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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.

Generating hydrogen through hydrolysis of metal magnesium with water is a very promising strategy for portable applications because it is clean, has high energy density and operability. In the present study, high purity ultrafine Mg powder was prepared using close-coupled gas atomization. Thereafter, the microstructure of the powder was investigated through X-ray diffraction and scanning electron microscopy. The results showed that increasing the speed of ball milling improved the reaction activity of Mg powder. Moreover, a higher water temperature was shown to be beneficial in improving hydrolysis. Moderate amounts of alcohol in water could also improve the yield of hydrogen.

Abstract We report on a patient with a distal 16.4-Mb duplication at 2q36.3-qter, who presented with severe intellectual disability, microcephaly, brachycephaly, prominent forehead, hypertelorism, prominent eyes, thin upper lip, and progenia. Copy number analysis using whole exome data detected a distal 2q duplication. This is the first report describing a distal 2q duplication at the molecular level.

The SMC5/6 complex is critical for genome stability. Here, the authors identify mutations in SLF2 and SMC5 as cause of Atelís Syndrome characterized by microcephaly, short stature, anemia, segmented chromosomes and mosaic variegated hyperploidy.

Objectives: We aimed to validate a newly developed antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 using anterior nasal specimens. Methods: Between February 12 and September 30, 2021, 16 patients (age range,

Right ventricular (RV) failure is clinically crucial, but there is no specific therapy. Here, the authors show that the complement alternative pathway is activated in RV failure and that blockade of the pathway ameliorates RV failure in mice.

In this study, double-multilayer monochromators that generate intense, high-energy, pink X-ray beams are designed, installed and evaluated at the SPring-8 medium-length (215 m) bending-magnet beamline BL20B2 for imaging applications. Two pairs of W/B4C multilayer mirrors are designed to utilize photon energies of 110 keV and 40 keV with bandwidths of 0.8% and 4.8%, respectively, which are more than 100 times larger when compared with the Si double-crystal monochromator (DCM) with a bandwidth of less than 0.01%. At an experimental hutch located 210 m away from the source, a large and uniform beam of size 14 mm (V) × 300 mm (H) [21 mm (V) × 300 mm (H)] was generated with a high flux density of 1.6 × 109 photons s−1 mm−2 (6.9 × 1010 photons s−1 mm−2) at 110 keV (40 keV), which marked a 300 (190) times increase in the photon flux when compared with a DCM with Si 511 (111) diffraction. The intense pink beams facilitate advanced X-ray imaging for large-sized objects such as fossils, rocks, organs and electronic devices with high speed and high spatial resolution.

Abstract Triple negative breast cancer (TNBC) is associated with worse outcomes and results in high mortality; therefore, great efforts are required to find effective treatment. In the present study, we suggested a novel strategy to treat TNBC using mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) to transform the behaviors and cellular communication of TNBC cells (BCC) with other non-cancer cells related to tumorigenesis and metastasis. Our data showed that, BCC after being internalized with EV derived from Wharton’s Jelly MSC (WJ-EV) showed the impaired proliferation, stemness properties, tumorigenesis and metastasis under hypoxic conditions. Moreover, these inhibitory effects may be involved in the transfer of miRNA-125b from WJ-EV to BCC, which downregulated the expression of HIF1α and target genes related to proliferation, epithelial-mesenchymal transition, and angiogenesis. Of note, WJ-EV-internalized BCC (wBCC) showed transformed behaviors that attenuated the in vivo development and metastatic ability of TNBC, the angiogenic abilities of endothelial cells and endothelial progenitor cells and the generation of cancer-associated fibroblasts from MSC. Furthermore, wBCC generated a new EV with modified functions that contributed to the inhibitory effects on tumorigenesis and metastasis of TNBC. Taken together, our findings suggested that WJ-EV treatment is a promising therapy that results in the generation of wBCC to interrupt the cellular crosstalk in the tumor environment and inhibit the tumor progression in TNBC.

Abstract Background Several methods are used for hearing loss screening; however, their benefits are uncertain. In this study, we aimed to determine the predictive factors of acute sensorineural hearing loss for clinical application by primary care doctors. Methods This retrospective, cross-sectional study included 365 patients with acute sensorineural hearing loss without prior therapy. The patients’ clinical data, demographic information, and medical histories were obtained, and they were asked about comorbidities. In addition, we assessed lifestyle factors such as stress level, alcohol consumption, marital status, and socioeconomic level. Logistic regression analysis was performed to investigate the diagnostic predictive ability of the selected factors associated with acute sensorineural hearing loss. The hearing levels of all patients were evaluated using pure tone audiometry. Results We identified significant predictive factors for acute sensorineural hearing loss. The absence of hyperacusis was a predictive factor for sudden sensorineural hearing loss. Younger age, female sex, and marital status were predictive factors for acute low-tone hearing loss. High body mass index, high socioeconomic level, low alcohol consumption, high stress level, hyperacusis, and vertigo/dizziness were predictive factors for Ménière’s disease. High body mass index and ear fullness were predictive factors for perilymph fistula. Low stress level was a predictive factor for acoustic tumours. Conclusions Our findings can be used to distinguish between the types of acute sensorineural hearing loss. Symptoms, physical status, and lifestyle factors identified during this study are useful markers for predicting acute sensorineural hearing loss occurrence.

Background: Although the feasibility of randomized trials for investigating the long-term association between oral health and cognitive decline is low, deriving causal inferences from observational data is challenging. We aimed to investigate the association between poor oral status and subjective cognitive complaints (SCC) using fixed-effects model to eliminate the confounding effect of unobserved time-invariant factors. Methods: We used data from Japan Gerontological Evaluation Study (JAGES) which was conducted in 2010, 2013, and 2016. β regression coefficients and 95% confidence intervals [CIs] were calculated using fixed-effects models to determine the effect of deteriorating oral status on developing SCC. Onset of SCC was evaluated using the Kihon Checklist-Cognitive function score. Four oral status variables were used: awareness of swallowing difficulty, decline in masticatory function, dry mouth, and number of teeth. Results: We included 13,594 participants (55.8% women) without SCC at baseline. The mean age was 72.4 (standard deviation [SD], 5.1) years for men and 72.4 (SD, 4.9) years for women. Within the 6-year follow-up, 26.6% of men and 24.9% of women developed SCC. The probability of developing SCC was significantly higher when participants acquired swallowing difficulty (β = 0.088; 95% CI, 0.065–0.111 for men and β = 0.077; 95% CI, 0.057–0.097 for women), decline in masticatory function (β = 0.039; 95% CI, 0.021–0.057 for men and β = 0.030; 95% CI, 0.013–0.046 for women), dry mouth (β = 0.026; 95% CI, 0.005–0.048 for men and β = 0.064; 95% CI, 0.045–0.083 for women), and tooth loss (β = 0.043; 95% CI, 0.001–0.085 for men and β = 0.058; 95% CI, 0.015–0.102 for women). Conclusion: The findings suggest that good oral health needs to be maintained to prevent the development of SCC, which increases the risk for future dementia.

Objective Predictors of prognosis are necessary for use in routine clinical practice for older patients with pneumonia, given the ageing of the population. Recently, the National Early Warning Score (NEWS), a comprehensive predictor of severity that consists solely of physiological indicators, has been proposed to predict the prognosis of pneumonia. The neutrophil/lymphocyte ratio (NLR) is a simple index of inflammation that may also be predictive of pneumonia. In the present study, we aimed to determine whether NEWS or a combination of NEWS and NLR predicts mortality in older patients with pneumonia.Design A retrospective cohort study.Setting A general hospital in Japan.Participants We collected data from patients aged ≥65 years with pneumonia who were admitted between 2018 and 2020 (n=282; age=85.3 (7.9)). Data regarding vital signs, demographics and the length of hospital stay, in addition to the NEWS and NLR, were extracted from the participants’ electronic medical records.Intervention The utility of the combination of NEWS and NLR was assessed using NEWS×NLR and NEWS+NLR.Main outcome measures Their predictive ability for 30-day mortality as the primary outcome was assessed using receiver operating characteristic (ROC) curve analysis.Results According to the NEWS classification, 80 (28.3%), 64 (22.7%) and 138 (48.9%) of the participants were at low, medium and high risk of mortality, respectively. The 30-day mortality for the entire cohort was 9.2% (n=26), and the mortality rate increased with the NEWS classification: low, 1.3%; medium, 7.8%; and high, 14.5%. The NLRs were 6.0 (4.2–9.8), 6.8 (4.8–10.4) and 14.6 (9.4–22.2), respectively (p

Background And Aims: Maintaining appendicular skeletal muscle mass is important for maintaining the quality of life of elderly patients with type 2 diabetes. The possibility of GLP-1 receptor agonists for maintaining appendicular skeletal muscle mass has previously been reported. We investigated changes in appendicular skeletal muscle mass, measured by body impedance analysis, in elderly patients who were hospitalized for diabetes self-management education. Methods: The study design was a retrospective longitudinal analysis of the changes in appendicular skeletal muscle mass in hospitalized patients over the age of 70 years. The study subjects consisted of consequential patients who received GLP-1 receptor agonist and basal insulin co-therapy or received basal insulin therapy. Body impedance analysis was performed on the day after admission and on the ninth day of admission. All patients received standard diet therapy and standard group exercise therapy 3 times per week. Results: The study subjects consisted of 10 patients who received GLP-1 receptor agonist and basal insulin co-therapy (co-therapy group) and 10 patients who received basal insulin (insulin group). The mean change in appendicular skeletal muscle mass was 0.78 ± 0.7 kg in co-therapy group and −0.09 ± 0.8 kg in the insulin group. Conclusions: This retrospective observational study suggests the possibility of favorable effects of GLP-1 receptor agonist and basal insulin co-therapy for maintaining appendicular skeletal muscle mass during hospitalization for diabetes self-management education.

We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts. Mice in an age-matched senescence-accelerated mouse resistant strain 1 (SAMR1) group were treated with CTR-Apts as controls. The soleus muscles were collected after the 8-week intervention for weight measurement and histological, RT-PCR, and immunofluorescence analyses. Grip strength was measured before and after the 8-week intervention. AGE-Apt treatment inhibited the progressive decrease in the grip strength of SAMP8 mice. SAMP8 mice had lower soleus muscle weight and fiber size than SAMR1 mice, which was partly restored by AGE-Apt treatment. Furthermore, AGE-Apt-treated SAMP8 mice had a lower interstitial fibrosis area of the soleus muscle than CTR-Apt-treated SAMP8 mice. The soleus muscle levels of AGEs, oxidative stress, receptor for AGEs, and muscle ring-finger protein-1 were increased in the CTR-Apt-treated mice, all of which, except for AGEs, were inhibited by AGE-Apt treatment. Our present findings suggest that the subcutaneous delivery of AGE-Apts may be a novel therapeutic strategy for aging-related decrease in skeletal muscle mass and strength.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55–75] years) were older than those in the continuation group (64 [53–71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented.

Oral health is essential for nutritional status; however, little is known about its association with weight change. This study aimed to investigate whether the risk of weight change differs according to the presence of each important component of oral hypofunction (fewer remaining teeth, low chewing efficiency, swallowing problems, and xerostomia) among independent older adults. This was a three-year follow-up cohort study based on self-reported questionnaires. The participants were independent older adults aged ≥65 from the Japan Gerontological Evaluation Study (JAGES). We used >5% weight loss/gain during follow-up as the outcome variables, and the number of remaining teeth (≥20/10–19/0–9), the presence of chewing difficulty, swallowing problems, and xerostomia (yes/no) as the exposure variables. We fitted the Poisson regression model, including possible confounders to estimate the risk ratios (RRs) and 95% confidence intervals (CIs). For weight loss, RRs were significantly higher among those with 0–9 remaining teeth (RR = 1.17; 95% CI = 1.11–1.23), chewing difficulty (RR = 1.12; 95% CI = 1.07–1.16), and xerostomia (RR = 1.11; 95% CI = 1.06–1.16), but there was no significant association with swallowing problems (RR = 1.01; 95% CI = 0.97–1.06). For weight gain, we also found similar associations with oral hypofunction. Oral hypofunction among older adults could have non-negligible health impacts on nutritional status.

A combined analytical method of NEXAFS measurement and DFT-calculation was employed for the evaluation of Cs states in clay minerals. The measured Cs M4,5 NEXAFS spectra of Cs halides were analyzed using the DFT-calculations in order to establish the analytical methods. The NEXAFS spectra of the Cs halides were well reproduced by incorporating the core-hole strength. The Cs M4,5 NEXAFS spectrum of the clay minerals was well reproduced by the DFT-calculations including the major transitions and tail structures with the established method. Further evaluation of this spectrum by charge density analysis suggested that these major transitions and the tail structures likely reflect the bonding state and the local environment around the Cs atoms. Comparison of electronic states of Cs in the clay mineral with those in the Cs halides by DFT-calculations has shown that the interaction between Cs and the nearest-neighbor atom is largest in the clay mineral, which differs from those of Cs halides. This happened due to the energy level of Cs-5s and 5p, which was closer to that of O-2s and 2p than the s and p orbitals of other alkali metal and alkali earth metal elements.

A combined analytical method of NEXAFS measurement and DFT-calculation was employed for the evaluation of Cs states in clay minerals. The measured Cs M4,5 NEXAFS spectra of Cs halides were analyzed using the DFT-calculations in order to establish the analytical methods. The NEXAFS spectra of the Cs halides were well reproduced by incorporating the core-hole strength. The Cs M4,5 NEXAFS spectrum of the clay minerals was well reproduced by the DFT-calculations including the major transitions and tail structures with the established method. Further evaluation of this spectrum by charge density analysis suggested that these major transitions and the tail structures likely reflect the bonding state and the local environment around the Cs atoms. Comparison of electronic states of Cs in the clay mineral with those in the Cs halides by DFT-calculations has shown that the interaction between Cs and the nearest-neighbor atom is largest in the clay mineral, which differs from those of Cs halides. This happened due to the energy level of Cs-5s and 5p, which was closer to that of O-2s and 2p than the s and p orbitals of other alkali metal and alkali earth metal elements.