Malaria circumsporozoite protein inhibits protein synthesis in mammalian cells.

Native Plasmodium circumsporozoite (CS) protein, translocated by sporozoites into the cytosol of host cells, as well as recombinant CS constructs introduced into the cytoplasm by liposome fusion or transient transfection, all lead to inhibition of protein synthesis in mammalian cells. The following findings suggest that this inhibition of translation is caused by a binding of the CS protein to ribosomes. (i) The distribution of native CS protein translocated by sporozoites into the cytoplasm as well as microinjected recombinant CS protein suggests association with ribosomes. (ii) Recombinant CS protein binds to RNase-sensitive sites on rough microsomes. (iii) Synthetic peptides representing the conserved regions I and II-plus of the P.falciparum CS protein displace recombinant CS protein from rough microsomes with dissociation constants in the nanomolar range. (iv) Synthetic peptides representing region I from the P.falciparum CS protein and region II-plus from the P.falciparum, P.berghei or P.vivax CS protein inhibit in vitro translation. We propose that Plasmodium manipulates hepatocyte protein synthesis to meet the requirements of a rapidly developing schizont. Since macrophages appear to be particularly sensitive to the presence of CS protein in the cytosol, inhibition of translation may represent a novel immune evasion mechanism of Plasmodium

Criteria to predict mid-term outcome after stenting of chronic iliac vein obstructions (PROMISE trial).

BACKGROUND Endovenous stent placement has become a first-line approach to prevent post-thrombotic syndrome in patients with chronic post-thrombotic obstruction (PTO) or non-thrombotic iliac vein lesions (NIVL) if conservative management fails. This study aims to identify factors associated with loss of patency to facilitate patient selection for endovenous stenting. METHODS We retrospectively analyzed 108 consecutive patients following successful endovenous stenting for chronic vein obstruction performed at a single institution from January 2008 to July 2020. Using multivariable logistic regression, we explored potential predictive factors for loss of stent patency, including baseline demographics, postthrombotic changes as well as peak flow velocities measured in the common femoral vein (CFV), deep femoral vein (DFV) and femoral vein (FV) using duplex ultrasound. RESULTS Mean follow-up duration was 41 ± 26 months and participants had a mean age of 47.4 ± 15.4 years with 46.3% women. Ninety (83.3%) patients had PTO and 18 (16.7%) had NIVL, predominantly due to May Thurner syndrome. Loss of patency occurred in 20 (18,5%) patients, all treated for PTO. Comorbidities, side of intervention and sex did not differ between patients with occluded and patent stents. Stent occlusion was more common with increasing number of stents implanted (p < 0.001) and with distal stent extension into and beyond the CFV (p < 0.001). Preinterventional predictive factors for stent occlusion were lower duplex ultrasound peak velocity in the CFV (OR 7.52 95% CI 2.54 - 22.28; p < 0.001) and FV (OR 10.75 95% CI 2.07 - 55.82; p < 0.005), as well as post-thrombotic changes in the DFV (OR 4.51 95% CI 1.53 - 13.25; p = 0.006) and FV (OR 3.62 95% CI 1.11 - 11.84; p = 0.033). Peak velocities of ≤ 7 cm/s (IQR 0-20) in the CVF and ≤ 8 cm/s (IQR 5-10) in the FV were significantly associated with loss of patency CONCLUSIONS: Insufficient venous inflow as assessed by low peak velocities in the CFV and FV as well as postthrombotic findings represent reliable risk predictors for stent occlusions, warranting their inclusion into the decision-making process for invasive treatment of PTO