Identification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma

Specific HPV DNA sequences are associated with more than 90% of invasive carcinomas of the uterine cervix. Viral E6 and E7 oncogenes are key mediators in cell transformation by disrupting TP53 and RB pathways. To investigate molecular mechanisms involved in the progression of invasive cervical carcinoma, we performed a gene expression study on cases selected according to viral and clinical parameters. Using Coupled Two-Way Clustering and Sorting Points Into Neighbourhoods methods, we identified a Cervical Cancer Proliferation Cluster composed of 163 highly correlated transcripts, many of which corresponded to E2F pathway genes controlling cell proliferation, whereas no primary TP53 targets were present in this cluster. The average expression level of the genes of this cluster was higher in tumours with an early relapse than in tumours with a favourable course (P=0.026). Moreover, we found that E6/E7 mRNA expression level was positively correlated with the expression level of the cluster genes and with viral DNA load. These findings suggest that HPV E6/E7 expression level plays a key role in the progression of invasive carcinoma of the uterine cervix via the deregulation of cellular genes controlling tumour cell proliferation. HPV expression level may thus correspond to a biological marker useful for prognosis assessment and specific therapy of the disease

The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral Access The Campeau Radial Paradox

AbstractObjectivesThe purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed.BackgroundThe recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted.MethodsLogistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort.ResultsA total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%.ConclusionsIn a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators

Mathematical modeling of the microtubule detyrosination/tyrosination cycle for cell-based drug screening design

International audienceMicrotubules and their post-translational modifications are involved in major cellular processes. In severe diseases such as neurodegenerative disorders, tyrosinated tubulin and tyrosinated microtubules are in lower concentration. We present here a mechanistic mathematical model of the microtubule tyrosination cycle combining computational modeling and high-content image analyses to understand the key kinetic parameters governing the tyrosination status in different cellular models. That mathematical model is parameterized, firstly, for neuronal cells using kinetic values taken from the literature, and, secondly, for proliferative cells, by a change of two parameter values obtained, and shown minimal, by a continuous optimization procedure based on temporal logic constraints to formalize experimental high-content imaging data. In both cases, the mathematical models explain the inability to increase the tyrosination status by activating the Tubulin Tyrosine Ligase enzyme. The tyrosinated tubulin is indeed the product of a chain of two reactions in the cycle: the detyrosinated microtubule depolymerization followed by its tyrosination. The tyrosination status at equilibrium is thus limited by both reaction rates and activating the tyrosination reaction alone is not effective. Our computational model also predicts the effect of inhibiting the Tubulin Carboxy Peptidase enzyme which we have experimentally validated in MEF cellular model. Furthermore, the model predicts that the activation of two particular kinetic parameters, the tyrosination and detyrosinated microtubule depolymerization rate constants, in synergy, should suffice to enable an increase of the tyrosination status in living cells

Causes of increased length of hospitalization on a general thoracic surgery service: a prospective observational study

ObjectiveTo characterize medical and nonmedical reasons for delayed discharge on a general thoracic surgery unit.DesignA prospective observational cohort study.SettingA university-affiliated tertiary care institution.PatientsBetween February 1999 and July 2000, the in-hospital progress of 130 patients who had undergone an elective thoracic surgical procedure was evaluated prospectively. Baseline characteristics (age, sex, comorbid conditions and pulmonary function test results) were documented.Main outcome measuresComplications that delayed the time when the patient was medically ready for discharge. The day the patient was deemed fit for discharge (medically required length of stay) was compared with the actual day of discharge (actual length of stay). [...]impact on medically required length of stay, social factors may also significantly delay discharge

Long-term outcomes of bioresorbable vascular scaffold in ST-elevation myocardial infarction

Background: Bioresorbable vascular scaffolds (BVS) implantation in selected patients with stable angina has been demonstrated feasible and safe. However, limited data are currently available on long-term outcomes after BVS implantation for ST-elevation myocardial infarction (STEMI). Therefore, we sought to assess the safety, efficacy and long-term results of BVS implantation in STEMI patients. Methods: Retrospective review of all STEMI patients treated with the Absorb® BVS (Abbott Vascular, Santa Clara, CA) or conventional drug eluting stent (DES) between 1 April 2013 and 30 March 2014. Primary outcomes were procedural success, device thrombosis and device-oriented composite endpoint (DOCE) including cardiac death, target vessel myocardial infarction and target lesion revascularization. The study included 54 BVS patients and 121 DES patients. Results: Patients were slightly younger in the BVS group (60 vs. 63 years old, p =.03). Other baseline characteristics were comparable between the two groups. Procedural success was achieved in all patients. Median follow-up was 901 days and 849 days for BVS and DES patients, respectively (p =.01). The cumulative incidence of DOCE was not significantly different between the BVS and DES groups (7.5% vs. 9.1%, hazard ratio [HR]: 0.74 [95% confidence interval (CI): 0.26–2.2], p = NS). Rate of probable/definite device thrombosis were not statistically different between both groups (3.7% vs. 3.3%, p = NS). Conclusions: The results of this single-centre retrospective study, one of the first assessing long-term safety and efficacy of BVS in STEMI, seems reassuring with similar long-term results as compared with patients treated with conventional DES.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pressure Infusion Cuff and Blood Warmer during Massive Transfusion: An Experimental Study About Hemolysis and Hypothermia

<div><p>Background</p><p>Blood warmers were developed to reduce the risk of hypothermia associated with the infusion of cold blood products. During massive transfusion, these devices are used with compression sleeve, which induce a major stress to red blood cells. In this setting, the combination of blood warmer and compression sleeve could generate hemolysis and harm the patient. We conducted this study to compare the impact of different pressure rates on the hemolysis of packed red blood cells and on the outlet temperature when a blood warmer set at 41.5°C is used.</p><p>Methods</p><p>Pressure rates tested were 150 and 300 mmHg. Ten packed red blood cells units were provided by Héma-Québec and each unit was sequentially tested.</p><p>Results</p><p>We found no increase in hemolysis either at 150 or 300 mmHg. By cons, we found that the blood warmer was not effective at warming the red blood cells at the specified temperature. At 150 mmHg, the outlet temperature reached 37.1°C and at 300 mmHg, the temperature was 33.7°C.</p><p>Conclusion</p><p>To use a blood warmer set at 41.5°C in conjunction with a compression sleeve at 150 or 300 mmHg does not generate hemolysis. At 300 mmHg a blood warmer set at 41.5°C does not totally avoid a risk of hypothermia.</p></div

Mounting and procedure.

<p>Mounting and procedure.</p

Box-plot of hemolysis (%) according to the pressure exerted.

<p>Box-plot of hemolysis (%) according to the pressure exerted.</p