Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour

Abstract Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals. Here, we investigated if faecal microbiota transplantation (FMT) from patients with MDD into rats could induce a depressive-like phenotype. We performed FMT from patients with MDD (FMT-MDD) and healthy individuals (FMT-Healthy) into male Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats and assessed depressive-like behaviour. No behavioural differences were observed in the FSL rats. In FRL rats, the FMT-Healthy group displayed significantly less depressive-like behaviour than the FMT-MDD group. However, there was no difference in behaviour between FMT-MDD FRL rats and negative controls, indicating that FMT-Healthy FRL rats received beneficial bacteria. We additionally found different taxa between the FMT-MDD and the FMT-Healthy FRL rats, which could be traced to the donors. Four taxa, three belonging to the family Ruminococcaceae and the genus Lachnospira, were significantly elevated in relative abundance in FMT-MDD rats, while the genus Coprococcus was depleted. In this study, the FMT-MDD group was different from the FMT-Healthy group based on behaviour and intestinal taxa

A clinically validated Drosophila S2 based vaccine platform for production of malaria vaccines

Drosophila S2 insect cell expression is less known than the extensively used Spodoptera or Trichoplusia ni (Hi-5) insect cell based Baculovirus expression system (BEVS). Nevertheless it has been used in research for almost 40 years. The cell line was derived from late stage Drosophila melanogaster (Fruit fly) embryos by Schneider in the 1970s, who named the cell line Drosophila Schneider line 2 (synonyms: S2, SL2, D.mel. 2). The system has been widely applied to fundamental research, where the availability of the whole genome sequence of Drosophila melanogaster (1, 2) and the S2 cells’ susceptibility to RNA interference methods (3, 4) have enabled genome wide RNAi screening and whole genome expression analysis techniques to be used to great effect. S2 cells have proved to be highly effective for the production of proteins from a great variety of protein classes (5), such as: viral proteins, toxins, membrane proteins, enzyme, etc. Recent publications have also shown the strength of the S2 system in expression of Virus Like Particles (VLPs) (6). ExpreS2ion has developed the ExpreS2, Drosophila S2 platform to achieve improved yields for difficult to express proteins. Furthermore, several technologies have been developed to improve the ease of use of the system, as well as enable fast and efficient screening of multiple constructs. S2 based production processes for two malaria vaccine clinical trails with The Jenner Institute, Oxford University (Rh5 (7,8), blood-stage malaria) and Copenhagen University (VAR2CSA (9) pregnancy associated malaria) have been developed. The placental malaria vaccine is currently in a phase Ia trail in Germany, and a Phase Ib trial in Benin. The blood-stage malaria vaccine is currently in Phase IIa trial and is expecting results by the end of 2018. Several transmission-blocking candidates have been identified over the years with some of the most prominent being pfs48/45, Pfs230C and Pfs25(10). Other vaccine targets focus on blood-stage malaria such as Rh5, PfRIPR and CyrPA. We will present data on the development of a high producing Pfs25 monoclonal cell line and the purification from said cell line,as well as expression data on a range of other malaria vaccine targets. This present the clinically validated ExpreS2 platform as a complete system for a wide range of malaria targeting vaccines. (1) Adams M.D. et al. Science 2000 287:2185-2195 (2) Ashburner M, et al. Genome Res. 2005 Dec;15(12):1661-7 (3) Neumüller RA, et al. Wiley Interdiscip Rev Syst Biol Med. 2011 Jul-Aug; 3(4):471-8 (4) D’Ambrosio M.V. et al. J. Cell Biol. Vol. 191 No. 3 471–478 (5) Schetz J.A. et al. Protein Expression in the Drosophila Schneider 2 Cell System, Current Protocols in Neuroscience, 2004 (6) Yang L. et al. J Virol. 2012, Jul;86(14):7662-76. (7) Wright K.E. et al. Nature, 2014 Nov 20;515(7527):427-30 (8) Hjerrild K.A. et al. Sci Rep. 2016 Jul 26;6:30357 (9) Nielsen M.A. et al. PLoS One. 2015 Sep 1;10(9):e0135406 (10) Chaturvedi N et al. Indian J Med Res. 2016 Jun;143(6):696-71

A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

SummaryAntigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans

Clinical decision-making style preferences of European psychiatrists : Results from the Ambassadors survey in 38 countries

Background While shared clinical decision-making (SDM) is the preferred approach to decision-making in mental health care, its implementation in everyday clinical practice is still insufficient. The European Psychiatric Association undertook a study aiming to gather data on the clinical decision-making style preferences of psychiatrists working in Europe. Methods We conducted a cross-sectional online survey involving a sample of 751 psychiatrists and psychiatry specialist trainees from 38 European countries in 2021, using the Clinical Decision-Making Style - Staff questionnaire and a set of questions regarding clinicians' expertise, training, and practice. Results SDM was the preferred decision-making style across all European regions ([central and eastern Europe, CEE], northern and western Europe [NWE], and southern Europe [SE]), with an average of 73% of clinical decisions being rated as SDM. However, we found significant differences in non-SDM decision-making styles: participants working in NWE countries more often prefer shared and active decision-making styles rather than passive styles when compared to other European regions, especially to the CEE. Additionally, psychiatry specialist trainees (compared to psychiatrists), those working mainly with outpatients (compared to those working mainly with inpatients) and those working in community mental health services/public services (compared to mixed and private settings) have a significantly lower preference for passive decision-making style. Conclusions The preferences for SDM styles among European psychiatrists are generally similar. However, the identified differences in the preferences for non-SDM styles across the regions call for more dialogue and educational efforts to harmonize practice across Europe.Peer reviewe

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.

The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters