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The trial may determine whether adding volatile anesthetic during cardiopulmonary bypass will attenuate the inflammatory response.
ClinicalTrials.gov NCT02672345 . Registered on February 2016 and updated on June 2020.
ClinicalTrials.gov NCT02672345 . Registered on February 2016 and updated on June 2020.
The low extracellular pH (pH
) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pH
on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia.
Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed.
NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O
consumption increased gradually with decreasing pH.
These data show that acidic pH
in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.
These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.
MiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.
Thirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n = 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20 mg/kg L) group (n = 8), saline (SA group, n = 8); and sham operation group (sham group, n = 8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time pn metabolism parameters as well as 24-h survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.
In the presence of heterogeneous treatment effects, it is desirable to divide patients into subgroups based on their expected response to treatment. This is formalised via a personalised treatment recommendation an algorithm that uses biomarker measurements to select treatments. It could be that multiple, rather than single, biomarkers better predict these subgroups. However, finding the optimal combination of multiple biomarkers can be a difficult prediction problem.
We described three parametric methods for finding the optimal combination of biomarkers in a personalised treatment recommendation, using randomised trial data a regression approach that models outcome using treatment by biomarker interactions; an approach proposed by Kraemer that forms a combined measure from individual biomarker weights, calculated on all treated and control pairs; and a novel modification of Kraemer's approach that utilises a prognostic score to sample matched treated and control subjects. Using Monte Carlo simulations unre sensitive to misspecification of the parametric models.
The method proposed by Kraemer does not perform better than a regression approach for combining multiple biomarkers. All methods are sensitive to misspecification of the parametric models.
In this review, we assess the state of Resuscitative Endovascular Occlusion of the Aorta (REBOA) today with respect to out-of-hospital (OOH) vs. inhospital (H) use in blunt and penetrating trauma, as well as discuss areas of promising research that may be key in further advancement of REBOA applications.
To analyze the trends in REBOA use, we conducted a review of the literature and identified articles with human or animal data that fit the respective inclusion and exclusion criteria. In separate tables, we compiled data extracted from selected articles in categories including injury type, zone and duration of REBOA, setting in which REBOA was performed, sample size, age, sex and outcome. Based on these tables as well as more detailed review of some key cases of REBOA usage, we assessed the current state of REBOA as well as coagulation and histological disturbances associated with its usage. All statistical tests were 2-sided using an alpha=0.05 for significance. Analysis was done using SAS 9.5 (Cary, NC)t involve realistic models of injury with severe clinical scenarios approximating human trauma and exsanguination, especially with long-term follow-up after injury.
Further research related to human use of REBOA must be focused on earlier initiation of REBOA after injury which may depend on development of rapid vascular access devices and techniques more so than on any new improvements in REBOA. Future animal studies should provide detailed multisystem organ assessment to accurately define organ injury and metabolic burden associated with REBOA application. Overall, animal studies must involve realistic models of injury with severe clinical scenarios approximating human trauma and exsanguination, especially with long-term follow-up after injury.
Dogs in the US are commonly infected with vector-borne pathogens, including heartworm and tick-borne disease agents. The geographic distribution of both arthropod vectors and the pathogens they transmit continues to expand.
To describe the current geographic distribution and prevalence of antigen of Dirofilaria immitis and antibody to Borrelia burgdorferi, Ehrlichia spp., and Anaplasma spp. in dogs, we summarized over 144million test results from 2013 to 2019, inclusive, by county, state, and region. Canine seroprevalence by state was compared to population-adjusted human reports of tick-borne diseases.
Results varied regionally, with D. immitis antigen and Ehrlichia spp. antibodies more frequently detected in the Southeast (2.6% and 5.2%, respectively) and antibody to B. burgdorferi and Anaplasma spp. most common in the Northeast (12.1% and 7.3%, respectively). Overall, percent positive test results to D. immitis decreased in the Southeast by 33.3% when compared to earlier summaries using the same straee tick-borne agents demonstrated evidence of geographic expansion.
Large scale analysis of results from screening dogs in practice for evidence of vector-borne infections, including those with zoonotic importance, continues to be a valuable strategy for understanding geographic trends in infection risk over time.
Large scale analysis of results from screening dogs in practice for evidence of vector-borne infections, including those with zoonotic importance, continues to be a valuable strategy for understanding geographic trends in infection risk over time.
Since January 2019, surgical castration of male piglets must be performed using local anaesthesia, if farmers deliver pigs to the primary exporting slaughterhouses according to the "Danish quality scheme"; a voluntary initiative taken by the Danish pig industry. The approved procedure for local anaesthesia in Denmark is a three-step injection method with procaine. A comparison of lidocaine and procaine with the same concentration and injection methods of local anaesthetics has not previously been studied. The purpose of this study was to investigate the effect of two injection methods and two local anaesthetics on piglets' avoidance behaviour (vocalisation and resistance movements) as well as the time spent on the procedures. The study included 203 male piglets that were randomly assigned to one of five treatments 1.
Sham-handling without injection of local anaesthesia, 2. Pro3 Procaine injection using a three-step method, 3. Pro2 Procaine injection using a two-step method, 4. Lid3 Lidocaine injection usi well as the time spent on castration.
The use of local anaesthesia, irrespective of the method and local anaesthetic, was effective in reducing vocalisation and resistance movements during surgery as well as the time spent on castration.
Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation.
We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I
values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control atients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.
Diabetes related foot complications are increasing in complexity, frequency and cost. The application of self-management strategies can reduce the risk of individuals developing foot complications. The type, range and nature of the literature focusing on interventions that support patients with diabetic foot self-management is unknown. UNC6852 mouse This scoping review aimed to i) identify self-management actions and risky behaviour avoidance strategies within interventions, ii) map the theoretical functions through which these behaviour change interventions have an effect, iii) display gaps in the research.
Arksey and Malley's (2003) 5 stage framework was followed to conduct the scoping study. This methodological framework was selected because it was developed specifically for scoping reviews and therefore offered clear methodological distinction from systematic review methodology. . Databases were searched from inception of the project until June 2020 supplemented by hand searching of reference lists. In total 988 papers were identified.