Cannabinoid receptor 1 (CB1) mediates the functional responses of Δ9-tetrahydrocannabinol. Although progress has been made in understanding cannabinoid binding and receptor activation, detailed knowledge of the dynamics involved in the activation mechanism of CB1 is lacking. Here, we use recently determined CB1 crystal structures to analyze its transition from inactive to active state by performing unbiased microsecond-length molecular dynamics (MD) simulations, totaling 32 μs, with and without bound potent cannabinoid agonist CP-55940. CB1 activation is characterized by an upward axial movement of transmembrane (TM) helix 3, inward movement of TM7, and outward movement of TM6. These conformational changes collectively allow Gi protein docking, although fully active states of the receptor occur only transiently during MD simulations. Additionally, positive allosteric modulation of CB1 by anionic phospholipids is found to increase action of the bound agonist. Specifically, this involves protein–lipid interactions at intracellular loop 3, TM6, and ionic lock residue Arg2143.50.

Spain declared the elimination of malaria in 1964. In non-endemic areas, the overwhelming majority of malaria cases are acquired abroad, and locally acquired infections are rare events. In Spain, malaria is a statutorily notifiable disease. During these fifty years more than ten thousand malaria cases have been reported, and about 0.8% of them did not have a history of recent travel. In this report, it was carried out a review of the ways in which malaria can be transmitted in non-endemic areas and a short description of the Spanish cases, aggregated by their transmission mechanisms. Four cases contracted malaria by mosquito bites; there were two autochthonous cases and two of “airport malaria”. The other 28 cases were: congenital malaria cases, transfusion-transmitted malaria, post-transplant cases, nosocomial transmission and cases in intravenous drug users. In addition, in 1971 there was an outbreak of 54 cases due to exposure to blood or blood products. So, while malaria usually is an imported disease in non-endemic areas, it should not be excluded in the differential diagnosis of persons who have fever of unknown origin, regardless of their travel history.

The characteristics of 67 confirmed congenital syphilis cases reported to the surveillance system in Spain (2000-2010) were analyzed. The incidence rates ranged from 0.00 to 2.23 per 100,000 live births. Median age at diagnosis was 4 days. Hepatosplenomegaly was the most common clinical finding, although almost 60% of the cases were asymptomatic. Missed opportunities for congenital syphilis prevention through antenatal care were identified.

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