Acceptability and efficacy of intra-rectal quinine alkaloids as a pre-transfer treatment of non-per os malaria in peripheral health care facilities in Mopti, Mali

<p>Abstract</p> <p>Background</p> <p>The acceptability and efficacy of a new kit with a new formulation of quinine alkaloids designed for the intra-rectal administration in the treatment of non-per os malaria was assessed in the peripheral health care system of Mopti, Mali.</p> <p>Methods</p> <p>A single-arm trial was conducted from August 2003 to January 2004. An initial dose of diluted quinine alkaloids (20 mg/kg Quinimax^®) was administered by the intra-rectal route to children with presumptive non per-os malaria at six peripheral heath care centres. The children were then referred to two referral hospitals where standard inpatient care including intravenous route were routinely provided. A malaria thick smear was done at inclusion and a second malaria thick smear after arrival at the referral facility, where a more complete clinical examination and laboratory testing was done to confirm diagnosis. Confirmed cases of severe malaria or others diseases were treated according to national treatment guidelines. Cases of non per-os malaria received a second dose of intra rectal quinine alkaloids. Primary outcome was acceptability of the intra rectal route by children and their parents as well as the ease to handle the kit by health care workers.</p> <p>Results</p> <p>The study included 134 children with a median age of 33 months and 53.7% were male. Most of the children (67%) and 92% of parents or guardians readily accepted the intra-rectal route; 84% of health care workers found the kit easy to use. At the peripheral health care centres, 32% of children had a coma score ≤ 3 and this was reduced to 10% at the referral hospital, following one dose of intra-rectal quinine alkaloids (IRQA). The mean time to availability of oral route treatment was 1.8 ± 1.1 days. Overall, 73% of cases were confirmed severe malaria and for those the case fatality rate was 7.2%.</p> <p>Conclusion</p> <p>IRQA was well accepted by children, their parents/guardians and by the health workers at peripheral health facilities in Mopti, Mali. There was also a quick recovery from deep coma and a reduced case fatality rate in severe malaria.</p

CD95L cell surface cleavage triggers a pro-metastatic signaling pathway in triple negative breast cancer.

International audienceTriple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here we report that serum levels of CD95L are higher in TNBC patients compared to other breast cancer patients. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility, due to formation of an unconventional CD95-containing receptosome termed the motility-inducing signaling complex. Formation of this complex was instrumental for Nox3-driven ROS generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a pro-metastatic function for metalloprotease-cleaved CD95L in triple-negative breast cancers, revisiting its role in carcinogenesis

Heavy-ion test of detectors with conventional and resistive Micromegas used in TPC configuration

International audienceWe have performed tests of Micromegas detector prototypes using the heavy-ion beams from the SIS synchrotron of GSI (Darmstadt, Germany). The beams varied from (12)C(6+) to (179)Au(65+) and from 250 to 1000 MeV per nucleon. We have tested two amplification technologies, conventional and resistive Micromegas, and two construction concepts, bulk-Micromegas and micro-meshes screwed on the PCB. The obtained position resolution below 200 mu m for 5 mm wide strips implies that the bulk resistive Micromegas technology might meet the requirements of the future R3B TPC project. We also developed a fast and very low noise front-end electronics connected directly to the Printed Circuit Board (PCB) of the detector itself. This concept has shown very good performances and robustness

HARMONI at ELT: overview of the capabilities and expected performance of the ELT's first light, adaptive optics assisted integral field spectrograph.

International audienc