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Nocturia is a common disease in patients with type 2 diabetes mellitus that can reduce the quality of life. Sodium glucose co-transporter 2 (SGLT2) inhibitors increase the urine volume and are often discontinued when polyuria occurs, although tofogliflozin, which has a short half-life in the blood, may improve nocturia by managing hyperglycemia and hypertension, without aggravating nocturia. As excessive sodium intake worsens nocturia and increases urine volume, sodium restriction is also effective in managing nocturia. This multicenter, open-label, randomized parallel-group trial will examine 80 patients with type 2 diabetes who experienced nocturia. After the baseline examination, the patients are randomly stratified into two groups and receive tofogliflozin treatment with or without sodium restriction for 12 weeks. The primary outcome is nocturia frequency at 12 weeks. The secondary outcomes are the frequency of daytime urine, changes in urine volume, and changes in home blood pressure.

Purpose. We report a case of neuroretinitis associated with cat scratch disease (CSD) in young children. Method. Case report. Results. A 16-month-old boy was admitted for a detailed examination and treatment of a fever of unknown origin. Blood tests revealed no significant findings other than a white blood cell count of 16,100/mm3 and C-reactive protein level of 9.89 mg/dL. Computed tomography revealed no relevant findings to determine the causative disease. Antibiotic therapy with cefotaxime was initiated; however, the fever did not resolve. The patient was referred to our department for further examination to detect the cause of the fever. Fundoscopy revealed neuroretinitis in the right eye. His mother reported a history of breeding cats. Cat scratch disease (CSD) was suspected based on the clinical course and fundus findings. Cefotaxime was discontinued, and azithromycin, rifampicin, and prednisolone were administered, following which the fever disappeared and fundus findings improved. Immunoglobulin G (IgG) and IgM antibodies against Bartonella henselae was positive, leading to a definitive diagnosis of CSD. Conclusion. Infants cannot complain of decreased visual acuity; therefore, these findings may be overlooked unless a fundus examination is performed. As in this case, the early detection of neuroretinitis by an ophthalmologist may help in the diagnosis of CSD. It is extremely difficult to capture a photograph of the fundus of an infant, and recording with a smartphone is relatively simple and useful for monitoring continuous changes. Summary. We describe a case of neuroretinitis associated with cat scratch disease (CSD) that was diagnosed on the basis of fundus findings. The findings suggest the importance of an aggressive ophthalmologic examination when CSD is suspected in young children who are unable to describe their symptoms.

This study aimed to assess the association between changes in metabolic phenotypes and incident type 2 diabetes.This retrospective cohort study included participants from a medical health checkup program conducted by the Panasonic Corporation, Japan, between 2008 and 2018. The metabolic phenotypes of the participants in 2008 and 2013 were assessed. The association between changes in metabolic phenotypes from 2008 to 2013 and incident type 2 diabetes (n = 58,638) were evaluated for a 5-year follow-up using Cox regression analyses.The stable, metabolically healthy obesity group was associated with a higher risk of incident type 2 diabetes than the stable, metabolically healthy nonobesity (MHNO) group (hazard ratio [HR] 3.22, 95% CI: 2.71-3.83). When participants with metabolically healthy obesity experienced a change to MHNO, their risk of incident type 2 diabetes was similar to that of participants in the stable MHNO group (HR 1.28, 95% CI: 0.78-1.90). Once the participants had metabolic abnormalities, the risk of incident type 2 diabetes was higher than that in the stable MHNO group, even after undergoing a change to MHNO.This study demonstrates that it is important to pay attention to the changes in metabolic phenotypes to prevent incident type 2 diabetes in Japanese populations.

Purpose Community pharmacists are highly accessible healthcare providers and studies in several countries have demonstrated a role for community pharmacists in delivering enhanced care to people with type 2 diabetes. The aim of this study is to evaluate the views and experiences of people with type 2 diabetes attending community pharmacies in Ireland. Methods A 13-item questionnaire, anchored on a 5-point Likert scale, was used. The study took place in seven pharmacies in the Munster region of Ireland. Participants were people attending a participating pharmacy who had type 2 diabetes and were aged ≥ 18 years. Results The questionnaire was answered by 125 people with type 2 diabetes. Mean age of participants was 65.7 ± 12.4 years and 59.2% were male. The statement “I am totally satisfied with my visit to this pharmacist”, was the item that participants most frequently agreed with (agree/strongly agree = 99.2%, mean score 4.9 ± 0.4). Over 80% of participants agreed or strongly agreed with the statement “It is easier to get to see the pharmacist than the doctor”, (mean score 4.3 ± 1.1). Conclusion In this population, people with type 2 diabetes were highly satisfied with the care provided to them by their community pharmacist. These data support the implementation of enhanced community pharmacy services for people with type 2 diabetes in Ireland.

Background Once older persons become frail, the risk of falls, bone fractures, and other problems increases. Exercise intervention is a form of prevention that has a high degree of evidence. Objective We investigated the effectiveness of frailty prevention consisting of exercise intervention by community pharmacists at 11 pharmacies operated by Osaka Pharma Plan. Methods In total, 103 older persons between 70 and 79 years of age (53 males and 50 females) who were suffering from chronic conditions and who visited one of 11 pharmacies between January and March 2021 were enrolled. They were then randomly assigned to either the Intervention group (IG: 6 pharmacies, 61 patients) who were subjected to intervention by a pharmacist, or the Usual Care group (UG: 5 pharmacies, 42 patients) who were not subjected to intervention. At the beginning of the trial and 6 month after, their muscle mass, etc. were measured using a body composition meter, and their Five-Times Sit-To-Stand Test results were also measured. Patients in the IG were provided with information by way of leaflets during the time they were guided regarding taking their medication for a period of one to six months that encouraged exercising at home. Those in the UG were given the standard guidance related to taking their medication. Results The amount of change in muscle mass was 1.08 ± 7.83% (95%CI: -1.24-3.41) in IG and − 0.43 ± 2.73% (95%CI:-1.58-0.72) in UG, indicating that there was a trend toward an increase in IG. The percent change in the Five Times Sit-To-Stand Test times at + 6 M was − 0.002 ± 0.24% (95%CI: -0.09-0.05) in IG and − 0.04 ± 0.21% (95%CI:-0.13-0.07) in UG, but in cases in which the second measured time was faster than the first measured time, the results were 65.2% for IG and 29.2% for UG, indicating a significant difference (p = 0.00563). Conclusion Despite the fact that the amount of time community pharmacists can devote to providing guidance on taking medications is limited, it has been previously reported that providing information to patients causes a change in patient behavior. The results of the present study are highly significant as they suggest the possibility that this may hold true even when used to prevent frailty, based on the evidence obtained. Trial registration This trial was registered at UMIN-CRT on 1st of January, 2021. The registration number is UMIN000042571.

Social prescribing (SP) has aroused widespread interest across countries. SP is a way of linking patients in primary care with sources of support within the community by empowering patients to coproduce solutions to improve their health and well-being. While previous research has demonstrated that SP contributes to reducing the total cost of the National Health Service, the analysis of its effects on patients is still inadequate. This literature review critically evaluated SP from the patient's perspective through the lens of medical anthropology. The review was made with respect to the three key concepts: treatment evaluation, coproduction, and empowerment. The study revealed that SP services in the UK enabled patients to feel comfort in many cases, but general practitioners, link workers, and patients should be collaborative with each other, and their interrelationships should not be hierarchical. Nevertheless, certain modifications may be needed to introduce SP in other healthcare systems.

The Japan Society of Clinical Oncology (JSCO) published the “JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients” in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.

We study SU(4)C × SU(2)L × U(1)R models with modular A4 symmetry that provide a unified description of the quark and lepton sectors including the flavor structures. The models are distinguished by the assignments of the modular weight to matter superfields. We carry out numerical χ2 analysis and search for parameter sets that accommodate the experimental results. We provide a benchmark point for each model to illustrate the implications of our models.

BackgroundDue to a lack of investigation on the association between the type of occupation and the development of type 2 diabetes among Japanese individuals, we aimed to assess this association in 98,935 Japanese individuals.MethodsThis long-term retrospective cohort study included participants selected from medical health checkup programs conducted at the Panasonic Corporation, Osaka, Japan, from 2008 to 2018. Cox regression analyses were used to evaluate the association between occupation type and the incidence of type 2 diabetes.ResultsFrom 2008 to 2018, 5,008 participants developed type 2 diabetes. The proportion of never smokers, those with slow eating speeds, and those working with a flextime system was higher in men with technical jobs than in salespersons, manufacturers, and office workers (p < 0.0001). Cox regression analyses revealed that occupation type was associated with an increased probability of type 2 diabetes development in men but not in women. Multivariate analyses showed that the hazard ratios were 1.15 [95% confidence interval (CI), 1.05–1.26], 1.20 (95% CI, 1.10–1.30), and 1.11 (95% CI, 1.02–1.21) in men working as salespersons, manufacturers, and office workers, respectively (reference group: men with technical jobs). On the other hand, the occupation type was not associated with the development of type 2 diabetes in women.ConclusionsThis study demonstrated that occupation type might be an independent factor in the development of type 2 diabetes in Japanese men.

AimThis study aimed to investigate the association between change in body weight (BW) and type 2 diabetes remission in Japanese men with new-onset type 2 diabetes.MethodsThis study enrolled 1,903 patients with new-onset type 2 diabetes between 2008 and 2013 from a medical health checkup program conducted by the Panasonic Corporation, Osaka, Japan. The baseline was defined as the year of new-onset diabetes. We assessed the type 2 diabetes remission five years after baseline and the association between the change in BW and type 2 diabetes remission using logistic regression analyses. To evaluate the predictive performance of the change in BW, we employed the receiver operating characteristic curves and the area under the receiver operating characteristic (ROC) curve (AUC).ResultsThe BW loss was associated with type 2 diabetes remission in the participants with a BMI ≥25 kg/m2 but not in the participants with a BMI 2. The odds ratios were 1.96 (95% CI: 1.19–3.29) and 3.72 (95% CI: 2.14–6.59) in the participants with a loss of 5–9.9% and loss of ≥10% for five years, respectively, in the participants with a BMI ≥25 kg/m2 (reference; stable group [0.9% gain to 0.9% loss]). The AUC and cut-off values for the rate of change in BW for type 2 diabetes remission were 0.59 and 5.0%.DiscussionBody weight loss of ≥5% effectively achieved diabetes remission in Japanese men with a BMI ≥25 kg/m2 and new-onset type 2 diabetes.

AIMS/INTRODUCTION Metformin is associated with the risk of gastrointestinal complications, and probiotic Bifidobacterium bifidum G9-1 (BBG9-1) can improve the symptoms of diarrhea. This study aimed to clarify the effects of probiotic BBG9-1 on the gastrointestinal symptoms of type 2 diabetes mellitus patients using metformin. MATERIALS AND METHODS In this open-label single-arm exploratory study, 40 patients (mean age 64.0 ± 9.4 years) were given probiotic BBG9-1 for 10 weeks. Changes in the gastrointestinal symptom rating scale total score, which was the primary end-point, gastrointestinal symptom rating scale subscale scores, glycated hemoglobin levels and gut microbiota after the administration of probiotic BBG9-1 were evaluated by the Student's t-test. RESULTS The gastrointestinal symptom rating scale total score significantly improved (from 2.02 ± 0.51 to 1.59 ± 0.43, change, -0.43 ± 0.49, P

Emergency contraceptive (EC) pills are used to prevent pregnancy after unprotected sexual intercourse. Levonorgestrel is an EC pill, which has been only approved in Japan; it is more effective the sooner it is used after intercourse and safe without serious side effects. EC pills are already available at accessible community pharmacies in more than 90 countries around the world. In Japan, citizens have signed a petition calling for the sale of emergency contraceptives at community pharmacies. However, little is known about the thoughts of pharmacists who engage with patients and sell medicines at pharmacies. Therefore, we conducted a web-based cross-sectional survey to determine the level of preparation in community pharmacies and the awareness of pharmacists regarding the sale of EC pills. A total of 1338 pharmacists responded to the survey from November 7, 2020, to December 16, 2020. In terms of the level of preparation for selling EC pills at pharmacies, 1067 (83.9%) respondents cited "lack of preparation of medical questionnaires and explanatory materials", and 975 (76.7%) respondents cited "lack of knowledge of pharmacists" as the most common reasons that were "barriers to EC pill sales at pharmacies". In terms of confidence level, only 289 (22.7%) respondents were confident about conducting the necessary checks while administering medicine. On the other hand, 944 (74.3%) respondents agreed to be able to sell EC pills at their pharmacies. The survey revealed that most of the pharmacists who participated in the survey believe that it is possible to sell EC pills in pharmacies.

This study aimed to assess outcomes of microdissection testicular sperm extraction (MD-TESE) and identify predictors for sperm retrieval (SR) in patients with non-mosaic Klinefelter syndrome (NM-KFS). We retrospectively evaluated 37 patients with NM-KFS who underwent MD-TESE. Data of age at operation, body mass index (BMI), testicular volume, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), preoperative and postoperative testosterone levels with reduction ratio between the two values, and FSH/preoperative testosterone ratio were analysed. These patients were divided into two groups according to success or failure of SR: the successful and failure groups. Factors related to SR were evaluated by statistical analyses using the Mann-Whitney U test and logistic regression modelling. Regarding these factors, the cut-off level was specified using the receiver operating characteristics (ROC) curve. Moreover, the percentage of SR at that level was assessed. A simple scoring model was developed based on the multivariate analysis. Fourteen patients underwent successful SR, whereas 23 experienced failure SR. Statistical analysis found preoperative testosterone and FSH levels to be significant factors associated with SR. On the ROC curve, the cut-off levels for preoperative testosterone and FSH were 2.34 ng/ml and 33.2 mIU/ml respectively. A new scoring model was developed, consisting of preoperative testosterone (≥2.34 ng/ml) and FSH (≤33.2 mIU/ml). The sperm retrieval rates (SRRs) were clearly discriminated by stratification according to the scoring model. The SRR of the cases of scores of 2, 1 and 0 were 87.5%, 31.6% and 10% respectively. At our hospital, the SRR of MD-TESE in patients with NM-KFS was 37.8%. The patients with high testosterone and low FSH levels tended to demonstrate successful SR.

We study a symmetry breaking of residual flavor symmetries realized at fixed points of the moduli space. In the supersymmetric modular invariant theories, a small departure of the modulus from fixed points is required to realize fermion mass hierarchies and sizable CP-breaking effects. We investigate whether one can dynamically fix the moduli values in the vicinity of the fixed points in the context of Type IIB string theory. It is found that the string landscape prefers $|\delta \tau| \simeq 10^{-5}$ for the deviation of the complex structure modulus from all fixed points and the CP-breaking vacuum is statistically favored. To illustrate phenomenological implications of distributions of moduli values around fixed points, we analyze the lepton sector on a concrete $A_4$ modular flavor model., Comment: 31 pages, 18 figures, v2: published version

Using scanning tunneling microscopy (STM) and density functional theory (DFT) calculations, we directly determine the spatial and energetic distributions of superatom molecular orbitals (SAMOs) of an Li@C60 monolayer adsorbed on a Cu(111) surface. Utilizing a weakly bonded [Li+@C60] NTf2- (NTf2-: bis(trifluoromethanesulfonyl)imide) salt makes it possible to produce a Li@C60 monolayer with high concentration of Li@C60 molecules. Because of the very uniform adsorption geometry of Li@C60 on Cu(111), the pz-SAMO, populated above the upper hemisphere of the molecule, exhibits an isotropic and delocalized nature, with an energy that is significantly lower compared to that of C60. The isotropic overlapping of pz-SAMOs in the condensed monolayer of Li@C60 results in a laterally homogeneous STM image contributing to the formation of a free-electron-like states. These findings make an important step toward further basic research and applicative utilization of Li@C60 SAMOs.

An efficient crack propagation (CP) simulation system based on a shell-solid finite element (FE) modeling is newly established. Three-dimensional (3D) CP simulation for a curvilinearly propagating surface crack in a steel circular hollow section (CHS) T-joint is carried out. Entire model is generated by a shell FEs, and cracked welded part is generated by a solid FEs. They are connected with a rigid body element (RBE). Stress intensity factors (SIFs) are computed for analyzing CP rate and CP direction of the crack employing the virtual crack closure-integral method (VCCM) with quadratic tetrahedral FEs. When the crack extends, only solid model is regenerated. To examine the effectiveness of the modeling, fatigue testing and simplified CP simulation results are employed. Hot spot stress (HSS) and weld toe magnification factor (Mk factor) formulas are used for the simplified CP method. CP phenomena of the fatigue test are studied through the fatigue assessment methods.

In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.

It is clear that matter is dominant in the Universe compared to antimatter. We call this problem baryon asymmetry. The baryon asymmetry is experimentally determined by both cosmic microwave background and big bang nucleosynthesis measurements. To resolve the baryon number asymmetry of the Universe as well as neutrino oscillations, we study a radiative seesaw model in a modular $A_4$ symmetry. Degenerate heavy Majorana neutrino masses can be naturally realized in an appropriate assignments under modular $A_4$ with large imaginary part of modulus $\tau$, and it can induce measured baryon number via resonant leptogenesis that is valid in around TeV scale energy theory. We also find that the dominant contribution to the CP asymmetry arises from Re[$\tau$] through our numerical analysis satisfying the neutrino oscillation data., Comment: 20 pages, 2 tables, 6 figures

To assess the long-term safety of tezepelumab in Japanese patients with severe uncontrolled asthma. This phase III, 52-week, open-label, single-arm study (NOZOMI, NCT04048343) evaluated the safety/tolerability of subcutaneous (SC) tezepelumab 210 mg every 4 weeks (Q4W) in Japanese patients aged 12–80 years with severe uncontrolled asthma using medium- to high-dose inhaled corticosteroids and at least one additional asthma controller medication, with/without oral corticosteroids. Exploratory outcomes included efficacy (asthma exacerbations, lung function, and asthma control), pharmacokinetic parameters, and immunogenicity. Among 65 patients (median age 52 years), 39 (60%) experienced 94 adverse events (AEs; predominantly nasopharyngitis [13/65]) of mild (49.2%), moderate (7.7%), or severe (3.1%) intensity. Two patients had transient injection site erythema related to tezepelumab. Four patients reported serious AEs unrelated to tezepelumab and one AE led to treatment discontinuation. AEs of special interest were infrequent and generally mild/moderate. Apart from a decrease in blood eosinophils (an expected pharmacodynamic effect), no notable trends/clinically relevant changes in hematology, clinical chemistry, or urinalysis parameters were observed. Among exploratory outcomes, tezepelumab was associated with a low annualized asthma exacerbation rate over the study period (0.11/patient-year), improved lung function (mean [standard deviation] change from baseline of 0.075 [0.226] L in pre-dose/pre-bronchodilator forced expiratory volume in 1 s), and better asthma control versus baseline (responder rate: 71.4% at Week 52). Tezepelumab 210 mg SC Q4W in Japanese patients with severe uncontrolled asthma showed safety/tolerability profiles similar to international data, with low exacerbation rates and improvements in lung function and asthma control.

Summary Background & aims Metabolic syndrome (MS) is associated with adverse outcomes, and visceral adipose tissue (VAT) is associated with MS. Recently, VAT has been classified into intraperitoneal VAT (IVAT) and retroperitoneal VAT (RVAT). This study aimed to evaluate the association of IVAT and RVAT with the prevalence of MS or its components. Methods In our cross-sectional study, the prevalence of MS or its components was analyzed in 803 middle-aged Japanese participants. The cross-sectional area of the abdominal adipose tissue was evaluated from an unenhanced computed tomography scan at the third lumbar vertebra, and IVAT or RVAT was analyzed using a specialized software. The areas were normalized for the square of the participants’ height in meters and described as the IVAT or RVAT area index. Results In age, sex, and BMI adjusted model, the IVAT, or RVAT area index was independently associated with the prevalence of MS. After simultaneous inclusion of IVAT, RVAT, and deep and superficial subcutaneous adipose tissue area indices for multivariate logistic regression analysis, the IVAT area index was found to be independently associated with the prevalence of MS (adjusted odds ratio [OR], 1.03; 95% confidence intervals [CI], 1.02–1.08) and its components, including waist circumference (OR, 1.07; 95% CI, 1.03–1.10), glucose (1.03; 1.01–1.05), triglycerides (1.03; 1.00–1.05), and high-density lipoprotein cholesterol (1.03; 1.00–1.05), whereas the RVAT area index was not. The RVAT area index was independently associated with the prevalence of component-blood pressure (1.06; 1.02–1.11), whereas the IVAT area index was not. Conclusions IVAT and RVAT are associated differently with the prevalence of MS and its components.

Objectives To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis. Methods Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups. Results We found no difference in the sperm recovery rate (P = .083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P Conclusions From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

This study aimed to identify the serum metabolites associated with sarcopenic risk in Japanese patients with type 2 diabetes, determine the effect of dietary protein intake on the serum metabolic profile, and examine its association with sarcopenia. Ninety-nine Japanese patients with type 2 diabetes were included, and sarcopenic risk was defined as low muscle mass or strength. Seventeen serum metabolites were quantified after gas chromatography–mass spectrometry analysis. The relationship between dietary protein intake and the metabolites concerning sarcopenia was analyzed, and the factors affecting sarcopenic risk were clarified. Twenty-seven patients were classified as being at risk of sarcopenia, the same as the general risk, which was associated with older age, a longer duration of the disease, and a lower body mass index. Low levels of leucine and glutamic acid were significantly associated with low muscle strength (p = 0.002 and p < 0.001, respectively), and leucine was also associated with muscle mass (p = 0.001). Lower levels of glutamic acid had higher odds of sarcopenic risk after being adjusted for age and HbA1c (adjusted OR 4.27, 95% CI 1.07–17.11, p = 0.041), but not for leucine. Leucine and glutamic acid can serve as useful biomarkers for sarcopenia, highlighting potential targets for its prevention.

ObjectiveTo assess measurement properties of 121 face and content validated quality indicators (QIs) for medication safety in geriatric pharmacotherapy in primary care.DesignA mixed methods study: a 6-month observational study in primary care (July–December 2020) and in-depth semistructured online interviews with participants (February–March 2021).SettingSixty community pharmacies in Japan.ParticipantsPatients aged 75 years and older who were regularly taking six or more prescription medicines for ˃4 weeks were eligible. The observational study included 457 patients. The interviews were undertaken with 26 community pharmacists, including pharmacy managers and owners.Primary and secondary outcome measuresFive measurement properties of QIs (applicability, improvement potential, acceptability, implementation issues and sensitivity to change) were evaluated. A web application was developed for data reporting and data visualisation.ResultsThis study showed that 53 QIs met the measurement properties of applicability, improvement potential, acceptability and implementation issues. Of 53 QIs, 17 also had a high sensitivity to change. Interviews identified eight themes (indicator characteristics, web application, policy, patient, time, competence, pharmacy administration and collaboration) in relation to the consequence of implementation of QIs.ConclusionsA set of 121 QIs for geriatric pharmacotherapy was field tested for their five measurement properties. This QI set can be used to identify patients who may benefit from clinician reviews of their medicines. These QIs may be applied at different levels within the healthcare system: patient, pharmacy, regional and national levels. Further mechanisms to automatically collect and report data should be established to facilitate sustainable quality improvement initiatives.

Here we report an anionic meso-tetrakis(4-carboxymethylthio-2,3,5,6-tetrafluorophenyl) zinc porphyrin (ZnTF4PPTC4–) to form a supramolecular complex with a cationic lithium endohedral [60]fullerene...

Background/aim Curcumin is a natural compound of turmeric, which inhibits prostate cancer cell proliferation. This study examined whether treatment of LNCaP prostate cancer cells with the combination of curcumin and dutasteride, a 5-alpha reductase inhibitor, affect proliferation and the amount of testosterone and dihydrotestosterone. Materials and methods LNCaP Cells were incubated with curcumin or the combination of curcumin and dutasteride and cell proliferation was measured at 72 h. LC-MS/MS was used to determine testosterone and dihydrotestosterone concentrations in prostate cancer cells. Results Curcumin combined with dutasteride suppressed proliferation and affected apoptosis of LNCaP cells. The combination of curcumin and dutasteride also reduced the amount of testosterone and dihydrotestosterone in LNCaP cells. The secretion of prostate-specific antigen was inhibited by the combination treatment in a dose-dependent manner. Conclusion Treatment with the combination of curcumin and dutasteride may interfere with the intra-tumoral androgen activity.

Quasi-Newton-based nonlinear finite element methods were extensively studied in the 1970s and 1980s. However, they have almost disappeared due to their poorer convergence performance than the Newton-Raphson method. An advantage of quasi-Newton methods over the Newton-Raphson method is shorter computational time even with a larger number of iterations. The speedup must grow as the number of degrees of freedom (DOFs) increases. Since computers and computational methods have been advancing steadily in the last 40 years, significant speedup can be expected at present. Therefore, we present a framework of a quasi-Newton-based parallel nonlinear finite element method consisting of a quasi-Newton method, implementation for parallel computing and a nonlinear material model. The advances of the present framework are a large number of DOFs and the use of a modern nonlinear material model. The number of DOFs exceeded 100 thousand in all analyses and reached one million in some analyses. This was enabled by the implementation of a quasi-Newton method for parallel computing and the use of a parallel sparse direct solver library. Note that, for more than several or ten million DOFs, an iterative linear solution method is generally preferred, resulting in the loss of the advantage of quasi-Newton methods. Furthermore, a modern finite-strain elastoplasticity material model with a realistic multilinear stress-strain curve was used in the present study, whereas an infinitesimal elastoplasticity model with a bilinear stress-strain curve was popular in the 1980s. Performance investigation of the present framework is given in the present paper. The quasi-Newton-based present framework achieved speedup of more than 30 times in modern large-deformation elastic-plastic analyses involving approximately one million DOFs, compared to the Newton-Raphson method.

Background The coexistence of hypertension and diabetes mellitus significantly increases the risk of macrovascular complications in patients with diabetes. Home blood pressure is important because it is more strongly associated with target organ damage and total mortality than clinic blood pressure measurements. Regular moderate aerobic exercise has antihypertensive effects. This study aims to examine the effect of aerobic exercise therapy on blood pressure at home in patients with diabetes. Patients and methods In this crossover randomized controlled trial, 110 patients with type 2 diabetes will be randomly assigned to two groups: an exercise preceding group and an exercise lagging group. During the exercise period, patients will be instructed to walk either 30 minutes twice each day or 60 minutes once each day for at least 3 days per week. During the non-exercise period, patients will be permitted to perform physical activity associated with activities of daily life. Patients will be followed up for 56 days. The primary outcome will be the mean nocturnal blood pressure from day 24 to 28 during the exercise period compared to that during the non-exercise period. The secondary outcome will include variation in nocturnal blood pressure, mean blood pressure values and variation of morning and evening blood pressure from day 24 to 28 in the exercise period compared to the non-exercise period, body weight, body mass index and bioelectrical impedance analysis. Biochemical tests such as hemoglobin A1c level, blood glucose level, serum lipid profile, renal function, uric acid levels and liver function tests will also be measured. Discussion This randomized controlled trial will provide critical information regarding the effectiveness of moderate exercise on nocturnal blood pressure reduction. If successful, the results of this randomized controlled trial may increase exercise motivation in people with diabetes and may lead to improvement or prevention of target organ damage and overall mortality. Trial registration Trial registration: University Hospital Medical Information Network, UMIN 000035973. Protocol version number: R000040969. Registration date: February 22, 2019. Recruitment began: June 19, 2019. The date of completion of recruitment: July 3, 2020. URL: http://www.umin.ac.jp.

Higher hemoglobin levels are associated with incident metabolic syndrome (MetS), and higher mean corpuscular volume (MCV) is associated with adverse outcomes. The objective of this study is to evaluate the combined effect of MCV and hemoglobin levels on incident MetS.In our cross-sectional study, we analyzed the prevalence of MetS in 20,162 middle-aged Japanese subjects without anemia and with normal MCV levels, as they underwent physical checkups. We subsequently analyzed incident MetS in 11,110 subjects. In order to evaluate the combined effect on incident MetS, the subjects were divided into four study groups according to cutoff values of hemoglobin and MCV for identifying the prevalence of MetS.In the cross-sectional study, hemoglobin (adjusted odds ratio [aOR], 1.02; P 0.0001 in men and OR, 1.04; P 0.0001 in women, per 1.0 g/L) and MCV (aOR, 0.93; P 0.0001 in men and OR, 0.94; P = 0.0005 in women, per 1.0 fL) were independently associated with the prevalence of MetS. In the longitudinal cohort study, hemoglobin (adjusted hazards ratio [aHR, 1.12; P = 0.0006, per 1.0 g/L) and MCV (aHR, 0.96; P 0.0001, per 1.0 fL) were independently associated with incident MetS in men but not in women. Then, the lower hemoglobin/higher MCV group showed decreased HRs for incidence of MetS compared with other groups of men but not of women.Among the subjects without anemia and with normal MCV levels, higher hemoglobin or lower MCV levels were associated with higher prevalence of MetS in men and women. In addition, lower hemoglobin with higher MCV showed a decreased risk of MetS in men. We suggested that the assessment of hemoglobin and MCV levels could be used as practical screening tool for MetS.

Background Insulin resistance, which is closely associated with type 2 diabetes mellitus (T2DM), is a cause of sarcopenia and people with T2DM have a high risk of sarcopenia. Keeping good oral condition by dental care is important for people with T2DM. Keeping good oral condition by dental care is important for people with T2DM. This study has investigated the association between dental care or oral conditions and sarcopenia in people with T2DM. Methods Dental care and oral conditions were evaluated based on a self-reported questionnaire. Individuals with both low handgrip strength and low skeletal muscle mass index were diagnosed with sarcopenia. Results Among 266 people with T2DM, the proportions of sarcopenia, not having a family dentist, not having a toothbrushing behavior, poor chewing ability, and use of complete dentures were 18.0%, 30.5%, 33.1%, 25.2%, and 14.3%, respectively. The proportions of sarcopenia in people not having a family dentist (27.2% vs. 14.1%, p = 0.017), those with poor chewing ability (26.9% vs. 15.1%, p = 0.047), and use of complete dentures (36.8% vs. 14.9%, p = 0.002) were higher than those in people without. The proportion of sarcopenia in people without toothbrushing behavior tended to be higher than that in people with toothbrushing behavior (25.0% vs. 14.6%, p = 0.057). Not having a family dentist (adjusted odds ratio [OR] 2.48 [95% confidence interval (CI): 1.21–5.09], p = 0.013), poor chewing ability (adjusted OR 2.12 [95% CI: 1.01–4.46], p = 0.048), and use of complete dentures (adjusted OR 2.38 [95% CI: 1.01–5.99], p = 0.046) were related to the prevalence of sarcopenia. Conclusions This study revealed that dental care and oral conditions were associated with the prevalence of sarcopenia.

This study aimed to investigate the effects of physical therapists’ exercise instructions in Japanese patients with type 2 diabetes. Thirty-six participants were recruited from the outpatient clinic at Matsushita Memorial Hospital, Osaka, Japan from June 2020 to September 2020 and were randomly assigned to either the non-intervention or intervention group. The intervention group received exercise instructions from physical therapists for 30 min at baseline (week 0) and at week 4 by referring to ambulatory accelerometer records. Laboratory parameters, physical activity, body composition, motor skill, and transtheoretical model were assessed in both the groups at baseline (week 0) and week 8. In week 8, patients in the intervention group had a statistically significant reduction in HbA1c levels compared with those in the non-intervention group (7.3% [6.8-%–7.9%] vs. 7.4% [7.3%–7.7%], P = 0.04). The number of steps per day (P = 0.001), energy expenditure (P = 0.01), lower extremity muscle strength (P = 0.002), and 6-min walk test results (P = 0.04) were significantly increased in the intervention group compared with those in the non-intervention group in week 8. The transtheoretical model varied between baseline (week 0) and week 8 only in the intervention group (P < 0.001). Thus, outpatient exercise instructions from physical therapists could improve glycemic control owing to physical activity by improving motor skills and changing the transtheoretical model in Japanese patients with type 2 diabetes.

The aim of this study was to calculate the cut-off values of liver enzymes to identify the risk of incident type 2 diabetes (DM) and to investigate the association between liver enzymes and incident DM in participants with or without obesity.The long-term cohort study included 70,688 subjects who underwent medical health checkups in 2008. The cut-off values of alanine aminotransferase (ALT) and the aminotransferase (AST)/ALT ratio for incident DM were evaluated using the time-dependent receiver operating characteristic curves. The risk of incident type 2 DM was examined according to cut-off values of liver enzymes and the group with body mass index (BMI) ≥25 kg/mIn total, 4181 of 70,688 subjects developed DM within 10 years. The area under the curve and cut-off values for the ALT and the AST/ALT ratio for incident type 2 DM at 10 years were 0.707 and 23 IU/L and 0.694 and 0.875, respectively. The risk of incident DM was higher in subjects with ALT ≥23 or AST/ALT ≤0.875 and BMI25 kg/mThe cut-off values of ALT and the AST/ALT ratio associated with the risk of incident type 2 DM were determined. Non-obese individuals with AST/ALT ≤0.875 had a higher risk of incident type 2 DM than obese individuals with AST/ALT0.875.

IntroductionSarcopenia index (SI), calculated by (serum creatinine/cystatin C)×100, is reported to be associated with sarcopenia. Few studies reported the association between SI and subclinical atherosclerosis. We evaluated the association between SI and subclinical atherosclerosis, assessed by brachial-ankle pulse wave velocity (baPWV).Research design and methodsOne hundred seventy-four patients with type 2 diabetes were included in this cross-sectional study. The relationship between SI and baPWV was assessed by Pearson’s correlation coefficient. To calculate area under the receiver operator characteristic (ROC) curve (AUC) of SI for the presence of subclinical atherosclerosis, which was defined as baPWV >1800 cm/s, ROC analysis was performed. Logistic regression analyses were performed to assess the effect of SI on the prevalence of subclinical atherosclerosis adjusting for covariates.ResultsMean age, duration of diabetes, baPWV, and SI were 66.9 (10.1) years, 17.7 (11.6) years, 1802 (372) cm/s, and 77.6 (15.8), respectively. There was an association between SI and baPWV (men; r=−0.25, p=0.001, and women; r=−0.37, p=0.015). The optimal cut-off point of SI for the presence of subclinical atherosclerosis was 77.4 (sensitivity=0.72, specificity=0.58, pConclusionsSI is associated with the prevalence of subclinical atherosclerosis in patients with type 2 diabetes.