Colchicine for gout

Colchicine is a drug that has been known for several millennia, since the days of Ancient Egypt, but has been successfully used to treat gout to this day. The action of colchicine is based on microtubule damage, mitosis suppression, as well as the ability to inhibit the activation of NLRP3 inflammasoma by monosodium urate crystals and block the release of interleu-kina (IL)-1p - key cytokine in the development of gout inflammation. However, the mechanism of action of colchicine is still not fully understood.Colchicine should be considered as the optimal drug not only for relieving an acute attack of arthritis in gout, but also as the best method for preventing attacks of gouty arthritis when choosing urate-lowering therapy. Recent studies have confirmed the good efficacy and safety profile of the drug when used correctly in patients with gout. Currently, it is recommended to use low doses of the drug (1-1.5 mg per day to relieve an acute attack of arthritis and 0.5-1.0 mg to prevent attacks when initiating uratelowering therapy). At the same time, according to the results of recent studies on the effectiveness, low doses are not inferior to high doses, but when low doses are used, the frequency of undesirable effects is much less. Unlike non-steroidal anti-inflammatory drugs and glucocorticoids, the drug does not have a negative effect on the cardiovascular system and can be used in patients with diabetes mellitus. This allows the drug to be used for a long time, which is especially important, since it is recommended to prevent arthritis attacks for at least 6 months from the start of taking urate-lowering drugs. This avoids the exacerbation of arthritis in most patients and significantly reduces their frequency. In addition, in the light of the accumulating data on the effect of the drug on the cardiovascular system of the drug, in conjunction with the high safety profile, other points of application should be considered where both anti-inflammatory and cardioprotective properties of colchicine can be used

Evaluation of the effect of long-term use of glucocorticoids on the risk of developing diabetes mellitus in patients with gout

BACKGROUND: Patients with gout often take glucocorticoids  (GCs) and are at high risk of developing  type 2 diabetes mellitus (DM2).AIM: Evaluation of the effect of long-term use of low doses of GCs on the risk of developing DM in patients with gout based on the results of a retrospective observationMATERIALS AND METHODS: 317 out of 444 patients with gout and no DM2 who participated in a prospective study of risk factors for DM2 were included. The sample did not include patients who used GCs during  the observation period to relieve an acute attack of arthritis, regardless of the method of their use (n=88) and who did not complete the study (n=39). The remaining  patients were retrospectively divided  into 2 groups: those who continuously  took prednisolone  at a dose of 5-10 mg/day for ≥180 days and did not use GCs during the observation period. Scheduled visits were carried out at least once every 2 years. During  the 1st visit, patients were prescribed or corrected both urate-lowering and prophylactic  antiinflammatory therapy, including  low doses of GCs. The primary end point was the development of DM2, carbohydrate metabolism indicators (HbA1c  levels, serum glucose levels) were compared at baseline and at the end of the study.RESULTS: Of 317 patients with gout, 76 patients (24%) were continuously taking prednisolone at a dose of 5-10 mg/day for ≥180 days, 241 patients (76%) did not receive GCs during  the entire follow-up period. The average dose of prednisolone in patients of the main group was 7.9±1.2 mg/day, the duration of treatment was 206.3±20.4 days.DM2 developed  during  the observation period in 20% of the main group and in 22% of the comparison group (p=0.73). Patients who took GC were older than those who did not take GC (p=0.01), they were more likely to have CHF (p=0.04). There were no significant differences between the groups for the rest of the compared parameters. In patients treated with low doses of GC — a significant increase in the average level of HbA1c  (p=0.002); an increase in the number of patients with glucose levels ≥6.1 mmol/l (p=0.004) by the end of the study relative to the baseline. The initial level of HbA1c  in patients who developed DM2 was expectedly higher, among them smokers were more often detected (p=0.01), they had a higher level of serum UA (p=0.001). The prevalence of other risk factors for DM in those who developed and did not develop DM2 did not differ significantly.CONCLUSION: Long-term use of low doses of GC in patients with gout does not significantly increase the risk of developing DM2, but may have a negative effect on carbohydrate metabolism

Do topology and ferromagnetism cooperate at the EuS/Bi2_2Se3_3 interface?

We probe the local magnetic properties of interfaces between the insulating ferromagnet EuS and the topological insulator Bi$_2$Se$_3$ using low energy muon spin rotation (LE-$\mu$SR). We compare these to the interface between EuS and the topologically trivial metal, titanium. Below the magnetic transition of EuS, we detect strong local magnetic fields which extend several nm into the adjacent layer and cause a complete depolarization of the muons. However, in both Bi$_2$Se$_3$ and titanium we measure similar local magnetic fields, implying that their origin is mostly independent of the topological properties of the interface electronic states. In addition, we use resonant soft X-ray angle resolved photoemission spectroscopy (SX-ARPES) to probe the electronic band structure at the interface between EuS and Bi$_2$Se$_3$. By tuning the photon energy to the Eu anti-resonance at the Eu $M_5$ pre-edge we are able to detect the Bi$_2$Se$_3$ conduction band, through a protective Al$_2$O$_3$ capping layer and the EuS layer. Moreover, we observe a signature of an interface-induced modification of the buried Bi$_2$Se$_3$ wave functions and/or the presence of interface states

Towards high-performance electrochemical thermal energy harvester based on ferrofluids

The ionic liquid-based thermo-electrochemical cells receive increasing attention as an inexpensive alternative to solid-state thermo-electrics for waste heat harvesting applications. Recently, it has been demonstrated that magnetic nanoparticles (MNPs) in liquid-based thermoelectric materials result in enhancement of the Seebeck effect opening new perspectives to the design of a thermoelectric device with relatively high efficiency and cost effectiveness. Here, the role of an interacting assembly of MNPs in the thermoelectric signal is studied for the first time. Based on a thermodynamic approach, an analytic expression has been derived for the Seebeck coefficient that includes the inter-particle magnetic interactions in the assembly and the nanoparticle's magnetic characteristics (saturation magnetization, magnetic anisotropy). Mesoscopic scale modelling with the implementation of the Monte Carlo Metropolis algorithm is performed to calculate their contribution to the Seebeck coefficient, for diluted assemblies of \u3b3-Fe2O3 and CoFe2O4 nanoparticles, materials commonly used in ferrofluids. The results demonstrate the increase of the size and temperature range of the Seebeck coefficient with the increase of nanoparticles\u2019 magnetic anisotropy paving the way for the detailed study of the magneto-thermal effects in high-performance thermoelectric materials based on ferrofluids

Assessment of the risk of developing type 2 diabetes mellitus in patients with gout based on the FINDRISС scale

BACKGROUND: Gout is associated with a high incidence of type 2 diabetes mellitus (T2DM).AIM: To calculate the risk of T2DM on the FINDRISС scale, to assess the sensitivity and specificity of the scale in patients with gout based on the results of prospective follow-up.MATERIALS AND METHODS: A prospective single-center study included 444 patients with gout over 18 years of age (49 women, 395 men) without diabetes. The duration of follow-up ranged from 2 to 8 years. Initially, the risk of developing diabetes mellitus 2 was calculated according to the Russian version of the FINDRISС scale. The risk of developing T2DM was assessed as «low» with a total score (CC) <7 points, slightly increased — from 7 to 11 points, moderate — from 12 to 14 points, high — from 15 to 20 points, and very high — ≥20 points. To assess the validity of using the FINDRISС scale, an analysis of sensitivity, specificity, construction of the ROC curve with the determination of the area under the curve was carried out. The presence and number of subcutaneous tophi, the number of arthritis attacks over the last year, the number of affected joints during the illness, serum levels of creatinine, uric acid, hs-CRP, glycated hemoglobin were determined.RESULTS: Over 5.66 [2.69; 7.64] years of follow-up, T2DM developed in 108 patients (24.3%). On the FINDRISС scale, low risk was found in 16 (4%), slightly increased in 187 (42%), moderate in 98 (22%), high in 80 (18%), very high in 63 (14%). The most common risk factors (RF) for T2DM included in FINDRISС were BMI> 25 kg / m2  — 85.6% of patients, taking antihypertensive drugs — 81.3% of patients, age over 45 years in 70.5% of patients. The sensitivity and specificity of the FINDRISС scale were 52.8% and 66.3%, respectively. According to these data, the quality of the model was assessed as moderate. 9% vs 31.1% (p = 0.014)), serum MK level ≤300 μmol / L. Developed type 2 diabetes 33.3% of patients with moderate / high / very high risk 18.1% of patients with low or slightly increased risk (p = 0.0002).CONCLUSION: The FINDRISС scale can have sufficient sensitivity (52.8%) and specificity (66.3%) and can be used to calculate the risk of T2DM in patients with gout

Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates

We present a soft x-ray angle-resolved photoemission spectroscopy study of the overdoped high-temperature superconductors La$_{2-x}$Sr$_x$CuO$_4$ and La$_{1.8-x}$Eu$_{0.2}$Sr$_x$CuO$_4$. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No $k_z$ dispersion is observed along the nodal direction, whereas a significant antinodal $k_z$ dispersion is identified. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van-Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La$_{2-x}$Sr$_x$CuO$_4$ can not be assigned to the van-Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat

Electronic phase separation at LaAlO3/SrTiO3 interfaces tunable by oxygen deficiency

Electronic phase separation is crucial for the fascinating macroscopic properties of the LaAlO3/SrTiO3 (LAO/STO) paradigm oxide interface, including the coexistence of superconductivity and ferromagnetism. We investigate this phenomenon using angle-resolved photoelectron spectroscopy (ARPES) in the soft-X-ray energy range, where the enhanced probing depth combined with resonant photoexcitation allow access to fundamental electronic structure characteristics (momentum-resolved spectral function, dispersions and ordering of energy bands, Fermi surface) of buried interfaces. Our experiment uses X-ray irradiation of the LAO/STO interface to tune its oxygen deficiency, building up a dichotomic system where mobile weakly correlated Ti t2g-electrons co-exist with localized strongly correlated Ti eg-ones. The ARPES spectra dynamics under X-ray irradiation shows a gradual intensity increase under constant Luttinger count of the Fermi surface. This fact identifies electronic phase separation (EPS) where the mobile electrons accumulate in conducting puddles with fixed electronic structure embedded in an insulating host phase, and allows us to estimate the lateral fraction of these puddles. We discuss the physics of EPS invoking a theoretical picture of oxygen-vacancy clustering, promoted by the magnetism of the localized Ti eg-electrons, and repelling of the mobile t2g-electrons from these clusters. Our results on the irradiation-tuned EPS elucidate the intrinsic one taking place at the stoichiometric LAO/STO interfaces.Comment: In review with Phys. Rev. Material

Нетипичное течение новой коронавирусной инфекции COVID-19 с поздним повышением уровня С-реактивного белка (клинические наблюдения)

Clinical signs of COVID-19 infection are non-specific and diagnosis is typically based on comprehensive evaluation of the patient’s history, clinical status, radiological and laboratory findings. A common finding in COVID-19 patients is increased C-reactive protein (CRP), though in some patients, CRP remains within normal range notwithstanding the presence of other criteria of severe disease. We describe two clinical cases of COVID-19 with severe bilateral pneumonia and late increase in CRP. Similar cases re quite challenging for making the diagnosis and indicating the antiinflammatory therapy.Клинические проявления COVID-19 неспецифичны, при этом основу диагностики составляет комплексная оценка данных. Одним из характерных лабораторных признаков, отражающих тяжесть течения COVID-19, является повышение уровня С-реактивного белка (СРБ). Однако в некоторых случаях уровень СРБ в течение длительного времени может оставаться в пределах нормальных значений, несмотря на присутствие других признаков тяжелого течения заболевания. В статье представлены два клинических наблюдения тяжелого течения двусторонней пневмонии, ассоциированной с COVID-19, у пациентов с поздним повышением уровня СРБ. Такие больные могут представлять определенные трудности при оценке тяжести течения и подборе патогенетической терапии