Giardia and Cryptosporidium and public health: the epidemiological scenario from the Italian perspective

Giardia and Cryptosporidium spp. are protozoa that cause human and animal disease worldwide and often exhibit zoonotic transmission. This review gives ample information concerning the epidemiology of these parasites in Italy, i.e. prevalence data in humans, farm and pet animals, shellfish and aquatic environment. Moreover, it reports genotyping results obtained from different isolates, with particular emphasis on the spread of host-specific and zoonotic species/genotypes of various origin, and on molecular data that make the Italian situation different from that of other countries. Finally, possible explanations are given for the infrequent reports of Giardia and Cryptosporidium spp. outbreaks, despite widespread faecal contamination by these parasites

Embryonal tumors in the WHO CNS5 classification: a review

Embryonal tumors are a heterogenous group of neoplasms mostly defined by recurrent genetic driver events. They have been, previously, broadly classified as either medulloblastoma or supratentorial primitive neuroectodermal tumors (PNETs). However, the application of DNA methylation/gene expression profiling in large series of neoplasms histologically defined as PNET, revealed tumors, which showed genetic events associated with glial tumors. These findings led to the definitive removal of the term "PNET" in the 2016 World Health Organization (WHO) classification of CNS tumors. Moreover, further studies on a large scale of methylation profiling have allowed the identification of new molecular-defined entities and have largely influenced the 5th edition of the WHO classification of CNS tumors (WHO CNS5) for both medulloblastomas and other CNS embryonal tumors. The importance of molecular characteristics in CNS embryonal tumors is well represented by the identification of different molecular groups and subgroups in medulloblastoma. So, in the CNS5, the emerged group 3 and group 4 belong to the classification, and the four molecular and morphologic types are now combined into a unique section. Among other embryonal tumors, two new recognized entities are introduced in CNS5: CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication (ITD). Embryonal tumor with multilayered rosettes (ETMR), already present in the previous classification now has a revised nomenclature as a result of the new DICER1 alteration, additional to the formerly known C19MC. Regarding atypical teratoid/rhabdoid tumor (AT/RT), three molecular subgroups are recognized in CNS5. The combination of histopathological and molecular features reflects the complexity of all these tumors and gives critical information in terms of prognosis and therapy. This encourages the use of a layered diagnostic report with the integrated diagnosis at the top, succeeded by layers including the histological, molecular, and other essential details

Sonic hedgehog medulloblastoma cancer stem cells mirnome and transcriptome highlight novel functional networks

Molecular classification has improved the knowledge of medulloblastoma (MB), the most common malignant brain tumour in children, however current treatments cause severe side effects in patients. Cancer stem cells (CSCs) have been described in MB and represent a sub population characterised by self-renewal and the ability to generate tumour cells, thus representing the reservoir of the tumour. To investigate molecular pathways that characterise this sub population, we isolated CSCs from Sonic Hedgehog Medulloblastoma (SHH MB) arisen in Patched 1 (Ptch1) heterozygous mice, and performed miRNA-and mRNA-sequencing. Comparison of the miRNA-sequencing of SHH MB CSCs with that obtained from cerebellar Neural Stem Cells (NSCs), allowed us to obtain a SHH MB CSC miRNA differential signature. Pathway enrichment analysis in SHH MB CSCs mirnome and transcriptome was performed and revealed a series of enriched pathways. We focused on the putative targets of the SHH MB CSC miRNAs that were involved in the enriched pathways of interest, namely pathways in cancer, PI3k-Akt pathway and protein processing in endoplasmic reticulum pathway. In silico analysis was performed in SHH MB patients and identified several genes, whose expression was associated with worse overall survival of SHH MB patients. This study provides novel candidates whose functional role should be further investigated in SHH MB

Synthetic turbulence generation for high-order scale-resolving simulations on unstructured grids

An extended version of the synthetic eddy method for generation of synthetic turbulence has been developed via a source term formulation and implemented in the open-source cross-platform solver PyFR. The method caters for the full space-dependent anisotropy of the target turbulent length scales, and it is agnostic of the space and time discretization of the underlying solver, which can be incompressible or compressible. Moreover, the method does not require each solution point to communicate with nearest neighbors; thus, it is well suited for modern, massively parallel, high-order unstructured codes which support mixed and possibly curved elements. The method has been applied to two test cases: incompressible plane channel flow at Reτ 180 and compressible flow over an SD7003 aerofoil at Re 66;000, Ma 0.2, and α 4 deg. The channel flow case was run on three topologically different meshes composed of hexahedra, prisms, and a combination of prisms and tetrahedra, respectively. Almost identical results have been obtained on the three meshes. Results also show that taking into account the anisotropy of the turbulent length scales can reduce the development length. For the SD7003 aerofoil case, the injection of synthetic turbulence improves agreement between numerical and experimental results

Human leukocyte antigen (Hla) haplotype does not influence the inflammatory pattern of duodenal lymphocytosis linked to irritable bowel syndrome

Background and objectives: Duodenal lymphocytosis (DL) is a condition characterized by enhanced infiltration of intraepithelial lymphocytes (IELs) in the duodenal mucosa, and it can be linked to both gluten-and non-gluten-related diseases, such as irritable bowel syndrome (IBS). Materials and methods: We retrospectively selected patients with DL linked to IBS. Formalin-embedded biopsy samples of the duodenum were collected. CD3 lymphocyte immunohistochemistry was used for IELs. The real-time polymerase chain reaction was used to quantify the amount of mRNA coding for tissue transglutaminase 2 (tTG2), interferon-gamma (IFNγ), toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88). All subjects underwent DQ2-8 haplotype analysis. Controls were represented by subjects with IBS without DL. Results: Thirty-two patients with IBS-DL were retrospectively recruited. Fourteen subjects (43.8%) had a DQ2-8 haplotype. DQ2-8 positive subjects had similar levels compared to negative ones for tTG2, IFNγ, TLR2, and MyD88. Cigarette smoke did not influence molecular expression in our study. Smokers had a statistically higher IELs count than non-smokers (54.2 ± 7.7 vs. 36.0 ± 8.8, p < 0.001). A significant, direct correlation between IELs and duodenal expression of IFNγ was found (r = 0.36, p = 0.04). Conclusions: IBS with DL showed higher expression of inflammatory markers than controls, but DQ2-8 haplotype did not seem to affect their expression. Smoking might increase IELs infiltration

QUADRUPLE RESCUE THERAPY AFTER FIRST AND SECOND LINE FAILURE FOR HELICOBACTER PYLORI TREATMENT: COMPARISON BETWEEN TWO TETRACYCLINE-BASED REGIMENS

Background & Aims: Antibiotic resistance is the main reason for failure of Helicobacter pylori (H. pylori) treatment. Currently, guidelines recommend a treatment guided by antimicrobial susceptibility testing after two failures. However, microbial culture is not feasible everywhere, and the limited number of effective antibiotics against the bacterium narrows the options; thus a rescue therapy combining antibiotics with a low resistance may be fitting. Methods: Patients who have failed a first-line treatment (either prolonged triple or sequential regimens) and, successively, a levofoxacin-based triple therapy were considered for the study. Subjects underwent urea breath test (UBT), stool antigen test (ST) and endoscopy/histology to confirm the diagnosis. Cytopenia and impaired liver and kidney function were exclusion criteria. Fify-four subjects were randomized 1:1 to two regimens: RMB abeprazole/Rifabutin/Minocycline/Bismuth sub-citrate or MTB Rabeprazole/Tinidazole/ Minocycline/Bismuth sub-citrate both for 10 days. Te results were checked 6 weeks afer the end of therapy with ST/UBT plus endoscopy when indicated. Results: RMB eradicated the bacterium in 21 patients. Two subjects dropped out. Te eradication rate was 77.7% (CI 62.0-93.4%) at intention-to-treat and 84.0% (CI 69.6-98.4%) at per-protocol analysis. MTB was successful in 14 patients (51.9%, CI 33.1-70.7%). No patient withdrew from the treatment for adverse events. Drug-related side effects were reported only in 3 subjects, but in all cases the treatment was carried on. Conclusions: Te association minocycline/rifabutin seems to have a synergic effect and a good therapeutic outcome in patients who have failed at least two previous regimens, although a trial on a large population is needed

Giardia and Cryptosporidium in inflowing water and harvested shellfish in a Lagoon in Southern Italy

Giardia and Cryptosporidium spp. are important enteric protozoan pathogens for humans and animals, and have been found to contaminate water as well as edible shellfish all over the world. This is the first study to simultaneously investigate the presence of Giardia and Cryptosporidium in inflowing water and harvested shellfish in a geographically closed environment (Varano Lagoon, Southern Italy). Samples of treated wastewater were collected each month - at the outlet from the treatment plant, and downstream at the inlet into the lagoon - from the channels flowing into the Lagoon, together with specimens of Ruditapes decussatus and Mytilus galloprovincialis from shellfish-farms on the same lagoon. Giardia cysts were found by immunofluorescence (IF) microscopy in 16 out of 21 samples of treated wastewater and in 7 out of 21 samples from downstream water channels, and viable cysts were also detected by a beta-giardin RT-PCR. G. duodenalis Assemblages A and B were identified by small ribosomal Subunit (18S-rDNA) and triosephosphate isomerase (tpi)-PCR, followed by sequencing. Cryptosporidium oocysts were found by IF in 5 out of 21 wastewater samples, and in 8 out of 21 samples from water channels. Molecular analysis identified the zoonotic species Cryptosporidium parvum by oocyst wall protein (COWP)-PCR and sequencing. Higher concentrations of Giardia cysts than Cryptosporidium oocysts were registered in almost all wastewater and water samples. IF and molecular testing of shellfish gave negative results for both protozoa. Wastewaters carrying Giardia and Cryptosporidium (oo)cysts are discharged into the Lagoon; however, the shellfish harvested in the same environment were found to be unaffected, thus suggesting that physical, ecological and climatic conditions may prevent contamination of harvested shellfish. (C) 2008 Published by Elsevier Ireland Ltd

Prevalence of Plasmodium spp. in malaria asymptomatic African migrants assessed by nucleic acid sequence based amplification

<p>Abstract</p> <p>Background</p> <p>Malaria is one of the most important infectious diseases in the world. Although most cases are found distributed in the tropical regions of Africa, Asia, Central and South Americas, there is in Europe a significant increase in the number of imported cases in non-endemic countries, in particular due to the higher mobility in today's society.</p> <p>Methods</p> <p>The prevalence of a possible asymptomatic infection with <it>Plasmodium </it>species was assessed using Nucleic Acid Sequence Based Amplification (NASBA) assays on clinical samples collected from 195 study cases with no clinical signs related to malaria and coming from sub-Saharan African regions to Southern Italy. In addition, base-line demographic, clinical and socio-economic information was collected from study participants who also underwent a full clinical examination.</p> <p>Results</p> <p>Sixty-two study subjects (31.8%) were found positive for <it>Plasmodium </it>using a pan <it>Plasmodium </it>specific NASBA which can detect all four <it>Plasmodium </it>species causing human disease, based on the small subunit 18S rRNA gene (18S NASBA). Twenty-four samples (38%) of the 62 18S NASBA positive study cases were found positive with a Pfs25 mRNA NASBA, which is specific for the detection of gametocytes of <it>Plasmodium falciparum</it>. A statistically significant association was observed between 18S NASBA positivity and splenomegaly, hepatomegaly and leukopaenia and country of origin.</p> <p>Conclusion</p> <p>This study showed that a substantial proportion of people originating from malaria endemic countries harbor malaria parasites in their blood. If transmission conditions are available, they could potentially be a reservoir. Thefore, health authorities should pay special attention to the health of this potential risk group and aim to improve their health conditions.</p

3D Ray Tracing Solver for Communication Blackout Analysis in Atmospheric Entry Missions

During the atmospheric entry phase at hypersonic speed, the radio communication from/to a space vehicle can be disrupted due to the formation of a plasma sheath within the surrounding flow field. In order to characterize such communication blackout phases, this work presents a numerical methodology combining Computational Fluid Dynamic (CFD) simulations of ionized chemically reacting entry flows by means of Computational Object-Oriented Libraries for Fluid Dynamics (COOLFluiD) and a ray tracing analysis by means of the newly developed BlackOut RAy Tracer (BORAT). The latter is based on the numerical solution of the 3D Eikonal system of equations, offering a fast, efficient and accurate method to analyse the interaction between electromagnetic signals and weakly ionised plasmas. The proposed methodology, and BORAT in particular, is first verified on popular benchmark cases and then used to analyse the European Space Agency (ESA) 2016 ExoMars Schiaparelli entry flight into Martian environment. The corresponding results demonstrate the validity of the proposed ray tracing approach for predicting communication blackout, where signals emitted from the on-board antenna undergo reflection and refraction from the plasma surrounding the entry vehicle, and the advantage of a 3D approach for analysing real flight configuration

Expanding the spectrum of EWSR1-PATZ1 rearranged CNS tumors: An infantile case with leptomeningeal dissemination

We report on a case of EWSR1-PATZ1 rearranged brain tumor occurring in a 17 month-old child, originally interpreted as an infantile glioblastoma. Our case shows important analogies with the 2 previously reported cases, including the intraventricular location, the histologic appearance (pushing borders, oligodendrocyte-like morphology, rich vascular network) and the glioneural immunophenotype, supporting the role of these features as relevant clues to the diagnosis. On the other hand, our case displays unique characteristics, i.e. the onset in an infant, the presence of a focal high-grade component and the leptomeningeal dissemination, pointing to the importance of considering this entity in the differential diagnosis of an infantile glial/glioneural tumor