Purpose
To obtain initial data on the effect of different levels of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA).
Methods
We designed a multicentre pilot trial with ...1:1:1 randomization to either 32 °C (
n
= 52), 33 °C (
n
= 49) or 34 °C (
n
= 49), via endovascular cooling devices during a 24-h period in comatose survivors of witnessed OHCA and initial shockable rhythm. The primary endpoint was the percentage of subjects surviving with good neurologic outcome defined by a modified Rankin Scale (mRS) score of ≤ 3, blindly assessed at 90 days.
Results
At baseline, different proportions of patients who had received defibrillation administered by a bystander were assigned to groups of 32 °C (13.5%), 33 °C (34.7%) and 34 °C (28.6%;
p
= 0.03). The percentage of patients with an mRS ≤ 3 at 90 days (primary endpoint) was 65.3, 65.9 and 65.9% in patients assigned to 32, 33 and 34 °C, respectively, non-significant (NS). The multivariate Cox proportional hazards model identified two variables significantly related to the primary outcome: male gender and defibrillation by a bystander. Among the 43 patients who died before 90 days, 28 died following withdrawal of life-sustaining therapy, as follows: 7/16 (43.8%), 10/13 (76.9%) and 11/14 (78.6%) of patients assigned to 32, 33 and 34 °C, respectively (trend test
p
= 0.04). All levels of cooling were well tolerated.
Conclusions
There were no statistically significant differences in neurological outcomes among the different levels of TTM. However, future research should explore the efficacy of TTM at 32 °C.
Clinical trial registration
ClinicalTrials.gov unique identifier: NCT02035839 (
http://clinicaltrials.gov
).
While tumor-tissue remains the ‘gold standard’ for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, ...we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care.
Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients.
Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity.
Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.
We discuss the excitation of polaritons-strongly coupled states of light and matter-by quantum light, instead of the usual laser or thermal excitation. As one illustration of the new horizons thus ...opened, we introduce "Mollow spectroscopy"-a theoretical concept for a spectroscopic technique that consists of scanning the output of resonance fluorescence onto an optical target-from which weak nonlinearities can be read with high precision even in strongly dissipative environments.
A novel synthesis methodology of fractional-order chaotic systems, from the level of nonlinear systems until their experimental verification using microcontrollers, is presented. Firstly, the ...integer-order behavioral model of the Lorenz’s, Rossler’s, Chen’s, Liu’s, Saturated Nonlinear Function Series at one- and two-direction systems is briefly reviewed. Secondly, a first-order transfer function that approximates the behavior of a fractional-order integrator, based on continued fraction expansion method, is substituting the integer-order integrator inside the revised previously chaotic systems. Thirdly, the minimum phase Al-Alaoui’s transformation method is used for synthesizing all fractional-order chaotic systems in the discrete domain and are programmed in MATLAB and in the Arduino DUE development board. For a fair comparison, the minimum phase Al-Alaoui’s algorithm not only is used for solving the integer-order chaotic systems and it is also programmed in MATLAB and Arduino DUE board, but same initial conditions are also used for both interger- and fractional-order chaotic systems. Finally, experimental results of the integer- and fractional-order chaotic oscillators are shown. The results obtained not only allow a simple synthesis methodology of fractional-order chaotic attractors and their experimental evidence on reconfigurable hardware, but also demonstrate the viability of fractional attractors to be used in various applications such as secure communications, robot control, cryptography and so on.
Four different antioxidant tests (ABTS
+, DPPH, ORAC, β-carotene–linoleate model system) were used to determine the free-radical scavenging activity of 39 extra virgin olive oils (EVOO) and compare ...the total phenol content by the Folin–Ciocalteu method. The correlation between the total phenols and antioxidant capacities measured by the four methods was very high, and highest with ABTS
+ (
R
2
=
0.9905). Some of these methods of measurement were applied to olive-oil samples (OO), with approximately a 50% decrease in the value of the antioxidant capacity in comparison with values found for EVOO. In conclusion, the results show that all the methods tested were suitable for determining the antioxidant capacity of olive oil. The Picual variety of extra-virgin olive oil showed high antioxidant activity.
Neuroprotective actions of flavonoids Gutierrez-Merino, C; Lopez-Sanchez, C; Lagoa, R ...
Current medicinal chemistry,
03/2011, Letnik:
18, Številka:
8
Journal Article
Recenzirano
The experimental evidences accumulated during last years point out a relevant role of oxidative stress in neurodegeneration. As anti-cellular oxidative stress agents flavonoids can act either as ...direct chemical antioxidants, the classic view of flavonoids as antioxidants, or as modulators of enzymes and metabolic and signaling pathways leading to an overshot of reactive oxygen species (ROS) formation, a more recently emerging concept. Flavonoids, a large family of natural antioxidants, undergo a significant hepatic metabolism leading to flavonoid-derived metabolites that are also bioactive as antioxidant agents. The development of more efficient flavonoid's based anti-oxidative stress therapies should also take into account their bioavailability in the brain using alternate administration protocols, and also that the major ROS triggering the cellular oxidative stress are not the same for all neurodegenerative insults and diseases. On these grounds, we have reviewed the reports on neuroprotection by different classes of flavonoids on cellular cultures and model animals. In addition, as they are now becoming valuable pharmacological drugs, due to their low toxicity, the reported adverse effects of flavonoids in model experimental animals and humans are briefly discussed.
Background: Tissue factor (TF) is the main initiator of the coagulation cascade and elements that may upregulate its expression might provoke thrombotic events. Systemic lupus erythematosus (SLE) and ...antiphospholipid syndrome (APS) are autoimmune diseases characterized by a high TF expression in monocytes. Objectives: To examine the role of microRNAs (miRNAs) in TF expression and to evaluate their levels in SLE and APS patients. Methods: An in silico search was performed to find potential putative binding sites of miRNAs in TF mRNA. In vitro validation was performed transfecting cells expressing TF (THP‐1 and MDA‐MB‐231) with oligonucleotide miRNA precursors and inhibitors. Additionally, reporter assays were performed to test for the binding of miR‐20a to TF mRNA. Levels of miRNAs and TF were measured by quantitative (qRT‐PCR) in patients with APS and SLE. Results: Overexpression of miRNA precursors, but not inhibitors, of two of the members of cluster miR‐17∼92, for example miR‐19b and miR‐20a, in cells expressing TF decreased TF mRNA, protein levels, and procoagulant activity between 30% and 60%. Reporter assays showed that miR‐20a binds to TF mRNA. Finally, we measured levels of miR‐19b and miR‐20a in monocytes from patients with APS and SLE and observed significantly lower miRNAs levels in comparison with healthy subjects inversely correlated with the levels of TF. Conclusions: Down‐regulation of miR‐19b and miR‐20a observed in patients with SLE and APS could contribute to increased TF expression and thus provoke the hypercoagulable state characteristic of these patients.
Summary
Temporal trends in hip fracture incidence have recently been reported in some developed countries. Such data in Spain has previously been incomplete; this study reports the stratified ...incidence of hip fractures in people over 65 in Spain during the last 14 years.
Introduction
The main objective is to establish whether temporal trends in hip fracture incidence in Spain exist.
Methods
Ecological study with data from hospital discharges nationwide. The study includes patients aged ≥65 years during a 14-year period (1997–2010). The analysis compares two periods of four years: 1997–2000 (P1) and 2007–2010 (P2).
Results
There were 119,857 fractures in men and 415,421 in women. Comparing periods (P1 vs P2) over 10 years, the crude incidence rate/100,000 inhabitant/year increased an average of 2.3 %/year in men and 1.4 % in women. After adjustment, the rate increased an average of 0.4 %/year in men (
p
< 0.0001), but decreased 0.2 %/year in women (
p
< 0.0001). In men, younger than 85, the decrease was not significant except in 70–74 years, and from 80 years, the adjusted rate increases significantly (
p
< 0.0001). In women under 80 years of age, the decrease in adjusted rate was significant; there was no change in 80–84 years, and the adjusted rate increased significantly in individuals 85 years and older (
p
< 0.0001). Mortality rates declined by 22 % in both sexes, and the index of overaging population rises 30.1 % in men and 25.2 % in women.
Conclusions
This study supports other international studies by showing changes in the incidence of hip fractures after age-population adjustment, which denotes a decrease in the younger age groups and among women and shows an increase in both groups over 85 years. The increase in the crude incidence rate of hip fracture in Spain reflects changes in population structure.
Objective
B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We ...evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE).
Methods
BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38–/ + naïve; CD19 + CD27 + CD38–/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs).
Results
Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower BCMA expression was associated with severe disease activity, glomerulonephritis, serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative correlation with Mex-SLEDAI score (r = –0.494, p = 0.006).
Conclusions
Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients.
The generation of biomimetic and biocompatible artificial tissues is the basic research objective for tissue engineering (TE). In this sense, the biofabrication of scaffolds that resemble the ...tissues' extracellular matrix is an essential aim in this field. Uncompressed and nanostructured fibrin-agarose hydrogels (FAH and NFAH, respectively) have emerged as promising scaffolds in TE, but their structure and biomechanical properties must be improved in order to broaden their TE applications. Here, we generated and characterized novel membrane-like models with increased structural and biomechanical properties based on the chemical cross-linking of FAH and NFAH with genipin (GP at 0.1%, 0.25%, 0.5% and 0.75%). Furthermore, the scaffolds were subjected to rheological (G, G', G″ modulus), ultrastructural and ex vivo biocompatibility analyses. Results showed that all GP concentrations increased the stiffness (G) and especially the elasticity (G') of FAH and NFAH. Ultrastructural analyses demonstrated that GP and nanostructuration of FAH allowed us to control the porosity of FAH. In addition, biological studies revealed that higher concentration of GP (0.75%) started to compromise the cell function and viability. Finally, this study demonstrated the possibility to generate natural and biocompatible FAH and NFAH with improved structural and biomechanical properties by using 0.1%-0.5% of GP. However, further in vivo studies are needed in order to demonstrate the biocompatibility, biodegradability and regeneration capability of these cross-linked scaffolds.
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