Evaluation of a novel digital environment for learning medical parasitology.

open access articleEukaryotic parasites represent a serious human health threat requiring health professionals with parasitology skills to counteract this threat. However, recent surveys highlight an erosion of teaching of parasitology in medical and veterinary schools, despite reports of increasing instances of food and water borne parasitic infections. To address this we developed a web-based resource, DMU e-Parasitology®, to facilitate the teaching and learning of parasitology, comprising four sections: theoretical; virtual laboratory; virtual microscopy; virtual clinical case studies. Testing the package was performed using a questionnaire given to ninety-five Pharmacy students in 2017/18 to assess effectiveness of the package as a teaching and learning tool. 89.5% of students reported appropriate acquisition of knowledge of the pathology, prevention and treatment of some parasitic diseases. 82.1% also welcomed the clinical specialism of the package as it helped them to acquire basic diagnostic skills, through learning infective features/morphology of the parasites

Molecular characterization of KPC-2–positive Klebsiella pneumoniae isolates from a neurosurgical centre in Argentina

Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide. Klebsiella pneumoniae is an important nosocomial pathogen with a high capacity for nosocomial spread. We described the occurrence of plasmid-encoded KPC-2–harbouring K. pneumoniae isolates recovered from a neurosurgical centre in Argentina. The blaKPC-2 gene was surrounded by ISkpn6 and ISkpn7.Fil: Montaña, Sabrina Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Hernandez, M.. California State University; Estados UnidosFil: Fernandez, J. S.. California State University; Estados UnidosFil: Penini, M.. Stamboulian Servicios de Salud; ArgentinaFil: Centron, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Sucari, A.. Stamboulian Servicios de Salud; ArgentinaFil: Iriarte, A.. Universidad de la República; UruguayFil: Ramirez, Maria Soledad. California State University; Estados Unido

Human Pleural Fluid Elicits Pyruvate and Phenylalanine Metabolism in Acinetobacter baumannii to Enhance Cytotoxicity and Immune Evasion

The CCAAT box-harboring proteins represent a family of heterotrimeric transcription factors which is highly conserved in eukaryotes. In fungi, one of the particularly important homologs of this family is the Hap complex that separates the DNA-binding domain from the activation domain and imposes essential impacts on regulation of a wide range of cellular functions. So far, a comprehensive summary of this complex has been described in filamentous fungi but not in the yeast. In this review, we summarize a number of studies related to the structure and assembly mode of the Hap complex in a list of representative yeasts. Furthermore, we emphasize recent advances in understanding the regulatory functions of this complex, with a special focus on its role in regulating respiration, production of reactive oxygen species (ROS) and iron homeostasis.Fil: Nyah, Rodman. California State University; Estados UnidosFil: Martinez, Jasmine. California State University; Estados UnidosFil: Fung, Sammie. California State University; Estados UnidosFil: Nakanouchi, Jun. California State University; Estados UnidosFil: Myers, Amber L.. California State University; Estados UnidosFil: Harris, Caitlin M.. California State University; Estados UnidosFil: Dang, Emily. California State University; Estados UnidosFil: Fernandez, Jennifer. California State University; Estados UnidosFil: Liu, Christine. California State University; Estados UnidosFil: Mendoza, Anthony M.. California State University; Estados UnidosFil: Jimenez, Verónica. California State University; Estados UnidosFil: Nikolaidis, Nikolas. California State University; Estados UnidosFil: Brennan, Catherine A.. California State University; Estados UnidosFil: Bonomo, Robert A.. Louis Stokes Cleveland Department of Veterans Affairs Medical Cente; Estados Unidos. Center for Antimicrobial Resistance and Epidemiology; Estados Unidos. Case Western Reserve University School of Medicine; Estados UnidosFil: Sieira, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ramirez, Maria Soledad. California State University; Estados Unido

Interspecies DNA acquisition by a naturally competent Acinetobacter baumannii strain

The human pathogen Acinetobacter baumannii possesses high genetic plasticity and frequently acquires antimicrobial resistance genes. Here we investigated the role of natural transformation in these processes. Genomic DNA from different sources, including from carbapenem-resistant Klebsiella pneumoniae strains, was mixed with A. baumannii A118 cells. Selected transformants were analysed by whole-genome sequencing. In addition, bioinformatics analyses and in silico gene flow prediction were also performed to support the experimental results. Transformant strains included some that became resistant to carbapenems or changed their antimicrobial susceptibility profile. Foreign DNA acquisition was confirmed by whole-genome analysis. The acquired DNA most frequently identified corresponded to mobile genetic elements, antimicrobial resistance genes and operons involved in metabolism. Bioinformatics analyses and in silico gene flow prediction showed continued exchange of genetic material between A. baumannii and K. pneumoniae when they share the same habitat. Natural transformation plays an important role in the plasticity of A. baumannii and concomitantly in the emergence of multidrug-resistant strains.Fil: Traglia, German Matias. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Place, Kori. California State University; Estados UnidosFil: Dotto, Cristian Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fernandez, Jennifer. California State University; Estados UnidosFil: Montaña, Sabrina Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Bahiense, Camila dos Santos. California State University; Estados UnidosFil: Soler Bistue, Alfonso J. C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Iriarte, Andres. Universidad de la Republica. Facultad de Medicina; UruguayFil: Perez, Federico. Louis Stokes Cleveland Department Of Veterans Affairs; Estados UnidosFil: Tolmasky, Marcelo E.. California State University; Estados UnidosFil: Bonomo, Robert A.. Louis Stokes Cleveland Department Of Veterans Affairs; Estados UnidosFil: Melano, Roberto Gustavo. Public Health Ontario Laboratories; CanadáFil: Ramirez, Maria Soledad. California State University; Estados Unido

Emergence and Spread of Plasmid-Borne tet(B)::ISCR2 in Minocycline-Resistant Acinetobacter baumannii Isolates

Resistance to minocycline has emerged in multidrug-resistant Acinetobacter baumannii isolates from Buenos Aires Hospitals. Few reports about the description and dispersion of tet genes were published in this species. We observed the presence of tet(B) in all minocycline resistant isolates. This gene was found associated to the ISCR2 mobile element, which could in part explain its dispersion.Fil: Vilacoba, Elisabet. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; ArgentinaFil: Almuzara, Marisa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos;Fil: Gulone, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Biotecnología; ArgentinaFil: Traglia, German Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Figueroa, Silvia A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos;Fil: Sly, Gabriela Edith. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos;Fil: Fernandez, Analia. Universidad de Buenos Aires; Argentina. Universidad Favaloro; ArgentinaFil: Centron, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Ramirez, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Human fluids alter DNA-acquisition in Acinetobacter baumannii

Transformation is one of the mechanisms of acquisition of foreign genetic material leading to the emergence of multidrug resistant (MDR) bacteria. Recently, human serum albumin (HSA) was shown to specifically increase transformation frequency in the nosocomial pathogen Acinetobacter baumannii. To further assess the relevance of HSA as a possible modulator of A. baumannii transformation in host-pathogen interactions, in this work we examined the effect of different human fluids. We observed a significant increase in transformation frequencies in the presence of pleural fluid, whole blood cells and liquid ascites, and to a lesser extent with urine. The observed effects correlate with both HSA and bacterial content found in the assayed patient fluids. Taken together, these results are in agreement with our previous findings that highlight HSA as a possible host signal with the ability to trigger natural transformation in A. baumannii.Fil: Martinez, Jasmine. California State University; Estados UnidosFil: Liu, Christine. California State University; Estados UnidosFil: Rodman, Nyah. California State University; Estados UnidosFil: Fernandez, Jennifer S.. California State University; Estados UnidosFil: Barberis, Claudia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Sieira, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Perez, Federico. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados UnidosFil: Bonomo, Robert A.. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados UnidosFil: Ramirez, Maria Soledad. California State University; Estados Unido

Toxicology and Biodistribution Studies for MGH2.1, an Oncolytic Virus that Expresses Two Prodrug-activating Genes, in Combination with Prodrugs

MGH2.1 is a herpes simplex virus type 1 (HSV1) oncolytic virus that expresses two prodrug-activating transgenes: the cyclophosphamide (CPA)-activating cytochrome P4502B1 (CYP2B1) and the CPT11-activating secreted human intestinal carboxylesterase (shiCE). Toxicology and biodistribution of MGH2.1 in the presence/absence of prodrugs was evaluated in mice. MGH2.1 ± prodrugs was cytotoxic to human glioma cells, but not to normal cells. Pharmacokinetically, intracranial MGH2.1 did not significantly alter the metabolism of intraperitoneally (i.p.) administered prodrugs in mouse plasma, brain, or liver. MGH2.1 did not induce an acute inflammatory reaction. MGH2.1 DNA was detected in brains of mice inoculated with 108 pfus for up to 60 days. However, only one animal showed evidence of viral gene expression at this time. Expression of virally encoded genes was restricted to brain. Intracranial inoculation of MGH2.1 did not induce lethality at 108 pfus in the absence of prodrugs and at 106 pfus in the presence of prodrugs. This study provides safety and toxicology data justifying a possible clinical trial of intratumoral injection of MGH2.1 with peripheral administration of CPA and/or CPT11 prodrugs in humans with malignant gliomas

Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: Implications for transformation

<p>Abstract</p> <p>Background</p> <p>Adult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-lymphotropic virus type-1 (HTLV-1); however, additional host factors are also required for T-cell transformation and development of ATLL. The HTLV-1 Tax protein plays an important role in the transformation of T-cells although the exact mechanisms remain unclear. Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of ATLL patients. However, PTHrP is also up-regulated in HTLV-1-carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients without hypercalcemia, indicating that PTHrP is expressed before transformation of T-cells. The expression of PTHrP and the PTH/PTHrP receptor during immortalization or transformation of lymphocytes by HTLV-1 has not been investigated.</p> <p>Results</p> <p>We report that PTHrP was up-regulated during immortalization of lymphocytes from peripheral blood mononuclear cells by HTLV-1 infection in long-term co-culture assays. There was preferential utilization of the PTHrP-P2 promoter in the immortalized cells compared to the HTLV-1-transformed MT-2 cells. PTHrP expression did not correlate temporally with expression of HTLV-1 tax. HTLV-1 infection up-regulated the PTHrP receptor (PTH1R) in lymphocytes indicating a potential autocrine role for PTHrP. Furthermore, co-transfection of HTLV-1 expression plasmids and PTHrP P2/P3-promoter luciferase reporter plasmids demonstrated that HTLV-1 up-regulated PTHrP expression only mildly, indicating that other cellular factors and/or events are required for the very high PTHrP expression observed in ATLL cells. We also report that macrophage inflammatory protein-1α (MIP-1α), a cellular gene known to play an important role in the pathogenesis of HHM in ATLL patients, was highly expressed during early HTLV-1 infection indicating that, unlike PTHrP, its expression was enhanced due to activation of lymphocytes by HTLV-1 infection.</p> <p>Conclusion</p> <p>These data demonstrate that PTHrP and its receptor are up-regulated specifically during immortalization of T-lymphocytes by HTLV-1 infection and may facilitate the transformation process.</p

A Mediterranean lifestyle reduces the risk of cardiovascular disease in the “Seguimiento Universidad de Navarra” (SUN) cohort

Background and aims: A healthy lifestyle is essential to prevent cardiovascular disease (CVD). However, beyond dietary habits, there is a scarcity of studies comprehensively assessing the typical traditional Mediterranean lifestyle with a multi-dimensional index. We assessed the association between the Mediterranean lifestyle (measured with the MEDLIFE index including diet, physical activity, and other lifestyle factors) and the incidence of CVD. Methods and results: The “Seguimiento Universidad de Navarra” (SUN) project is a prospective, dynamic and multipurpose cohort of Spanish university graduates. We calculated a MEDLIFE score, composed of 28 items on food consumption, dietary habits, physical activity, rest, social habits, and conviviality, for 18,631 participants by assigning 1 point for each typical Mediterra- nean lifestyle factor achieved, for a theoretically possible final score ranging from 0 to 28 points. During an average follow-up of 11.5 years, 172 CVD cases (myocardial infarction, stroke or cardio- vascular death) were observed. An inverse association between the MEDLIFE score and the risk of primary cardiovascular events was observed, with multivariable-adjusted hazard ratio (HR) Z 0.50; (95% confidence interval, 0.31e0.81) for the highest MEDLIFE scores (14e23 points) compared to the lowest scores (0e9 points), p (trend) Z 0.004. Conclusion: A higher level of adherence to the Mediterranean lifestyle was significantly associ- ated with a lower risk of CVD in a Spanish cohort. Public health strategies should promote the Mediterranean lifestyle to preserve cardiovascular health

CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway

Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). Patients with CD44high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44high GBM but not from CD44low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN), increased expression of phosphorylated AKT in CD44high GBM, but not in CD44low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKTpathway