The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation

We thank Manuel Kulagin for technical help, Pierre Bonnaventure for portal vein blood sampling, Francisco Sepulveda for technical assistance in GS-MS acquisition, and Dorothee Hahne (Metabolomics Australia, University of Western Australia) for human samples SCFA isolation, acquisition, and analysis. We also thank Cristina Cartoni (Phenotyping Unit, EPFL) for Milliplex analysis, Jessica Dessimoz and her team from the Histology Core Facility (EPFL), Miguel Garcia and his team from the Flow Cytometry Core Facility (EPFL), and staff from the EPFL CPG animal house for excellent animal care. The computations were partially performed at the Vital-IT Center for high-performance computing of the SIB Swiss Institute of Bioinformatics (http://www.vital-it.ch). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 310948. Funding for A.W.W. and a subset of the 16S rRNA gene sequencing was provided by the Wellcome Trust (grant number WT 098051). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Risk of Getting COVID-19 in People With Multiple Sclerosis

Background and Objectives Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). Methods Acase-control (1:2) studywas set up. Cases included PwMSwith a confirmed diagnosis ofCOVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administeredDMT, previousDMTsequences, or the place where the last treatment was administered. Results A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02)with a higher risk of contractingCOVID-19. Patients receiving natalizumab as last DMT(OR[95%CI]: 2.38 [1.66–3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. Discussion This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. Classification of Evidence This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective

IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity.

Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β(-/-)), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity

Rethinking Sustainability within the Viticulture Realities Integrating Economy, Landscape and Energy

Sustainability is often explained through three dimensions (society, economy and environment). However, such a definition currently appears to be restricted. Sustainable development often includes the energy issue. An example of realities founded on bioenergy are agro-energy districts. These realities involve all the three dimensions of sustainability, integrating also the energy dimension and fueling a potential circular economy. Based on these premises, the most affluent rural subdivision in Italy is that of wine. The wine sector has experienced a recent growth of its economic market, diverging from other agricultural activities and enlarging its cultivated surface areas. In this sense, the local landscape has also changed. Owing to the strong inclination of the wine sector in adopting sustainable strategies and measures, agro-energy districts can be the following future phase in viticulture realities as a cutting-edge business in the modern agricultural sector, implementing new strategies and opportunities

Juxta-articular Myxoma of the Hip: A Rare Pediatric Tumor

Juxta-articular myxoma (JAM) is a very rare myxoid tumor in pediatric age. JAM is frequently located at large joints, particularly in the knee, and most lesions present as palpable swelling sometimes associated with pain or tenderness. Only three cases of pediatric JAM have been reported in the literature to date. We describe a case of JAM in a 12-year-old boy, characterized by several unique aspects related to age, site of onset, size, and associated symptoms

Rural districts between urbanization and land abandonment: Undermining long-term changes in mediterranean landscapes

The present study investigates changes in the rural landscapes of a Mediterranean country (Greece) over a long time period (1970-2015) encompassing economic expansions and recessions. Using a spatial distribution of 5 basic agricultural land-use classes (arable land, garden crop, vineyards, tree crop and fallow land) derived from official statistics at 6 years (1970, 1979, 1988, 1997, 2006, 2015), a quantitative analysis based on correlation and multivariate techniques was carried out to identify recent changes in the Greek agricultural landscape at prefectural level during different economic waves. Empirical results evidenced both intuitive and counter-intuitive landscape transformations, including: (i) a progressive, spatially-homogeneous reduction of cropland; (ii) a (more or less) rapid decrease in the surface of high-input crops, including arable land, horticulture and vineyards; (iii) a parallel increase in the surface of tree crops, especially olive; (iv) a spatially-heterogeneous decrease of fallow land concentrated in metropolitan and tourism districts, especially in the last decade; and, finally, (v) increasingly diversified landscapes in rural, accessible areas close to the sea coast. Based on a correlation analysis with background socioeconomic indicators, our findings reflect the multiple impacts of urbanization and land abandonment on the composition and diversity of rural landscapes. Changes in agricultural land-use were moulded by multiple drivers depending on latent transformations in rural systems and inherent conflicts with expanding urban regions. Together with market conditions and the Common Agricultural Policy subsidy regime, social contexts and the economic cycle are important when identifying long-term changes in agricultural landscapes, especially in transitional socio-ecological systems

Fast and minimally invasive determination of the unsaturation index of white fat depots by micro-Raman spectroscopy.

In the last 20 years increasing interest has been devoted to the investigation of white adipose tissue (WAT) because hypo- or hyperfunction of WAT is involved in the pathogenesis of obesity and other pathologies. The investigation and discrimination of different characteristics in adipose tissues by means of spectroscopic techniques appears as a topic of current interest, also in view of possible medical-technological applications. The aim of this work was to establish micro-Raman spectroscopy as a tool for the characterization of mammals fat tissue. After preliminary tests aimed at defining a suitable sample preparation protocol, Raman spectra of WAT specimens excised from mice of different ages were recorded in the energy range 750-3,350 cm(-1). Quantitative values of the unsaturation index were obtained through the calibration with HR-NMR spectra of lipid extracts. Raman spectroscopy detected a sharp increase in the unsaturation index between 22 and 30 days of age in close correspondence with the weaning of mice (21 days). The present results show that Raman spectroscopy is an inexpensive, fast and robust technique to analyze the unsaturation index of mammals fat tissues that could be routinely used in bioptic samples

Lymphotoxin-Dependent B Cell-FRC Crosstalk Promotes De Novo Follicle Formation and Antibody Production following Intestinal Helminth Infection

Summary: Secondary lymphoid tissues provide specialized niches for the initiation of adaptive immune responses and undergo a remarkable expansion in response to inflammatory stimuli. Although the formation of B cell follicles was previously thought to be restricted to the postnatal period, we observed that the draining mesenteric lymph nodes (mLN) of helminth-infected mice form an extensive number of new, centrally located, B cell follicles in response to IL-4Rα-dependent inflammation. IL-4Rα signaling promoted LTα1β2 (lymphotoxin) expression by B cells, which then interacted with CCL19 positive stromal cells to promote lymphoid enlargement and the formation of germinal center containing B cell follicles. Importantly, de novo follicle formation functioned to promote both total and parasite-specific antibody production. These data reveal a role for type 2 inflammation in promoting stromal cell remodeling and de novo follicle formation by promoting B cell-stromal cell crosstalk. : Intestinal helminth infection drives type 2 immune responses in the draining mLN. Dubey et al. demonstrate in mice that type 2 inflammation drives lymphoid remodeling resulting from lymphotoxin-dependent crosstalk between B cells and FRCs. Such crosstalk promotes de novo follicle formation and supports the production of parasite-specific antibodies