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Impulsive stimulated Raman scattering (ISRS) using a single short femtosecond pump pulse to excite molecular vibrations offers an elegant pump-probe approach to perform vibrational imaging below 200cm−1. One shortcoming of ISRS is its inability to offer vibrational selectivity as all the vibrational bonds whose frequencies lie within the short pump-pulse bandwidth are excited. To date, several coherent control techniques have been explored to address this issue and selectively excite a specific molecular vibration by shaping the pump pulse. There has not been any systematic work that reports an analogous shaping of the probe pulse to implement preferential detection. In this work, we focus on vibrational imaging and report vibrational selective detection by shaping the probe pulse in time. We demonstrate numerically and experimentally two pulse-shaping strategies with one functioning as a vibrational notch filter and the other functioning as a vibrational low-pass filter. This enables fast (25μs/pixel) and selective hyperspectral imaging in the low-frequency regime (

Purpose: NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor microenvironments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK-cell elimination of osteosarcoma tumor-initiating cells. In this report, we used NKG2D–NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA− memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR).Experimental Design: CD45RA− cells from healthy donors were transduced with NKG2D CARs containing 4-1BB and CD3z signaling domains. NKG2D CAR expression was analyzed by flow cytometry. In vitro cytotoxicity of NKG2D-CAR+ CD45RA− T cells against osteosarcoma was evaluated by performing conventional 4-hour europium-TDA release assays. For the in vivo orthotopic model, 531MII YFP-luc osteosarcoma cells were used as targets in NOD-scid IL2Rgnull mice.Results: Lentiviral transduction of NKG2D-4-1BB-CD3z markedly increased NKG2D surface expression in CD45RA− cells. Genetic stability was preserved in transduced cells. In vitro, NKG2D-CAR+ memory T cells showed significantly increased cytolytic activity than untransduced cells against osteosarcoma cell lines, while preserving the integrity of healthy cells. NKG2D-CAR+ memory T cells had considerable antitumor activity in a mouse model of osteosarcoma, whereas untransduced T cells were ineffective.Conclusions: Our results demonstrate NKG2D-4-1BB-CD3z CAR–redirected memory T cells target NKG2DL-expressing osteosarcoma cells in vivo and in vitro and could be a promising immunotherapeutic approach for patients with osteosarcoma. Clin Cancer Res; 23(19); 5824–35. ©2017 AACR.

Time-lapse: NKG2D-CAR Memory T cells target osteosarcoma cells

531MII YFP-luc cells are only found in the lungs of those mice untreated (control) or treated with untransduced memory T cells.

Different T cell subpopulations contained in the CD45RA- compartment

Participants in the coastal socio-economy of the Mediterranean Sea, such as industries, aquaculture, urban populations, conglomerates, and tourists, create intense anthropogenic pressures on marine ecosystems (such as the release of trace metals). This raises concerns about their impact on the surrounding environment and on marine organisms, including those collected for human consumption. This study introduces the possibility of using Patella caerulea (Linnaeus 1758), indigenous to the Mediterranean Sea, as a biosentinel of marine pollution. This study proposes coupling environmental (bioaccumulation) and toxicological (redox homeostasis) measures of bioavailability with genetic variability (COI mtDNA) assessments. Concentrations of six trace metals (cadmium, copper, iron, lead, nickel, and zinc) were measured in surface seawater and in P. caerulea individuals collected from four coastal stations on the Tunisian coast where different levels of metal contamination have occurred. The quantified biomarkers involved the determination of antioxidant defense enzymes, catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD), and the measurement of lipid peroxidation indicated by malondialdehyde (MDA) levels. Our study identified critical levels of metal contamination among locations in the Gulf of Gabes. Concomitantly, the induction of antioxidant biomarkers (especially SOD and GPX) was observed, highlighting the potential of P. caerulea to acclimate to stressful pollution conditions. Molecular analysis of COI (mtDNA) revealed low discrimination between the four P. caerulea populations, highlighting the role of marine currents in the Mediterranean Sea in the dispersal and passive transportation of limpet larvae, allowing an exchange of individuals among physically separated, P. caerulea populations.

International audience; Objectives: There is no specific recommendation about antimicrobial treatment length for documented infections in chemotherapy induced febrile neutropenia (FN). Practices have changed along time in our center regarding length of antibiotic treatment. The aim of this study was to compare long versus short antibiotic course for bloodstream infection (BSI) treatment in acute myeloid leukemia (AML) patients during FN. Methods: This monocentric retrospective comparative study included all consecutive BSI episodes among AML patients with FN for 3 years (2017-2019). Episodes were classified regarding the length of antibiotic treatment, considered as short course if the treatment lasted ≤ 7 days, except for nonfermenting bacteria and Staphylococcus aureus or lugdunensis for which the threshold was ≤ 10 days and ≤ 14 days, respectively. The primary outcome was the number of BSI relapses in both groups within 30 days of antibiotic discontinuation. Results: Among 71 AML patients, 104 BSI episodes were included; 48 (46%) received short course treatment. Only 8 (7.6%) BSI episodes relapsed within 30 days of antibiotic discontinuation, 5 having received short course treatment. No association was found between risk of relapse and short course of antibiotic treatment (p = 0.37). The only risk factor significantly associated with BSI relapse was neutropenia duration (p = 0.005). Conclusion: Antibiotic short course seemed as effective as prolonged treatment for BSI in AML patients during FN, with very few relapses at day 30. These encouraging findings should be confirmed through prospective studies.

Resume Hypothese/Contexte La reparation de la coiffe des rotateurs par arthroscopie donne generalement de bons resultats cliniques, neanmoins les facteurs predictifs influencant le resultat final sont mal connus. Objectif Le but de notre etude etait d’evaluer les resultats cliniques apres cicatrisation du tendon sus-epineux chez des patients ayant subi une chirurgie reparatrice par arthroscopie de la coiffe des rotateurs, et d’identifier les facteurs pre- et perioperatoires predictifs d’un bon resultat clinique. Methodes Une etude multicentrique prospective a suivi 188 patients apres arthroscopie reparatrice d’une dechirure isolee et cicatrisation du tendon du sus-epineux. Les criteres d’inclusion etaient les suivants : âge inferieur a 70 ans, dechirure isolee du sus-epineux, infiltration graisseuse de stade 0 a I, cicatrisation du tendon du sus-epineux un an apres l’intervention chirurgicale, et meme methode de reparation de la coiffe des rotateurs par arthroscopie a double rangee pour tous les patients. L’evaluation clinique reposait sur le score de Constant (ou CMS, pour Constant Murley Score) et la Valeur Subjective de l’epaule (ou SSV pour Subjective Shoulder Value) evalues en preoperatoire et un an apres l’intervention. Une echographique de controle evaluait la qualite de la reparation du tendon selon la classification de Sugaya. Les Types I-II-III etaient consideres comme cicatrises. Resultats L’âge moyen de notre cohorte etait de 57,57 ans (min-max : 41-70 ans) et le ratio femmes/hommes etait de 1,14 (100/87). La moyenne des CMS preoperatoires etait de 53,75 ± 13,50 (moyenne ± ecart type [ET] ; min-max : 16-83). A la fin du suivi, le CMS moyen etait de 79,95 ± 12,05 (moyenne ± ET ; min-max : 28-100). 12,22 % (23/188) des patients avaient un CMS inferieur a 70 indiquant une difference cliniquement significative par rapport au CMS moyen, la difference minimale cliniquement importante (DMCI) etant de 10 points pour ce score. Une analyse statistique montrait que seule la predominance des femmes etait significative chez les patients ayant les plus bas scores (p = 0,001). Aucune difference n’etait trouvee pour l’âge, le CMS preoperatoire, la degenerescence graisseuse, ou les autres facteurs analyses. Conclusion Notre etude a montre que tous les patients avaient une cicatrisation du sus-epineux, mais tous n’avaient pas un bon resultat clinique final. Le seul facteur impactant le resultat clinique final etait le sexe feminin. Aucun autre facteur structurel n’a semble influencer le resultat clinique final. Les futures etudes devraient se concentrer davantage sur l’analyse des traits de personnalite et autres facteurs psychosociaux qui jouent un role important dans la determination du resultat final apres une arthroscopie reparatrice de la coiffe des rotateurs. Niveau de preuve III, etude de cohorte retrospective.