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Molecular medical imaging is intended to increase the accuracy of diagnosis, particularly in cardiovascular and cancer-related diseases, where early detection could significantly ...increase the treatment success rate. In this study, we present mixed micelles formed from four building blocks as a magnetic resonance imaging targeted contrast agent for the detection of atheroma and cancer cells. The building blocks are a gadolinium-loaded DOTA ring responsible for contrast enhancement, a fibrin-specific CREKA pentapeptide responsible for targeting, a fluorescent dye and DSPE-PEG2000. The micelles were fully characterized in terms of their size, zeta potential, stability, relaxivity and toxicity. Target binding assays performed on fibrin clots were quantified by fluorescence and image signal intensities and proved the binding power. An additional internalization assay showed that the micelles were also designed to specifically enter into cancer cells. Overall, these multimodal mixed micelles represent a potential formulation for MRI molecular imaging of atheroma and cancer cells.
Immune checkpoints and their ligands are important actors of lymphocytes and monocytes activation's regulation. Their expression level within T cells changes with aging. Despite the major impact of ...aging on monocytes, there is no data about the expression of ICs on monocytes from old patients. The objective of our study is to describe the expression of ICs and their ligands on monocytes from young individuals compared to old patients.
We included 18 old control (>75 years old), 10 young control (<55 years old) and 45 old patients with hip fracture (HF). Phenotypical and functional analyses were performed on cryopreserved PBMCs.
There is a differential expression of immune checkpoints and their ligands within monocyte subtypes regardless of age at baseline. After stimulation, a differential expression of immune checkpoints in young subjects but not in old subjects was observed which would be in favor of a regulation defect in old subjects. We hypothesize that this lack of regulation could partially explain the excess production of pro-inflammatory cytokines by the stimulated monocytes in old subjects. In HF, we also observe a differential expression of immune checkpoints, especially in old patients with a poor prognosis.
Our results suggest that the immune regulation which should take place post-acute stress may be affected in old individuals.
Marine polysaccharides are part of the huge seaweeds resources and present many applications for several industries. In order to widen their potential as additives or bioactive compounds, some ...structural modifications have been studied. Among them, simple hydrophobization reactions have been developed in order to yield to grafted polysaccharides bearing acyl-, aryl-, alkyl-, and alkenyl-groups or fatty acid chains. The resulting polymers are able to present modified physicochemical and/or biological properties of interest in the current pharmaceutical, cosmetics, or food fields. This review covers the chemical structures of the main marine polysaccharides, and then focuses on their structural modifications, and especially on hydrophobization reactions mainly esterification, acylation, alkylation, amidation, or even cross-linking reaction on native hydroxyl-, amine, or carboxylic acid functions. Finally, the question of the necessary requirement for more sustainable processes around these structural modulations of marine polysaccharides is addressed, considering the development of greener technologies applied to traditional polysaccharides.
Enterococcus cecorum, a commensal Gram-positive bacterium of the chicken gut, has emerged as a worldwide cause of lameness in poultry, particularly in fast-growing broilers. It is responsible for ...osteomyelitis, spondylitis, and femoral head necrosis, causing animal suffering, mortality, and antimicrobial use. Research on the antimicrobial resistance of E. cecorum clinical isolates in France is scarce, and epidemiological cutoff (ECOFF) values are unknown. To determine tentative ECOFF (CO
) values for
and to investigate the antimicrobial resistance patterns of isolates from mainly French broilers, we tested the susceptibility of a collection of commensal and clinical isolates (
= 208) to 29 antimicrobials by the disc diffusion (DD) method. We also determined the MICs of 23 antimicrobials by the broth microdilution method. To detect chromosomal mutations conferring antimicrobial resistance, we investigated the genomes of 118
isolates obtained mainly from infectious sites and described previously in the literature. We determined the CO
values for more than 20 antimicrobials and identified two chromosomal mutations explaining fluoroquinolone resistance. The DD method appears better suited for detecting
antimicrobial resistance. Although tetracycline and erythromycin resistances were persistent in clinical and nonclinical isolates, we found little or no resistance to medically important antimicrobials.
X-linked moesin associated immunodeficiency (X-MAID) is a primary immunodeficiency disease in which patients suffer from profound lymphopenia leading to recurrent infections. The disease is caused by ...a single point mutation leading to a R171W amino acid change in the protein moesin (moesin
). Moesin is a member of the ERM family of proteins, which reversibly link the cortical actin cytoskeleton to the plasma membrane. Here, we describe a novel mouse model with global expression of moesin
that recapitulates multiple facets of patient disease, including severe lymphopenia. Further analysis reveals that these mice have diminished numbers of thymocytes and bone marrow precursors. X-MAID mice also exhibit systemic inflammation that is ameliorated by elimination of mature lymphocytes through breeding to a Rag1-deficient background. The few T cells in the periphery of X-MAID mice are highly activated and have mostly lost moesin
expression. In contrast, single-positive (SP) thymocytes do not appear activated and retain high expression levels of moesin
. Analysis of
CD4 SP thymocytes reveals defects in chemotactic responses and reduced migration on integrin ligands. While chemokine signaling appears intact, CD4 SP thymocytes from X-MAID mice are unable to polarize and rearrange cytoskeletal elements. This mouse model will be a valuable tool for teasing apart the complexity of the immunodeficiency caused by moesin
, and will provide new insights into how the actin cortex regulates lymphocyte function.
Violence in emergency care: can we do better? Revue, Eric; Boyle, Adrian; Chauvin, Anthony ...
Canadian journal of emergency medicine,
03/2022, Volume:
24, Issue:
2
Journal Article
Abstract Background The GINECO led three multicentric prospective phase II studies, Elderly Woman Ovarian Trials 1 (EWOT1), EWOT2, and EWOT3, to evaluate the impact of geriatric covariates on the ...outcome of elderly patients treated with six courses of first-line chemotherapy for FIGO stage III IV ovarian cancer. This pooled analysis was designed to evaluate the validity of the geriatric vulnerability parameters identified in EWOT3 (Falandry et al., 2013). Patients and methods From 1997 to 2011, 266 patients were recruited: 83 in EWOT1, 72 in EWOT2, and 111 in EWOT3, which evaluated respectively a 4-weekly carboplatin-cyclophosphamide regimen, a 3-weekly standard carboplatin-paclitaxel doublet and a carboplatin monotherapy. All patients were analyzed in this pooled analysis for treatment completion, toxicity, and overall survival. Results The global treatment completion rate was 73% and ranged from 68% in EWOT2 to 74% in EWOT3. Toxicities were generally manageable: neutropenia was more frequent in EWOT2 and thrombopenia in EWOT1 and EWOT3. In multivariate analysis, covariates associated with decreased survival were: being “depressed” according to the investigators' assessment, hypoalbuminemia < 35 g/L, and FIGO stage IV. In addition, a Hospital Anxiety and Depression Scale (HADS) score > 14 and Instrumental Activities of Daily Living (IADL) score < 25 confirmed a deleterious impact in the EWOT2 + EWOT3 population subanalysis. Conclusions Despite moderate heterogeneity among the studies, this pooled analysis confirmed the deleterious effects on overall survival of emotional disorders (“depressed”, as assessed by investigators or the HADS score), and decreased functionality (IADL score), in addition to FIGO stage.
Immersive virtual reality (VR) is a promising tool to reduce pain in clinical setting. Digital scripts displayed by VR disposals can be enriched by several analgesic interventions, which are widely ...used to reduce pain. One of these techniques is hypnosis induced through the VR script (VRH) which is facilitated by immersive environment and particularly efficient even for low hypnotizable patients. The aim of this study is to assess the efficacy of a VRH script on experimentally induced cold pain perception (intensity and unpleasantness) and physiological expression. 41 healthy volunteers had been recruited in this within-subjects study. They received 9 stimulations of 20 s (3 non-nociceptive cold; 3 low nociceptive cold and 3 highly nociceptive cold) during a VRH session of 20 min (VRH condition) or without VRH (noVRH condition). Physiological monitoring during the cold pain stimulation protocol consisted of recording heart rate, heart rate variability and respiratory frequency. Maximum cold pain intensity perception, measured through the visual analog scale (VAS) on 10, was of 3.66 ± 1.84 (VAS score/10) in noVRH condition and 2.46 ± 1.54 in VRH (Wilcoxon,
p
< 0.0001). Considering pain unpleasantness perception, 3.68 ± 2.06 in noVRH and 2.21 ± 1.63 in VRH (Wilcoxon,
p
< 0.0001). Hypnotizability negatively correlated with the decrease in VAS intensity from noVRH to VRH (Spearman
r
= −0.45;
p
= 0.0038). In our sample, we found that 31/41 volunteers (75.6%) displayed a reduction of more than 10% of their VAS pain intensity and unpleasantness scores. Trait anxiety was the best predictor of the VRH responders, as well as heart rate variability. In addition, respiratory rate was diminished under VRH in every subgroup. VRH is an effective tool to reduced pain intensity and unpleasantness in a vast majority of healthy subjects. We further indicate in this study that heart rate variability parameter RMSSD (root mean square of successive differences) is a good predictor of this effect, as well as anxiety as a personality trait (but not state anxiety). Further studies are expected to determine more precisely to whom it will be the most useful to offer tailored, non-pharmacological pain management solutions to patients.
Aspergillosis is a fungal disease due to Aspergillus molds that can affect both humans and animals. As routine diagnosis remains difficult, improvement of basic knowledge with respect to its ...pathophysiology is critical to search for new biomarkers of infection and new therapeutic targets. Large-scale proteomics allows assessment of protein changes during various disease processes. In the present study, mass spectrometry iTRAQ® (isobaric tags for relative and absolute quantitation) protocol was used for direct identification and relative quantitation of host proteins in diseased fluids and tissues collected from an experimental rat model challenged with Aspergillus, as well as in blood obtained from naturally-infected penguins. In all, mass spectrometry analysis revealed that proteome during aspergillosis was mostly represented by proteins that usually express role in metabolic processes and biological process regulation. Ten and 17 proteins were significantly ≥4.0-fold overrepresented in blood of Aspergillus-diseased rats and penguins, respectively, while five and 39 were negatively ≥4.0-fold depleted within the same samples. In rat lungs, 33 proteins were identified with positive or negative relative changes versus controls and were quite different from those identified in the blood. Except for some zinc finger proteins, kinases, and histone transferases, and while three pathways were common (Wnt, cadherin and FGF), great inter-species variabilities were observed regarding the identity of the differentially-represented proteins. Thus, this finding confirmed how difficult it is to define a unique biomarker of infection. iTRAQ® protocol appears as a convenient proteomic tool that is greatly suited to ex vivo exploratory studies and should be considered as preliminary step before validation of new diagnostic markers and new therapeutic targets in humans.
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