Integration of miRNA and gene expression profiles suggest a role for miRNAs in the pathobiological processes of acute Trypanosoma cruzi infection.

Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop severe heart lesions.

Clustering based on unsupervised binary trees to define subgroups of cancer patients according to symptom severity in cancer.

Background: Studies have suggested that clinicians do not feel comfortable with the interpretation of symptom severity, functional status, and quality of life (QoL). Implementation strategies of these types of measurements in clinical practice imply that consensual norms and guidelines regarding data interpretation are available. The aim of this study was to define subgroups of patients according to the levels of symptom severity using a method of interpretable clustering that uses unsupervised binary trees.

Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 'CREATE'.

Background: Clear-cell sarcoma (CCSA) is an orphan malignancy, characterized by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic CCSA.

Patients And Methods: Patients with CCSA received oral crizotinib 250 mg twice daily.

Is gestational diabetes an independent risk factor of neonatal severe respiratory distress syndrome after 34 weeks of gestation? A prospective study.

Purpose: To evaluate if neonates delivered after 34 weeks from mothers diagnosed with gestational diabetes (GD) are exposed to an increased risk of neonatal severe respiratory distress syndrome (SRDS).

Methods: Women with singleton pregnancy in labour after 34 weeks of gestation or admitted for planned caesarean section and who had been systematically screened for GD were eligible to participate to this prospective cohort study. Diagnosis of SRDS was defined by the association of clinical signs of early neonatal respiratory distress, with consistent radiologic features and requiring mechanical ventilation with a fraction of inspired oxygen (FiO) >0.

Heart rate recovery improves after exercise in water when compared with on land.

Background: Water immersion has demonstrated its effectiveness in the recovery process after exercise. This study presents for the first time the impact of water immersion on heart rate recovery after low-intensity cycle exercise.

Methods: Sixteen male volunteers were involved in the study.

The Accuracy of Large Loop Excision of the Transformation Zone Specimen Dimensions in Determining Volume: A Multicentric Prospective Observational Study.

Objective: The aim of the study was to determine which mathematical formula of specimen dimensions is the most accurate method of determining volume of the excised specimen at loop excision of the transformation zone.

Materials And Methods: A multicenter prospective observational study was conducted. A total of 258 patients who had a loop excision of the transformation zone performed as treatment of cervical intraepithelial neoplasia 2-3 were included.

Histone Purification from Saccharomyces cerevisiae.

The nucleosome structure consists of a histone octamer made by a tetramer of H3-H4 histones and two dimers of H2A-H2B. Nucleosomes undergo extensive posttranslational modifications that regulate nucleosome interactions, position, and stability.We describe a protocol allowing the robust purification of histones from the yeast Saccharomyces cerevisiae.

Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis.

Background: Pazopanib is a multitargeted tyrosine kinase inhibitor approved for the treatment of patients with selective subtypes of advanced soft tissue sarcoma (STS) who have previously received standard chemotherapy including anthracyclines. Data on the efficacy in vascular sarcomas are limited. The main objective of this study was to investigate the activity of pazopanib in vascular sarcomas.

Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma.

Introduction: Currently, very few studies are available concerning the mammalian Hippo pathway in bone sarcomas. YAP/TAZ transcription co-activators are key downstream effectors of this pathway and may also have oncogenic properties. Additionally, recent in-vitro experiments showed that expression of β1-integrin promoted metastasis in osteosarcomas.

ER stress in temozolomide-treated glioblastomas interferes with DNA repair and induces apoptosis.

Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor. Radiation in combination with temozolomide (TMZ), the current chemotherapeutic for GBMs, only provides 12-14 months survival post diagnosis. Because GBMs are dependent on both activation of the DNA damage pathway and the endoplasmic reticulum (ER) stress response, we asked if a novel ER stress inducing agent, JLK1486, increases the efficacy of TMZ.

Determination of Water Vapor Pressure Over Corrosive Chemicals Versus Temperature Using Raman Spectroscopy as Exemplified with 85.5% Phosphoric Acid.

A method to determine the water vapor pressure over a corrosive substance was developed and tested with 85.5 ± 0.4% phosphoric acid.

RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT.

Nonrelapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditioning (RIC) regimens have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of the current retrospective study was to compare transplantation outcomes of acute myeloid leukemia (AML) patients given UCBT after either RIC or MAC.

Low-Permeability Poly(ether Ether Ketone)-Based Ampholytic Membranes.

Ion-exchange membranes based on sulfonated and sulfaminated poly(ether ether ketone) were prepared by a modified sulfamination route. In a first step, poly(ether ether ketone) was sulfonated. The sulfonic acid groups were then transformed into chlorosulfonic moieties by reaction with thionyl chloride.

Haploidentical transplantation: selecting optimal conditioning regimen and stem cell source.

Recently, haploidentical donor transplant (HIDT) has emerged as a viable option for patients in need of an allogeneic stem cell transplant without an immediately available well-matched human leukocyte antigen (HLA) sibling or unrelated donor. Given the near immediate availability of haploidentical donors, along the high likelihood of a haploidentical match within a patient's first-degree family, HIDT is becoming increasing attractive, particularly for patients with high-risk disease. In the last decade, several strategies of T-cell-replete bone marrow or peripheral blood HIDT has been developed with diverse conditioning regimens and graft-versus-host disease prophylaxis based on diverse in vivo T-cell modulation strategies conducting to a wide development for the treatment of benign and malignant hematological disorders.

Haploidentical T Cell-Replete Transplantation with Post-Transplantation Cyclophosphamide for Patients in or above the Sixth Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an Human Leukocyte Antigen-Matched Related or Unrelated Donor.

It has recently been shown that a T cell-replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD).

Hypertension (HTN) as a potential biomarker of efficacy in pazopanib-treated patients with advanced non-adipocytic soft tissue sarcoma. A retrospective study based on European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 trials.

Background: Reliable biomarkers of pazopanib's efficacy in soft tissue sarcoma (STS) are lacking. Hypertension (HTN) is an on-target effect of vascular endothelial growth factor (VEGF)-receptor inhibitors such as pazopanib. We evaluated the association of pazopanib-induced HTN with antitumour efficacy in patients with metastatic non-adipocytic STS.

MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes.

Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms. Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase.

RPA prevents G-rich structure formation at lagging-strand telomeres to allow maintenance of chromosome ends.

Replication protein A (RPA) is a highly conserved heterotrimeric single-stranded DNA-binding protein involved in DNA replication, recombination, and repair. In fission yeast, the Rpa1-D223Y mutation provokes telomere shortening. Here, we show that this mutation impairs lagging-strand telomere replication and leads to the accumulation of secondary structures and recruitment of the homologous recombination factor Rad52.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Sgs1 and Sae2 promote telomere replication by limiting accumulation of ssDNA.

In budding yeast, DNA ends are processed by the consecutive action of MRX/Sae2 and two redundant pathways dependent on Sgs1/Dna2 and Exo1, and this processing is counteracted by Ku heterodimer. Here we show that DNA end resection by Sae2 and Sgs1 is dispensable for normal telomere maintenance by telomerase. Instead, these proteins facilitate telomere replication and limit the accumulation of single-strand DNA (ssDNA) at replication fork pause sites.

MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy.

Background/methods: Chagas disease is caused by an intracellular parasite, Trypanosoma cruzi, and it is a leading cause of heart failure in Latin America. The main clinical consequence of the infection is the development of a Chronic Chagas disease Cardiomyopathy (CCC), which is characterized by myocarditis, hypertrophy and fibrosis and affects about 30% of infected patients. CCC has a worse prognosis than other cardiomyopathies, like idiopathic dilated cardiomyopathy (DCM).