data suggested that NLR might be important as a potential factor for evaluating patients with a higher degree of albuminuria among diabetic outpatients.

Background: Elevated serum uric acid (SUA) levels are associated with glucose control. However, whether baseline and changes in SUA predict long-term follow-up glucose control [e.g., glycated hemoglobin (HbA1c)] remains unclear., Methods: The subjects comprised 393 women aged 71 ± 8 years and 279 men aged 71 ± 10 years from a rural village. We have identified participants who underwent a similar examination 11 years prior, and subjects were divided into four groups based on the tertiles of baseline and changes in SUA, and examined the relationship between baseline and changes in SUA, and glucose control evaluated by follow-up HbA1c after 11-years., Results: In both genders, follow-up SUA were significantly higher in Group 4 (i.e., women: Group 4, baseline SUA ≥ 4.0 mg/dL and changes in SUA ≥ 0.8 mg/dL; men: Group 4, ≥ 5.3 mg/dL and ≥ 0.4 mg/dL) than in the other Groups, but eGFR was significantly lower. Only in women, there were significant differences among the four groups regarding follow-up HbA1c, and follow-up HbA1c was highest in Group 4. In addition, the interaction between baseline and changes in SUA (F = 5.391, p  = 0.021) as well as baseline low-density lipoprotein cholesterol (LDL-C) (F = 13.793, p  < 0.001), estimated glomerular filtration ratio (F = 10.715, p  = 0.001), HbA1c (F = 118.285, p  < 0.001), SUA (F = 9.457, p  = 0.002), and changes in SUA (F = 7.757, p  = 0.006) was a significant and independent determinant of follow-up HbA1c. Multivariate-adjusted follow-up HbA1c ( p  = 0.002) were significantly higher in Group 4 than the other groups., Conclusions: These results suggested that combined assessment of baseline and changes in SUA provides increased information for long-term predictive glucose control, independent of other confounding factors in community-dwelling women.

Skin barrier function is often deficient in obese individuals, but the underlying molecular mechanisms remain unclear. This study investigated how skin structure and lipid metabolism, factors strongly associated with barrier function, differed among 50 Japanese women of greatly varying body mass index (BMI). Subjects receiving breast reconstruction surgery were chosen for analysis to obtain skin samples from the same site. The subjects were classified into two groups, control (BMI < 25 kg/m2) and obese (25 kg/m2 ≤ BMI < 35 kg/m2), according to standards in Japan. Hematoxylin and eosin staining was used to assess skin thickness, Ki-67 immunostaining to examine keratinocyte proliferation, and real-time polymerase chain reaction to measure skin expression levels of genes associated with lipid metabolism. Total lipids, cholesterol, and fatty acids were also measured from these same skin samples. In the obese group, structural changes included epidermal thickening and an increase in the number of Ki-67-positive (proliferating) cells. Both skin cholesterol and fatty acid levels exhibited an "inverted-U" relationship with BMI, suggesting that there is an optimal BMI for peak lipid content and barrier function. Decreased lipid levels at higher BMI were accompanied by downregulated expression of PPARδ and other genes related to lipid metabolism, including those encoding acetyl-CoA carboxylase and HMG-CoA reductase, the rate-limiting enzymes for fatty acid and cholesterol synthesis, respectively. Thus, elevated BMI may lead to deficient skin barrier function by suppressing local lipid synthesis.

Objective: Obesity-associated diabetes causes aging-like changes to skin physiology in animal models, but there have been no clinical studies focusing on human obese diabetic patients. The purpose of this study was to examine the hypothesis that obesity-associated diabetes accelerates aging-like skin changes in Japanese people., Methods: This cross-sectional study enrolled obese-diabetes patients (body mass index ≥ 25 kg m-2) and healthy volunteers (body mass index < 25 kg m -2 ) as controls. Skin physiology parameters relating to aging (stratum corneum hydration, transepidermal water loss, skin pH, advanced glycation end-products, and dermal collagen density) were evaluated in the two groups., Results: About 37 subjects participated (16 in a control group and 21 in an obese-diabetes group). Age was not significantly different between the groups. The stratum corneum hydration level was significantly lower in the obese-diabetes group. Transepidermal water loss and levels of advanced glycation end-products were significantly higher in this group. Skin pH was not significantly different between groups. Dermal collagen density decreased in the obese-diabetes group., Conclusion: We showed that obese-diabetes patients have decreased stratum corneum hydration, increased transepidermal water loss, higher skin advanced glycation end-products and decreased dermal collagen fiber density compared with normal-weight subjects. These results indicate that the ordinary age-related physiological skin changes seen in the elderly can also occur in obese-diabetes patients aged in their 40s., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Doctors give prescriptions after considering the medical conditions of patients. Pharmacists check the prescription and give information about the effects of the drugs to the patients, including their side effects. Nurses observe patients to determine the effects and side effects of the administered drugs, and then report these to doctors. Each specialist plays a role, allowing medication to be completed. However, in order to fully attain the effects of a drug, we need to consider the method of its administration. For example, it is difficult to attain the effects of laxatives for a person who eats irregularly; however, they are uniformly administered. Pharmacology education in nursing focuses on the mechanism of drugs and the way of maintaining their therapeutic effects and safeness, based on the viewpoint of "curing". Furthermore, nursing science focuses on the differences in efficacy depending on the characteristics of a patient, and also on the side effects of drugs, based on the viewpoint of "caring". However, education where care and cure are integrated needs to be provided, so that nurses can acquire applied skills to consider individual patient's bodies, lives, and psychological situations comprehensively, and then suggest the optimal method of administration. Also, there is Eastern medicine as well as Western medicine. Administration of Chinese medicine should be related to the patient's lifestyle. Nurses have to learn how each medicine is related to the patient's lifestyle, and what aspects in the patient they have to focus on.

Aim of the Study: Our previous research suggested that obesity induces structural fragility in the skin. Elastic fibers impart strength and elasticity. In this study, we determined whether elastic fibers decrease in the skin of obese mice., Materials and Methods: To confirm alterations in elastic fiber content due to obesity, we used spontaneously obese model mice (TSOD) and control mice (TSNO). Furthermore, to evaluate the elastin structure and gene expression dependent on the severity of obesity, an obesity-enhanced mouse model was developed by feeding a high fat diet to TSOD (TSOD-HF). Back skin samples were stained with hematoxylin and eosin and Elastica van Gieson for microscopic examination, and the samples were stained for immunohistochemical analysis of neprilysin. Gene expression levels were determined using a real-time PCR system., Results: The abundance of elastic fibers beneath the epidermis was remarkably reduced and fragmented in TSOD as compared with TSNO. Fibrillin-1 mRNA levels in TSOD were significantly suppressed compared with those in TSNO, whereas neprilysin mRNA levels and immunohistochemical expression in TSOD were significantly increased, as compared with those in TSNO. The reduction of elastic fibers was enhanced and the expression levels of elastic fiber formed factors were significantly suppressed in TSOD-HF, as compared with those in the TSOD., Conclusions: The abundance of elastic fibers was reduced and fragmented in obesity, suggesting that the reduction in elastic fibers is initially caused by increased neprilysin and decreased fibrillin-1 expression, which may inhibit formation and stabilization of elastic fibers, resulting in skin fragility in obesity.

Obesity results from excessive energy intake and physical inactivity, and predisposes one to various diseases. One of these reasons is that enlargement of adipocytes raises the lipid metabolic abnormalities that affect various organs. The skin is one such organ, and it has been reported that subcutaneous adipocyte cells secrete various factors and these factors are involved in reduction of dermal collagen fibers and fragility of the skin in obesity. The present study explored the efficacy of Kaempferia parviflora (KP) in preventing obesity-induced dermatopathy. We used Tsumura Suzuki obese diabetes (TSOD) mice as an obesity model. TSOD mice were fed a standard diet (MF) mixed with either an ethanol extract from KP (KPE), polymethoxyflavonoid-rich extract from KP (PMF), or polymethoxyflavonoid-poor extract from KP (X). We then evaluated the effect of these three KP fractions on aging-like skin damage induced by UVB irradiation. KPE and PMF caused a significant decrease of mouse body weight, and suppressed the increase in the thickness of the subcutaneous fat layer. In addition, KPE shifted the frequency of subcutaneous adipocyte sizes towards smaller cells possibly via its polypharmacological actions. Scanning electron microscopy revealed that the stereostructure of the collagenous fibers in the dermis was better retained in the KPE and PMF groups, in that order. These results offer the first evidence that KPE can attenuate obesity-induced dermatopathy more effectively than PMF, suggesting that KPE (or KP) might be a candidate supplement for preventing obesity-related skin disorders.

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

Proteoglycans (PGs), a family of glycosaminoglycan (GAG)-protein glycoconjugates, contribute to animal physiology through interactions between their glycan chains and growth factors, chemokines and adhesion molecules. However, it remains unclear how GAG structures are changed during the aging process. Here, we found that polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin. In cultured cell lines, the EXT1 and EXT2 enzymes, initiating HS biosynthesis, were stimulated at the translational level by polyamines. Interestingly, the initiation codon recognition by 43S preinitiation complex during EXT2 translation is suppressed by let-7b, a member of the let-7 microRNA family, through binding at the N-terminal amino acid coding sequence in EXT2 mRNA. Let-7b-mediated suppression of initiation codon depends on the length of 5'-UTR of EXT2 mRNA and its suppression is inhibited in the presence of polyamines. These findings provide new insights into the HS biosynthesis related to miRNA and polyamines.