The metastatic process in breast cancer is related to the expression of the epithelial-to-mesenchymal transition transcription factors (EMT-TFs) SNAIL, SLUG, SIP1 and TWIST1. EMT-TFs and nuclear ...factor-κB (NF-κB) activation have been associated with aggressiveness and metastatic potential in carcinomas. Here, we sought to examine the role of NF-κB in the aggressive properties and regulation of EMT-TFs in human breast cancer cells. Blocking NF-κB/p65 activity by reducing its transcript and protein levels (through siRNA-strategy and dehydroxymethylepoxyquinomicin DHMEQ treatment) in the aggressive MDA-MB-231 and HCC-1954 cell lines resulted in decreased invasiveness and migration, a downregulation of SLUG, SIP1, TWIST1, MMP11 and N-cadherin transcripts and an upregulation of E-cadherin transcripts. No significant changes were observed in the less aggressive cell line MCF-7. Bioinformatics tools identified several NF-κB binding sites along the promoters of SNAIL, SLUG, SIP1 and TWIST1 genes. Through chromatin immunoprecipitation and luciferase reporter assays, the NF-κB/p65 binding on TWIST1, SLUG and SIP1 promoter regions was confirmed. Thus, we suggest that NF-κB directly regulates the transcription of EMT-TF genes in breast cancer. Our findings may contribute to a greater understanding of the metastatic process of this neoplasia and highlight NF-κB as a potential target for breast cancer treatment.
Previous studies investigating the effects of transcranial direct current stimulation (tDCS) on muscle strength showed no consensus. Therefore, the purpose of this article was to systematically ...review the literature on the effects of single dose tDCS to improve muscle strength. A systematic literature search was conducted on PubMeb, ISI Web of Science, SciELO, and Scopus using search terms regarding tDCS and muscle strength. Studies were included in accordance with Population, Intervention, Comparison, Outcomes, and Setting (PICOS) including criteria. Healthy men and women, strength training practitioners or sedentary were selected. The acute effects of single dose anode stimulus of tDCS (a-tDCS) and the placebo stimulus of tDCS (sham) or no interventions were considered as an intervention and comparators, respectively. Measures related to muscle strength were analyzed. To conduct the analyses a weighted mean difference (WMD) and the standardized mean difference (SMD) were applied as appropriate. A total of 15 studies were included in this systematic review and 14 in meta-analysis. Regarding the maximal isometric voluntary contraction (MIVC), a small effect was seen between tDCS and Sham with significant difference between the conditions (SMD = 0.29; CI95% = 0.05 to 0.54; Z = 2.36; p = 0.02). The muscular endurance measured by the seconds sustaining a percentage of MIVC demonstrated a large effect between tDCS and Sham (WMD = 43.66; CI95% = 29.76 to 57.55; Z = 6.16; p < 0.001), showing an improvement in muscular endurance after exposure to tDCS. However, muscular endurance based on total work showed a trivial effect between tDCS and Sham with no significant difference (SMD = 0.22; CI95% = -0.11 to 0.54; Z = 1.32, p = 0.19). This study suggests that the use of tDCS may promote increase in maximal voluntary contraction and muscular endurance through isometric contractions.
To compare the psychological responses to continuous (CT) and high-intensity interval training (HIT) sessions.
Fifteen men attended one CT session and one HIT session. During the first visit, the ...maximum heart rate, VO2Peak and respiratory compensation point (RCP) were determined through a maximal cardiopulmonary exercise test. The HIT stimulus intensity corresponded to 100% of VO2Peak, and the average intensity of both sessions was maintained at 15% below the RCP. The order of the sessions was randomized. Psychological and physiological variables were recorded before, during and after each session.
There were no significant differences between the average percentages of VO2 during the two exercise sessions (HIT: 73.3% vs. CT: 71.8%; p = 0.779). Lower responses on the feeling scale (p≤0.01) and higher responses on the felt arousal scale (p≤0.001) and the rating of perceived exertion were obtained during the HIT session. Despite the more negative feeling scale responses observed during HIT and a greater feeling of fatigue (measured by Profile of Mood States) afterwards (p<0.01), the physical activity enjoyment scale was not significantly different between the two conditions (p = 0.779).
Despite the same average intensity for both conditions, similar psychological responses under HIT and CT conditions were not observed, suggesting that the higher dependence on anaerobic metabolism during HIT negatively influenced the feeling scale responses.
ABSTRACT Alfvénic fluctuations are a common feature in the solar wind and are found especially in the trailing edges of fast wind streams. The slow wind usually has a lower degree of Alfvénicity, ...being more strongly intermixed with structures of non-Alfvénic nature. In the present paper we show the first evidence in the interplanetary space of two different kinds of slow solar wind: one coming from coronal streamers or active regions and characterized by non-Alfvénic structures and the other one being highly Alfvénic and originating from the boundary of coronal holes. The Alfvénic character of fluctuations, either outward or inward, can be studied by means of the normalized cross-helicity, , which is an indicator of the alignment. The evolution of toward lower values with increasing radial distance is interpreted both as a decrease of the presence of the outward modes and as a continuous production of inward modes within those regions such as stream shears where some plasma instability is active. On the other hand, the decrease of is often related also to magnetic field and/or density enhancements which specifically act on the destruction of the alignment. In the present analysis we study the role of compressibility presenting both case studies and a statistical analysis over different phases of solar cycle 23. Our findings indicate that the presence of regions of magnetic field compression generally play a major role in the depletion of and thus in the destruction of the alignment.
The theory of nearly incompressible magnetohydrodynamics (NI MHD) was developed largely in the early 1990s, together with an important extension to inhomogeneous flows in 2010. Much of the focus in ...the earlier work was to understand the apparent incompressibility of the solar wind and other plasma environments, and the relationship of density fluctuations to apparently incompressible manifestations of turbulence in the solar wind and interstellar medium. Further important predictions about the "dimensionality" of solar wind turbulence and its relationship to the plasma beta were made and subsequently confirmed observationally. However, despite the initial success of NI MHD in describing fluctuations in the solar wind, a detailed application to solar wind turbulence has not been undertaken. Here, we use the equations of NI MHD to describe solar wind turbulence, rewriting the NI MHD system in terms of Elsässer variables. Distinct descriptions of 2D and slab turbulence emerge naturally from the Elsässer formulation, as do the nonlinear couplings between 2D and slab components. For plasma beta order 1 or less regions, predictions for 2D and slab spectra result from the NI MHD description, and predictions for the spectral characteristics of density fluctuations can be made. We conclude by presenting a NI MHD formulation describing the transport of majority 2D and minority slab turbulence throughout the solar wind. A preliminary comparison of theory and observations is presented.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis ...pain in a network meta-analysis.
For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose–response relation, we used preparation-specific covariates assuming linearity on log relative dose.
We identified 8973 manuscripts from our search, of which 76 randomised trials with a total of 58 451 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size ES −0·37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES −0·57, 95% credibility interval CrI −0·69 to −0·45) and etoricoxib 60 mg/day (ES −0·58, −0·74 to −0·43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for naproxen (p=0·034). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis.
On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients.
Swiss National Science Foundation (grant number 405340-104762) and Arco Foundation, Switzerland.
There is debate on how the methodological quality of clinical trials should be assessed. We compared trials of physical therapy (PT) judged to be of adequate quality based on summary scores from the ...Physiotherapy Evidence Database (PEDro) scale with trials judged to be of adequate quality by Cochrane Risk of Bias criteria.
Meta-epidemiological study within Cochrane Database of Systematic Reviews.
Meta-analyses of PT trials were identified in the Cochrane Database of Systematic Reviews. For each trial PeDro and Cochrane assessments were extracted from the PeDro and Cochrane databases. Adequate quality was defined as adequate generation of random sequence, concealment of allocation, and blinding of outcome assessors (Cochrane criteria) or as trials with a PEDro summary score ≥5 or ≥6 points. We combined trials of adequate quality using random-effects meta-analysis.
Forty-one Cochrane reviews and 353 PT trials were included. All meta-analyses included trials with PEDro scores ≥5, 37 (90.2%) included trials with PEDro scores ≥6 and only 22 (53.7%) meta-analyses included trials of adequate quality according to the Cochrane criteria. Agreement between PeDro and Cochrane was poor for PeDro scores of ≥5 points (kappa = 0.12; 95% CI 0.07 to 0.16) and slight for ≥6 points (kappa 0.24; 95% CI 0.16-0.32). When combining effect sizes of trials deemed to be of adequate quality according to PEDro or Cochrane criteria, we found that a substantial difference in the combined effect size (≥0.15) was evident in 9 (22%) out of the 41 meta-analyses for PEDro cutoff ≥5 and 10 (24%) for cutoff ≥6.
The PeDro and Cochrane approaches lead to different sets of trials of adequate quality, and different combined treatment estimates from meta-analyses of these trials. A consistent approach to assessing RoB in trials of physical therapy should be adopted.
Objective
To assess the outcomes of implant‐supported full‐arch fixed dental prostheses (ISFAFDPs) and the supporting implants.
Material and methods
This retrospective study included patients treated ...with ISFAFDPs at one specialist clinic. Implant/prosthesis failure and complications were the outcomes analyzed. Survival analysis methods were used.
Results
A total of 709 patients with 869 ISFAFDPs (4,797 implants) were included, with a mean ± SD follow‐up of 10.7 ± 7.2 years. A total of 353 implants and 62 prostheses failed. Estimated cumulative survival rates were as follows: 93.3% (95% CI 91.3, 95.3) after 10 years and 87.1% (95% CI 83.4, 90.8) after 20 years. Implants installed in bruxers, smokers, and maxilla had a lower survival than implants installed in non‐bruxers, non‐smokers, and mandible, respectively. A total of 415 ISFAFDPs (47.8%) presented technical complications, of which 67 (7.7%) presented only occurrences of loss/fracture of implant access hole sealing. Bruxism was a factor to exert a higher risk of screw loosening (HR 3.302; also in younger patients), screw fracture (HR 4.956), ceramic chipping/fracture (HR 5.685), and loss/fracture of acrylic teeth (HR 2.125; this last complication with higher risk also in men, in maxillae, and when the opposing jaw presented natural dentition or fixed prostheses). Patients with bruxism had a statistically significant higher risk of prosthesis failure than non‐bruxers (HR 3.276).
Conclusions
ISFAFDPs presented good long‐term prognosis. Failure of several supporting implants was the main reason for failure. The results of the present study strongly suggest that bruxism is an important contributor to implant and prosthesis failure, as well as to an increased prevalence of technical complications in ISFAFDPs.
Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic ...respiratory failure.
To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure.
The following bibliographic databases were searched from inception until April 2020: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race.
Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy.
Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a bayesian framework to derive risk ratios (RRs) and risk differences along with 95% credible intervals (CrIs) were conducted. GRADE methodology was used to rate the certainty in findings.
The primary outcome was all-cause mortality up to 90 days. A secondary outcome was endotracheal intubation up to 30 days.
Twenty-five randomized clinical trials (3804 participants) were included. Compared with standard oxygen, treatment with helmet noninvasive ventilation (RR, 0.40 95% CrI, 0.24-0.63; absolute risk difference, -0.19 95% CrI, -0.37 to -0.09; low certainty) and face mask noninvasive ventilation (RR, 0.83 95% CrI, 0.68-0.99; absolute risk difference, -0.06 95% CrI, -0.15 to -0.01; moderate certainty) were associated with a lower risk of mortality (21 studies 3370 patients). Helmet noninvasive ventilation (RR, 0.26 95% CrI, 0.14-0.46; absolute risk difference, -0.32 95% CrI, -0.60 to -0.16; low certainty), face mask noninvasive ventilation (RR, 0.76 95% CrI, 0.62-0.90; absolute risk difference, -0.12 95% CrI, -0.25 to -0.05; moderate certainty) and high-flow nasal oxygen (RR, 0.76 95% CrI, 0.55-0.99; absolute risk difference, -0.11 95% CrI, -0.27 to -0.01; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies 3804 patients). The risk of bias due to lack of blinding for intubation was deemed high.
In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.
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