A fixed combination of probiotics and herbal extracts attenuates intestinal barrier dysfunction from inflammatory stress in an in vitro model using Caco-2 cells.

Background: Inflammatory Bowel Diseases (IBD), are considered a growing global disease, with about ten million people being affected worldwide. Maintenance of intestinal barrier integrity is crucial for preventing IBD onset and exacerbations. Some recent patents regarding oily formulations containing probiotics (WO2010122107A1 and WO2010103374A9) and the use of probiotics for gastrointestinal complaints (US20110110905A1 and US9057112B2) exist, or are pending application. Objective: In this work, we studied the effect of a fixed combination of registered Lactobacillus reuteri and Lactobacillus acidophilus strains and herbal extracts in an in vitro inflammation experimental model. Methods: Caco-2 cell monolayer was exposed to INF-\u3b3+TNF-\u3b1 or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin Tight Junctions (TJs) were also investigated by mean of immunofluorescence. Results: Pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. Conclusions: In summary, the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBD conditions

A proposed design for the evaluation of change in a small reference group.

Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection and allow recognition of an original pathophysiologic mechanism underlying gastrointestinal diseases as well as identification of novel therapeutic targets

Weak selection and stability of localized distributions in Ostwald ripening

We support and generalize a weak selection rule predicted recently for the self-similar asymptotics of the distribution function (DF) in the zero-volume-fraction limit of Ostwald ripening (OR). An asymptotic perturbation theory is developed that, when combined with an exact invariance property of the system, yields the selection rule, predicts a power-law convergence towards the selected self-similar DF and agrees well with our numerical simulations for the interface- and diffusion-controlled OR.Comment: 4 pages, 2 figures, submitted to PR

Acetylsalicylic acid prevents intermittent hypoxia-induced vascular remodeling in a murine model of sleep apnea

Study objectives: Chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA), induces accelerated atherogenesis as well as aorta vascular remodeling. Although the cyclooxygenase (COX) pathway has been proposed to contribute to the cardiovascular consequences of OSA, the potential benefits of a widely employed COX-inhibitor such (acetylsalicylic acid, ASA) on CIH-induced vascular pathology are unknown. Therefore, we hypothesized that a common non-selective COX inhibitor such as ASA would attenuate the aortic remodeling induced by CIH in mice. Methods: 40 wild-type C57/BL6malemice were randomly allocated to CIH or normoxic exposures (N) and treated with daily doses of ASA or placebo for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization (ED), elastin fragmentation (EF), length between fragmented fiber endpoints (LFF), aortic wall collagen abundance (AC) and mucoid deposition (MD) were assessed. Results: Compared to N, CIH promoted significant increases in IMT (52.58 ± 2.82μm vs. 46.07 ± 4.18μm, p < 0.003), ED (25.29 ± 14.60% vs. 4.74 ± 5.37%, p < 0.001), EF (5.80 ± 2.04 vs. 3.06 ± 0.58, p < 0.001), LFF (0.65 ± 0.34% vs. 0.14 ± 0.09%, p < 0.001), AC (3.43 ± 1.52% vs. 1.67 ± 0.67%, p < 0.001) and MD (3.40 ± 2.73 μm2 vs. 1.09 ± 0.72 μm2, p < 0.006). ASA treatment mitigated the CIH-induced alterations in IMT: 44.07 ± 2.73μm; ED: 10.57 ± 12.89%; EF: 4.63 ± 0.88; LFF: 0.25 ± 0.17% and AC: 0.90 ± 0.13% (p<0.05 for all comparisons). Conclusions: ASA prevents the CIH-induced aortic vascular remodeling, and should therefore be prospectively evaluated as adjuvant treatment in patients with OSA.This work was supported by the Spanish Respiratory Society (SEPAR), SOCAP, the Associació Lleidatana de Respiratori (ALLER), and the Spanish Fondo de Investigaciones Sanitarias (PI14/00486 and PI14-00004), Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”. DG is supported by National Institutes of Health grant HL130984

A Multimethod Approach for Investigating Algal Toxicity of Platinum Nanoparticles

The ecotoxicity of platinum nanoparticles (PtNPs) widely used in for example automotive catalytic converters, is largely unknown. This study employs various characterization techniques and toxicity end points to investigate PtNP toxicity toward the green microalgae Pseudokirchneriella subcapitata and Chlamydomonas reinhardtii. Growth rate inhibition occurred in standard ISO tests (EC50 values of 15–200 mg Pt/L), but also in a double-vial setup, separating cells from PtNPs, thus demonstrating shading as an important artifact for PtNP toxicity. Negligible membrane damage, but substantial oxidative stress was detected at 0.1–80 mg Pt/L in both algal species using flow cytometry. PtNPs caused growth rate inhibition and oxidative stress in P. subcapitata, beyond what was accounted for by dissolved Pt, indicating NP-specific toxicity of PtNPs. Overall, P. subcapitata was found to be more sensitive toward PtNPs and higher body burdens were measured in this species, possibly due to a favored binding of Pt to the polysaccharide-rich cell wall of this algal species. This study highlights the importance of using multimethod approaches in nanoecotoxicological studies to elucidate toxicity mechanisms, influence of NP-interactions with media/organisms, and ultimately to identify artifacts and appropriate end points for NP-ecotoxicity testing

Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice

Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF-and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity

Expanding the medical physicist curricular and professional programme to include Artificial Intelligence

Purpose: To provide a guideline curriculum related to Artificial Intelligence (AI), for the education and training of European Medical Physicists (MPs). Materials and methods: The proposed curriculum consists of two levels: Basic (introducing MPs to the pillars of knowledge, development and applications of AI, in the context of medical imaging and radiation therapy) and Advanced. Both are common to the subspecialties (diagnostic and interventional radiology, nuclear medicine, and radiation oncology). The learning outcomes of the training are presented as knowledge, skills and competences (KSC approach). Results: For the Basic section, KSCs were stratified in four subsections: (1) Medical imaging analysis and AI Basics; (2) Implementation of AI applications in clinical practice; (3) Big data and enterprise imaging, and (4) Quality, Regulatory and Ethical Issues of AI processes. For the Advanced section instead, a common block was proposed to be further elaborated by each subspecialty core curriculum. The learning outcomes were also translated into a syllabus of a more traditional format, including practical applications. Conclusions: This AI curriculum is the first attempt to create a guideline expanding the current educational framework for Medical Physicists in Europe. It should be considered as a document to top the sub-specialties' curriculums and adapted by national training and regulatory bodies. The proposed educational program can be implemented via the European School of Medical Physics Expert (ESMPE) course modules and - to some extent - also by the national competent EFOMP organizations, to reach widely the medical physicist community in Europe.Peer reviewe

Radiation-grafted anion-exchange membranes for CO2 electroreduction cells: an unexpected effect of using a lower excess of N-methylpiperidine in their fabrication

Giron Rodriguez et al. [ACS Sustainable Chem. Eng., 2023, 11, 1508] previously showed that radiation-grafted anion-exchange membranes containing N-benzyl-N-methylpiperidinium headgroups (MPIP-RG-AEM) are promising for use in CO2 electrolysis (cf. commercial and other RG-AEM types). For a more sustainable synthesis, MPIP-RG-AEMs have now been fabricated using a reduced 1.1 times excess of amine reagent (historically made using >5 times excess). A resulting RG-AEM promisingly had a bulk amination level that was comparable to those made with the traditional large excess. Unexpectedly, however, it had a significantly reduced water content, with two further batches showing that this observation was repeatable (and reproducible via measurements collected on a single batch using different techniques in different labs). The ionic conductivities of the RG-AEM made with a controlled 1.1 excess of amine were also lower, with higher activation energies. Terahertz time-domain spectroscopy measurements showed that the lower water uptake RG-AEMs, made with the 1.1 amine excess, contained smaller amounts of bulk water relative to bound water (a repeatable observation with different counter-anions). This lack of bulk water, yielding reduced water diffusion coefficients, led to a change in the water management when such RG-AEMs were tested in CO2 electrolysis cells, with significantly affected in situ performances. Small angle scattering data (X-ray and neutron) indicated that MPIP-RG-AEM fabrication with the 1.1 excess of amine reduced the size of the amorphous lamella domains on hydration, and this change is suspected to be the cause of the lower water uptakes and swelling. The finding that chemically similar AEMs can have significantly different hydration properties is potentially important to all ion-exchange membrane users and developers (beyond the CO2 electrolysis scope of this study)

The Muon Anomalous Magnetic Moment and the Standard Model

The muon anomalous magnetic moment measurement, when compared with theory, can be used to test many extensions to the standard model. The most recent measurement made by the Brookhaven E821 Collaboration reduces the uncertainty on the world average of a_mu to 0.7 ppm, comparable in precision to theory. This paper describes the experiment and the current theoretical efforts to establish a correct standard model reference value for the muon anomaly.Comment: Plenary Talk; PANIC'02 XVI Particles and Nuclear International Conference, Osaka, Japan; Sept. 30 - Oct. 4, 2002; Report describes the published 0.7 ppm result and updates the theory statu