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The sporozoite, the stage of the malaria parasite transmitted by the mosquito, first develops for ∼2 weeks in an oocyst. Rupture of the oocyst capsule is required for release of sporozoites, which then transfer to the salivary gland where they are injected into a new host. Here we identify two parasite proteins that we call oocyst rupture proteins 1 (ORP1) and ORP2. These proteins have a histone-fold domain (HFD) that promotes heterodimer formation in the oocyst capsule at the time of rupture. Oocyst rupture is prevented in mutants lacking either protein. Mutational analysis confirms the HFD as essential for ORP1 and ORP2 function, and heterodimer formation was verified in vitro. These two proteins are potential targets for blocking transmission of the parasite in the mosquito., Oocyst rupture and release of malaria sporozoites is needed for transmission of parasites from vector to humans. Here the authors identify two proteins, which they name ORP1 and ORP2, that form heterodimers and are required for oocyst rupture.

To evaluate the characteristics of patients referred for dizziness to a Syncope Unit. This is a retrospective study. Of 491 patients referred to the Syncope Unit of Careggi Hospital in 2015, 198 (40.3%) who experienced dizziness alone or associated with a history of transient loss of consciousness were enrolled. All the patients underwent an initial evaluation according to the European Society of Cardiology guidelines on syncope. We compared the clinical characteristics and final diagnosis of patients referred for dizziness alone (n = 64) to those of patients with dizziness and history of transient loss of consciousness (n = 134). The study population had a mean age of 62 ± 20 years (range 16–96 years) and 101 (51%) were female. A final diagnosis of pre-syncope was made in about the 80% of the patients without a previous history of transient loss of consciousness. In this group, other diagnoses were benign paroxysmal positional vertigo (6.3%), transient ischemic attack (4.7%) or psychogenic dizziness (7.8%). Syncope was diagnosed in the 82.7% of the patients with dizziness and history of transient loss of consciousness. Dizziness was the main reason for referral to the Syncope Unit in almost one-third of the patients, in whom pre-syncope was the most frequent final diagnosis. Otological, neurological and psychiatric disorders should be also considered as differential diagnosis, highlighting the importance of a multidisciplinary approach.

Background: Malaria still remains a serious health burden in developing countries, causing more than 1 million deaths annually. Given the lack of an effective vaccine against its major etiological agent, Plasmodium falciparum, and the growing resistance of this parasite to the currently available drugs repertoire and of Anopheles mosquitoes to insecticides, the development of innovative control measures is an imperative to reduce malaria transmission. Paratransgenesis, the modification of symbiotic organisms to deliver anti-pathogen effector molecules, represents a novel strategy against Plasmodium development in mosquito vectors, showing the potential to reduce parasite development. However, the field application of laboratory-based evidence of paratransgenesis imposes the use of more realistic confined semi-field environments.Methods: Large cages were used to evaluate the ability of bacteria of the genus Asaia expressing green fluorescent protein (Asaia gfp), to diffuse in Anopheles stephensi and Anopheles gambiae target mosquito populations. Asaia gfp was introduced in large cages through the release of paratransgenic males or by sugar feeding stations. Recombinant bacteria transmission was directly detected by fluorescent microscopy, and further assessed by molecular analysis.Results: Here we show the first known trial in semi-field condition on paratransgenic anophelines. Modified bacteria were able to spread at high rate in different populations of An. stephensi and An. gambiae, dominant malaria vectors, exploring horizontal ways and successfully colonising mosquito midguts. Moreover, in An. gambiae, vertical and trans-stadial diffusion mechanisms were demonstrated.Conclusions: Our results demonstrate the considerable ability of modified Asaia to colonise different populations of malaria vectors, including pecies where its association is not primary, in large environments. The data support the potential to employ transgenic Asaia as a tool for malaria control, disclosing promising perspective for its field application with suitable effector molecules.