Single and Synergistic Effects of Fenbendazole and Metronidazole Against Subclinical Infection by Giardia duodenalis in Non-Human Primates in a Zoological Garden in Southern Italy

The aim of this study was to assess the single and synergistic effects of fenbendazole (Fenb) and metronidazole (Metro) for the treatment of Giardia duodenalis infection in different species of non-human primates (NHPs) housed in a zoological garden of southern Italy. Moreover, the study also aimed to better define the circulation of G. duodenalis zoonotic assemblages in NHP and the potential occurrence of zoonotic transmission between the staff from the zoo and NHP. Briefly, six species that belonged to four families (Lemuridae, Cercopithecidae, Atelidae, and Hylobatidae) of NHP and housed in six cages (CG) were identified as Giardia positive and divided into two groups. Group F (N = 16 animals) was treated with Fenb (50 mg/kg, every 24 h for 5 consecutive days) and Group M (N = 7 animals) was treated with Metro (25 mg/kg, two times a day for 5 consecutive days). After the first round of therapy, all the animals were retreated for 5 days by inverting the drugs in each group. On each sampling day [study days (SDs) 3-24], the samples were tested for the presence of Giardia cysts using the FLOTAC technique. Multiple fecal tests for the antigen detection of Giardia, such as rapid ELISA and direct immunofluorescence (IFA), were performed at each sampling point only on samples that resulted in positive for Giardia cysts with FLOTAC. The efficacy of Fenb ranged from 30 to 67% and for Metro ranged from 82 to 96%. The results showed the synergistic effects of Metro and Fenb (98-100%) over the combination of Fenb and Metro (52-90%) against the infection by Giardia in NHPs. The overall k agreement between FLOTAC and IFA was reached 0.858 (p = 0.0001). In contrast, all the samples had a negative antigen result when using ELISA. At molecular analysis, six samples were confirmed positive for Giardia by nested PCR. Only two positive samples were successfully sequenced that showed 100% of identity with assemblage B. All the samples from the humans included in the study resulted in negative for Giardia cysts. Overall, the study emphasizes the need for regular monitoring of Giardia infections in NHP housed in zoos by traditional diagnostic tools combined with molecular characterization of the parasite

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft

Transcriptional profiling of human bronchial epithelial cell BEAS-2B exposed to diesel and biomass ultrafine particles

Background: Emissions from diesel vehicles and biomass burning are the principal sources of primary ultrafine particles (UFP). The exposure to UFP has been associated to cardiovascular and pulmonary diseases, including lung cancer. Although many aspects of the toxicology of ambient particulate matter (PM) have been unraveled, the molecular mechanisms activated in human cells by the exposure to UFP are still poorly understood. Here, we present an RNA-seq time-course experiment (five time point after single dose exposure) used to investigate the differential and temporal changes induced in the gene expression of human bronchial epithelial cells (BEAS-2B) by the exposure to UFP generated from diesel and biomass combustion. A combination of different bioinformatics tools (EdgeR, next-maSigPro and reactome FI app-Cytoscape and prioritization strategies) facilitated the analyses the temporal transcriptional pattern, functional gene set enrichment and gene networks related to cellular response to UFP particles.Results: The bioinformatics analysis of transcriptional data reveals that the two different UFP induce, since the earliest time points, different transcriptional dynamics resulting in the activation of specific genes. The functional enrichment of differentially expressed genes indicates that the exposure to diesel UFP induces the activation of genes involved in TNFa signaling via NF-kB and inflammatory response, and hypoxia. Conversely, the exposure to ultrafine particles from biomass determines less distinct modifications of the gene expression profiles. Diesel UFP exposure induces the secretion of biomarkers associated to inflammation (CCXL2, EPGN, GREM1, IL1A, IL1B, IL6, IL24, EREG, VEGF) and transcription factors (as NFE2L2, MAFF, HES1, FOSL1, TGIF1) relevant for cardiovascular and lung disease. By means of network reconstruction, four genes (STAT3, HIF1a, NFKB1, KRAS) have emerged as major regulators of transcriptional response of bronchial epithelial cells exposed to diesel exhaust.Conclusions: Overall, this work highlights modifications of the transcriptional landscape in human bronchial cells exposed to UFP and sheds new lights on possible mechanisms by means of which UFP acts as a carcinogen and harmful factor for human health

High-Resolution Conformational Analysis of RGDechi-Derived Peptides Based on a Combination of NMR Spectroscopy and MD Simulations

The crucial role of integrin in pathological processes such as tumor progression and metastasis formation has inspired intense efforts to design novel pharmaceutical agents modulating integrin functions in order to provide new tools for potential therapies. In the past decade, we have investigated the biological proprieties of the chimeric peptide RGDechi, containing a cyclic RGD motif linked to an echistatin C-terminal fragment, able to specifically recognize αvβ3 without cross reacting with αvβ5 and αIIbβ3 integrin. Additionally, we have demonstrated using two RGDechi-derived peptides, called RGDechi1-14 and ψRGDechi, that chemical modifications introduced in the C-terminal part of the peptide alter or abolish the binding to the αvβ3 integrin. Here, to shed light on the structural and dynamical determinants involved in the integrin recognition mechanism, we investigate the effects of the chemical modifications by exploring the conformational space sampled by RGDechi1-14 and ψRGDechi using an integrated natural-abundance NMR/MD approach. Our data demonstrate that the flexibility of the RGD-containing cycle is driven by the echistatin C-terminal region of the RGDechi peptide through a coupling mechanism between the N- and C-terminal regions

Costs of clinical trials with anticancer biological agents in an Oncologic Italian Cancer Center using the activity-based costing methodology

The aim of the present study was to assess the estimated "per patient" total cost for a single Oncologic Italian Cancer Center participating in a multicenter clinical trial with new anticancer biological agents using the activity-based costing (ABC) methodology

A new hexapeptide from the leader peptide of rMnSOD enters cells through the oestrogen receptor to deliver therapeutic molecules

A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Here, we demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the oestrogen receptor (ER). We analysed the internalization of the synthetic hexapeptide and the cytotoxic activity of the hexapeptide conjugated to cisplatin on a cell line panel. In most cell lines, the hexapeptide delivered an amount of cisplatin that was 2 to 8 times greater than that released by cisplatin when the drug was used alone. This increased delivery increases the therapeutic index of cisplatin and reduces side effects caused by a high dosage or long-term treatment times. We may consider this hexapeptide a new molecular carrier to deliver molecules with therapeutic activity into ER+ cells for diagnostic purposes and clinical or immune therapy

Ultra diffuse galaxies in the Hydra I cluster from the LEWIS Project: Phase-Space distribution and globular cluster richness

Although ultra diffuse galaxies (UDGs) are found in large numbers in clusters of galaxies, the role of the cluster environment in shaping their low surface brightness and large sizes is still uncertain. Here we examine a sample of UDGs in the Hydra I cluster (D = 51 Mpc) with new radial velocities obtained as part of the LEWIS (Looking into the faintest with MUSE) project using VLT/MUSE data. Using a phase-space, or infall diagnostic, diagram we compare the UDGs to other known galaxies in the Hydra I cluster and to UDGs in other clusters. The UDGs, along with the bulk of regular Hydra I galaxies, have low relative velocities and are located near the cluster core, and thus consistent with very early infall into the cluster. Combining with literature data, we do not find the expected trend of GC-rich UDGs associated with earlier infall times. This result suggests that quenching mechanisms other than cluster infall should be further considered, e.g. quenching by strong feedback or in cosmic sheets and filaments. Tidal stripping of GCs in the cluster environment also warrants further modelling.Comment: 6 pages, 2 figures, MNRAS, 525, 9

Realising the health and wellbeing of adolescents

Adolescence is a critical stage of life characterised by rapid biological, emotional, and social development. It is during this time that every person develops the capabilities required for a productive, healthy, and satisfying life. In order to make a healthy transition into adulthood, adolescents need to have access to health education, including education on sexuality1; quality health services, including sexual and reproductive; and a supportive environment both at home and in communities and countries.The global community increasingly recognises these vital needs of adolescents, and there is an emerging consensus that investing intensively in adolescents’ health and development is not only key to improving their survival and wellbeing but critical for the success of the post-2015 development agenda.2 The suggested inclusion of adolescent health in the United Nations secretary general’s Global Strategy for Women’s and Children’s Health is an expression of this growing awareness and represents an unprecedented opportunity to place adolescents on the political map beyond 2015. Ensuring that every adolescent has the knowledge, skills, and opportunities for a healthy, productive life and enjoyment of all human rights3 is essential for achieving improved health, social justice, gender equality, and other development goals.We argue that the priority in the revised Every Women Every Child Global Strategy needs to be giving adolescents a voice, expanding their choices and control over their bodies, and enabling them to develop the capabilities required for a productive, healthy, and satisfying life. We call for a global, participatory movement to improve the health of the world’s adolescents as part of a broader agenda to improve their wellbeing and uphold their rights

Looking into the faintEst WIth MUSE (LEWIS): on the nature of ultra-diffuse galaxies in the Hydra-I cluster.I. Project description and preliminary results

Looking into the faintEst WIth MUSE (LEWIS) is an ESO large observing programme aimed at obtaining the first homogeneous integral-field spectroscopic survey of 30 extremely low-surface brightness (LSB) galaxies in the Hydra I cluster of galaxies, with MUSE at ESO-VLT. The majority of LSB galaxies in the sample (22 in total) are ultra-diffuse galaxies (UDGs). The distribution of systemic velocities Vsys ranges between 2317 km/s and 5198 km/s and is centred on the mean velocity of Hydra I (Vsys = 3683 $\pm$ 46 km/s). Considering the mean velocity and the velocity dispersion of the cluster, 17 out of 20 targets are confirmed cluster members. To assess the quality of the data and demonstrate the feasibility of the science goals, we report the preliminary results obtained for one of the sample galaxies, UDG11. For this target, we derived the stellar kinematics, including the 2-dimensional maps of line-of-sight velocity and velocity dispersion, constrained age and metallicity, and studied the globular cluster (GC) population hosted by the UDG. Results are compared with the available measurements for UDGs and dwarf galaxies in literature. By fitting the stacked spectrum inside one effective radius, we find that UDG11 has a velocity dispersion $\sigma = 20 \pm 8$ km/s, it is old ($10\pm1$ Gyr), metal-poor ([M/H]=-1.17$\pm$0.11 dex) and has a total dynamical mass-to-light ratio M$/L_V\sim 14$, comparable to those observed for classical dwarf galaxies. The spatially resolved stellar kinematics maps suggest that UDG11 does not show a significant velocity gradient along either major or minor photometric axes. We find two GCs kinematically associated with UDG11. The estimated total number of GCs in UDG11, corrected for the spectroscopic completeness limit, is $N_{GC}= 5.9^{+2.2}_ {-1.8}$, which corresponds to a GC specific frequency of $S_N = 8.4^{+3.2}_{-2.7}$.Comment: Accepted for publication in Astronomy and Astrophysic

La diversidad en la formación hace a lo integral del Ingeniero

La cátedra de Materiales contiene a un plantel docente rentado de 8 ingenieros y 3 estudiantes de ingeniería. A su vez colaboran ad-honorem 1 profesional y 1 alumno. Este plantel atiende cerca de 600 alumnos por año y desde el año 2015 también se encarga de la materia Materiales de la sede de la Facultad de Ingeniería en Bolívar. Si bien por la cantidad de alumnos se pensaría en una cátedra tradicional tendiendo más bien a las clases teóricas, debido a la concepción que tienen los docentes involucrados se está frente a una cátedra que realiza clases teóricas, ejercitación áulica de práctica, laboratorios experimentales (con no más de 18 alumnos por comisión), debates en clases, actividades de extensión y evaluaciones. Todo este sin fin de actividades están pensadas en función del objetivo primordial de la cátedra que es la formación integral del Ingeniero, y es en el presente trabajo donde se describe la propuesta de la cátedra para colaborar en la educación sin descuidar lo técnico pero fortaleciendo las otras áreas de la formación.Eje 1: La enseñanza universitaria en el contexto actual: transformaciones y propuestas. Reflexiones y experiencias en la enseñanza de las Ciencias Exactas.Secretaría de Asuntos Académico