Bidirectional synaptic plasticity in the dentate gyrus of the awake freely behaving mouse

There is significant interest in in vivo synaptic plasticity in mice due to the many relevant genetic mutants now available. Nevertheless, use of in vivo models remains limited. To date long-term potentiation (LTP) has been studied infrequently, and long-term depression (LTD) has not been characterized in the mouse in vivo. Herein we describe protocols and improved methodologies we developed to record hippocampal synaptic plasticity reliably from the dentate gyrus of the awake freely behaving mouse. Seven days prior to recording, we implanted microelectrodes encapsulated within a lightweight, low profile head stage assembly. On the day of recording, we induced either LTP or LTD in the awake freely behaving animal, and monitored subsequent changes in population spike amplitude for at least 24h. Using this protocol we attained 80% success in inducing and maintaining either LTP or LTD. Recording from a chronic implant using this improved methodology is best suited to reveal naturally occurring brain activity and avoids both acute effects of local electrode insertion and drifts in neuronal excitability associated with anesthesia. Ultimately a reliable freely behaving mouse model of bi-directional synaptic plasticity is invaluable for full characterization of genetic models of disease states and manipulations of the mechanisms implicated in learning and memory.     

Malaria chemoprophylaxis: what do the travelers choose, and how does pretravel consultation influence their final decision

Three different drugs (mefloquine, atovaquone/proguanil, doxycycline) are recommended for malaria chemoprophylaxis, each with approximately the same efficacy but various adverse event profiles, regimens, and prices. We investigated which medication the travelers would have chosen on the basis of written evidence-based information and the impact that pretravel consultation had on their decision. A prospective study was performed in a travel clinic and private practice, and 1073 travelers were included; 45% chose mefloquine (Lariam or Mephaquine), 21% atovaquone/proguanil (Malarone), 18% doxycycline (Supracycline), 5% "no prophylaxis," and 11% "do not know." Lariam was principally chosen because of prior experience (38%), Mephaquine because of low price (34%), and doxycycline and Malarone because of the profile of adverse events (55% and 43%, respectively). Based on objective written information, travelers most frequently chose mefloquine for chemoprophylaxis. This suggests that evidence-based information weighs more heavily than negative publicity. Taking into account the perspective of the user should improve appropriateness of the pretravel advice.     

An MR-compatible device for delivering smoked marijuana during functional imaging

Smoking is the preferred method of administration for two of the most frequently abused drugs, marijuana and nicotine. The high temporal and spatial resolution of functional magnetic resonance imaging (fMRI) make it a natural choice for studying the neurobiological effects of smoked drugs if the challenges of smoking in a magnetic resonance (MR) scanner can be overcome. We report on a design for an MR-compatible smoking device that can be used for smoking marijuana (or tobacco) during fMRI examinations. Nine volunteers smoked marijuana cigarettes (3.51% Delta9-THC) on two occasions: with and without the device. The device allowed subjects to smoke while they lay in the scanner, while containing all smoke and odors. Plasma Delta9-THC, subjective reports of intoxication, and heart rate increases are reported, and were all similar in individuals smoking marijuana either with or without the device. The use of this device will help advance research studies on smoked drugs including marijuana, tobacco and crack cocaine.     

Social factors associated with the use of obstetrical health care services among Cameroonian teenagers

Social factors associated with the use of obstetrical health care services among Cameroonian teenagers. The specific objective of this study is to research the social factors of the use of obstetrical health care services among Cameroonian teenagers. We used data from the 2004 Cameroon Demographic and Health Survey (DHS). We focussed in this study the analyses on the last births of the last five years preceding the survey: 747 mothers of 15-19 years old were therefore concerned by the study. 85.6 % of teenagers used modern health services during their last pregnancies but only 20.6 % of them respected all the current standards on antenatal consultations. Also, 60.4 % of them used modern health services during their last deliveries. The traditional socio-cultural barriers, the weak opening to modernity, the economic poverty of families and the physical estrangement of health services were the main negative factors of the use of modern health services during pregnancy and/or delivery by the Cameroonian teenagers. The identification of these social factors should help the Cameroonian deciders improving teenagers' maternal and infantile health programs.     

Modelling and expression studies of two novel mutations causing factor V deficiency

Human coagulation factor V (FV), a non-enzymatic cofactor of the prothrombinase complex, is required for the rapid generation of thrombin. FV deficiency is a rare autosomal recessive bleeding disorder. We describe two novel mutations, Tyr91Asn and Asp2098Tyr, found in two probands with a residual FV activity of 51% and 4%, respectively. Modelling and structural analysis of these mutations were performed following short-duration molecular dynamics (MD) simulation. Asp2098Tyr lead to abolishment of the highly conserved salt bridge Asp2098-Arg2171 presumably required for structural integrity of the C2 domain. MD studies suggest that additional conformational changes resulting from this mutation involve local rearrangements at Tyr2063 and Tyr2064 and so affect the phospholipid-membrane binding. MD modelling of the Try91Asn mutant revealed a conformational change nearby the Cu(2+) binding site that could affect overall stabilization of the heavy and light chains. These findings suggest that both mutations influence the structural integrity of FV protein. Transient expression data of wild-type and mutant FV variants in 293T human embryonic kidney cells showed FV-specific activity reduced to 26% for Asp2098Tyr and 56% for Tyr91Asn compared to that of wild-type. Thus, both the data from the short duration molecular dynamic simulation and from expression analysis indicate alterations of the FV protein variants that explain the clinical phenotype.     

Role of secretory IgA in infection and maintenance of homeostasis

An important activity of mucosal surfaces is the production of antibodies (Abs) referred to as secretory immunoglobulin A (SIgA) that serve as a first line of defense to repel pathogenic microorganisms and provide a finely tuned balance to guarantee controlled survival of essential commensal bacteria. By excluding bacteria from the epithelial cell, SIgA participates in the cross-talk between the host and its intestinal content, ensuring appropriate homeostasis under normal conditions. Besides the classical view of immune exclusion function, SIgA Abs exhibit the striking feature to adhere to gastrointestinal M cells residing in the follicle-associated epithelium in organized structures called Peyer's patches. Selective binding of SIgA results in transport across the microfold (M) cells, a process that facilitates the association of the Ab with dendritic cells (DCs) located in the underlying subepithelial dome region of Peyer's patches. Limited entry of free SIgA and SIgA-coated bacteria via this pathway is crucial to the modulation of local immune responses in an environment that limits the onset of pro-inflammatory circuits. Such a mechanism would ensure homeostasis by allowing antigen recognition under neutralized conditions and by avoiding tissue dissemination, two features that endow SIgA with non-inflammatory properties in the mucosal environment.