Subtelomeric I-scei-mediated Double-strand Breaks Are Repaired By Homologous Recombination In Trypanosoma Cruzi

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Trypanosoma cruzi chromosome ends are enriched in surface protein genes and pseudogenes (e.g., trans-sialidases) surrounded by repetitive sequences. It has been proposed that the extensive sequence variability among members of these protein families could play a role in parasite infectivity and evasion of host immune response. In previous reports we showed evidence suggesting that sequences located in these regions are subjected to recombination. To support this hypothesis we introduced a double-strand break (DSB) at a specific target site in a T. cruzi subtelomeric region cloned into an artificial chromosome (pTAC). This construct was used to transfect T. cruzi epimastigotes expressing the I-SceI meganuclease. Examination of the repaired sequences showed that DNA repair occurred only through homologous recombination (HR) with endogenous subtelomeric sequences. Our findings suggest that DSBs in subtelomeric repetitive sequences followed by HR between them may contribute to increased variability in T. cruzi multigene families. © 2016 Chiurillo, Moraes Barros, Souza, Marini, Antonio, Cortez, Curto, Lorenzi, Schijman, Ramirez and da Silveira.7DEC11/51475-3, FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo11/51693-0, FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo306591/2015-4, CNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Impact Of Hospital Infections On Patients Outcomes Undergoing Cardiac Surgery At Santa Casa De Misericórdia De Marília [impacto Das Infecções Hospitalares Na Evolução De Pacientes Submetidos à Cirurgia Cardíaca Na Santa Casa De Misericórdia De Marília]

Objective: this study aimed to determine the incidence of nosocomial infections, the risk factors and the impact of these infections on mortality among patients undergoing to cardiac surgery. Methods: Retrospective cohort study of 2060 consecutive patients from 2006 to 2012 at the Santa Casa de Misericórdia de Marília. Results: 351 nosocomial infections were diagnosed (17%), 227 non-surgical infections and 124 surgical wound infections. Major infections were mediastinitis (2.0%), urinary tract infection (2.8%), pneumonia (2.3%), and bloodstream infection (1.7%). The in-hospital mortality was 6.4%. Independent variables associated with non-surgical infections were age ≥ 60 years (OR 1.59, 95% CI 1.09 to 2.31), ICU stay ≥ 2 days (OR 5, 49, 95% CI 2.98 to 10, 09), mechanical ventilation ≥ 2 days (OR11, 93, 95% CI 6.1 to 23.08), use of urinary catheter ≥ 3 days (OR 4.85 95% CI 2.95-7.99). Non-surgical nosocomial infections were more frequent in patients with surgical wound infection (32.3% versus 7.2%, OR 6.1, 95% CI 4.03 to 9.24). Independent variables associated with mortality were age greater than 60 years (OR 2.0; 95% CI 1.4 to3.0), use of vasoactive drugs (OR 3.4, 95% CI 1.9 to 6, 0), insulin use (OR 1.8; 95% CI 1.2 to 2.8), surgical reintervention (OR 4.4; 95% CI 2.1 to 9.0) pneumonia (OR 4.3; 95% CI 2.1 to 8.9) and bloodstream infection (OR = 4.7, 95% CI 2.0 to 11.2). Conclusion: Non-surgical hospital infections are common in patients undergoing cardiac surgery; they increase the chance of surgical wound infection and mortality.292167176(2011), World Health Organization. Report on the burden of endemic health care-associated infection worldwide. Geneva: WHO Document Production ServicesUmscheid, C.A., Mitchell, M.D., Doshi, J.A., Agarwal, R., Williams, K., Brennan, P.J., Estimating the proportion of healthcare associated infections that are reasonably preventable and the related mortality and costs (2011) Infect Control Hosp Epidemiol, 32 (2), pp. 101-114Kollef, M.H., Sharpless, L., Vlasnik, J., Pasque, C., Murphy, D., Fraser, V.J., The impact of nosocomial infections on patient outcomes following cardiac surgery (1997) Chest, 112 (3), pp. 666-675Hortal, J., Muñoz, P., Cuerpo, G., Litvan, H., Rosseel, P., Bouza, E., Ventilator-associated pneumonia in patients undergoing major heart surgery: An incidence study in European (2009) Crit Care, 13 (3), p. 80. , European Study Group on Nosocomial InfectionEuropean Workgroup of Cardiothorac IntensivistsBouza, E., Hortal, J., Muñoz, P., Pascau, J., Pérez, M.J., Hiesmayr, M., Postoperative infections after major heart surgery and prevention of ventilator-associated pneumonia: A one-day European prevalence study (ESGNI-008) (2006) J Hosp Infect, 64 (3), pp. 224-230. , European Study Group on Nosocomial InfectionsEuropean Workgroup of Cardiothoracic IntensivistsLe Guillou, V., Tavolacci, M.P., Baste, J.M., Hubscher, C., Bedoit, E., Bessou, J.P., Surgical site infection after central venous catheter-related infection in cardiac surgery (2011) Analysis of a Cohort of 7557 Patients. J Hosp Infect, 79 (3), pp. 236-241Horan, T.C., Andrus, M., Dudeck, M.A., CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting (2008) Am J Infect Control, 36 (5), pp. 309-332Fowler Jr., V.G., O'Brien, S.M., Muhlbaier, L.H., Corey, G.R., Ferguson, T.B., Peterson, E.D., (2005) Clinical Predictors of Major Infections After Cardiac Surgery. Circulation, 30 (9 SUPPL.), pp. 358-365. , 112de Santo, L.S., Bancone, C., Santarpino, G., Romano, G., de Feo, M., Scardone, M., Microbi-ologically documented nosocomial infections after cardiac surgery: An 18-month prospective tertiary care center report (2008) Eur J Cardiothorac Surg, 33 (4), pp. 666-672Manniën, J., Wille, J.C., Kloek, J.J., van Benthem, B.H., Surveillance and epidemiology of surgical site infections after cardiothoracic surgery in The Netherlands (2011) J Thorac Cardio-vasc Surg, 141 (4), pp. 899-904. , 2002-2007Berg, T.C., Kjørstad, K.E., Akselsen, P.E., Seim, B.E., Løwer, H.L., Stenvik, M.N., National sur-veillance of surgical site infections after coronary artery bypass grafting in Norway: Inci-dence and risk factors (2011) Eur J Cardiothorac Surg, 40 (6), pp. 1291-1297Vosylius, S., Sipylaite, J., Ivaskevicius, J., Determinants of outcome in elderly patients admitted to the intensive care unit (2005) Age Ageing, 34 (2), pp. 157-162Sá, M.P., Soares, E.F., Santos, C.A., Figueiredo, O.J., Lima, R.O., Escobar, R.R., Risk factors for mediastinitis after coronary artery bypass grafting surgery (2011) Rev Bras Cir Cardio-vasc, 26 (1), pp. 27-35Tiveron, M.G., Fiorelli, A.I., Mota, E.M., Mejia, O.A.V., Brandão, C.M.A., Dallan, L.A.O., Fatores de risco pré-operatórios para mediastinite após cirurgia cardíaca: Análise de 2768 pacientes (2012) Rev Bras Cir Cardiovasc, 27 (2), pp. 203-210Magedanz, E.H., Bodanese, L.C., Guaragna, J.C.V.C., Albuquerque, L.C., Martins, V., Minossi, S.D., Elaboração de escore de risco para mediastinite pós-cirurgia de revascularização do miocárdio (2010) Rev Bras Cir Cardiovasc, 25 (2), pp. 154-159Steingrimsson, S., Gottfredsson, M., Kristinsson, K.G., Gudbjartsson, T., Deep sternal wound in-fections following open heart surgery in Iceland: A population-based study (2008) Scand Cardio-vasc J, 42 (3), pp. 208-213Risnes, I., Abdelnoor, M., Almdah, S.M., Svennevig, J.L., Mediastinitis after coronary artery by-pass grafting risk factors and long-term survival (2010) Ann Thorac Surg, 89 (5), pp. 1502-1509Filsoufi, F., Castillo, J.G., Rahmanian, P.B., Broumand, S.R., Silvay, G., Carpentier, A., Epide-miology of deep sternal wound infection in cardiac surgery (2009) J Cardiothorac Vasc Anesth, 23 (4), pp. 488-494Knapik, P., Nadziakiewicz, P., Urbanska, E., Saucha, W., Herdynska, M., Zembala, M., Cardiopul-monary bypass increases postoperative glycemia and insulin consumption after coronary surgery (2009) Ann Thorac Surg, 87 (6), pp. 1859-1865Riera, M., Ibáñez, J., Herrero, J., De Ibarra, J.I.S., Enríquez, F., Campillo, C., Respiratory tract in-fections after cardiac surgery: Impact on hospital morbidity and mortality (2010) J Cardiovasc Surg (Torino), 51 (6), pp. 907-914Garey, K.W., Kumar, N., Dao, T., Tam, V.H., Gentry, L.O., Risk factors for postoperative chest wound infections due to gram-negative bactéria in cardiac surgery patients (2006) J Chemother, 18 (4), pp. 402-408Inkster, T., Antibiotic prophylaxis for cardiac surgery: A shift away from traditional cephalosporins? (2009) J Cardiothorac Vasc Anesth, 23 (6), pp. 933-935Rahmanian, P.B., Adams, D.H., Castillo, J.G., Carpentier, A., Filsoufi, F., Predicting hospital mor-tality and analysis of long-term survival after major noncardiac complications in cardiac surgery patients (2010) Ann Thorac Surg, 90 (4), pp. 1221-1229Cove, M.E., Spelman, D.W., Maclaren, G., Infectious complications of cardiac surgery: A clinical review (2012) J Cardiothorac Vasc Anesth, 26 (6), pp. 1094-1100Flodgren, G., Conterno, L.O., Mayhew, A., Omar, O., Pereira, C.R., Shepperd, S., Interventions to improve professional adherence to guidelines for prevention of device-related infections (2013) Cochrane Database Syst Rev, 3. , CD00655

Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}=2.76 TeV

The elliptic, $v_2$, triangular, $v_3$, and quadrangular, $v_4$, azimuthal anisotropic flow coefficients are measured for unidentified charged particles, pions and (anti-)protons in Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. Results obtained with the event plane and four-particle cumulant methods are reported for the pseudo-rapidity range $|\eta|<0.8$ at different collision centralities and as a function of transverse momentum, $p_{\rm T}$, out to $p_{\rm T}=20$ GeV/$c$. The observed non-zero elliptic and triangular flow depends only weakly on transverse momentum for $p_{\rm T}>8$ GeV/$c$. The small $p_{\rm T}$ dependence of the difference between elliptic flow results obtained from the event plane and four-particle cumulant methods suggests a common origin of flow fluctuations up to $p_{\rm T}=8$ GeV/$c$. The magnitude of the (anti-)proton elliptic and triangular flow is larger than that of pions out to at least $p_{\rm T}=8$ GeV/$c$ indicating that the particle type dependence persists out to high $p_{\rm T}$.Comment: 16 pages, 5 captioned figures, authors from page 11, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186

Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm{NN}}} = 2.76 TeV

The inclusive transverse momentum ($p_{\rm T}$) distributions of primary charged particles are measured in the pseudo-rapidity range $|\eta|<0.8$ as a function of event centrality in Pb-Pb collisions at $\sqrt{s_{\rm{NN}}}=2.76$ TeV with ALICE at the LHC. The data are presented in the $p_{\rm T}$ range $0.15<p_{\rm T}<50$ GeV/$c$ for nine centrality intervals from 70-80% to 0-5%. The Pb-Pb spectra are presented in terms of the nuclear modification factor $R_{\rm{AA}}$ using a pp reference spectrum measured at the same collision energy. We observe that the suppression of high-$p_{\rm T}$ particles strongly depends on event centrality. In central collisions (0-5%) the yield is most suppressed with $R_{\rm{AA}}\approx0.13$ at $p_{\rm T}=6$-7 GeV/$c$. Above $p_{\rm T}=7$ GeV/$c$, there is a significant rise in the nuclear modification factor, which reaches $R_{\rm{AA}} \approx0.4$ for $p_{\rm T}>30$ GeV/$c$. In peripheral collisions (70-80%), the suppression is weaker with $R_{\rm{AA}} \approx 0.7$ almost independently of $p_{\rm T}$. The measured nuclear modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/284

Measurement of charm production at central rapidity in proton-proton collisions at s=2.76\sqrt{s} = 2.76 TeV

The $p_{\rm T}$-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D$^0$, D$^+$, and D$^{*+}$ in the rapidity range $|y|<0.5$, and for transverse momentum $1< p_{\rm T} <12$ GeV/$c$, were measured in proton-proton collisions at $\sqrt{s} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. The analysis exploited the hadronic decays D$^0 \rightarrow$K$\pi$, D$^+ \rightarrow$K$\pi\pi$, D$^{*+} \rightarrow$D$^0\pi$, and their charge conjugates, and was performed on a $L_{\rm int} = 1.1$ nb$^{-1}$ event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at $\sqrt{s} = 2.76$ TeV and at 7 TeV was evaluated by extrapolating to the full phase space the $p_{\rm T}$-differential production cross sections at $\sqrt{s} = 2.76$ TeV and our previous measurements at $\sqrt{s} = 7$ TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cdbar D mesons produced in a vector state was also determined.Comment: 20 pages, 5 captioned figures, 4 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/307

Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The yield of charged particles associated with high-$p_{\rm T}$ trigger particles ($8 < p_{\rm T} < 15$ GeV/$c$) is measured with the ALICE detector in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jet-like correlation peaks in azimuthal di-hadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta $p_{\rm T}> 3$ GeV/$c$ on the away-side drops to about 60% of that observed in pp collisions, while on the near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350