307 research outputs found
Malignant osteopetrosis: bone marrow transplantation
A osteopetrose Ă© uma osteopatia hereditĂĄria caracterizada pela deficiĂȘncia na reabsorção Ăłssea que ocorre por disfunção dos osteoclastos. Com o acĂșmulo de material osteĂłide que oblitera o canal medular, ocorre hematopoiese extramedular (hepato-esplenomegalia), obliteração dos forames dos nervos cranianos (cegueira, surdez, paralisias faciais), macrocefalia, protusĂŁo da fronte, hipertelorismo, exoftalmo, aumento da pressĂŁo intracraniana, retardo na erupção dentĂĄria, atraso no crescimento, atraso no desenvolvimento neuropsicomotor, e a morte ocorre precocemente nos primeiros anos de vida. A Ășnica alternativa terapĂȘutica curativa Ă© o transplante de medula Ăłssea (TMO) de doador HLA idĂȘntico, pois restabelece a hematopoiese e a função monĂłcito-macrĂłfago, com melhora das lesĂ”es Ăłsseas e anormalidades hematopoiĂ©ticas, embora nĂŁo reverta as alteraçÔes sensoriais jĂĄ instaladas. Os autores relatam casos de duas crianças portadoras de osteopetrose maligna submetidas ao transplante de medula Ăłssea com sucesso. A primeira encontra-se no dia +1260 do TMO, com melhora evidente da radiologia esquelĂ©tica, sem progressĂŁo das deficiĂȘncias neurolĂłgicas que apresentava, e com biĂłpsia Ăłssea sem sinais de osteopetrose. O segundo paciente encontra-se no dia + 700, com sinais de reabsorção Ăłssea e sem progressĂŁo dos danos neurolĂłgicos. Os autores chamam a atenção para a necessidade de diagnĂłstico precoce da osteopetrose e o rĂĄpido encaminhamento para o transplante de medula Ăłssea antes da instalação de seqĂŒelas neurolĂłgicas definitivas.Osteopetrosis is an inherited disorder characterized by the inability to reabsorb and remodel bone due to osteoclast dysfunction. The encroachment by bone and mineralized cartilage of the medullary cavities leads to extramedullary hematopoiesis (hepatosplenomegaly) and cranial-nerve foramina leads to blindness, auditory nerve damage, and occulomotor and facial nerve palsies. Defective bone re-absorption also leads to macrocephaly, frontal bossing, hypertelorism, exophthalmos, increased intracranial pressure, retarded tooth eruption, retarded linear growth and psychomotor delay. Death occurs within the first years of life. The only curative therapy is allogeneic bone marrow transplantation with a HLA-identical donor, which restores hematopoiesis, monocyte-macrophage function and bone recovery, but there is no sensorial deficit restoration once present. The authors report two cases of allogeneic bone marrow transplant for infantile malignant osteopetrosis. The first child, on day 1260 after bone marrow transplantation (BMT), showed radiologic bone recovery and no progression of neurological deficits with a bone biopsy showing no signs of osteopetrosis. The second child showed signs of bone re-absorption and no progression of neurological deficits on day 700. The authors emphasize the importance of early diagnosis of osteopetrosis and the necessity of bone marrow transplantation before neurological deficits have begun
Transcription profiling in papillary thyroid carcinoma reveals potential diagnostic markers and drug targets
Financial support FAPESP and CAPES
Modelo de gestiĂłn organizacional: barreras y oportunidades en la conformaciĂłn y fortalecimiento de una red institucional de investigaciĂłn en salud
En este proyecto se pretende describir los factores que favorecen y/u
obstaculizan la constituciĂłn de una red institucional de investigaciĂłn para
la salud, desde las propias expresiones de los actores/agentes del Estado
(Ministerio de Salud) y de las instituciones académicas de la provincia
de Mendoza. Es un estudio descriptivo de corte transversal, que realizarĂĄ
un anĂĄlisis centrado en el concepto de problema, desde la concepciĂłn
de planificaciĂłn situacional. Se utilizarĂĄn tĂ©cnicas de recolecciĂłn de informaciĂłn con una metodologĂa mixta cuanti
y cualitativa. La poblaciĂłn accesible de este estudio estĂĄ conformada por las ĂĄreas de investigaciĂłn formalmente
establecidas, por norma, de los ministerios de Salud de las provincias de Mendoza, San Luis y La Rioja y las Universidades
con sus unidades acadĂ©micas y/o facultades del sector pĂșblico y privado de la provincia de Mendoza,
quedando excluidas las universidades y/o facultades que no posean carreras afines a la salud de la provincia de
Mendoza, y el årea de investigación del ministerio de Salud de San Juan por no contar con referente técnico de investigación
a nivel ministerial. Se pretende indagar sobre factores que permitan la posterior elaboraciĂłn de indicadores
para medir las acciones de la red local y la posible construcciĂłn de una red regional como polĂtica de Salud
Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins
Background:Trypanosoma cruzi ribosomal P proteins, P2ÎČ and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with ÎČ1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2ÎČ, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2ÎČ or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos MejĂa"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. FernĂĄndez"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Instituto de Investigaciones BiotecnolĂłgicas. Universidad Nacional de San MartĂn. Instituto de Investigaciones BiotecnolĂłgicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Instituto de Investigaciones BiotecnolĂłgicas. Universidad Nacional de San MartĂn. Instituto de Investigaciones BiotecnolĂłgicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura MĂłnica. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos MejĂa"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos MejĂa"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: 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"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica; Argentin
Socioeconomic status, non-communicable disease risk factors, and walking speed in older adults: Multi-cohort population based study
Objective To assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical inactivity, smoking) with loss of physical functioning at older ages. Design Multi-cohort population based study. Setting 37 cohort studies from 24 cou
Determinants of the exclusive breastfeeding abandonment: psychosocial factors
OBJECTIVE To assess the determinants of exclusive breastfeeding abandonment. METHODS Longitudinal study based on a birth cohort in Viçosa, MG, Southeastern Brazil. In 2011/2012, 168 new mothers accessing the public health network were followed. Three interviews, at 30, 60, and 120 days postpartum, with the new mothers were conducted. Exclusive breastfeeding abandonment was analyzed in the first, second, and fourth months after childbirth. The Edinburgh Postnatal Depression Scale was applied to identify depressive symptoms in the first and second meetings, with a score of â„ 12 considered as the cutoff point. Socioeconomic, demographic, and obstetric variables were investigated, along with emotional conditions and the new mothersâ social network during pregnancy and the postpartum period. RESULTS The prevalence of exclusive breastfeeding abandonment at 30, 60, and 120 days postpartum was 53.6% (n = 90), 47.6% (n = 80), and 69.6% (n = 117), respectively, and its incidence in the fourth month compared with the first was 48.7%. Depressive symptoms and traumatic delivery were associated with exclusive breastfeeding abandonment in the second month after childbirth. In the fourth month, the following variables were significant: lower maternal education levels, lack of homeownership, returning to work, not receiving guidance on breastfeeding in the postpartum period, motherâs negative reaction to the news of pregnancy, and not receiving assistance from their partners for infant care. CONCLUSIONS Psychosocial and sociodemographic factors were strong predictors of early exclusive breastfeeding abandonment. Therefore, it is necessary to identify and provide early treatment to nursing mothers with depressive symptoms, decreasing the associated morbidity and promoting greater duration of exclusive breastfeeding. Support from health professionals, as well as that received at home and at work, can assist in this process
Chagas Cardiomiopathy: The Potential of Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage
Chagas disease remains a major cause of morbidity and mortality in several
countries of Latin America and has become a potential public health problem in
countries where the disease is not endemic as a result of migration flows.
Cardiac involvement represents the main cause of mortality, but its diagnosis is
still based on nonspecific criteria with poor sensitivity. Early identification
of patients with cardiac damage is desirable, since early treatment may improve
prognosis. Diastolic dysfunction and elevated brain natriuretic peptide levels
are present in different cardiomyopathies and in advanced phases of Chagas
disease. However, there are scarce data about the role of these parameters in
earlier forms of the disease. We conducted a study to assess the diastolic
function, regional systolic abnormalities and brain natriuretic peptide levels
in the different forms of Chagas disease. The main finding of our investigation
is that diastolic dysfunction occurs before any cardiac dilatation or motion
abnormality. In addition, BNP levels identify patients with diastolic
dysfunction and Chagas disease with high specificity. The results reported in
this study could help to early diagnose myocardial involvement and better
stratify patients with Chagas disease
Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor
AbstractDespite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment
Automatic segmentation of cerebral infarcts in follow-up computed tomography images with convolutional neural networks
Background and purpose: Infarct volume is a valuable outcome measure in treatment trials of acute ischemic stroke and is strongly associated with functional outcome. Its manual volumetric assessment is, however, too demanding to be implemented in clinical practice. Objective: To assess the value of convolutional neural networks (CNNs) in the automatic segmentation of infarct volume in follow-up CT images in a large population of patients with acute ischemic stroke. Materials and methods: We included CT images of 1026 patients from a large pooling of patients with acute ischemic stroke. A reference standard for the infarct segmentation was generated by manual delineation. We introduce three CNN models for the segmentati
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