Abstract Introduction Hyaluronic acid (HA) and corticosteroid (CS) injections are frequently used in the management of osteoarthritis (OA) of the knee, despite a lack of strong evidence supporting ...their efficacy in the literature. The purpose of this study is to evaluate trends in HA and CS usage in Medicare patients over the past 15 years. Methods The Medicare 5% national sample database was used to identify 581,022 patients (representing an estimated 11.6 million) with a diagnosis of knee OA between 1999 and 2013. Results The percentage of newly diagnosed knee OA patients who received any injection trended from 39% in 1999 to 47% in 2006 and then declined to 37.5% in 2013. However, the mean number of injections per newly diagnosed OA patient nearly doubled from 0.27 to 0.45 for CS and from 0.18 to 0.36 for HA. Among those having both HA and CS injections, 69% had CS as first-line treatment, whereas 31% had HA first. Conclusion The percentage of newly diagnosed knee OA patients receiving injections peaked in 2007 and then decreased steadily through 2013, as did the proportion of patients receiving HA injections as first-line therapy. However, the number of injections per patient has increased significantly over the past 15 years in both groups.
Bryophytes are rich sources of diverse secondary metabolites with a wide range of biological activities, including anti-inflammatory, antitumor and antimicrobial effects. The aim of this study was to ...investigate the chemical composition of extracts from two different genotypes (Serbian and Hungarian) of the axenic moss
and evaluate the immunomodulatory potential of the prepared extracts in vitro. Both genotypes of moss samples were cultivated in vitro and subsequently extracted in a Soxhlet apparatus with methanol or ethyl acetate. The highest concentration of total phenolic compounds was found in the methanolic extract of the Serbian genotype (54.25 mg GAE/g extract), while the ethyl acetate extract of the Hungarian genotype showed the highest concentration of phenolic acids (163.20 mg CAE/extract), flavonoids (35.57 mg QE/extract), and flavonols (2.25 mg QE/extract). The extracts showed anti-neuroinflammatory properties by reducing the production of reactive oxygen species, nitric oxide, and tumor necrosis factor alpha by lipopolysaccharide-stimulated microglial cells. Moreover, they mitigated the cytotoxic effects of the pro-inflammatory mediators produced by activated microglia on neurons. The data obtained suggest that extracts from
moss have promising anti-neuroinflammatory and neuroprotective properties, making them interesting candidates for further research to combat neuroinflammation.
Cannabidiol (CBD) is a non-psychoactive cannabinoid, and available evidence suggests potential efficacy in the treatment of many disorders. DehydraTECH™2.0 CBD is a patented capsule formulation that ...improves the bioabsorption of CBD. We sought to compare the effects of CBD and DehydraTECH™2.0 CBD based on polymorphisms in CYP P450 genes and investigate the effects of a single CBD dose on blood pressure. In a randomized and double-blinded order, 12 females and 12 males with reported hypertension were given either placebo capsules or DehydraTECH™2.0 CBD (300 mg of CBD, each). Blood pressure and heart rate were measured during 3 h, and blood and urine samples were collected. In the first 20 min following the dose, there was a greater reduction in diastolic blood pressure (
= 0.025) and mean arterial pressure MAP (
= 0.056) with DehydraTECH™2.0 CBD, which was probably due to its greater CBD bioavailability. In the CYP2C9*2*3 enzyme, subjects with the poor metabolizer (PM) phenotype had higher plasma CBD concentrations. Both CYP2C19*2 (
= 0.037) and CYP2C19*17 (
= 0.022) were negatively associated with urinary CBD levels (beta = -0.489 for CYP2C19*2 and beta = -0.494 for CYP2C19*17). Further research is required to establish the impact of CYP P450 enzymes and the identification of metabolizer phenotype for the optimization of CBD formulations.
•Upon exocytosis vesicular cholesterol transfers to the plasmalemma.•Cholesterol enrichment decreases, depletion increases the fusion pore conductance.•A model of cholesterol-dependent force ...preventing fusion pore widening is developed.•Disease-related increase in vesicle cholesterol reduces the fusion pore conductance.
In some lysosomal storage diseases (LSD) cholesterol accumulates in vesicles. Whether increased vesicle cholesterol affects vesicle fusion with the plasmalemma, where the fusion pore, a channel between the vesicle lumen and the extracellular space, is formed, is unknown. Super-resolution microscopy revealed that after stimulation of exocytosis, pituitary lactotroph vesicles discharge cholesterol which transfers to the plasmalemma. Cholesterol depletion in lactotrophs and astrocytes, both exhibiting Ca2+-dependent exocytosis regulated by distinct Ca2+sources, evokes vesicle secretion. Although this treatment enhanced cytosolic levels of Ca2+ in lactotrophs but decreased it in astrocytes, this indicates that cholesterol may well directly define the fusion pore. In an attempt to explain this mechanism, a new model of cholesterol-dependent fusion pore regulation is proposed. High-resolution membrane capacitance measurements, used to monitor fusion pore conductance, a parameter related to fusion pore diameter, confirm that at resting conditions reducing cholesterol increases, while enrichment with cholesterol decreases the conductance of the fusion pore. In resting fibroblasts, lacking the Npc1 protein, a cellular model of LSD in which cholesterol accumulates in vesicles, the fusion pore conductance is smaller than in controls, showing that vesicle cholesterol controls fusion pore and is relevant for pathophysiology of LSD.
Display omitted Top: stages through which a vesicle interacts with the plasmalemma. Stage A denotes hemifusion, which proceeds to stage B, with a narrow fusion pore, which can then reversibly open (stage C), before widening fully (stage D). Bottom: redistribution of cholesterol from the vesicle to the plasmalemma regulates the fusion pore.
Awake craniotomy is a neurosurgical technique that allows neurophysiological testing with patient cooperation during the resection of brain tumour in regional anaesthesia. This allows identification ...of vital functional (i.e. eloquent) brain areas during surgery and avoidance of their injury. The aim of the study was to present clinical experience with awake craniotomy for the treatment of gliomas at the University Medical Centre Ljubljana from 2015 to 2019.
Awake craniotomy was considered in patients with a gliomas near or within the language brain areas, in all cases of insular lesions and selected patients with lesions near or within primary motor brain cortex. Each patient was assessed before and after surgery.
During the 5-year period, 24 awake craniotomies were performed (18 male and 6 female patients; average age 41). The patient's cooperation, discomfort and perceived pain assessed during the awake craniotomy were in majority of the cases excellent, slight, and moderate, respectively. After surgery, mild neurological worsening was observed in 13% (3/24) of patients. Gross total resection, in cases of malignant gliomas, was feasible in 60% (6/10) and in cases of low-grade gliomas in 29% (4/14). The surgery did not have important negative impact on functional status or quality of life as assessed by Karnofsky score and Short-Form 36 health survey, respectively (p > 0.05).
The results suggest that awake craniotomy for treatment of gliomas is feasible and safe neurosurgical technique. The proper selection of patients, preoperative preparation with planning, and cooperation of medical team members are necessary for best treatment outcome.
•Dibasic phosphate and monobasic phosphite groups are formed at C6 and C3 hydroxyls.•60-Fold higher surface charge density on NFC is created under homogenous conditions.•The phosphorylations do not ...affect the crystallinity of NC.•The weight loss is noticeably prevented during the pyrolysis process.•High hydrolytic stability to water at all pH mediums is proved.
Nano-sized cellulose ester derivatives having phosphoryl side groups were synthesised by phosphorylation of nanofibrilated cellulose (NFC) and nanocrystaline cellulose (NCC), using different heterogeneous (in water) and homogeneous (in molten urea) processes with phosphoric acid as phosphoryl donor. The phosphorylation mechanism, efficacy, stability, as well as its influence on the NC crystallinity and thermal properties, were evaluated using ATR-FTIR and 13C NMR spectroscopies, potentiometric titration, capillary electrophoresis, X-ray diffraction, colorimetry, thermogravimmetry and SEM. Phosphorylation under both processes created dibasic phosphate and monobasic tautomeric phosphite groups at C6 and C3 positioned hydroxyls of cellulose, yielded 60-fold (∼1173mmol/kg) and 2-fold (∼1038mmol/kg) higher surface charge density for p-NFC and p-NCC, respectively, under homogenous conditions. None of the phosphorylations affected neither the NC crystallinity degree nor the structure, and noticeably preventing the derivatives from weight loss during the pyrolysis process. The p-NC showed high hydrolytic stability to water at all pH mediums. Reusing of the treatment bath was examined after the heterogeneous process.
Endothelial cell activation leading to leukocyte recruitment and adhesion plays an essential role in the initiation and progression of atherosclerosis. Vitamin D has cardioprotective actions, while ...its deficiency is a risk factor for the progression of cardiovascular damage. Our aim was to assess the role of basal levels of vitamin D receptor (VDR) on the early leukocyte recruitment and related endothelial cell-adhesion-molecule expression, as essential prerequisites for the onset of atherosclerosis. Knockdown of VDR in endothelial cells (shVDR) led to endothelial cell activation, characterized by upregulation of VCAM-1, ICAM-1 and IL-6, decreased peripheral blood mononuclear cell (PBMC) rolling velocity and increased PBMC rolling flux and adhesion to the endothelium. shVDR cells showed decreased IκBα levels and accumulation of p65 in the nucleus compared to shRNA controls. Inhibition of NF-κB activation with super-repressor IκBα blunted all signs of endothelial cell activation caused by downregulation of VDR in endothelial cells. In vivo, deletion of VDR led to significantly larger aortic arch and aortic root lesions in apoE-/- mice, with higher macrophage content. apoE-/-VDR-/-mice showed higher aortic expression of VCAM-1, ICAM-1 and IL-6 when compared to apoE-/-VDR+/+ mice. Our data demonstrate that lack of VDR signaling in endothelial cells leads to a state of endothelial activation with increased leukocyte-endothelial cell interactions that may contribute to the more severe plaque accumulation observed in apoE-/-VDR-/- mice. The results reveal an important role for basal levels of endothelial VDR in limiting endothelial cell inflammation and atherosclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The paper analyses the effects and measures the intensity of economic cooperation that Serbia has achieved with the member countries of the Visegrad Group (V4 Group) from 2000 until today. The ...starting hypothesis is that the common cultural and historical heritage, the geographical proximity of the market and the common experience of the economic transition process can be an incentive for the development of economic cooperation between Serbia and the countries of the V4 Group. A gravity econometric model Poisson Pseudo Maximum Likelihood (PPML) estimator was used to test the hypothesis. The results of the research confirm a significantly positive impact of the GDP of Serbia and the observed countries, a significantly negative impact of distance and a significantly positive effect of the neighbourhood on bilateral trade flows. Predictors related to the quality of institutions also have a significant positive effect on increasing bilateral trade cooperation between Serbia and the V4 Group.
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