The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 in combination with palonosetron (PALO), a ...second‐generation 5‐HT3 receptor antagonist, for chemotherapy‐induced nausea and vomiting (CINV) in non‐anthracycline and cyclophosphamide (AC) moderately‐emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi‐center, randomized, open‐label, non‐inferiority design. Patients who received non‐AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2–3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non‐inferiority margin was set at −15% (study treatment group − control group). From April 2011 to March 2013, 305 patients who received non‐AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non‐inferior to PALO plus DEX days 1–3 (difference, 2.5%; 95% confidence interval CI: −7.8%–12.8%; P‐value for non‐inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti‐emetic DEX administration on days 2–3 may be eliminated when used in combination with PALO in patients receiving non‐AC MEC.
In this study, we evaluated the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 with palonosetron (PALO), for chemotherapy‐induced nausea and vomiting (CINV) in non‐AC (anthracycline and cyclophosphamide) moderately‐emetogenic chemotherapy (MEC) in the phase III study. Our randomized phase III study successfully demonstrated non‐inferiority of DEX administration only on day 1 compared to days 1–3 when used in combination with PALO during non‐AC MEC.
Type 2 diabetes mellitus (T2DM) is a risk factor for depression. Since brain insulin resistance plays a potential role in depression, the future risk of depression in patients with T2DM may be ...altered depending on the class of oral hypoglycemic agent (OHA) used for T2DM therapy. The aim of the present study was to determine if specific classes of OHAs are associated with a risk for comorbid depression in T2DM. Japanese adult patients with T2DM (n = 40 214) were divided into a case group (with depression; n = 1979) and control group (without depression; n = 38 235). After adjustment for age adjusted odds ratio (AOR) for 10 years: 1.03; 95% confidence interval (CI): 0.99‐1.07; P = .1211, sex AOR for female: 1.39; 95% CI: 1.26‐1.53; P < .0001, hemoglobin A1c AOR for 1.0%: 1.18; 95% CI: 1.11‐1.26; P < .0001, duration of T2DM AOR for 1 year: 1.00; 95% CI: 0.99‐1.01; P = .4089, and history of seven medical conditions, the odds ratios for the development of depression was significantly lower for dipeptidyl peptidase‐4 (DPP‐4) inhibitors AOR: 0.31; 95% CI: 0.24‐0.42; P < .0001. However, there was no significant association for the other classes of OHAs. Therefore, this study finds that there is less risk of depression associated with the use of DPP‐4 inhibitors for the treatment of T2DM.
Abnormal aggregation of misfolded proteins and their deposition as inclusion bodies in the brain have been implicated as a common molecular pathogenesis of neurodegenerative diseases including ...Alzheimer, Parkinson, and the polyglutamine (poly(Q)) diseases, which are collectively called the conformational diseases. The poly(Q) diseases, including Huntington disease and various types of spinocerebellar ataxia, are caused by abnormal expansions of the poly(Q) stretch within disease-causing proteins, which triggers the disease-causing proteins to aggregate into insoluble β-sheet-rich amyloid fibrils. Although oligomeric structures formed in vitro are believed to be more toxic than mature amyloid fibrils in these diseases, the existence of oligomers in vivo has remained controversial. To explore oligomer formation in cells, we employed fluorescence correlation spectroscopy (FCS), which is a highly sensitive technique for investigating the dynamics of fluorescent molecules in solution. Here we demonstrate direct evidence for oligomer formation of poly(Q)-green fluorescent protein (GFP) fusion proteins expressed in cultured cells, by showing a time-dependent increase in their diffusion time and particle size by FCS. We show that the poly(Q)-binding peptide QBP1 inhibits poly(Q)-GFP oligomer formation, whereas Congo red only inhibits the growth of oligomers, but not the initial formation of the poly(Q)-GFP oligomers, suggesting that FCS is capable of identifying poly(Q) oligomer inhibitors. We therefore conclude that FCS is a useful technique to monitor the oligomerization of disease-causing proteins in cells as well as its inhibition in the conformational diseases.
The ion-shadow method, an ion milling process using carbon particles as the mask material, is investigated as a means of preparing resistance random access memory (ReRAM) samples for in situ ...transmission electron microscopy (TEM). With a milling time of 1hour (Ar+, 5kV, 1mA), multiple long needles (>5μm), on which there are miniaturized ReRAM devices comprising a ReRAM insulating layer sandwiched by two metallic electrodes, are formed on the substrate. Device sizes of up to several hundreds of nm are easily obtained with the method. The internal part of small devices (i.e., up to 100nm) can be observed by TEM. Electrical measurements using an in situ TEM holder demonstrate that sufficient electric contact is obtained without any electric shortage between the electrodes due to re-deposition of milled material. The ion-shadow method is confirmed to be a quick and easy method suitable for in situ TEM experiments, especially for ReRAM devices which are highly susceptible to destruction during the switching operation.
► Preparation method of in situ transmission electron microscopy samples is shown. ► Long and sharp needle-shaped samples are formed with the ion-shadow method. ► Resistive switching samples are formed at the tips of needle-shaped samples. ► Current–voltage characteristics obtained in an electron microscope are shown.
The aim of this study was to investigate the association between statin use and new-onset diabetes in clinical settings and to assess its effect modification (heterogeneity) among patients with ...various medical histories and current medications.
In a total of 12,177 Japanese patients without diabetes, from December 2004 to November 2012, we identified 500 statin users and 500 matched non-users using propensity-score matching. Patients were followed until December 2017. We estimated the hazard ratios of new-onset diabetes associated with statin use. We also tested the heterogeneity of the treatment effect by evaluating subgroup interactions in subgroups according to sex, age, medical history, and current medication.
New-onset diabetes had occurred in 71 patients (13.6%) with statin use and 43 patients (8.3%) with non-use at 5 years (hazard ratio, 1.66; 95% confidence interval CI, 1.11 to 2.48; P = 0.0143), and in 78 patients (15.6%) with statin use and 48 patients (9.6%) with non-use at 10 years (hazard ratio, 1.61; 95% CI, 1.10 to 2.37; P = 0.0141). There were no significant treatment-by-subgroup interactions in all subgroups defined according to sex, age, medical history, and current medication.
In patients with various clinical backgrounds, those who received statin therapy had a higher risk of new-onset diabetes at 5 and 10 years than those who did not receive it. Effect modification of statins on new-onset diabetes was not found in patient populations defined according to various comorbid diseases or concomitant drugs.
Performance of in-situ-transmission electron microscopy (TEM) applied to analysis of the resistive random access memory (ReRAM) is reported. Recent progress of ReRAMs makes it indispensable to ...understand the resistive switching mechanism in order to guarantee the reliability of ReRAMs. Since the TEM provides a high resolution images of the nanostructure, in-situ TEM should be a powerful tool for the analysis if electrical characteristics of ReRAMs can be measured in the TEM. The two sample fabrication methods are applied to two different ReRAM devices. Switching characteristics, which are almost the same as those measured at the outside of TEM by the use of conventional ReRAM cells, are achieved together with clear images of formation and rupture of conductive filaments corresponding to the low and high resistance states. In addition, retention characteristics longer than 10
6
s, and SET/RESET pulse operation more than 100k times are confirmed during TEM observation. These results indicate that the in-situ TEM will be a powerful tool to analyze the reliability of ReRAMs.
Purpose
Mesalazine and sulfasalazine are commonly used drugs for the treatment of inflammatory bowel disease. However, there have been few reports with a strict statistical analysis comparing the ...effects of mesalazine and sulfasalazine on laboratory test results. Therefore, we designed a retrospective cohort study to investigate whether or not differences in clinical laboratory parameters exist between mesalazine and sulfasalazine users.
Methods
We used data from the Clinical Data Warehouse of Nihon University School of Medicine to identify cohorts of new mesalazine users (
n
= 303) and sulfasalazine users (
n
= 67). We used a multivariate regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between mesalazine and sulfasalazine users, and compared serum levels of creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and hematological parameters including red and white blood cell counts and platelet count.
Results
After adjustment, in sulfasalazine users, the mean values for all tests showed no significant change between baseline and during the exposure period. In contrast, in mesalazine users, the mean WBC and platelet counts during the exposure period were significantly lower than those at baseline. Furthermore, mean serum urea nitrogen level during the exposure period was significantly higher than that at baseline. In terms of mean changes in laboratory test values during the exposure period compared with baseline, the reduction of platelet count in mesalazine users was significant in comparison to that in sulfasalazine users.
Conclusion
Our findings suggested that the hematological adverse effects of mesalazine treatment might be greater than those of sulfasalazine treatment.
Both angiotensin II type I receptor blockers (ARBs) and calcium channel blockers (CCBs) are widely used antihypertensive drugs. Many clinical studies have demonstrated and compared the ...organ-protection effects and adverse events of these drugs. However, few large-scale studies have focused on the effect of these drugs as monotherapy on laboratory parameters. We evaluated and compared the effects of ARB and CCB monotherapy on clinical laboratory parameters in patients with concomitant hypertension and type 2 diabetes mellitus.
We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of new ARB users (n = 601) and propensity-score matched new CCB users (n = 601), with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We used a multivariate-adjusted regression model to adjust for differences between ARB and CCB users, and compared laboratory parameters including serum levels of triglyceride (TG), total cholesterol (TC), non-fasting blood glucose, hemoglobin A1c (HbA1c), sodium, potassium, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), hemoglobin and hematocrit, and white blood cell (WBC), red blood cell (RBC) and platelet (PLT) counts up to 12 months after the start of ARB or CCB monotherapy.
We found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and RBC count and a significant increase of serum potassium in ARB users, and a reduction of serum TC and hemoglobin in CCB users, from the baseline period to the exposure period. The reductions of RBC count, hemoglobin and hematocrit in ARB users were significantly greater than those in CCB users. The increase of serum potassium in ARB users was significantly greater than that in CCB users.
Our study suggested that hematological adverse effects and electrolyte imbalance are greater with ARB monotherapy than with CCB monotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Photo-excited carriers in Si quantum islands and their surrounded area exhibit interesting features due to electron-hole generation. We show Si single- hole transistor (SHT) characteristics in a Si ...single-electron transistor (SET) comprising n-type source and drain electrodes under illumination. Holes excited in the Si are expected to flow through the SET island by applying negative gate voltages. Interesting phenomenon is the co-existence of electrons and holes around the island. In a SET, when holes generated by photo-excitation are trapped in the one side (either top or bottom side) of the SET island under the vertical electric field, the SET characteristics are changed depending on the number of trapped holes because effective total number of electrons can be negative. Here, we show the characteristics of photo-excited SETs without strong vertical electric fields.
Aberrant crypt foci were described by Bird as lesions consisting of large, thick crypts in methylene blue–stained specimens of colon from mice treated with a carcinogen (azoxymethane).
1
...Subsequently, they were identified in rat colon, appearing a few weeks after treatment with a carcinogen and becoming larger with time, with more marked nuclear atypia or dysplasia.
2
In the rat model, the formation of aberrant crypt foci was enhanced by cancer promoters (such as chenodiol) and suppressed by chemopreventive agents (docosahexaenoic acid and aspirin).
3
–
5
Increased proliferative activity and K-
RAS
mutations of aberrant crypt foci were also demonstrated.
6
–
13
Aberrant crypt . . .
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