Design and preclinical testing of an anti-CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia

Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7-AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP-positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7-AMkL cell population after 24 h of co-culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti-CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio.     

Intranasal PUVA phototherapy in nasal polyposis--a pilot study

Nasal polyposis (NP) affects 4% of the general population, representing a major health problem. In spite of complex (surgical and medical) treatment, the relapse rate is high and it has a negative impact on the quality of life. Recently we found that intranasal photochemotherapy with ultraviolet A light (PUVA) is effective in allergic rhinitis. In the present study PUVA was administered for 6 weeks in 7 patients with NP. Nasal lavages were performed in all patients before and at the end of the treatment; from four patients a biopsy specimen was also collected. Eosinophils significantly decreased in patients with NP and slightly in a patient who had associated aspirin sensitivity. IL-5 and eosinophil cationic protein (ECP) levels showed a decreasing trend in patients with NP and an increasing trend in patients with associated aspirin sensitivity. Our results suggest that intranasal PUVA might represent a future therapeutic method in a subset of patients with NP.     

Bored Bivalves in Upper Triassic (Norian) Event Beds,Northeastern British Columbia,Canada

Skeletobionts are important components of most shallow marine ecosystems. Prior to the fossils reported herein, evidence of skeletobionts was absent from Upper Triassic successions on the northwestern margin of Pangaea. The boring Talpina ramosa is reported from bivalve body fossils from the Upper Triassic (Lower Norian) lower Pardonet Formation at Pink Mountain in northeastern British Columbia. This Ichnotaxon penetrates through both the outer and inner surface of articulated and disarticulated bivalve shells preserved within sharp-based event beds. The occurrence of these trace fossils underscores the paucity of borings, bioerosional structures, and encrusting taxa from Triassic successions in the western Pangaean realm. Due to erosional removal of shallow water strata by a post-Triassic unconformity, these event beds provide the only available information regarding the ecological health of Late Triassic depositional systems in the study area.