Use of probiotics in medical devices applied to some common pathologies.

Probiotics, defined as “living microorganisms that, whether ingested in useful amount, may have beneficial effects on human body”, are widely used in various products for human use, such as dietary supplements, medical devices and pharmaceutical products. The European Directive on medical devices (MDs) (DDM 93/42), also includes those MDs containing live microorganisms, particularly probiotics, that may have various destinations of use, including that of assisting the therapy of several human pathologies. In this brief note we analyzed the use of probiotics in MDs and how probiotics administration could represent one of the new frontiers of scientific research on the prevention and treatment of various diseases. We’ll analyze the literature on probiotics based MDs, to review their major targets in the therapy of some of the most common human pathologies: bacterial vaginosis and vaginitis, atopic dermatitis, infant colic, obesity, type 2 diabetes, and pharyngotonsillitis

PRENOLIN project. Results of the validation phase at sendai site

One of the objectives of the PRENOLIN project is the assessment of uncertainties associated with non-linear simulation of 1D site effects. An international benchmark is underway to test several numerical codes, including various non-linear soil constitutive models, to compute the non-linear seismic site response. The preliminary verification phase (i.e. comparison between numerical codes on simple, idealistic cases) is now followed by the validation phase, which compares predictions of such numerical estimations with actual strong motion data recorded from well-known sites. The benchmark presently involves 21 teams and 21 different non-linear computations. Extensive site characterization was performed at three sites of the Japanese KiK-net and PARI networks. This paper focuses on SENDAI site. The first results indicate that a careful analysis of the data for the lab measurement is required. The linear site response is overestimated while the non-linear effects are underestimated in the first iteration. According to these observations, a first set of recommendations for defining the non-linear soil parameters from lab measurements is proposed. PRENOLIN is part of two larger projects: SINAPS@, funded by the ANR (French National Research Agency) and SIGMA, funded by a consortium of nuclear operators (EDF, CEA, AREVA, ENL)

Hybrid reconnaissance mission to the 30 October 2020 Aegean sea earthquake and tsunami (Izmir, Turkey & Samos, Greece): description of data collection methods and damage

On 30 October 2020, an earthquake of Mw 6.9 hit the Aegean coasts of Turkey and Greece. The epicentre was some 14 km northeast of Avlakia on Samos Island, and 25 km southwest of Seferihisar, Turkey, triggering also a tsunami. The event has been followed by >4,000 aftershocks up to Mw 5.2 The Earthquake Engineering Field Investigation Team (EEFIT) has immediately gathered a team to conduct a hybrid reconnaissance study,bringing together remote and field investigation techniques. The mission took place between 16 November and 17 December, inclusive of three sets of field study carried out by the field crews for building damage assessment in the affected areas in Turkey and Greece under the coordination of the remote team. The mission also aimed to assess the viability of alternative data sources for an appraisal of the future viability of hybrid missions. This paper summarises the mission setup and findings, and discusses the benefits of and difficulties encountered during this hybrid reconnaissance activity

Abnormal P-selectin localization during megakaryocyte development determines thrombosis in the gata1low model of myelofibrosis.

Abstract Patients with primary myelofibrosis have increased risk for bleeding and thrombosis. It is debated whether propensity to thrombosis is due to increased numbers of platelet microparticles and/or to pathological platelet-neutrophil interactions. Platelet neutrophil interactions are mediated by P-selectin and even though the megakaryocytes of myelofibrosis patients express normal levels of P-selectin, it remains abnormally localized to the demarcation membrane system rather than being assembled into the α-granules in platelets. Mice carrying the hypomorphic Gata1(low) mutation express the same megakaryocyte abnormalities presented by primary myelofibrosis patients, including abnormal P-selectin localization to the DMS and develop with age myelofibrosis, a disease that closely resembles human primary myelofibrosis. Whether these mice would also develop thrombosis has not been investigated as yet. The aim of this study was to determine whether Gata1(low) mice would develop thrombosis with age and, in this case, the role played by P-selectin in the development of the trait. To this aim, Gata1(low) mice were crossed with P-sel(null) mice according to standard genetic protocols and Gata1(low)P-sel(wt), Gata1(low)P-sel(null) and Gata1(WT)P-sel(null) or Gata1(wt)P-sel(wt) (as controls) littermates obtained. It was shown that platelet counts, but not hematocrit, are reduced in Gata1(low) mice. Moreover, platelet microparticles are reduced in Gata1(low) mice and P-selectin positive platelet microparticles were not found. To determine the phenotypic implications of the different mutations, bleeding time was estimated by a tail cut procedure. Mutant mice were sacrificed and presence of thrombosis was determined by immunohistological staining of organs. Gata1(low) mice with or without the P-selectin null trait had a prolonged bleeding time compared to wild type mice. However, in Gata1(low) mice significantly higher frequency of thrombotic events was seen in adult and old Gata1(low) mice compared to Gata1(low)P-sel(null) mice. Thus, presence of the P-selectin null trait rescued Gata1(low) mice from the thrombotic phenotype, but did not change the level of platelet microparticles. Taken together these data indicate that abnormal localization of P-selectin, induced by the Gata1(low) mutation, and thus, increased pathological interactions with leucocytes, is responsible for the increased presence of thrombosis seen in these mice

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

OBJECTIVE: To assess whether alterations in the SDF-1/CXCR4 occur in patients with primary myelofibrosis (PMF) and in Gata1(low) mice, an animal model for myelofibrosis, and whether these abnormalities might account for increased stem/progenitor cell trafficking. MATERIALS AND METHODS: In the mouse, SDF-1 mRNA levels were assayed in liver, spleen and marrow. SDF-1 protein levels were quantified in plasma and marrow and CXCR4 mRNA and protein levels were evaluated on stem/progenitor cells and megakaryocytes purified from the marrow. SDF-1 protein levels were also evaluated in plasma and in marrow biopsy specimens obtained from normal donors and PMF patients. RESULTS: In Gata1(low) mice, the plasma SDF-1 protein was 5-times higher than normal in younger animals. Furthermore, SDF-1 immuno-staining of marrow sections progressively increased with age. Similar abnormalities were observed in PMF patients. In fact, the plasma SDF-1 levels in PMF patients were significantly higher (by 2-fold) than normal (p<0.01) and SDF-1 immuno-staining of marrow biopsiy specimens demonstrated increased SDF-1 deposition in specific areas. In two of the patients, SDF-1 deposition was normalized by curative therapy with allogenic stem cell transplantation. Similarly to what already has been reported for PMF patients, the marrow from Gata1(low) mice contained fewer CXCR4(pos)CD117(pos) cells and these cells expressed low levels of CXCR4 mRNA and protein. CONCLUSION: Similar abnormalities in the SDF-1/CXCR4 axis are observed in PMF patients and in the Gata1(low) mice model of myelofibrosis. We suggest that these abnormalities contribute to the increased stem/progenitor cell trafficking observed in this mouse model as well as patients with PMF

Hybrid Reconnaissance Mission to the 30 October 2020 Aegean Sea Earthquake and Tsunami (Izmir, Turkey &amp; Samos, Greece): Description of Data Collection Methods and Damage

On 30 October 2020, an earthquake of Mw 6.9 hit the Aegean coasts of Turkey and Greece. The epicentre was some 14 km northeast of Avlakia on Samos Island, and 25 km southwest of Seferihisar, Turkey, triggering also a tsunami. The event has been followed by &amp;gt;4,000 aftershocks up to Mw 5.2 The Earthquake Engineering Field Investigation Team (EEFIT) has immediately gathered a team to conduct a hybrid reconnaissance study, bringing together remote and field investigation techniques. The mission took place between 16 November and 17 December, inclusive of three sets of field study carried out by the field crews for building damage assessment in the affected areas in Turkey and Greece under the coordination of the remote team. The mission also aimed to assess the viability of alternative data sources for an appraisal of the future viability of hybrid missions. This paper summarises the mission setup and findings, and discusses the benefits of and difficulties encountered during this hybrid reconnaissance activity.</jats:p

Hybrid Reconnaissance Mission to the 30 October 2020 Aegean Sea Earthquake and Tsunami (Izmir, Turkey & Samos, Greece): Description of Data Collection Methods and Damage

On 30 October 2020, an earthquake of Mw 6.9 hit the Aegean coasts of Turkey and Greece. The epicentre was some 14 km northeast of Avlakia on Samos Island, and 25 km southwest of Seferihisar, Turkey, triggering also a tsunami. The event has been followed by &amp;gt;4,000 aftershocks up to Mw 5.2 The Earthquake Engineering Field Investigation Team (EEFIT) has immediately gathered a team to conduct a hybrid reconnaissance study, bringing together remote and field investigation techniques. The mission took place between 16 November and 17 December, inclusive of three sets of field study carried out by the field crews for building damage assessment in the affected areas in Turkey and Greece under the coordination of the remote team. The mission also aimed to assess the viability of alternative data sources for an appraisal of the future viability of hybrid missions. This paper summarises the mission setup and findings, and discusses the benefits of and difficulties encountered during this hybrid reconnaissance activity.</jats:p

Dynamic regulation of Gata1 expression during the maturation of conventional dendritic cells

Objectives: To identify the regulatory sequences driving Gata1 expression in conventional dendritic cells (cDC). Materials and Methods: The number and expression levels of Gata1, Gata1-target genes and hypersensitive site (HS) 2 (the eosinophil-specific enhancer)-driven green fluorescent protein (GFP) reporter of cDCs from mice lacking HS1 (the erythroid/megakaryocytic-specific enhancer, Gata1lowmutation) and wild-type littermates, as well as the response to lipopolysaccharide of ex vivo-generated wild-type and Gata1lowDCs were investigated. Results: cDC maturation was associated with bell-shaped changes in Gata1 expression that peaked in cDCs precursors from blood. The Gata1lowmutation did not affect Gata1 expression in cDC precursors and these cells expressed the HS2-driven reporter, indicating that Gata1 expression is HS2-driven in these cells. By contrast, the Gata1lowmutation reduced Gata1 expression in mature cDCs and these cells did not express GFP, indicating that mature cDCs express Gata1 driven by HS1. In blood, the number of cDC precursors expressing CD40/CD80 was reduced in Gata1lowmice, while CD40pos/CD80poscDC precursors from wild-type mice expressed the HS2-GFP reporter, suggesting that Gata1 expression in these cells is both HS1- and HS2-driven. In addition, the antigen and accessory molecules presentation process induced by lipopolysaccharide in ex vivo-generated wild-type DC was associated with increased acetylated histone 4 occupancy of HS1, while ex vivo-generated Gata1lowcDCs failed to respond to lipopolysaccharide, suggesting that HS1 activation is required for cDC maturation. Conclusion: These results identify a dynamic pattern of Gata1 regulation that switches from an HS1 to an HS2-dependent phase during the maturation of cDCs associated with the antigen-presentation process in the blood