Prenatal Screening and Genetics

Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were more precisely observed

Serratiopeptidase reduces the invasion of osteoblasts by Staphylococcus aureus

Finding new strategies to counteract periprosthetic infection and implant failure is a main target in orthopedics. Staphylococcus aureus, the leading etiologic agent of orthopedic implant infections, is able to enter and kill osteoblasts, to stimulate pro-inflammatory chemokine secretion, to recruit osteoclasts, and to cause inflammatory osteolysis. Moreover, by entering eukaryotic cells, staphylococci hide from the host immune defenses and shelter from the extracellular antibiotics. Thus, infection persists, inflammation thrives, and a highly destructive osteomyelitis occurs around the implant. The ability of serratiopeptidase (SPEP), a metalloprotease by Serratia marcescens, to control S. aureus invasion of osteoblastic MG-63 cells and pro-inflammatory chemokine MCP-1 secretion was evaluated. Human osteoblast cells were infected with staphylococcal strains in the presence and in the absence of SPEP. Cell proliferation and cell viability were also evaluated. The release of pro-inflammatory chemokine MCP-1 was evaluated after the exposure of the osteoblast cells to staphylococcal strains. The significance of the differences in the results of each test and the relative control values was determined with Student’s t-test. SPEP impairs their invasiveness into osteoblasts, without affecting the viability and proliferation of bone cells, and tones down their production of MCP-1. We recognize SPEP as a potential tool against S. aureus bone infection and destruction

Von willebrand and factor VIII portosystemic circulation gradient in cirrhosi. Implications for portal vein thrombosis

OBJECTIVES: Portal vein thrombosis seems to be dependent on local hypercoagulation and venous stasis; data regarding endothelial damage are lacking. METHODS: von Willebrad factor, a marker of endothelial damage/perturbation, factor VIII, and lipopolysaccharides (LPS) were studied in the portal and systemic circulation of 20 cirrhotic patients undergoing transjugular intrahepatic portosystemic procedure. RESULTS: von Willebrad factor, factor VIII, and LPS were higher in the portal compared with systemic circulation, with a significant correlation between LPS and the other 2 variables. DISCUSSION: Endothelial damage and hypercoagulation coexist in the portal tree of patients with cirrhosis, and both could contribute to portal vein thrombosis. LPS may be a potential trigger of endothelial damage

JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients

Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LT

Glutamatergic neurons induce expression of functional glutamatergic synapses in primary myotubes.

The functioning of the nervous system depends upon the specificity of its synaptic contacts. The mechanisms triggering the expression of the appropriate receptors on postsynaptic membrane and the role of the presynaptic partner in the differentiation of postsynaptic structures are little known.To address these questions we cocultured murine primary muscle cells with several glutamatergic neurons, either cortical, cerebellar or hippocampal. Immunofluorescence and electrophysiology analyses revealed that functional excitatory synaptic contacts were formed between glutamatergic neurons and muscle cells. Moreover, immunoprecipitation and immunofluorescence experiments showed that typical anchoring proteins of central excitatory synapses coimmunoprecipitate and colocalize with rapsyn, the acetylcholine receptor anchoring protein at the neuromuscular junction.These results support an important role of the presynaptic partner in the induction and differentiation of the postsynaptic structures

Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration

All authors were employees of (or in the case of MID, seconded full-time to) 4D Pharma Research Ltd while engaged in the research project. This work was supported by funding provided by 4D Pharma PLC. 4D Pharma Research Ltd owns a family of patent applications which are pending internationally which are derived from International Patent Publication No. WO2016/203223 which protect the treatment of severe asthma using MRx0004. George Grant, Angela Patterson, Imke Mulder, Seanin McCluskey and Emma Raftis are named as inventors for this patent family. The authors declare no other competing interests.Peer reviewedPublisher PD

Analysis of limited-diffractive and limited-dispersive X-waves generated by finite radial waveguides

International audienceIn this work, we analyze the spatial and temporal features of electromagnetic X-waves propagating in free space and generated by planar radiating apertures. The performance of ideal X-waves is discussed and compared to practical cases where the important effects related to the finiteness of the radiating aperture and the wavenumber dispersion are taken into account. In particular, a practical device consisting of a radial waveguide loaded with radiating slots aligned along a spiral path is considered for the practical case in the millimeter-wave range. A common mathematical framework is defined for a precise comparison of the spatiotemporal properties and focusing capabilities of the generated X-wave. It is clearly shown that the fractional bandwidth of the radiating aperture has a key role in the longitudinal confinement of an X-wave in both ideal and practical cases. In addition, the finiteness of the radiating aperture as well as the wavenumber dispersion clearly affect both the transverse and the longitudinal profiles of the generated radiation as it travels beyond the depth-of-field of the generated X-wave. Nevertheless, the spatiotemporal properties of the X-wave are preserved even in this "dispersive-finite" case within a defined region and duration related to the nondiffractive range and fractional bandwidth of the spectral components of the generated X-wave. The proposed analysis may open new perspectives for the efficient generation of X-waves over finite radiating apertures at millimeter waves where the dispersive behavior of realistic devices is no longer negligible. Published by AIP Publishing

Rho GTPase-dependent plasticity of dendritic spines in the adult brain.

Brain activity is associated with structural changes in the neural connections. However, in vivo imaging of the outer cortical layers has shown that dendritic spines, on which most excitatory synapses insist, are predominantly stable in adulthood. Changes in dendritic spines are governed by small GTPases of the Rho family through modulation of the actin cytoskeleton. Yet, while there are abundant data about this functional effect of Rho GTPases in vitro, there is little evidence that Rho GTPase signaling in the brain is associated with changes in neuronal morphology. In the present work, both chronic in vivo two-photon imaging and Golgi staining reveal that the activation of Rho GTPases in the adult mouse brain is associated with little change of dendritic spines in the apical dendrites of primary visual cortex pyramidal neurons. On the contrary, considerable increase in spine density is observed i) in the basal dendrites of the same neurons ii) in both basal and apical dendrites of the hippocampal CA1 pyramidal cells. Moreover, functional analysis shows increase in basal glutamatergic neurotrasmission and activity-dependent plasticity only in CA1 neurons. While confirming that Rho-GTPase dependent increase in spine density can be substantial, the study indicates region and dendrite selectivity with relative stability of superficial cortical circuits

In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties

Acknowledgments The authors are grateful to Dr. Nicole Reichardt and the 4D Pharma Isolation Team for their technical assistance with bacterial culture. Funding This work was privately funded by 4D Pharma PLC. The authors of the study, who are employees of (or in the case of MID, are funded by) 4D Pharma Research Ltd., a wholly owned subsidiary of the funder, were responsible for the design and execution of the study, as well as the analysis of the results obtained. Author Contributions In vitro experiments: AE, SA, and AB designed the experiments; SA, PF, NV, MG, SB, GB-A, and MD performed the majority of the in vitro experiments; SR, HD, and AB validated, performed, and analyzed the microbiological-related data output; AE coordinated and managed the research project; AE, SA, PF, and AB analyzed the data. IM oversaw the overall research plan. AE wrote the manuscript with the assistance of SA and AB. All authors have read and commented on the manuscript and have approved the final version of the manuscript. Data Availability: 16S gene sequences for MRx0005 and MRx0029 are disclosed in International Patent Publication Nos. WO2018/229189 and WO2018/229216, respectively, filed by 4D Pharma Research Ltd. The data supporting the findings in this paper are available within the article and its Supplementary Information Files.Peer reviewedPublisher PD

Oxidative Stress and Gut-Derived Lipopolysaccharides in Neurodegenerative Disease: Role of NOX2

Background. Neurodegenerative diseases (ND) as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis represent a growing cause of disability in the developed countries. The underlying physiopathology is still unclear. Several lines of evidence suggest a role for oxidative stress and NADPH oxidase 2 (NOX2) in the neuropathological pathways that lead to ND. Furthermore, recent studies hypothesized a role for gut microbiota in the neuroinflammation; in particular, lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut is believed to play a role in causing ND by increase of oxidative stress and inflammation. The aim of this study was to assess NOX2 activity as well as serum 8-iso-prostaglandin F2α (8-iso-PGF2α), serum H2O2, and LPS in patients with ND compared to controls. Methods. One hundred and twenty-eight consecutive subjects, including 64 ND patients and 64 controls (CT) matched for age and gender, were recruited. A cross-sectional study was performed to compare serum activity of soluble NOX2-dp (sNOX2-dp), blood levels of isoprostanes, serum H2O2, and LPS in these two groups. Serum zonulin was used to assess gut permeability. Results. Compared with CT, ND patients had higher values of sNOX2-dp, 8-iso-PGF2α, H2O2, and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.441; p<0.001), zonulin (Rs=0.411; p<0.001), serum H2O2 (Rs=0.329; p<0.001), and 8-iso-PGF2α (Rs=0.244; p=0.006). LPS significantly correlated with serum zonulin (Rs=0.818; p<0.001) and 8-iso-PGF2α (Rs=0.280; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX2-dp. LPS (SE, 0.165; standardized coefficient β, 0.459; p<0.001) and 8-iso-PGF2α (SE, 0.018; standardized coefficient β, 0.220; p=0.005) emerged as the only independent predictive variables associated with sNOX2-dp (R2=57%). Conclusion. This study provides the first report attesting that patients with ND have high NOX2 activation that could be potentially implicated in the process of neuroinflammation