Summary
This study investigated the alterations of mineral metabolism in patients with Graves’ disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and ...phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status.
Introduction
FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves’ disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved.
Methods
A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups.
Results
Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group.
Conclusion
Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations.
Trial registration
Registration number: NCT01660308 and NCT02620085
Because the surface-to-volume ratio of quasi-two-dimensional materials is extremely high, understanding their surface characteristics is crucial for practically controlling their intrinsic properties ...and fabricating p-type and n-type layered semiconductors. Van der Waals crystals are expected to have an inert surface because of the absence of dangling bonds. However, here we show that the surface of high-quality synthesized molybdenum disulfide (MoS2) is a major n-doping source. The surface electron concentration of MoS2 is nearly four orders of magnitude higher than that of its inner bulk. Substantial thickness-dependent conductivity in MoS2 nanoflakes was observed. The transfer length method suggested the current transport in MoS2 following a two-dimensional behavior rather than the conventional three-dimensional mode. Scanning tunneling microscopy and angle-resolved photoemission spectroscopy measurements confirmed the presence of surface electron accumulation in this layered material. Notably, the in situ-cleaved surface exhibited a nearly intrinsic state without electron accumulation.
Summary
Background
Mercaptopurine and azathioprine (AZA) are efficacious in treating IBD. 6‐tioguanine (6‐TGN) levels correlate with therapeutic efficacy, whereas high 6‐methylmercaptopurine (6‐MMP) ...levels are associated with hepatotoxicity and myelotoxicity. Some IBD patients exhibit dose‐limiting preferential 6‐MMP production, which may lead to undesired side effects and impact efficacy.
Aim
To review the outcomes of thiopurine split‐dosing in patients with preferential 6‐MMP metabolism.
Methods
A retrospective chart review of 179 IBD patients treated at the Cedars‐Sinai IBD Center with AZA or mercaptopurine was performed. Preferential 6‐MMP metabolisers with 6‐MMP levels greater than 7000 pmol/8 × 108 erythrocytes who underwent split‐dosing were identified and assessed for biochemical and clinical responses to these dose modifications.
Results
A total of 20 of 179 patients met the criteria for preferential 6‐MMP metabolism and underwent thiopurine split‐dosing. Dividing the total daily thiopurine dose led to a reduction in 6‐MMP levels (11785 vs. 5324 pmol/8 × 108 erythrocytes; P < 0.0001) without negatively affecting clinical disease activity or 6‐TGN levels (239 vs. 216 pmol/8 × 108 erythrocytes; P = N.S.) and led to resolution of 6‐MMP associated side effects (elevated transaminases, leucopenia and flu‐like symptoms) in all but two patients. After mean follow‐up of 36 months, 12 patients remained in clinical remission on split‐dose mercaptopurine. Five of the remaining eight patients escalated to anti‐TNF therapy, two progressed to surgery, and one switched to tioguanine therapy.
Conclusion
Split‐dose administration of mercaptopurine/AZA represents an alternative option in IBD patients with preferential 6‐MMP metabolism who might otherwise require steroid exposure or escalation of therapy.
We hypothesised that intraoperative non-depolarising neuromuscular blocking agent (NMBA) dose is associated with 30-day hospital readmission.
Data from 13,122 adult patients who underwent abdominal ...surgery under general anaesthesia at a tertiary care hospital were analysed by multivariable regression, to examine the effects of intraoperatively administered NMBA dose on 30-day readmission (primary endpoint), hospital length of stay, and hospital costs.
Clinicians used cisatracurium (mean dose SD 0.19 mg kg−1 0.12), rocuronium (0.83 mg kg−1 0.53) and vecuronium (0.14 mg kg−1 0.07). Intraoperative administration of NMBAs was dose-dependently associated with higher risk of 30-day hospital readmission (adjusted odds ratio 1.89 95% Confidence Interval (CI) 1.26–2.84 for 5th quintile vs 1st quintile; P for trend: P<0.001), prolonged hospital length of stay (adjusted incidence rate ratio aIRR 1.20 95% CI 1.11–1.29; P for trend: P<0.001) and increased hospital costs (aIRR 1.18 95% CI 1.13-1.24; P for trend: P<0.001). Admission type (same-day vs inpatient surgery) significantly modified the risk (interaction term: aOR 1.31 95% CI 1.05–1.63, P=0.02), and the adjusted odds of readmission in patients undergoing ambulatory surgical procedures who received high-dose NMBAs vs low-dose NMBAs amounted to 2.61 95% CI 1.11–6.17, P for trend: P<0.001. Total intraoperative neostigmine dose increased the risk of 30-day readmission (aOR 1.04 1.0–1.08, P=0.048).
In a retrospective analysis, high doses of NMBAs given during abdominal surgery was associated with an increased risk of 30-day readmission, particularly in patients undergoing ambulatory surgery.
Intestinal fibrostenosis is among the hallmarks of severe Crohn's disease. Patients with certain TNFSF15 (gene name for TL1A) variants over-express TL1A and have a higher risk of developing ...strictures in the small intestine. In addition, sustained Tl1a expression in mice leads to small and large intestinal fibrostenosis under colitogenic conditions. The aim of this study was to determine whether established murine colonic fibrosis could be reversed with Tl1a antibody (Ab). Treatment with neutralizing Tl1a Ab reversed colonic fibrosis back to the original pre-inflamed levels, potentially as a result of lowered expression of connective tissue growth factor, Il31Ra, transforming growth factor β1 and insulin-like growth factor-1. In addition, blocking Tl1a function by either neutralizing Tl1a Ab or deletion of death domain receptor 3 (Dr3) reduced the number of fibroblasts and myofibroblasts, the primary cell types that mediate tissue fibrosis. Primary intestinal myofibroblasts expressed Dr3 and functionally responded to direct Tl1a signaling by increasing collagen and Il31Ra expression. These data demonstrated a direct role for TL1A-DR3 signaling in tissue fibrosis and that modulation of TL1A-DR3 signaling could inhibit gut fibrosis.
In other species characterized to date, aging, as a function of reproductive potential, results in the breakdown of proteaostasis and a decreased capacity to mount responses by the heat shock ...response (HSR) and other proteostatic network pathways. Our understanding of the maintenance of stress pathways, such as the HSR, in honey bees, and in the reproductive queen in particular, is incomplete. Based on the findings in other species showing an inverse relationship between reproductive potential and HSR function, one might predict that that HSR function would be lost in the reproductive queens. However, as queens possess an atypical uncoupling of the reproduction-maintenance trade-off typically found in solitary organisms, HSR maintenance might also be expected. Here we demonstrate that reproductive potential does not cause loss of HSR performance in honey bees as queens induce target gene expression to levels comparable to those induced in attendant worker bees. Maintenance of HSR function with advent of reproductive potential is unique among invertebrates studied to date and provides a potential model for examining the molecular mechanisms regulating the uncoupling of the reproduction-maintenance trade-off in queen bees, with important consequences for understanding how stresses impact different types of individuals in honey bee colonies.
For almost a century, magnetic oscillations have been a powerful “quantum ruler” for measuring Fermi surface topology. In this study, we used Landau-level spectroscopy to unravel the energy-resolved ...valley-contrasting orbital magnetism and large orbital magnetic susceptibility that contribute to the energies of Landau levels of twisted double-bilayer graphene. These orbital magnetism effects led to substantial deviations from the standard Onsager relation, which manifested as a breakdown in scaling of Landau-level orbits. These substantial magnetic responses emerged from the nontrivial quantum geometry of the electronic structure and the large length scale of the moiré lattice potential. Going beyond traditional measurements, Landau-level spectroscopy performed with a scanning tunneling microscope offers a complete quantum ruler that resolves the full energy dependence of orbital magnetic properties in moiré quantum matter.
Editor’s summary
In a perpendicular magnetic field, electrons in two-dimensional (2D) materials occupy discrete energy levels known as Landau levels. These levels are described by the so-called Onsager relation. Slot
et al
. used scanning tunneling spectroscopy to measure the Landau levels in twisted double-bilayer graphene with an intermediate twist angle of 1.74° between the two bilayers. By comparing their results against the theoretical expectations, the researchers were able to measure deviations from the standard form of the Onsager relation stemming from the orbital magnetism in the system. —Jelena Stajic
Scanning tunneling spectroscopy was used to measure the Landau levels in twisted double-bilayer graphene.
Type Ia supernovae are thought to result from a thermonuclear explosion of an accreting white dwarf in a binary system, but little is known of the precise nature of the companion star and the ...physical properties of the progenitor system. There are two classes of models: double-degenerate (involving two white dwarfs in a close binary system) and single-degenerate models. In the latter, the primary white dwarf accretes material from a secondary companion until conditions are such that carbon ignites, at a mass of 1.38 times the mass of the Sun. The type Ia supernova SN 2011fe was recently detected in a nearby galaxy. Here we report an analysis of archival images of the location of SN 2011fe. The luminosity of the progenitor system (especially the companion star) is 10-100 times fainter than previous limits on other type Ia supernova progenitor systems, allowing us to rule out luminous red giants and almost all helium stars as the mass-donating companion to the exploding white dwarf.
Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that ...cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.
Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.
Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.
Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.
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