Human colonic in vitro fermentation of water-soluble arabinoxylans from hard and soft wheat alters Bifidobacterium abundance and short-chain fatty acids concentration

The human intestinal microbiome plays an important role in health due to the large number of beneficial effects related to the bacterial profile and the metabolites generated in the intestine. Arabinoxylans are compounds present in different cereals such as wheat and they can modulate the profile and functioning of some beneficial bacteria from human intestinal microbiota. In the present work, a colonic in vitro fermentation with human faecal inoculum was done using arabinoxylans extracted from Argentinian hard and soft wheat as substrates. Molecular size alteration of arabinoxylans were studied during fermentation and Lactobacillus and Bifidobacterium abundance as well as short chain fatty acids concentrations were determined. The arabinoxylans fermentation was proved to induce the growth of Bifidobacterium and the release of short-chain fatty acids. The speed and efficiency of fermentation were different for each of the arabinoxylan extracted from both wheat genotypes, perhaps because of differences in their chemical and physical structures. The consumption of water-extractable arabinoxylans (WE-AX) (either supplemented or enriched) to maintain the balance or modulate in a favorable way the profile of Bifidobacterium can be an important contribution to the human health.Fil: Paesani, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Sciarini, Lorena Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Moiraghi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Salvucci, Emiliano Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Prado, Samira B. R.. Universidade de Sao Paulo; BrasilFil: Perez, Gabriela Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Fabi, João Paulo. Universidade de Sao Paulo; Brasi

Efficacy and safety of dasatinib vs. Imatinib in Latin american subpopulation from the dasision trial in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP)

sem informação100120th Congress of European-Hematology-Associationsem informaçã

Energías para un futuro sustentable: experencia en la feria de ciencia y arte -Cuatrociencia- de la Universidad Nacional de Córdoba

En el contexto de un crecimiento social inteligente y sustentable, el uso de la energía cumple un rol estratégico. Su uso se considera sustentable si la disponibilidad de un dado recurso energético está asegurada y su impacto ambiental sobre la naturaleza de su abastecimiento, transporte y uso es limitado. Este concepto se amplía como sustentabilidad inteligente, que consiste en una estrategia sistémica que busca la mayor eficiencia de la performance del sistema completo, considerando no solamente el funcionamiento de los componentes y subsistemas, sino del sistema como un todo. Aparecen entonces en el escenario las fuentes de energías sustentables, las cuales necesitan, en general, un vector energético para su aprovechamiento. Este consiste en sustancias o dispositivos que almacenan energía, de tal manera que ésta pueda liberarse posteriormente en forma controlada. Se pueden señalar tres grandes vectores energéticos: combustibles líquidos, electricidad (vía red o baterías) e hidrógeno, donde cada uno requiere de una infraestructura singular para su implementación. Asimismo es fundamental el conocimiento público de estos conceptos, para lo cual la difusión de estos temas de manera amplia es imprescindible para la sensibilización social. Con este objetivo se montó un stand mostrando dos maquetas interactivas, representando la matriz energética actual y futura sustentable, respectivamente. Se llevaron a cabo experiencias demostrativas con dos dipositivos. En uno se producía hidrógeno electrolítico mediante electricidad proveniente de paneles solares. Este hidrógeno se utilizó luego en una celda de combustible para producir electricidad y accionar con ella un dispositivo eléctrico. En un panel de fondo se expusieron ploteos, banners y videos explicativos y didácticos sobre la temática. También se contó con una cocina y un calefón solares. La experiencia fue muy positiva dado que los espectadores se interesaron mucho en la temática y se propone montar este stand durante la realización del HYFUSEN.http://www.hyfusen.com/libro.htmlFil: Robledo, C. B. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico Química de Córdoba; Argentina.Fil: Robledo, C. B. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Matemática y Física; Argentina.Fil: Bonafé, F. R. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico Química de Córdoba; Argentina.Fil: Bonafé, F. R. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Matemática y Física; Argentina.Fil: Sigal, A. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Robledo, J. I. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Subirada, P. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Moiraghi, B. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; Argentina.Fil: Rodríguez, R. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Matemática; Argentina.Otras Ciencias de la Tierra y relacionadas con el Medio Ambient

Detection of leukemic stem cell (CD26+) in patients with chronic myeloid leukemia with different molecular response

La leucemia mieloide crónica (LMC) se caracteriza por la t(9;22)(q34;q11), generando el gen de fusión BCR-ABL1 que codifica la oncoproteina P210 con actividad constitutiva de tirosina kinasa. Los pa-cientes que presentan una profunda y sostenida res-puesta molecular a los inhibidores de tirosina kinasa (ITK) pueden interrumpir el tratamiento. Sin em-bargo, aproximadamente el 50% de los casos presen-tan recurrencia molecular, probablemente debido a la persistencia de la stem cell leucémica (SCL) quies-cente (no replicativa, transcripcionalmente silente). Recientes publicaciones han demostrado que la ex-presión de la enzima dipeptidil peptidasa IV (CD26) está restringida a la fracción CD45+/CD34+/CD38- de la SCL en LMC y no se ha detectado en otras SCL mieloides/linfoides ni en medula ósea normal. Por esta razón CD26 es considerado un nuevo y especí-fico bio-marcador de LMC.El objetivo del trabajo fue detectar las SCL CD26+ en pacientes con LMC con diferente respuesta molecular (RM) y determinar si estas células persisten aun en casos con respuesta molecular profunda (RMP).Se analizaron 193 muestras de pacientes con LMC (107 sexo masculino y 86 femenino) para evaluar la SCL mediante citometría de flujo usando el panel de anticuerpos monoclonales: CD45, CD34, CD38, CD26, CD117, CD123, CD3 y HLA-DR. En para-lelo se realizó el estudio de la respuesta molecular mediante qRT-PCR BCR-ABL1 (Método Taqman). Ambos estudios se realizaron en simultáneo en la misma muestra, durante el seguimiento en diferen-tes momentos bajo tratamiento con ITK (imatinib, nilotinib o dasatinib). Los pacientes con una reducción de BCR-ABL1 ≥ a 3 log tenían una significativa menor proporción de casos con SCL CD26+ comparado con aquellos que tenían <3 log de reducción de los transcriptos (p<0.0003, OR: 3.4, 95% CI: 1,7 - 6,8). Consideran-do los 76 casos con RMP (33 RM4.0; 38 RM4.5 y 5 RM5.0), solamente 12/76 (16%) mostraron per-sistencia de la SCL CD26+. La presencia de la SCL CD26+ se redujo acorde aumenta la profundidad de la RM: 21%, 13% y 0% en RM4.0, RM4.5 y RM5.0 respectivamente. Nuestros resultados muestran que los pacientes con buena RM (≥3log), se asociaron con baja propor-ción de casos con SCL CD26+. Cuando la detección de SCL se evaluó exclusivamente en los casos con RMP, se observó que el decrecimiento de la SCL se asoció a mayor profundidad de la RM. La stem cell leucémica es altamente quiescente por lo cual podría estar presente aun en casos con respuesta molecular indetectable. En nuestro estudio la persistencia de SCL fue del 16% en casos con respuesta molecular profunda, indicando que la SCL persiste a pesar de la RM alcanzada. Este nuevo abordaje investigando la SCL podría ser útil en el seguimiento a largo plazo y de gran importancia en la evaluación de la recu-rrencia molecular en los casos incluidos en protoco-los de discontinuación.Chronic Myeloid Leukemia (CML) is characterized by the reciprocal translocation t(9;22)(q34;q21) resulting in the BCR-ABL1 fusion gene encoding the P210 oncoprotein with a constitutive tyrosine kinase (TK) activity. It is known that patients with at least two years in deep and sustained molecular response could stop TK inhibitor (TKI) treatment. However, half of them show molecular recurrence, probably due to the persistence of transcriptionally quiescent leukemic stem cells (LSC). Recent studies show that the expression of the enzyme dipeptidylpeptidase IV (CD26) is mainly restricted to the CD45+/CD34+/ CD38- fraction in CML LSC, and it is not found in other myeloid/lymphoid LSC or in normal bone marrow. For this reason, CD26 is considered a novel specific biomarker in CML. The aim of this study was to detect the CD26+ LSC in CML patients with different molecular responses (MR) and to assess if these cells remain even in deep molecular response (DMR). We have evaluated 193 CML patients (107 males and 86 females) for detection of LSC by flow cytometry using the panel: CD45, CD34, CD38, CD26, CD117, CD123, CD3 and HLA-DR and the BCR-ABL1 quantification by qRT-PCR (Taqman method). Both studies were carried out simultaneously on the same sample, during the follow up at different time points under TKI treatment (Imatinib, Nilotinib, Dasatinib). Patients with ≥ 3 BCR-ABL1 log reduction had a significantly lower percentage of cases with CD26+ LSC compared with those who had < 3 log reduction (p<0.0003, OR: 3.4, 95% CI: 1,7 - 6,8). Out of the 76 patients with DMR (33 in MR4.0, 38 in MR4.5 and 5 in MR5.0) only 12/76 (16%) showed persistence of CD26+ LSC. Furthermore, the presence of CD26+ LSC decreased accordingly to the achieved DMR: 21%, 13% and 0% in MR4.0, MR4.5 and MR5.0 respectively, without significant differences. Our results show that patients with good MR (≥3log) were significantly associated with a lower proportion of cases with LSC presence. When the LSC analysis was performed exclusively in cases with DMR, we observed that the decrease of LSC accompanied the deepness of the molecular response. Since the LSC is highly quiescent, it could be present even in cases with undetectable MR. In our study persistence of LSC in cases with DMR was 16%, indicating that these cells remain despite the MR achieved. This new approach to the study of the LSC could be useful in long-term follow-up and of great importance in the evaluation of molecular recurrence in cases included in discontinuation protocols.Fil: Bengio, R. M.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Peña, M.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Palacios, F.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Moiraghi, B.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Negri Aranguren, P.. Instituto Privado de Hematologia y Hemoterapia; ArgentinaFil: Enrico, A.. Hospital Italiano de La Plata; ArgentinaFil: Mariano, R.. Provincia de Entre Rios. Hospital San Martin; ArgentinaFil: Toloza, Maria Jazmin Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Health burden and economic impact of measles-related hospitalizations in Italy in 2002–2003

Background: A large measles outbreak occurred in Italy in 2002 - 2003. This study evaluates the health burden and economic impact of measles- related hospitalizations in Italy during the specified period. Methods: Hospital discharge abstract data for measles hospitalizations in Italy during 2002 - 2003 were analysed to obtain information regarding number and rates of measles hospitalizations by geographical area and age group, length of hospital stay, and complications. Hospitalization costs were estimated on the basis of Diagnosis- Related Groups. Results: A total of 5,154 hospitalizations were identified, 3,478 ( 67%) of which occurred in children < 15 years of age. Most hospitalizations occurred in southern Italy ( 71 %) and children below 1 year of age presented the greatest hospitalization rates ( 46.2/ 100,000 and 19.0/ 100,000, respectively in 2002 and 2003). Pneumonia was diagnosed in 594 cases ( 11.5%) and encephalitis in 138 cases ( 2.7%). Total hospital charges were approximately (sic) 8.8 million. Conclusion: The nationwide health burden associated with measles during the 2002 - 2003 outbreak was substantial and a high cost was incurred by the Italian National Health Service for the thousands of measles- related hospitalizations which occurred. By assuming that hospital costs represent 40 - 50% of the direct costs of measles cases, direct costs of measles for the two years combined were estimated to be between (sic)17.6 - 22.0 million, which equates to the vaccination of 1.5 - 1.9 million children ( 3 - 4 birth cohorts) with one dose of MMR. The high cost of measles and the severity of its complications fully justify the commitment required to reach measles elimination

High cell-free DNA is associated with disease progression, inflammasome activation and elevated levels of inflammasome-related cytokine IL-18 in patients with myelofibrosis

Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder classified among chronic myeloproliferative neoplasms, characterized by exacerbated myeloid and megakaryocytic proliferation and bone marrow fibrosis. It is induced by driver (JAK2/CALR/MPL) and high molecular risk mutations coupled to a sustained inflammatory state that contributes to disease pathogenesis. Patient outcome is determined by stratification into risk groups and refinement of current prognostic systems may help individualize treatment decisions. Circulating cell-free (cf)DNA comprises short fragments of double-stranded DNA, which promotes inflammation by stimulating several pathways, including inflammasome activation, which is responsible for IL-1β and IL-18 maturation and release. In this work, we assessed the contribution of cfDNA as a marker of disease progression and mediator of inflammation in MF. cfDNA was increased in MF patients and higher levels were associated with adverse clinical outcome, a high-risk molecular profile, advanced disease stages and inferior overall survival, indicating its potential value as a prognostic marker. Cell-free DNA levels correlated with tumor burden parameters and markers of systemic inflammation. To mimic the effects of cfDNA, monocytes were stimulated with poly(dA:dT), a synthetic double-stranded DNA. Following stimulation, patient monocytes released higher amounts of inflammasome-processed cytokine, IL-18 to the culture supernatant, reflecting enhanced inflammasome function. Despite overexpression of cytosolic DNA inflammasome sensor AIM2, IL-18 release from MF monocytes was shown to rely mainly on the NLRP3 inflammasome, as it was prevented by NLRP3-specific inhibitor MCC950. Circulating IL-18 levels were increased in MF plasma, reflecting in vivo inflammasome activation, and highlighting the previously unrecognized involvement of this cytokine in MF cytokine network. Monocyte counts were higher in patients and showed a trend towards correlation with IL-18 levels, suggesting monocytes represent a source of circulating IL-18. The close correlation shown between IL-18 and cfDNA levels, together with the finding of enhanced DNA-triggered IL-18 release from monocytes, suggest that cfDNA promotes inflammation, at least in part, through inflammasome activation. This work highlights cfDNA, the inflammasome and IL-18 as additional players in the complex inflammatory circuit that fosters MF progression, potentially providing new therapeutic targets

Clinical activity of ponatinib in one patient with chronic myeloid leukemia in chronic phase with e19a2 transcript and T315I mutation

Background: Chronic myeloid leukemia (CML) is a hematological disorder that in rare cases, mainly in CML neutrophilic, presents the e19a2 rearrangement. The encoded product is a 230-KDa protein. Despite the remarkable responses to treatment of most patients, a small but significant fraction of them develop clinical resistance to the tyrosine kinase inhibitors (TKIs). The most common mechanism of resistance is point mutations in the ABL1 kinase domain. The recently approved third-generation TKI ponatinib demonstrated remarkable activity in patients with multi-TKI-resistant disease. Particularly impressive was its efficacy in patients with T315I mutation that is resistant to all other TKIs. Methods: Qualitative PCR was carried out by multiplex approach. Relative transcripts quantification was performed by one-step realtime PCR, with a specific Taqman probe and primers for the e19a2 rearrangement. We carried out a mutational screening by high-resolution melting, and the mutation was identified by Sanger method. The mutation burden was quantified by quantitative PCR using allele-specific primers. Results: In a patient with CML, we identified a PCR product corresponding to e19a2 rearrangement harboring T315I mutation. At the time of mutational analysis, during dasatinib treatment, the T315I clone was 100% and the quantification of BCR-ABL1 was 18%. After ponatinib therapy, the T315I mutation burden decreased down to undetectable levels and the BCR-ABL1 transcripts showed a very low value (0.011%). Conclusions: Here, we report the hematological, cytogenetic, and molecular response of a patient with refractory CML in chronic phase with e19a2 transcripts, carrying T315I mutation that was successfully treated with ponatinib.Fil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bengió, Raquel M.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Moiraghi, Elena B.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Gonzalez, Mariana Selena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Noriega, Maria Fernanda. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

The average cost of measles cases and adverse events following vaccination in industrialised countries.

BACKGROUND: Even though the annual incidence rate of measles has dramatically decreased in industrialised countries since the implementation of universal immunisation programmes, cases continue to occur in countries where endemic measles transmission has been interrupted and in countries where adequate levels of immunisation coverage have not been maintained. The objective of this study is to develop a model to estimate the average cost per measles case and per adverse event following measles immunisation using the Netherlands (NL), the United Kingdom (UK) and Canada as examples. METHODS: Parameter estimates were based on a review of the published literature. A decision tree was built to represent the complications associated with measles cases and adverse events following immunisation. Monte-Carlo Simulation techniques were used to account for uncertainty. RESULTS: From the perspective of society, we estimated the average cost per measles case to be US$276, US$307 and US$254 for the NL, the UK and Canada, respectively, and the average cost of adverse events following immunisation per vaccinee to be US$1.43, US$1.93 and US$1.51 for the NL, UK and Canada, respectively. CONCLUSIONS: These average cost estimates could be combined with incidence estimates and costs of immunisation programmes to provide estimates of the cost of measles to industrialised countries. Such estimates could be used as a basis to estimate the potential economic gains of global measles eradication