Shaping the edges using flowdrill technology

In this paper, was presented the results of experimental studies of the edgetrimming process obtained using technology Flowdrill, shows distributions of thickness and height of recurving edging and its microhardness made of aluminum, mild steel and stainless steel

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

Changes in Employment Uncertainty and the Fertility Intention-Realization Link: An Analysis Based on the Swiss Household Panel.

How do changes in employment uncertainty matter for fertility? Empirical studies on the impact of employment uncertainty on reproductive decision-making offer a variety of conclusions, ranging from gender and socio-economic differences in the effect of employment uncertainty on fertility intentions and behaviour, to the effect of employment on changes in fertility intentions. This article analyses the association between a change in subjective employment uncertainty and fertility intentions and behaviour by distinguishing male and female partners' employment uncertainty, and examines the variation in these associations by education. Using a sample of men and women living in a couple from the Swiss Household Panel (SHP 2002-2011), we examine through multinomial analysis how changes in employment uncertainty and selected socio-demographic factors are related to individual childbearing decisions. Our results show strong gendered effects of changes in employment uncertainty on the revision of reproductive decisions among the highly educated population

Inter-fraction motion robustness and organ sparing potential of proton therapy for cervical cancer

Purpose: Large-field photon radiotherapy is current standard in the treatment of cervical cancer patients. However, with the increasing availability of Pencil Beam Scanning Proton Therapy (PBS-PT) and robust treatment planning techniques, protons may have significant advantages for cervical cancer patients in the reduction of toxicity. In this study, PBS-PT and photon Volumetric Modulated Arc Therapy (VMAT) were compared, examining target coverage and organ at risk (OAR) dose, taking inter- and intra-fraction motion into account. Materials and methods: Twelve cervical cancer patients were included in this in-silico planning study. In all cases, a planning CT scan, five weekly repeat CT scans (reCTs) and an additional reCT 10 min after the first reCT were available. Two-arc VMAT and robustly optimised two- and four-field (2F and 4F) PBS-PT plans were robustly evaluated on planCTs and reCTs using set-up and range uncertainty. Nominal OAR doses and voxel-wise minimum target coverage robustness were compared. Results: Average voxel-wise minimum accumulated doses for pelvic target structures over all patients were adequate for both photon and proton treatment techniques (D98 > 95%, [91.7–99.3%]). Average accumulated dose of the para-aortic region was lower than the required 95%, D98 > 94.4% [91.1–98.2%]. With PBS-PT 4F, dose to all OARs was significantly lower than with VMAT. Major differences were observed for mean bowel bag V15Gy: 60% [39–70%] for VMAT vs 30% [10–52%] and 32% [9–54%] for PBS-PT 2F and 4F and for mean bone marrow V10Gy: 88% [82–97%] for VMAT vs 66% [60–73%] and 67% [60–75%] for PBS-PT 2F and 4F. Conclusion: Robustly optimised PBS-PT for cervical cancer patients shows equivalent target robustness against inter- and intra-fraction variability compared to VMAT, and offers significantly better OAR sparing

Future research demands of the United European Gastroenterology (UEG) and its member societies

AIMS: The purpose of this study was to initiate and stimulate collaborative research efforts to support United European Gastroenterology Federation (UEG) member societies facilitating digestive health research in European on the one hand and, on the other hand, to increase EU-funded digestive health research by providing evidence and advice to funding bodies on priority areas. The UEG Research Committee initiated a survey of the current and future research interests of each individual UEG ordinary member society (specialist societies). METHODS: A questionnaire was sent by mail to 17 UEG ordinary member societies asking them to specify research demands related to the most urgent medical need including basic science research, translational research, clinical research, patient management research and research on disease prevention, in an open fashion but with limited word count. RESULTS: The responses from 13 societies were analysed in a semi-quantitative and in a qualitative way, and were clustered into five domains with two aspects each that were consented and shared between three and seven of the responding 13 societies. These clusters resemble topics such as ‘Hot topics’ (e.g. life-style, nutrition, microbial-host interaction), Biomarkers (genetic profiling, gut-brain interaction), Advanced technology (artificial intelligence, personalised medicine), Global research tools (bio-banking, EU trials), and Medical training (education, prevention). CONCLUSION: The generated topic list allows both collaboration between individual specialist societies as well as initiating and fostering future research calls at the EU level and beyond when approaching stakeholders

Influence of eye movement on lens dose and optic nerve target coverage during craniospinal irradiation

PURPOSE: Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. METHODS: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. RESULTS: Mean eye structures’ shift from neutral position was greatest in caudal gaze; −5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98(OON)) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range −8.1 to 10.0 Gy], and mean D98(OON) decreased up to 3.3 Gy [total ΔD98(OON) range −13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98(OON) became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98(OON) significantly changed in 1 of 10 volunteers. CONCLUSION: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of <10% of prescribed dose

Advancing patient‐centered care: Recent developments in UEG's patient relations

info:eu-repo/semantics/publishedVersio

Perspectives of Phage Therapy in Non-bacterial Infections

While the true value of phage therapy (PT) in human bacterial infections still awaits formal confirmation by clinical trials, new data have been accumulating indicating that in the future PT may be applied in the treatment of non-bacterial infections. Thus, “phage guests” may interact with eukaryotic cells and such interactions with cells of the immune system may protect human health (Guglielmi, 2017) and cause clinically useful immunomodulatory and anti-inflammatory effects when administered for therapeutic purposes (Górski et al., 2017; Van Belleghem et al., 2017). Recently, a vision of how these effects could translate into advances in novel means of therapy in a variety of human pathologies secondary to immune disturbances and allergy was presented (Górski et al., 2018a). In this article we present what is currently known about anti-microbial effects of phage which are not directly related to their antibacterial action and how these findings could be applied in the future in treatment of viral and fungal infections

Gliadin Peptide P31-43 Localises to Endocytic Vesicles and Interferes with Their Maturation

BACKGROUND: Celiac Disease (CD) is both a frequent disease (1:100) and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR)-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs-mediated maturation to late endosomes in cells and intestinal biopsies. Consequently, in P31-43-treated cells, Receptor Tyrosine Kinase (RTK) activation is extended. This finding may explain the role played by gliadin peptides in inducing proliferation and other effects in enterocytes from CD biopsies

Standard methods for Apis mellifera venom research

Honey bees have a sting which allows them to inject venomous substances into the body of an opponent or attacker. As the sting originates from a modified ovipositor, it only occurs in the female insect, and this is a defining feature of the bee species that belong to a subclade of the Hymenoptera called Aculeata. There is considerable interest in bee venom research, primarily because of an important subset of the human population who will develop a sometimes life threatening allergic response after a bee sting. However, the use of honey bee venom goes much further, with alleged healing properties in ancient therapies and recent research. The present paper aims to standardize selected methods for honey bee venom research. It covers different methods of venom collection, characterization and storage. Much attention was also addressed to the determination of the biological activity of the venom and its use in the context of biomedical research, more specifically venom allergy. Finally, the procedure for the assignment of new venom allergens has been presented. Las abejas meliferas tienen un aguijon que les permite inyectar sustancias venenosas en el cuerpo de un oponente o atacante. El aguijon es un ovipositor modificado que solo se manifiesta en el insecto hembra, siendo este una caracteristica que define a las especies de abejas que pertenecen al subclado de himenopteros llamada Aculeata. Hay un interes considerable en la investigacion del veneno de abeja, principalmente debido a que un porcentaje importante de la poblacion humana desarrollara una respuesta alergica - a veces mortal - a la picadura de abeja. Sin embargo, el uso del veneno de la abeja melifera abarca mucho mas, con presuntas propiedades curativas en terapias antiguas e investigaciones recientes. El presente trabajo tiene como objetivo estandarizar metodos seleccionados para la investigacion del veneno de las abejas meliferas. Cubre diferentes metodos de recoleccion, caracterizacion y almacenamiento de veneno. Tambien se presto mucha atencion a la determinacion de la actividad biologica del veneno y su uso en el contexto de la investigacion biomedica, mas especificamente la alergia al veneno. Finalmente, se ha presentado el procedimiento para la asignacion de nuevos alergenos de veneno