It is well known that sulphonylureas (SUs), commonly used in the treatment of type 2 diabetes mellitus, stimulate insulin secretion by closing ATP‐sensitive K+ (KATP) channels in pancreatic β‐cells ...by binding to the SU receptor SUR1. SUs are now known also to activate cAMP sensor Epac2 (cAMP‐GEFII) to Rap1 signalling, which promotes insulin granule exocytosis. For SUs to exert their full effects in insulin secretion, they are required to activate Epac2 as well as to inhibit the β‐cell KATP channels. As Epac2 is also necessary for potentiation of glucose‐induced insulin secretion by cAMP‐increasing agents, such as incretin, Epac2 is a target of both cAMP and SUs. The distinct effects of various SUs appear to be because of their different actions on Epac2/Rap1 signalling as well as KATP channels. Differently from other SUs, gliclazide is unique in that it is specific for β‐cell KATP channel and does not activate Epac2.
A ground‐based network of Global Navigation Satellite Systems receivers has been used to monitor medium‐scale traveling ionospheric disturbances (MSTIDs). MSTIDs were studied using total electron ...content perturbation maps and keograms over south‐southeast of Brazil during the period from December 2012 to February 2016. In total, 826 MSTIDs were observed mainly in daytime, thus presenting median values of horizontal wavelength, period, and horizontal phase velocity of 452 ± 107 km, 24 ± 4 min. and 323 ± 81 m/s, respectively. The direction of propagation varies on the season: during the winter (June–August), the waves preferentially propagated to north‐northeast, while in the other seasons the waves propagated to other directions. The anisotropy observed in the MSTID propagation direction could be associated with the region of the gravity wave generation that takes place in the troposphere. We also found that the MSTIDs were observed most frequently during the daytime, between 11 and 15 local time in winter and near to dusk solar terminator (17–19 local time) in the other seasons. Furthermore, the occurrence of MSTIDs was higher in winter. We suggest that atmospheric gravity waves in the thermosphere, mesosphere, and troposphere could play an important role in generating the MSTIDs and the propagation direction may depend on location of the wave sources.
Key Points
The paper presents the statistical study of MSTIDs in equatorial latitudes over south‐southeast of Brazil
The propagation direction of MSTIDs changes according to the seasons
The MSTIDs can be originated by gravity waves that propagate from the lower atmosphere
The authors report the polarisation insensitive operation of an arrayed waveguide grating using a polarisation rotator/splitter (PRS) waveguide device which attains identical wavelength ...characteristics and optical losses for both transverse electric (TE) and transverse magnetic (TM) polarisations. The proposed PRS device is composed of a rib structure waveguide and an asymmetrical directional coupler (ADC). The rib waveguide converts TM fundamental mode to TE first-order mode. The ADC splits TE first-order mode into the TE fundamental mode propagating in the sub-adjacent waveguide. Experimental results confirm that the proposed device operates independently of light polarisations; channel isolation is nearly 20 dB, and no transmission wavelength shift or polarisation dependent loss are observed between TE and TM polarisations.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted ...in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg x day(-1); low-dose, 1,200 mg x day(-1); or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.
Summary
Background
Although thiopurines have a proven role in maintenance therapy for Crohn's disease, an alternative therapy is needed for patients intolerant or resistant to thiopurines.
Aim
To ...evaluate the effectiveness of home enteral nutrition as a maintenance therapy regimen in which half of the daily calorie requirement is provided by an elemental diet and the remaining half by a free diet. We refer to this home enteral nutrition therapy as ‘half elemental diet’.
Methods
Between 2002 and 2005, 51 patients in remission from two hospitals were randomly assigned to a half elemental diet group (n = 26) or a free diet group (n = 25). The primary outcome measure of this study was the occurrence of relapse over the 2‐year period.
Results
The relapse rate in the half elemental diet group was significantly lower 34.6% vs. 64.0%; multivariate hazard ratio 0.40 (95% CI: 0.16–0.98) than that in the free diet group after a mean follow‐up of 11.9 months. Compliance was similar in the two groups. No adverse event occurred in any of the patients throughout the study.
Conclusion
This randomized‐controlled trial shows the effectiveness of an half elemental diet, which is a promising maintenance therapy for Crohn's disease patients.
Aims
To assess the effects of renal impairment (RI) on the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus (T2DM).
Methods
A cohort of Japanese patients with T2DM and ...mild to moderate RI and poor glycaemic control, despite diet/exercise therapy alone or diet/exercise therapy in combination with an oral hypoglycaemic agent (an α‐glucosidase inhibitor, a sulfonylurea, or pioglitazone), were randomized in a double‐blind manner to 50 mg ipragliflozin or placebo once daily for 24 weeks. The patients continued open‐label ipragliflozin for a 28‐week extension period (total treatment duration: 52 weeks).
Results
Ipragliflozin significantly decreased glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels and body weight from baseline to week 24 (last observation carried forward) compared with placebo in all patients with RI. The decreases in HbA1c and FPG levels were statistically significant in patients with mild RI, but not in patients with moderate RI. Ipragliflozin significantly reduced body weight in both RI groups. The improvements in glycaemic control were maintained in the 28‐week extension period. Ipragliflozin was associated with no clinically significant safety concerns, and its safety profiles were not influenced by the severity of RI.
Conclusions
Ipragliflozin significantly improved glycaemic control and body weight in patients with T2DM with mild RI, but did not improve glycaemic control in patients with moderate RI. Ipragliflozin is a valid treatment option for patients with mild RI but not those with moderate RI.
Topologically nontrivial materials host protected edge states associated with the bulk band inversion through the bulk-edge correspondence. Manipulating such edge states is highly desired for ...developing new functions and devices practically using their dissipation-less nature and spin-momentum locking. Here we introduce a transition-metal dichalcogenide VTe
, that hosts a charge density wave (CDW) coupled with the band inversion involving V3d and Te5p orbitals. Spin- and angle-resolved photoemission spectroscopy with first-principles calculations reveal the huge anisotropic modification of the bulk electronic structure by the CDW formation, accompanying the selective disappearance of Dirac-type spin-polarized topological surface states that exist in the normal state. Thorough three dimensional investigation of bulk states indicates that the corresponding band inversion at the Brillouin zone boundary dissolves upon the CDW formation, by transforming into anomalous flat bands. Our finding provides a new insight to the topological manipulation of matters by utilizing CDWs' flexible characters to external stimuli.
The purpose of this study was to explore risk factors affecting the incidence of chronic kidney disease (CKD) in general population. We conducted a 10-year follow-up study with 123764 (male: 41012, ...female: 82752) adults aged 40 years and over who received community-based annual examinations. The primary outcome for the analysis was the development of CKD during the follow-up period. Predictors for the development of CKD were obtained by the significant hazard ratios (HR) in Cox regression model by sex. During the follow-up period, 4307 subjects (male: 2048, female: 2259) developed CKD stage I or II, and 19411 subjects (male: 4257, female: 15154) developed CKD stage III or higher. The baseline-adjusted predictor of developing CKD included age, glomerular filtration rate, hematuria, hypertension, diabetes, serum lipids, obesity, smoking status, and consumption of alcohol. Treated diabetes in male subjects, and treated hypertension, systolic blood pressure >160mm Hg and/or diastolic blood pressure >100mm Hg, diabetes, and treated diabetes in female subjects were associated with more than a doubling of the HR. For the development of CKD stage III or higher, proteinuria of ≥++, and proteinuria and hematuria were associated with more than a doubling of the HR in male subjects. The prevalence of newly developed CKD over 10 years was 23718 subjects (19.2%) in adults. This study suggested that not only hypertension and diabetes but also several metabolic abnormalities were independent risk factors for developing CKD.
A spin valve is a microelectronic device in which high- and low-resistance states are realized by using both the charge and spin of carriers. Spin-valve structures used in modern hard-drive read ...heads and magnetic random access memoriescomprise two ferromagnetic electrodes whose relative magnetization orientations can be switched between parallel and antiparallel configurations, yielding the desired giant or tunnelling magnetoresistance effect. Here we demonstrate more than 100% spin-valve-like signal in a NiFe/IrMn/MgO/Pt stack with an antiferromagnet on one side and a non-magnetic metal on the other side of the tunnel barrier. Ferromagneticmoments in NiFe are reversed by external fields of approximately 50 mT or less, and the exchange-spring effect of NiFe on IrMn induces rotation of antiferromagnetic moments in IrMn, which is detected by the measured tunnelling anisotropic magnetoresistance. Our work demonstrates a spintronic element whose transport characteristics are governed by an antiferromagnet. It demonstrates that sensitivity to low magnetic fields can be combined with large, spin-orbit-coupling-induced magnetotransport anisotropy using a single magnetic electrode. The antiferromagnetic tunnelling anisotropic magnetoresistance provides a means to study magnetic characteristics of antiferromagnetic films by an electronic-transport measurement.
Introduction
Occupational burnout has become a pervasive problem in human services. Medical professionals are particularly vulnerable to burnout, which may lead to reduced motivation, medical errors, ...and voluntary absenteeism. To ensure effect functioning of medical systems, better understanding of burnout among medical professionals is warranted.
Objectives
We aimed to investigate the structural brain correlates of burnout severity among medical professionals.
Methods
Nurses in active service underwent structural magnetic resonance imaging. We assessed their burnout severity using self-reported psychological questionnaires. This study was approved by the Committee on Medical Ethics of Kyoto University and was conducted in accordance with the Code of Ethics of the World Medical Association.
Results
The results reflected considerable individual differences in burnout severity in our sample. Our findngs revealed that the levels of burnout severity were associated with the regional gray matter volumes in brain areas such as ventromedial prefrontal cortex and insula.
Conclusions
Since the outbreak of the COVID-19 pandemic, medical professionals have faced even greater stress. We hope that our findings will contribute to a better understanding of the mechanisms of burnout and offer useful insights for developing effective interventions to manage stress and burnout.
Disclosure
No significant relationships.
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