Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses

Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified. We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show that both natural and recombinant omega-1 alone are sufficient to generate Th2 responses in vivo, even in the absence of IL-4R signaling. Finally, omega-1–depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1–mediated effects. Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial

Funding Information: The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foamVR kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD

Collagen fleeces do not improve colonic anastomotic strength but increase bowel obstructions in an experimental rat model

To investigate whether a collagen fleece kept in place by fibrin glue might seal off a colorectal anastomosis, provide reinforcement, and subsequently improve anastomotic healing. Wistar rats underwent a 1-cm left-sided colonic resection followed by a 4-suture end-to-end anastomosis. They were then randomly assigned to one of three treatment groups: no additional intervention (control, n = 20), the anastomosis covered with fibrin glue (fibrin glue, n = 20), the anastomosis covered with a collagen fleece, kept in place with fibrin glue (collagen fleece, n = 21). At either 3 or 7 days follow-up, anastomotic bursting pressure was measured and tissue was obtained for histology and collagen content assessment after which animals were sacrificed. Three rats in the control (15%), three in the fibrin glue (15%), and one in the collagen group (4.8%) died due to anastomotic complications (P = 0.497). Anastomotic bursting pressures were not significantly different between groups at 3 and 7 days follow-up (P = 0.659 and P = 0.427, respectively). However, bowel obstructions occurred significantly more often in the collagen group compared to the control group (14/21 vs. 3/20, P = 0.003). Collagen contents were not different between groups, but histology showed a more severe inflammation in the collagen group compared to the other groups at both 3 and 7 days follow-up. A collagen fleece kept in place by fibrin glue does not improve healing of colonic anastomoses in rats. Moreover, this technique induces significantly more bowel obstructions in rats, warranting further study before being translated to a clinical settin

A heterogenized copper phenanthroline system to catalyze the oxygen reduction reaction

Upon the electrochemical reduction of an in situ generated 5-diazo-1,10-phenanthroline ion, phenanthroline was covalently attached to a gold electrode. The grafted molecules act as a ligand when brought in contact with a copper-containing electrolyte solution. As the ligands are limited in spatial movement, the exclusive formation of the active species with only one phenanthroline ligand coordinated was expected. The in situ generated complexes have been investigated for activity in the oxygen reduction reaction, for which an overpotential of 800 mV is observed. During catalysis, initially a thick copper layer is formed on top of an organic layer that is still present on the gold surface. Upon deterioration of the organic layer underneath the copper over time, the amount of copper on the electrode and thereby the electrocatalytic activity decreases

Detangling catalyst modification reactions from the oxygen evolution reaction by online mass spectrometry

Here we showcase the synthesis and catalytic response of the anionic iridium(III) complex [IrCl(pic)(MeOH)] ([1], pic = picolinate) toward the evolution of oxygen. Online electrochemical mass spectrometry experiments illustrate that an initial burst of CO due to catalyst degradation is expelled before the oxygen evolution reaction commences. Electrochemical features and XPS analysis illustrate the presence of iridium oxide, which is the true active species.Generous financial support from the MINECO/FEDER (CTQ2014-53033-P; C.T.) and Gobierno de Aragon/FSE (GA/FSE, Inorganic Molecular Architecture Group, E70; C.T.) is gratefully acknowledged. P.A. and M.P.d.R. thank the MINECO/FEDER for a fellowship and a JdC contract, respectively.Peer Reviewe

Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses

Therapeutic vaccination with human papillomavirus type 16 synthetic long peptides (HPV16-SLPs) results in T cell-mediated regression of HPV16-induced premalignant lesions but fails to install clinically effective immunity in patients with HPV16-positive cervical cancer. We explored whether HPV16-SLP vaccination can be combined with standard carboplatin and paclitaxel chemotherapy to improve immunity and which time point would be optimal for vaccination. This was studied in the HPV16 E6/E7-positive TC-1 mouse tumor model and in patients with advanced cervical cancer. In mice and patients, the presence of a progressing tumor was associated with abnormal frequencies of circulating myeloid cells. Treatment of TC-1-bearing mice with chemotherapy and therapeutic vaccination resulted in superior survival and was directly related to a chemotherapy-mediated altered composition of the myeloid cell population in the blood and tumor. Chemotherapy had no effect on tumor-specific T cell responses. In advanced cervical cancer patients, carboplatin-paclitaxel also normalized the abnormal numbers of circulating myeloid cells, and this was associated with increased T cell reactivity to recall antigens. The effect was most pronounced starting 2 weeks after the second cycle of chemotherapy, providing an optimal immunological window for vaccination. This was validated with a single dose of HPV16-SLP vaccine given in this time window. The resulting proliferative HPV16-specific T cell responses were unusually strong and were retained after all cycles of chemotherapy. In conclusion, carboplatin-paclitaxel therapy fosters vigorous vaccine-induced T cell responses when vaccination is given after chemotherapy and has reset the tumor-induced abnormal myeloid cell composition to normal value

CCDC 1909362: Experimental Crystal Structure Determination

Related Article: Marta Olivares, Cornelis J. M. van der Ham, Velabo Mdluli, Markus Schmidtendorf, Helge Müller-Bunz, Tiny W.G.M Verhoeven, Mo Li, Hans J. W. Niemantsverdriet, Dennis G. H. Hetterscheid, Stefan Bernhard, Martin Albrecht, J. W. Hans Niemantsverdriet|2020|Eur.J.Inorg.Chem.|2020|801|doi:10.1002/ejic.20200009

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial: A randomized non-inferiority trial

STUDY QUESTION: Does hysterosalpingo-foam sonography (HyFoSy) lead to similar pregnancy outcomes, compared with hysterosalpingography (HSG), as first-choice tubal patency test in infertile couples? SUMMARY ANSWER: HyFoSy and HSG produce similar findings in a majority of patients and clinical management based on the results of either HyFoSy or HSG, leads to comparable pregnancy outcomes. HyFoSy is experienced as significantly less painful. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during fertility work-up is performed by HSG. HyFoSy is an alternative imaging technique lacking ionizing radiation and iodinated contrast medium exposure which is less expensive than HSG. Globally, there is a shift towards the use of office-based diagnostic methods, such as HyFoSy. STUDY DESIGN, SIZE, DURATION: This multicentre, prospective, comparative study with a randomized design was conducted in 26 hospitals in The Netherlands. Participating women underwent both HyFoSy and HSG in randomized order. In case of discordant results, women were randomly allocated to either a management strategy based on HyFoSy or one based on HSG. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included infertile women between 18 and 41 years old who were scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male infertility or a known iodine contrast allergy were excluded. The primary outcome for the comparison of the HyFoSy- and HSG-based strategies was ongoing pregnancy leading to live birth within 12 months after inclusion in an intention-to-treat analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 women underwent HyFoSy and HSG. HyFoSy was inconclusive in 97 of them (9.5%), HSG was inconclusive in 30 (2.9%) and both were inconclusive in 9 (0.9%). In 747 women (73%) conclusive tests results were concordant. Of the 143/1026 (14%) with discordant results, 105 were randomized to clinical management based on the results of either HyFoSy or HSG. In this group, 22 of the 54 women (41%) allocated to management based on HyFoSy and 25 of 51 women (49%) allocated to management based on HSG had an ongoing pregnancy leading to live birth (Difference -8%; 95% CI: -27% to 10%). In total, clinical management based on the results of HyFoSy was estimated to lead to a live birth in 474 of 1026 women (46%) versus 486 of 1026 (47%) for management based on HSG (Difference -1.2%; 95% CI: -3.4% to 1.5%). Given the pre-defined margin of -2%, statistically significant non-inferiority of HyFoSy relative to HSG could not be demonstrated (P = 0.27). The mean pain score for HyFoSy on the 1-10 Visual Analogue Scale (VAS) was 3.1 (SD 2.2) and the mean VAS pain score for HSG was 5.4 (SD 2.5; P for difference < 0.001). LIMITATIONS, REASONS FOR CAUTION: Since all women underwent both tubal patency tests, no conclusions on a direct therapeutic effect of tubal flushing could be drawn. WIDER IMPLICATIONS OF THE FINDINGS: HyFoSy or HSG produce similar tubal pathology findings in a majority of infertile couples and, where they differ, a difference in findings does not lead to substantial difference in pregnancy outcome, while HyFoSy is associated with significantly less pain. STUDY FUNDING/COMPETING INTEREST(S): The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foam® kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports travel and speaker fees from Guerbet. F.J.M.B. reports personal fees as a member of the external advisory board for Merck Serono, The Netherlands, and a research support grant from Merck Serono, outside the submitted work. C.B.L. reports speakers' fee from Ferring in the past, and his department receives research grants from Ferring, Merck and Guerbet. J.S. reports a research agreement with Takeda on MR of motility outside the submitted work. M.V.W. reports leading The Netherlands Satellite of the Cochrane Gynaecology and Fertility Group. B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.J.M. reports consultancy for Guerbet and research funding from Merck and Guerbet. V.M. reports non-financial support from IQ medicals ventures, during the conduct of the study; grants and personal fees from Guerbet, outside the submitted work. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: NTR4746/NL4587 (https://www.trialregister.nl). TRIAL REGISTRATION DATE: 19 August 2014. DATE OF FIRST PATIENT’S ENROLMENT: 7 May 2015