Prospective Investigation of the Performance of 2 Gamma-Hydroxybutyric Acid Tests: DrugCheck GHB Single Test and Viva-E GHB Immunoassay

Background: Gamma-hydroxybutyric acid (GHB) is a recreational drug with central nervous system depressing effects that is often abused. A urine GHB point-of-care test can be of great diagnostic value. The objective of this prospective study was to determine the performance of the new DrugCheck GHB Single Test and the Viva-E GHB immunoassay for urine samples in emergency department patients. Methods: Patients presented to the emergency department of the OLVG hospital in Amsterdam with a Glasgow Coma Scale score ,15 and potential drug of abuse intoxication were included in the study. Between June 2016 and October 2017, 375 patients were included. Using the DrugCheck GHB Single Test (Express Diagnostics Int’l, Blue Earth, MN) and the Viva-E GHB immunoassay (Siemens Healthineers, The Hague, the Netherlands), patients’ urine samples were tested for GHB (cutoff for a positive result, 10 or 50 mcg/mL GHB). To ensure quality, the results obtained were compared with those generated using a validated gas chromatography method. The tests were considered reliable if specificity and sensitivity were both .90%. Possible cross-reactivity with ethanol was investigated by analyzing ethanol concentrations in patients’ samples. Results: Seventy percentage of the included patients was men, and the median age was 34 years old. The DrugCheck GHB Single Test’s specificity and sensitivity were 90.0% a

Selection and optimization of proteolytically stable llama single-domain antibody fragments for oral immunotherapy

We previously demonstrated that oral application of the recombinant single-domain antibody fragment (VHH) clone K609, directed against Escherichia coli F4 fimbriae, reduced E. coli-induced diarrhoea in piglets, but only at high VHH doses. We have now shown that a large portion of the orally applied K609 VHH is proteolytically degraded in the stomach. Stringent selection for proteolytic stability identified seven VHHs with 7- to 138-fold increased stability after in vitro incubation in gastric fluid. By DNA shuffling we obtained four clones with a further 1.5- to 3-fold increased in vitro stability. These VHHs differed by at most ten amino acid residues from each other and K609 that were scattered over the VHH sequence and did not overlap with predicted protease cleavage sites. The most stable clone, K922, retained 41% activity after incubation in gastric fluid and 90% in jejunal fluid. Oral application of K922 to piglets confirmed its improved proteolytic stability. In addition, K922 bound to F4 fimbriae with higher affinity and inhibited fimbrial adhesion at lower VHH concentrations. K922 is thus a promising candidate for prevention of piglet diarrhoea. Furthermore, our findings could guide selection and improvement by genetic engineering of other recombinant antibody fragments for oral use

The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity

A bright, high rotation-measure FRB that skewers the M33 halo

We report the detection of a bright fast radio burst, FRB\,191108, with Apertif on the Westerbork Synthesis Radio Telescope (WSRT). The interferometer allows us to localise the FRB to a narrow 5\arcsec\times7\arcmin ellipse by employing both multibeam information within the Apertif phased-array feed (PAF) beam pattern, and across different tied-array beams. The resulting sight line passes close to Local Group galaxy M33, with an impact parameter of only 18\,kpc with respect to the core. It also traverses the much larger circumgalactic medium of M31, the Andromeda Galaxy. We find that the shared plasma of the Local Group galaxies could contribute $\sim$10\% of its dispersion measure of 588\,pc\,cm$^{-3}$. FRB\,191108 has a Faraday rotation measure of +474\,$\pm\,3$\,rad\,m$^{-2}$, which is too large to be explained by either the Milky Way or the intergalactic medium. Based on the more moderate RMs of other extragalactic sources that traverse the halo of M33, we conclude that the dense magnetised plasma resides in the host galaxy. The FRB exhibits frequency structure on two scales, one that is consistent with quenched Galactic scintillation and broader spectral structure with $\Delta\nu\approx40$\,MHz. If the latter is due to scattering in the shared M33/M31 CGM, our results constrain the Local Group plasma environment. We found no accompanying persistent radio sources in the Apertif imaging survey data

Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells

During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B (Breg) cells play a significant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg-inducing proteins in SEA, we fractionated SEA by size exclusion chromatography and found 6 fractions able to induce IL-10 production by B cells (out of 18) in the high, medium and low molecular weight (MW) range. The high MW fractions were rich in heavily glycosylated molecules, including multi-fucosylated proteins. Using SEA glycoproteins purified by affinity chromatography and synthetic glycans coupled to gold nanoparticles, we investigated the role of these glycan structures in inducing IL-10 production by B cells. Then, we performed proteomics analysis on active low MW fractions and identified a number of proteins with putative immunomodulatory properties, notably thioredoxin (SmTrx1) and the fatty acid binding protein Sm14. Subsequent splenic murine B cell stimulations and hock immunizations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production by B cells both in vitro and in vivo. Identification of unique Breg cells-inducing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.Author summaryWorm parasites, such as schistosomes, are master regulators of the human immune system, manipulating the host response in order to prolong their survival in their host. As a bystander effect, they also reduce immune responses to allergens and/or auto antigens, thus protecting their host against inflammatory and auto-immune diseases. One of the immune cells involved in immune regulation is the IL-10-producing regulatory B (Breg) cells. Schistosome eggs release various molecules that induce the development of Breg cells, but the identity of these molecules is not yet fully known. In this study, the authors aimed to identify some of these molecules. They investigated both the involvement of glycans on high molecular weight schistosomal egg molecules, as well as dissected the role of proteins with a lower molecular weight coming from schistosomal eggs. Using proteomics, they targeted various interesting molecules, which they recombinantly expressed and confirmed the IL-10 inducing capacity in B cells in vitro and in vivo for 2 molecules. This new knowledge may explain the hyporesponsiveness found in chronic schistosome-infected people and may pave the way to new innovative therapies for inflammatory and auto-immune diseases.Bio-organic Synthesi

An Evaluation of the COVID-19 Pandemic and Perceived Social Distancing Policies in Relation to Planning, Selecting, and Preparing Healthy Meals: An Observational Study in 38 Countries Worldwide

Objectives: To examine changes in planning, selecting, and preparing healthy foods in relation to personal factors (time, money, stress) and social distancing policies during the COVID-19 crisis. Methods: Using cross-sectional online surveys collected in 38 countries worldwide in April-June 2020 (N = 37,207, Mage 36.7 SD 14.8, 77% women), we compared changes in food literacy behaviors to changes in personal factors and social distancing policies, using hierarchical multiple regression analyses controlling for sociodemographic variables. Results: Increases in planning (4.7 SD 1.3, 4.9 SD 1.3), selecting (3.6 SD 1.7, 3.7 SD 1.7), and preparing (4.6 SD 1.2, 4.7 SD 1.3) healthy foods were found for women and men, and positively related to perceived time availability and stay-at-home policies. Psychological distress was a barrier for women, and an enabler for men. Financial stress was a barrier and enabler depending on various sociodemographic variables (all p < 0.01). Conclusion: Stay-at-home policies and feelings of having more time during COVID-19 seem to have improved food literacy. Stress and other social distancing policies relate to food literacy in more complex ways, highlighting the necessity of a health equity lens. Copyright 2021 De Backer, Teunissen, Cuykx, Decorte, Pabian, Gerritsen, Matthys, Al Sabbah, Van Royen and the Corona Cooking Survey Study Group.This research was funded by the Research Foundation Flanders (G047518N) and Flanders Innovation and Entrepreneurship (HBC.2018.0397). These funding sources had no role in the design of the study, the analysis and interpretation of the data or the writing of, nor the decision to publish the manuscript.Scopu

Prevalence of Frailty in European Emergency Departments (FEED): an international flash mob study

Introduction Current emergency care systems are not optimized to respond to multiple and complex problems associated with frailty. Services may require reconfiguration to effectively deliver comprehensive frailty care, yet its prevalence and variation are poorly understood. This study primarily determined the prevalence of frailty among older people attending emergency care. Methods This cross-sectional study used a flash mob approach to collect observational European emergency care data over a 24-h period (04 July 2023). Sites were identified through the European Task Force for Geriatric Emergency Medicine collaboration and social media. Data were collected for all individuals aged 65 + who attended emergency care, and for all adults aged 18 + at a subset of sites. Variables included demographics, Clinical Frailty Scale (CFS), vital signs, and disposition. European and national frailty prevalence was determined with proportions with each CFS level and with dichotomized CFS 5 + (mild or more severe frailty). Results Sixty-two sites in fourteen European countries recruited five thousand seven hundred eighty-five individuals. 40% of 3479 older people had at least mild frailty, with countries ranging from 26 to 51%. They had median age 77 (IQR, 13) years and 53% were female. Across 22 sites observing all adult attenders, older people living with frailty comprised 14%. Conclusion 40% of older people using European emergency care had CFS 5 + . Frailty prevalence varied widely among European care systems. These differences likely reflected entrance selection and provide windows of opportunity for system configuration and workforce planning