35 research outputs found
Ex vivo characterization of Breg cells in patients with chronic Chagas disease
Despite the growing importance of the regulatory function of B cells in many infectious diseases, their immunosuppressive role remains elusive in chronic Chagas disease (CCD). Here, we studied the proportion of different B cell subsets and their capacity to secrete IL-10 ex vivo in peripheral blood from patients with or without CCD cardiomyopathy. First, we immunophenotyped peripheral blood mononuclear cells from patients according to the expression of markers CD19, CD24, CD38 and CD27 and we showed an expansion of total B cell and transitional CD24highCD38high B cell subsets in CCD patients with cardiac involvement compared to non-infected donors. Although no differences were observed in the frequency of total IL-10 producing B cells (B10) among the groups, CCD patients with cardiac involvement showed an increased proportion of naĂŻve B10 cells and a tendency to a higher frequency of transitional B10 cells compared to non-infected donors. Our research demonstrates that transitional B cells are greatly expanded in patients with the cardiac form of CCD and these cells retain the ability to secrete IL-10. These findings provide insight into the phenotypic distribution of regulatory B cells in CCD, an important step towards new strategies to prevent cardiomyopathy associated with T. cruzi infection.Fil: Girard, MagalĂ Celeste. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: Acevedo, Gonzalo RaĂșl. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: Ossowski, Micaela Soledad. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: FernĂĄndez, Marisa. DirecciĂłn Nacional de Instituto de InvestigaciĂłn. AdministraciĂłn Nacional de Laboratorio e Instituto de Salud "Dr. C. G. MalbrĂĄn". Instituto Nacional de ParasitologĂa "Dr. Mario Fatala Chaben"; ArgentinaFil: HernĂĄndez, Yolanda. DirecciĂłn Nacional de Instituto de InvestigaciĂłn. AdministraciĂłn Nacional de Laboratorio e Instituto de Salud "Dr. C. G. MalbrĂĄn". Instituto Nacional de ParasitologĂa "Dr. Mario Fatala Chaben"; ArgentinaFil: Chadi, RaĂșl. Gobierno de la Ciudad AutĂłnoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; Argentin
Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease
The clinical evolution of patients with chronic Chagas disease (CCD) is mainly associated with an excessive inflammation and a defective immunomodulatory profile caused by the interaction between T. cruzi and the host. Regulatory B (Breg) cells exert immune suppression mostly through IL-10 production (B10 cells), but also through IL-10-independent mechanisms. Previously, we demonstrated that CCD patients with cardiomyopathy show changes in the ex vivo Breg cell phenotypic distribution although maintain IL-10 production capacity. Here, we sought to identify potential alterations on Breg cells upon in vitro stimulation. Isolated B cells from CCD patients with or without cardiomyopathy and non-infected (NI) donors were stimulated with T. cruzi lysate or CpG + CD40L, and characterized by flow cytometry based on the expression of CD24, CD27, CD38, and the regulatory molecules IL-10 and PD-L1. IL-10 and IL-17 secretion in the supernatant of B cells was evaluated by ELISA. Data showed that T. cruzi stimulation diminished the expression of CD24 and CD38 on CD27â B cells while reducing the percentage of CD24high inside CD27+ B cells. Furthermore, T. cruzi induced a regulatory B cell phenotype by increasing B10 cells and IL-10 secretion in all the groups. The innate-like B10 cells expansion observed in patients with cardiomyopathy would be associated with CD27â B10 cell subsets, while no predominant phenotype was found in the other groups. Patients with cardiomyopathy also displayed higher IL-17 secretion levels in T. cruziâactivated B cells. CpG + CD40L stimulation revealed that B cells from CCD patients and NI donors had the same ability to differentiate into B10 cells and secrete IL-10 in vitro. Additionally, CCD patients showed an increased frequency of CD24âCD27â B cells and a reduction in the percentage of CD24highCD27+ Breg cells, which appeared to be inversely correlated with the presence of T. cruzi DNA in blood. Finally, CCD patients exhibited a higher frequency of PD-L1+ B cells in T. cruziâstimulated samples, suggesting that IL-10-independent mechanisms could also be tangled in the control of inflammation. Altogether, our results provide evidence about the potential role of Breg cells in the immune response developed against T. cruzi and its contribution to chronic Chagas cardiomyopathy.Fil: Girard, MagalĂ Celeste. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: Ossowski, Micaela Soledad. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: Muñoz Calderon, Arturo Alejandro. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: FernĂĄndez, Marisa. Instituto Nacional de ParasitologĂa âDr. Mario Fatala ChabĂ©nâ; ArgentinaFil: Hernandez Vasquez, Yolanda Maria. Instituto Nacional de ParasitologĂa Dr. Mario Fatala C; ArgentinaFil: Chadi, RaĂșl. Gobierno de la Ciudad AutĂłnoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; Argentin
Phenotypic Characteristics and Clonal Relationships of Stenotrophomonas maltophilia Isolates in Hospitalized Adults from a Private Center in Lima, Peru
The impact of surgical practice on oncological outcomes in robot-assisted radical hysterectomy for early-stage cervical cancer, Spanish National Registry
Minimal invasive surgery (MIS) has been associated with lower disease-free survival than open surgery among women who underwent radical hysterectomy for early-stage cervical cancer. However, the mechanisms by which MIS increases mortality in cervical cancer remain uncertain. We aimed to determine if surgical practice among centers using robotic surgery has an impact on oncological outcomes. We evaluated 215 women with early-stage cervical cancer (â€IB1 or IIA1, FIGO 2009) who underwent robot-assisted radical hysterectomy in five Spanish tertiary centers between 2009 and 2018. A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed for the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes in all surgical approaches. Abstract: This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (â€IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A (n = 118) and group B (n = 97), with recurrence rates of 10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13-1.15, p-value = 0.001; death OR = 1.10, 95% CI = 1.02-1.18, p-value = 0.012; disease-specific mortality ORr = 1.11, 95% CI = 1.04-1.19, p-value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer
The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases
The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article
Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study
Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9â27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6â16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2â1.8), stage II (OR 1.6; 95% CI 1.4â1.9), and stage III or worse (OR 2.8; 95% CI 2.3â3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat
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Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study
Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9â27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6â16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2â1.8), stage II (OR 1.6; 95% CI 1.4â1.9), and stage III or worse (OR 2.8; 95% CI 2.3â3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat
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Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study
The original version of this article unfortunately contained a mistake
DeterminaciĂłn de la activaciĂłn de los linfocitos T CD4+ T. cruzi-especĂficos en pacientes con diferentes estados clĂnicos de la enfermedad de Chagas crĂłnica
El estudio de las cĂ©lulas T CD4+ antĂgenoespecĂficas es fundamental para comprender los mecanismos que llevan a un paciente con la Enfermedad de Chagas crĂłnica (ECC) a desarrollar cardiomiopatĂa. Asi, en paralelo al estudio del uso de la metodologĂa de expresiĂłn de marcadores de activaciĂłn (AIM) para detectar cĂ©lulas parĂĄsito-especĂficas en estos pacientes, decidimos evaluar la eficacia de este ensayo en los diferentes cuadros clĂnicos. Para ello, se aislaron cĂ©lulas mononucleares de sangre perifĂ©rica de pacientes con ECC sin sintomatologĂa clĂnica, con cardiomiopatĂa y donantes no infectados. Las cĂ©lulas se incubaron durante 24 horas sin estĂmulo antigĂ©nico, con lisado de T. cruzi provenientes de diferentes cepas (Dm28c, Sylvio, CL Brener) y PHA (control positivo). Se utilizĂł la combinaciĂłn dual OX40/CD25 y OX40/CD137 para el ensayo AIM, y CD45RA y CCR7 para analizar la distribuciĂłn fenotĂpica en las subpoblaciones naĂŻve, dememoria central, de memoria efectora y de memoria efectora terminal. Nuestros resultadosmuestran que la co-expresiĂłn de OX40/CD25 y OX40/CD137 permite determinar la presencia de cĂ©lulas T CD4+ parĂĄsito-especĂficas en ambos grupos de pacientes y con todas las cepas de T.cruzi; CL-Brener fue la menos reactiva. Un hallazgo interesante fue el hecho que los pacientes sin sintomatologĂa clĂnica tienen una tendencia a mostrar un perfil de activaciĂłn mayor que los individuos con cardiomiopatĂa. Aunque las cĂ©lulas activadas fueron en su mayorĂa cĂ©lulas de memoria efectora, el fenotipo fue variable en funciĂłn de la cepa utilizada para la estimulaciĂłn, asi como tambiĂ©n si las mismas procedĂan de pacientes sin o con sintomatologĂa.Nuestros resultados muestran que estas combinaciones duales de AIM permiten determinar la activaciĂłn de las cĂ©lulas T CD4+ de pacientes en cualquiera de las formas clĂnicas, siendo en su mayorĂa cĂ©lulas que ya han âvistoâ al antĂgeno.Fil: Cruz, Karen MagalĂ. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: Ferragut, Fatima Eneida del Valle. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: Hernandez Vasquez, Yolanda Maria. DirecciĂłn Nacional de Instituto de InvestigaciĂłn. AdministraciĂłn Nacional de Laboratorio e Instituto de Salud âDr. C. G. MalbrĂĄnâ. Instituto Nacional de ParasitologĂa "Dr. Mario Fatala Chabenâ; ArgentinaFil: Fernandez, Marisa. DirecciĂłn Nacional de Instituto de InvestigaciĂłn. AdministraciĂłn Nacional de Laboratorio e Instituto de Salud âDr. C. G. MalbrĂĄnâ. Instituto Nacional de ParasitologĂa "Dr. Mario Fatala Chabenâ; ArgentinaFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaXXXIII ReuniĂłn de la Sociedad Argentina de ProtozoologĂaCiudad AutĂłnoma Buenos AiresArgentinaSociedad Argentina de ProtozoologĂ