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Plasmodium falciparum extensively modifies its chosen host cell, the mature human erythrocyte. This remodelling is carried out by parasite-encoded proteins that are exported into the host cell. To gain access to the human red blood cell, these proteins must cross the parasitophorous vacuole, a membrane bound compartment surrounding the parasite that is generated during the invasion process. Many exported proteins carry a so-called PEXEL/HT signal that directs their transport. We recently reported the unexpected finding of a species-restricted parasite-encoded Hsp70, termed PfHsp70x, which is exported into the host erythrocyte cytosol. PfHsp70x lacks a classical PEXEL/HT motif, and its transport appears to be mediated by a 7 amino acid motif directly following the hydrophobic N-terminal secretory signal. In this report, we analyse this short targeting sequence in detail. Surprisingly, both a reversed and scrambled version of the motif retained the capacity to confer protein export. Site directed mutagenesis of glutamate residues within this region leads to a block of protein trafficking within the lumen of the PV. In contrast to PEXEL-containing proteins, the targeting signal is not cleaved, but appears to be acetylated. Furthermore we show that, like other exported proteins, trafficking of PfHsp70x requires the vacuolar translocon, PTEX.

Plasmodium falciparum infections can cause severe malaria, but not every infected person develops life-threatening complications. In particular, carriers of the structural haemoglobinopathies S and C and infants are protected from severe disease. Protection is associated with impaired parasite-induced host actin reorganization, required for vesicular trafficking of parasite-encoded adhesins, and reduced cytoadherence of parasitized erythrocytes in the microvasculature. Here we show that aberrant host actin remodelling and the ensuing reduced cytoadherence result from a redox imbalance inherent to haemoglobinopathic and fetal erythrocytes. We further show that a transient oxidative insult to wild-type erythrocytes before infection with P. falciparum induces the phenotypic features associated with the protective trait of haemoglobinopathic and fetal erythrocytes. Moreover, pretreatment of mice with the pro-oxidative nutritional supplement menadione mitigate the development of experimental cerebral malaria. Our results identify redox imbalance as a causative principle of protection from severe malaria, which might inspire host-directed intervention strategies.

PURPOSE: One of the goals of mandible resection and reconstruction is achieving optimal occlusion. Therefore, the aim of the present study was to evaluate the pre- and post-operative condyle distances. PATIENTS AND METHODS: All computed tomography (CT) scans of 32 patients with a partial mandible resection who were treated between 2006 and 2011 were evaluated retrospectively. The distances between the condyle centres were measured before and after mandible resection. RESULTS: The preoperative intercondylar distance of the 32 patients was between 85.8 and 109.5 mm (median = 100.5 mm), and the post-operative distance was between 87.0 and 110.5 mm (median = 100.6 mm). There was no significant difference between pre- and post-operative distances. CONCLUSION: Reconstruction plates and bony reconstructions do not significantly change the intercondylar distance.

OBJECTIVES: Oral and oropharyngeal squamous cell carcinoma puts the patient at risk for bilateral neck lymph node metastasis. For this reason, routine bilateral neck dissection is preferred by some surgeons as the treatment of choice, even in N0-necks, despite the morbidity of this procedure. METHODS: Utilising data of 496 patients with squamous cell carcinoma of the head and neck region treated at the Department of Otorhinolaryngology and Head and Neck at the Medical University Hospital, Graz from 1999 to 2009, we retrospectively evaluated the effect of bilateral neck dissection on recurrence-free and overall survival rates in patients with oral and oropharyngeal cancer. RESULTS: Long-term survival of 152 patients with oral and oropharyngeal cancer did not show a statistical benefit of elective contralateral neck dissection in patients with contralateral clinically negative neck. Neither locoregional recurrence-free survival nor overall survival rates differed. CONCLUSION: We could not find a statistical benefit for operating on patients with oral and oropharyngeal squamous cell carcinoma with an elective neck dissection in contralateral clinically negative neck.

INTRODUCTION: Knowledge of independent prognostic factors in patients with head and neck squamous cell carcinoma is important for appropriate treatment decisions. Given the availability of aggressive therapeutic options with known side effects and burdens for the patient, choosing the correct treatment option is vital. MATERIALS AND METHODS: Using a retrospective database of patients treated over a 10-year period, independent prognostic factors for disease-free survival and overall survival were assessed. Univariate analysis was used to identify significant variables, and multivariate Cox regression analysis was used to determine independent prognostic factors. RESULTS: Between 1 January 1999 and 31 December 2009, 291 patients with head and neck squamous cell carcinomas were analysed to identify prognostic factors for disease-free survival and overall survival. Although univariate analysis identified several significant factors, multivariate Cox regression analysis showed that capsule penetration and lymph node ratio were the only significant factors for disease-free survival and overall survival. CONCLUSION: Lymph node ratio is an independent predictor of survival and should be examined in every patient undergoing neck dissection. Capsule penetration of lymph nodes was another independent prognostic factor. In cases of capsule penetration or inappropriate lymph node ratio, adjuvant therapies are necessary.