Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics.

BACKGROUND: Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial. METHODS: Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m2 were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is noninferiority for time to first MACE of tirzepatide vs dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority vs a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis). RESULTS: Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m2. Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had a prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing. CONCLUSION: SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.

Loss of Purkinje cells in the developing cerebellum strengthens the cerebellothalamic synapses.

Cerebellar damage early in life often causes long-lasting motor, social, and cognitive impairments, suggesting the roles of the cerebellum in developing a broad spectrum of behaviors. This recent finding has promoted research on how cerebellar damage affects the development of the cerebral cortex, the brain region responsible for higher-order control of all behaviors. However, the cerebral cortex is not directly connected to the cerebellum. The thalamus is the direct postsynaptic target of the cerebellum, sending cerebellar outputs to the cerebral cortex. Despite its crucial position in cerebello-cerebral interaction, thalamic susceptibility to cerebellar damage remains largely unclear. Here, we studied the consequences of early cerebellar perturbation on thalamic development. Whole-cell patch-clamp recordings showed that the synaptic organization of the cerebellothlamic circuit is similar to that of the primary sensory thalamus, in which aberrant sensory activity alters synaptic circuit formation. The hemizygous deletion of the tuberous sclerosis complex-1 ( Tsc1 ) gene in the Purkinje cell-known to cause Purkinje cell hypoactivity and autistic behaviors-did not alter cerebellothalamic synapses or intrinsic membrane properties of thalamic neurons. However, the ablation of Purkinje cells in the developing cerebellum strengthened the cerebellothalamic synapses and enhanced thalamic suprathreshold activities. These results suggest that the cerebellothalamic circuit is resistant to moderate perturbation in the developing cerebellum, such as the reduced firing rate of Purkinje cells, and that autistic behaviors are not necessarily linked to thalamic abnormality. Still, Purkinje cell loss alters the thalamic circuit, suggesting the vulnerability of the thalamus to substantial disturbance in the developing cerebellum.

Physicochemical insights into semiconductor properties of a semitransparent tantalum nitride photoanode for solar water splitting.

The self-conductivity of tantalum nitride (Ta3N5) thin film-based semitransparent photoanodes was found to promote the current originating from the photoelectrochemical oxygen evolution reaction (PEC OER) without a conducting substrate. With surface modification by the NiFeOx-electrocatalyst, an optimized Ta3N5 thin film fabricated directly on a transparent insulating quartz substrate generated a photocurrent density of ∼5.9 ± 0.1 mA cm-2 at 1.23 V vs. the reversible hydrogen electrode under simulated AM 1.5G solar illumination. The correlation between the PEC OER performance of NiFeOx-modified Ta3N5 photoanodes and the electrical properties of Ta3N5 thin films was investigated based on the Hall effect measurements. By changing the nitridation conditions, these properties can be tuned so that the higher the Hall mobility (0.2 to 1.7 cm2 V-1 s-1) and the lower the carrier concentration (1020 to 1019 cm-3). The surface chemical states of Ta3N5 thin films were investigated using X-ray photoelectron spectroscopy as a means of evaluating surface oxygen impurities and nitrogen vacancies, which may correlate with the PEC OER performance and the electrical properties of the material.

Connecting the dots in the associations between diet, obesity, cancer, and microRNAs.

The prevalence of obesity has reached pandemic levels worldwide, leading to a lower quality of life and higher health costs. Obesity is a major risk factor for noncommunicable diseases, including cancer, although obesity is one of the major preventable causes of cancer. Lifestyle factors, such as dietary quality and patterns, are also closely related to the onset and development of obesity and cancer. However, the mechanisms underlying the complex association between diet, obesity, and cancer remain unclear. In the past few decades, microRNAs (miRNAs), a class of small non-coding RNAs, have been demonstrated to play critical roles in biological processes such as cell differentiation, proliferation, and metabolism, highlighting their importance in disease development and suppression and as therapeutic targets. miRNA expression levels can be modulated by diet and are involved in cancer and obesity-related diseases. Circulating miRNAs can also mediate cell-to-cell communications. These multiple aspects of miRNAs present challenges in understanding and integrating their mechanism of action. Here, we introduce a general consideration of the associations between diet, obesity, and cancer and review the current knowledge of the molecular functions of miRNA in each context. A comprehensive understanding of the interplay between diet, obesity, and cancer could be valuable for the development of effective preventive and therapeutic strategies in future.

Effects of acute strawberry consumption on serum levels of vitamin C and folic acid, the antioxidant potential of LDL and blood glucose response: a randomised cross-over controlled trial.

Strawberry contains many bioactive compounds such as vitamin C and polyphenols as well as folate, a vitamin that is especially important for women of childbearing age. We investigated the effects of the acute consumption of strawberry on the serum levels of vitamin C and folate, and on the antioxidant potential of low-density lipoprotein (LDL). In a randomised, placebo-controlled, double-blind, crossover study, twenty-three healthy female volunteers (age 22⋅5 ± 1⋅4 years) ingested 500 g of a strawberry purée beverage or a sugar content-matched placebo beverage. Blood samples were collected at fasting and at 0⋅5, 1, 2 and 4 h post-ingestion. The serum concentrations of vitamin C and folate were significantly elevated from 0⋅5 to 4 h after the strawberry beverage ingestion (P < 0⋅001); the levels peaked at 2 h, with peak levels of 15⋅0 ± 2⋅5 µg/ml for vitamin C and 14⋅4 ± 7⋅0 ng/ml for folate. Notably, at 1 h after the strawberry beverage ingestion, the LDL oxidation lag time was significantly prolonged (P < 0⋅05), suggesting that the antioxidant potential of LDL was increased. After the ingestion of either beverage, the serum levels of glucose and insulin reached a peak at 0⋅5 h and then quickly returned to baseline levels. These results suggest that strawberries are a useful source of vitamin C and folate and may help enhance the antioxidant potential of LDL in healthy young women.

Ovarian strumal carcinoid: a case report.

BACKGROUND: Carcinoid tumors of the ovary are rare tumors, histopathologically classified as monodermal teratomas and somatic-type tumors arising from dermoid cysts. Their malignancy varies from borderline to malignant. Carcinoid tumors can occur in young and elderly women, and are sometimes seen in mature teratoma, struma ovarii, or mucinous cystadenoma as a nodule or tumor. Strumal carcinoid and mucinous carcinoid present as special types of carcinoid tumors of the ovary. CASE REPORT: This report describes a 56-year-old woman who presented with a large pelvic mass on abdominal ultrasonography during a medical examination. The diameter of the pelvic tumor was approximately 11 cm and was suspected to be ovarian cancer. The values of CA125 and CEA were above their reference intervals on preoperative examination. Abdominal total hysterectomy and bilateral salpingo-oophorectomy were performed. Intraoperative frozen-section histopathology suggested a diagnosis of mucinous adenocarcinoma; therefore, partial omentectomy and pelvic lymphadenectomy were also performed. Permanent-section histopathology led to a final diagnosis of strumal carcinoid of the ovary, stage IA (FIGO 2014). Six years post-operation, the patient had no sign of recurrence.

Granule Cells Constitute One of the Major Neuronal Subtypes in the Molecular Layer of the Posterior Cerebellum.

The migration of neurons from their birthplace to their correct destination is one of the most crucial steps in brain development. Incomplete or incorrect migration yields ectopic neurons, which cause neurologic deficits or are negligible at best. However, the granule cells (GCs) in the cerebellar cortex may challenge this traditional view of ectopic neurons. When animals are born, GCs proliferate near the pia mater and then migrate down to the GC layer located deep in the cerebellar cortex. However, some GC-like cells stay in the molecular layer, a layer between the pia mater and GC layer, even in normal adult animals. These cells were named ectopic GCs nearly 50 years ago, but their abundance and functional properties remain unclear. Here, we have examined GCs in the molecular layer (mGCs) with a specific marker for mature GCs and transgenic mice in which GCs are sparsely labeled with a fluorescent protein. Contrary to the previous assumption that mGCs are a minor neuronal population, we have found that mGCs are as prevalent as stellate or basket cells in the posterior cerebellum. They are produced during a similar period as regular GCs (rGCs), and in vivo time-lapse imaging has revealed that mGCs are stably present in the molecular layer. Whole-cell patch-clamp recordings have shown that mGCs discharge action potentials similarly to rGCs. Since axonal inputs differ between the molecular layer and GC layer, mGCs might be incorporated in different micro-circuits from rGCs and have a unique functional role in the cerebellum.

Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.

Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled tirzepatide groups and control groups. A stratified Cox proportional hazards model, with treatment as a fixed effect and trial-level cardiovascular risk as the stratification factor, was used for the estimation of hazard ratios (HRs) and confidence intervals (CIs) comparing tirzepatide to control. Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed. Overall, 142 participants, 109 from the trial with high cardiovascular risk and 33 from the six trials with lower cardiovascular risk, had at least one MACE-4 event. The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57-1.11) for MACE-4; 0.90 (95% CI, 0.50-1.61) for cardiovascular death; and 0.80 (95% CI, 0.51-1.25) for all-cause death. No evidence of effect modifications was observed for any subgroups, although the evidence was stronger for participants with high cardiovascular risk. Tirzepatide did not increase the risk of major cardiovascular events in participants with T2D versus controls.

Microelectrode-based transient amperometry of O2 adsorption and desorption on a SrTiO3 photocatalyst excited under water.

Oxygen evolution at water-solid interfaces is a key reaction for sustainable energy production. Although some intermediate states have been detected in transient absorption spectroscopy, the O2 evolution kinetics after the multi-step, four-electron oxidation of water remain unknown. In this study, transient amperometry with a microelectrode was applied to operando O2 detection over Al-doped SrTiO3 particles doubly loaded with RhCrOx and CoOy cocatalysts, an efficient photocatalyst for the overall water-splitting reaction. Electrochemical O2 detection at intervals of 0.1 s unexpectedly indicated instantaneous O2 adsorption and desorption in addition to steady, photocatalytic O2 evolution on the photocatalyst modified under intense light irradiation. We hypothesized that electrons excited in the conduction band were transferred to O2 in water thorough Ti cations neighboring an oxygen anion vacancy on the modified Al-doped SrTiO3. The negatively charged O2 was then bound to the Ti cations. It was neutralized and released when shaded through electron back-transfer to the conduction band. The hypothesized mechanism for O2 adsorption and desorption was compared with the photoinduced O2 desorption known to occur on anion vacancies of TiO2(110). The microelectrode-based transient amperometry demonstrated in this paper will be applied to many other phenomena at liquid-solid interfaces.

Long-term Efficacy and Safety of Ultra Rapid Lispro in Japanese Patients With Type 1 Diabetes: Subpopulation Analysis of the 52-Week PRONTO-T1D Study.

INTRODUCTION: The PRONTO-T1D study evaluated the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes mellitus. After 26 weeks of treatment, mealtime and postmeal URLi provided effective and comparable glycemic control in a prespecified subpopulation analysis of Japanese patients from PRONTO-T1D. We present the results of a 52-week study which evaluated the long-term efficacy and safety of URLi in Japanese patients. METHODS: After an 8-week lead-in period to optimize basal insulin treatment, Japanese patients were randomized to one of three treatment groups: the 52-week double-blind mealtime URLi (n = 62) or mealtime lispro (n = 59) group, respectively, or the 52-week open-label postmeal URLi (n = 46) group. RESULTS: At week 52, there were no statistically significant differences in change from baseline in hemoglobin A1c (HbA1c) between Japanese patients on URLi and those on lispro; the least-squares mean (LSM) treatment difference was 0.04% (95% confidence interval [CI] - 0.18, 0.25) between mealtime URLi and lispro, and 0.04% (95% CI - 0.19, 0.28) between postmeal URLi and mealtime lispro. No significant between-group differences were observed in the number of patients achieving the HbA1c target of < 7.0% (20.0, 30.5 and 16.3% of those on mealtime URLi, mealtime lispro and postmeal URLi, respectively). Daily average blood glucose levels in the 10-point self-monitored blood glucose profiles at week 52 were similar between treatments. However, compared with lispro, lower blood glucose levels were observed for the mealtime URLi group at the morning 1- and 2-h postmeal time points with LSM differences of - 32.7 mg/dL (- 1.82 mmol/L) (p = 0.005) and - 23.2 mg/dL (- 1.29 mmol/L) (p = 0.029), respectively. There were no significant treatment differences in the incidences of treatment-emergent adverse events, documented hypoglycemia and severe hypoglycemia; however, the rate of documented hypoglycemia was lower in the mealtime URLi arm compared with the lispro arm. CONCLUSIONS: Overall glycemic control and improved postprandial glucose via self-monitoring was maintained in Japanese patients following 52 weeks of treatment with URLi versus lispro, including postmeal URLi administration. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03214367.

Photocatalytic solar hydrogen production from water on a 100-m2 scale.

The unprecedented impact of human activity on Earth's climate and the ongoing increase in global energy demand have made the development of carbon-neutral energy sources ever more important. Hydrogen is an attractive and versatile energy carrier (and important and widely used chemical) obtainable from water through photocatalysis using sunlight, and through electrolysis driven by solar or wind energy1,2. The most efficient solar hydrogen production schemes, which couple solar cells to electrolysis systems, reach solar-to-hydrogen (STH) energy conversion efficiencies of 30% at a laboratory scale3. Photocatalytic water splitting reaches notably lower conversion efficiencies of only around 1%, but the system design is much simpler and cheaper and more amenable to scale-up1,2-provided the moist, stoichiometric hydrogen and oxygen product mixture can be handled safely in a field environment and the hydrogen recovered. Extending our earlier demonstration of a 1-m2 panel reactor system based on a modified, aluminium-doped strontium titanate particulate photocatalyst4, we here report safe operation of a 100-m2 array of panel reactors over several months with autonomous recovery of hydrogen from the moist gas product mixture using a commercial polyimide membrane5. The system, optimized for safety and durability, and remaining undamaged on intentional ignition of recovered hydrogen, reaches a maximum STH of 0.76%. While the hydrogen production is inefficient and energy negative overall, our findings demonstrate that safe, large-scale photocatalytic water splitting, and gas collection and separation are possible. To make the technology economically viable and practically useful, essential next steps are reactor and process optimization to substantially reduce costs and improve STH efficiency, photocatalyst stability and gas separation efficiency.

Egg white hydrolyzate reduces mental fatigue: randomized, double-blind, controlled study.

OBJECTIVES: This study aimed to show that ingesting egg white hydrolyzate (EWH) could improve antioxidant capacity and reduce mental fatigue. Two clinical trials were conducted to examine the antioxidant capacity and the fatigue reduction function of EWH. In Study 1, 19 athlete students were received a single dose of EWH (5 g/day) or placebo. In Study 2, 74 athlete students ingested EWH (5 g/day) or placebo before training for 2 weeks. RESULTS: Single dose of EWH significantly increased the antioxidant ability compared with the placebo group (p < 0.05), and there was no significant difference between the groups in the oxidative stress test results on Study 1. Two-week intake of EWH significantly decreased mental fatigue compared with the placebo (p < 0.05). This study showed that ingesting EWH improved antioxidant capacity with a single dose and reduced mental fatigue after 2 weeks of ingestion. Trial Registration Japan Medical Association Center for Clinical Trials identifier; JMA-IIA00395 (Study1) and JMA-IIA00396 (Study2), both trials were retrospectively registered on 26 October, 2018.

Increasing vegetable intake 400 g/day to control body weight and lipid profile in overweight hyperlipidemia menopausal women.

Background: Indonesia suffers growing health problems such as obesity, diabetes, and other metabolic syndromes with dietary habit as one of risk factors. To control the lipid and glycaemic profile, high fibre intake has been recommended. This study administered 400g/day vegetable intake with its fiber contents and observed the effects in lipid profile and glycaemic control. Design: A parallel study of 30 pairs of menopausal women match paired in overweight, menopause, hyperlipidaemia, age, etc randomly divided into two groups (vegetable and control). The baseline data obtained from questionnaire and preliminary bloodwithdrawn of consented participants, then matched the characteristics included the results of lipid profile and glycated albumin. The administration was conducted for 21days by providing 400g/day of vegetable to the vegetable group subjects. Nutrition assessments were conducted at the baseline, middle, and final period. The data were analysed by using the unpaired and paired t-test. Results: Significant results (p<0.05) were seen in biochemical variables in the lipid profile of total cholesterol, LDL cholesterol, and HDL cholesterol and body weight and BMI within the vegetable group. Significant results for the same variables were shown between vegetable and control group at the final data (p<0.05). The nutrition assessments result showed significances (p<0.05) within vegetable group and between two groups on the final data. After 21 days, significant decreases were found on the intakes of energy, lipids, carbohydrates (p<0.05), while vegetable intake and fiber intake showed significant increases (p<0.05). Conclusion: These data suggest that maintaining a healthy diet of 400g/d vegetable can be effective in weight management and lipid profile control.

Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer.

BACKGROUND: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. RESULTS: The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). CONCLUSIONS: It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

Ultra-Rapid Lispro Efficacy and Safety Compared to Humalog® in Japanese Patients with Type 1 Diabetes: PRONTO-T1D Subpopulation Analysis.

INTRODUCTION: We evaluated the efficacy and safety of ultra-rapid lispro (URLi) in comparison to lispro in a subgroup analysis of Japanese adults with type 1 diabetes mellitus from the phase 3 PRONTO-T1D trial. METHODS: After an 8-week lead-in to optimize basal insulin treatment, patients were randomized to 52-week double-blind mealtime URLi or lispro, or 26-week open-label postmeal URLi. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline (week 0) to week 26 between mealtime URLi and lispro. The multiplicity adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a meal test between mealtime URLi and lispro, and change in HbA1c from baseline to week 26 between postmeal URLi and mealtime lispro. RESULTS: This manuscript presents pre-specified exploratory analyses of 26-week data from Japanese patients randomized to double-blind URLi (n = 62) or lispro (n = 59), or open-label URLi (n = 46). Mean baseline HbA1c levels were 7.52% for mealtime URLi, 7.44% for lispro, and 7.51% for postmeal URLi at randomization. At week 26, the least squares mean (LSM) difference compared to lispro was 0.04% (95% confidence interval [CI] - 0.14 to 0.22) for mealtime URLi, and 0.16% (95% CI - 0.04 to 0.35) for postmeal URLi. In comparison to lispro, mealtime URLi resulted in statistically significantly lower 1- and 2-h PPG excursions during the mixed-meal tolerance test. LSM differences were - 40.5 mg/dL, 95% CI - 59.5 to 21.4 (- 2.25 mmol/L, 95% CI - 3.3 to - 1.2) for 1-h PPG excursions and - 51.7 mg/dL, 95% CI - 81.7 to - 21.8 (- 2.87 mmol/L, 95% CI - 4.5 to - 1.2) for 2-h PPG excursions at week 26. There were no significant treatment differences in rates of severe/overall hypoglycemia, or incidence of treatment-emergent adverse events. CONCLUSIONS: Mealtime and postmeal URLi provide effective and comparable glycemic control in Japanese patients. Mealtime URLi demonstrated more effective PPG control compared to lispro. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03214367.

Ultra-Rapid Lispro Efficacy and Safety Compared to Humalog® in Japanese Patients With Type 2 Diabetes: PRONTO-T2D Subpopulation Analysis.

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of ultra-rapid lispro (URLi) versus lispro in a subgroup analysis of Japanese adults with type 2 diabetes mellitus (T2DM) from the phase 3 PRONTO-T2D trial. METHODS: After an 8-week lead-in period during which patients transitioned to insulin lispro 3 times a day before main meals in association with basal insulin (glargine or degludec), the patients were randomized to 26 weeks of double-blind URLi or lispro injected immediately prior to meals. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline to week 26 between URLi and lispro. The multiplicity-adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a test meal and change in HbA1c from baseline to week 26 in the URLi and lispro groups. RESULTS: Results were obtained from prespecified exploratory analyses of 26-week data in Japanese patients randomized to receive URLi (n = 47) or lispro (n = 46). Mean baseline HbA1c levels significantly improved during the lead-in period to a baseline value of 7.50% and 7.60% in patients subsequently randomized to the URLi and lispro treatment groups, respectively. At week 26, the least squares mean (LSM) difference in HbAc1 between the URLi and lispro groups was 0.13% (95% confidence interval [CI] - 0.12 to 0.39) (1.4 mmol/mol, 95% CI - 1.3 to 4.2). Although there were no significant differences in PPG excursions at any time-point, numerically smaller PPG excursions were consistently observed from 30 min to 3 h during the mixed-meal tolerance test in patients on URLi compared to those on lispro. LSM differences in PPG excursions at week 26 were - 10.5 mg/dL (95% CI - 32.7 to 11.7) (- 0.58 mmol/L, 95% CI - 1.82 to 0.65) at 1 h and - 14.9 mg/dL (95% CI - 40.3 to 10.5) (- 0.83 mmol/L, 95% CI - 2.24 to 0.58) at 2 h. There were no significant differences between treatments in rates of severe/overall hypoglycemia or incidence of treatment-emergent adverse events. CONCLUSIONS: URLi administered as prandial insulin in combination with basal insulin provides effective glycemic control when administered immediately before a meal in Japanese patients with T2DM. URLi was well tolerated in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03214380.

Association of One-Leg Standing Time with Discontinuation of Injectable Medications During Hospitalization Among Patients with Type 2 Diabetes.

INTRODUCTION: Persons with type 2 diabetes (T2D) are known to experience impaired physical ability even at the early stages of the disease. However, less attention has been paid to increasing physical ability than to increasing physical activity in the treatment of T2D. The aim of this study was to assess whether improved physical ability parameters are associated with the discontinuation of injectable medications once glycemic targets have been achieved among inpatients with inadequately controlled T2D across a wide range of ages. METHODS: Forty-three patients with glycated hemoglobin levels of ≥ 7.5% (58 mmol/mol) aged between 19 and 82 years who received insulin, glucagon-like peptide-1 receptor agonists or both at admission were enrolled in the study. Muscle strength for knee extension, one-leg standing time with eyes open test(OLST), whole-body reaction time and maximal oxygen uptake were assessed as parameters of physical ability. RESULTS: At admission, patients who during hospitalization discontinued injectable medications (n = 29; Discontinued group) had a shorter duration of diabetes, lower fat mass and higher skeletal muscle mass and performed better on all of the physical ability test parameters than those who continued on injectable medications during hospitalization (n = 14; Continued group). At discharge, patients in the Discontinued group had achieved better glycemic control than those in the Continued group, as indicated by lower mean plasma glucose levels according to the 7-point profile. Stepwise logistic regression analysis that included those variables that were significantly different between the Continued group and the Discontinued group, with the aim to identify candidate(s) of explanatory variables, revealed that only OLST was significantly associated with the discontinuation of injectable medication. Patients with an OLST of ≥ 60 s were more likely to discontinue injectable medication than those with an OLST of < 60 s (odds ratio 18.9; 95% confidence interval 2.0-178.8; p = 0.011). CONCLUSIONS: Among inpatients with inadequately controlled T2D diabetes, longer OLST appear to be associated with discontinuing injectable medications during hospitalization. OLST could possibly be useful as a novel patient factor to consider in de-intensifying injectable medication.

Efficient Water Oxidation Using Ta3 N5 Thin Film Photoelectrodes Prepared on Insulating Transparent Substrates.

Photoelectrochemical (PEC) water splitting using visible-light-responsive photoelectrodes is the preferred approach to converting solar energy into hydrogen as a renewable energy source. A transparent Ta3 N5 photoanode embedded within a PEC cell having a tandem configuration is a promising configuration that may provide a high solar-to-hydrogen energy conversion efficiency. Ta3 N5 thin films are typically prepared by heating precursor films in an NH3 flow at high temperatures, which tends to degrade the transparent conductive layer, such that producing efficient Ta3 N5 transparent photoanodes is challenging. Herein, the direct preparation of transparent Ta3 N5 photoanodes on insulating quartz substrates was demonstrated without the insertion of a transparent conductive layer. The resulting devices generated a photocurrent of 6.0 mA cm-2 at 1.23 V vs. a reversible hydrogen electrode under simulated sunlight. This study provides a new strategy for the preparation of transparent photoelectrodes that mitigates current challenges.

Clinical and reproductive outcomes of fertility-sparing surgery in stage I epithelial ovarian cancer.

The aim of the present study was to evaluate the oncologic safety and reproductive outcome in patients with stage I epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). Women aged ≤40 years with stage I EOC who had undergone FSS between 2000 and 2010 were retrospectively reviewed. Survival was examined using the Kaplan-Meier method and statistical significance was analyzed using the log-rank test. A total of 29 EOC patients (stage IA, n=14; stage IC1 n=6; stage IC3, n=9) from seven participating institutions belonging to the Tohoku Gynecologic Cancer Unit were enrolled. After a median follow-up duration of 60.6 months (range, 6-135 months), five patients (17.2%) experienced tumor recurrence. The respective five-year relapse-free survival (RFS) and overall survival (OS) rates were 90.9 and 100% for stage IA/IC1, and 43.8 and 87.5% for stage IC3. Significant differences in RFS were observed between stage IA/IC1 and IC3 patients (P=0.026). However, there was no significant difference in OS between patients with 1A/1C1 and those with 1C3 (P=0.712). After FSS, seven pregnancies occurred in five patients, which resulted in the birth of six healthy children. The results of the present study confirmed that FSS may be an acceptable treatment method for stage IA and IC1 EOC, exhibiting a favorable reproductive outcome. However, the safety of FSS for treating stage IC3 EOC is uncertain and warrants further investigation.

An Al-doped SrTiO3 photocatalyst maintaining sunlight-driven overall water splitting activity for over 1000 h of constant illumination.

Photocatalytic water splitting is a viable approach to the large-scale production of renewable solar hydrogen. The apparent quantum yield for this reaction has been improved, but the lifespan of photocatalysts functioning under sunlight at ambient pressure have rarely been examined, despite the critical importance of this factor in practical applications. Herein, we show that Al-doped SrTiO3 (SrTiO3:Al) loaded with a RhCrO x (rhodium chromium oxide) cocatalyst splits water with an apparent quantum yield greater than 50% at 365 nm. Moreover, following the photodeposition of CoOOH and TiO2, this material maintains 80% of its initial activity and a solar-to-hydrogen energy conversion efficiency greater than or equal to 0.3% over a span of 1300 h under constant illumination by simulated sunlight at ambient pressure. This result is attributed to reduced dissolution of Cr in the cocatalyst following the oxidative photodeposition of CoOOH. The photodeposition of TiO2 further improves the durability of this photocatalyst. This work demonstrates a concept that could allow the design of long-term, large-scale photocatalyst systems for practical sunlight-driven water splitting.