Low-probability transmission of neocortical and entorhinal impulses through the perirhinal cortex

One model of episodic memory posits that during slow-wave sleep (SWS), the synchronized discharges of hippocampal neurons in relation to sharp waves "replay" activity patterns that occurred during the waking state, facilitating synaptic plasticity in the neocortex. Although evidence of replay was found in the hippocampus in relation to sharp waves, it was never shown that this activity reached the neocortex. Instead, it was assumed that the rhinal cortices faithfully transmit information from the hippocampus to the neocortex and reciprocally. Here, we tested this idea using 3 different approaches. 1) Stimulating electrodes were inserted in the entorhinal cortex and temporal neocortex and evoked unit responses were recorded in between them, in the intervening rhinal cortices. In these conditions, impulse transfer occurred with an extremely low probability, in both directions. 2) To rule out the possibility that this unreliable transmission resulted from the artificial nature of electrical stimuli, crosscorrelation analyses of spontaneous neocortical, perirhinal, and entorhinal firing were performed in unanesthetized animals during the states of waking and SWS. Again, little evidence of propagation could be obtained in either state. 3) To test the idea that propagation occurs only when large groups of neurons are activated within a narrow time window, we computed perievent histograms of neocortical, perirhinal, and entorhinal neuronal discharges around large-amplitude sharp waves. However, these synchronized entorhinal discharges also failed to propagate across the perirhinal cortex. These findings suggest that the rhinal cortices are more than a relay between the neocortex and hippocampus, but rather a gate whose properties remain to be identified.     

Infectious viral diarrheas. Comparison of research methods for rotaviruses

Radioimmunoassay and enzyme immunoassay (EIA) are generally recommended for routine diagnosis of rotavirus infection in childhood gastroenteritis. Expensive and delicate, these techniques are ill-suited for processing a small number of samples. Recently, Latex agglutination tests have been introduced than can be performed by non specialized hospital laboratories. However, some questions have been raised as to the sensitivity and specificity of these tests. We have sought a direct appraisal of latex agglutination testing by comparing two enzyme immunoassays and two latex tests (Rotazyme, Enzygnost-Rotavirus, Rotalex, Slidex Rota-kit). Three comparative studies that involved 1217 stool samples from children with gastroenteritis were carried out. Specificity, sensitivity, of latex tests compared favorably with the more sophisticated EIA, they represent a very convenient alternative for routine laboratory use provided latex tests with low rate of non-specific agglutinations are chosen.     

Major histocompatibility complex class II-restricted presentation of secreted and endoplasmic reticulum resident antigens requires the invariant chains and is sensitive to lysosomotropic agents

We have tested the involvement of the invariant chains (Ii) p31 and p41 in the presentation of peptides derived from hen egg lysozyme (HEL) constructs targeted to different intracellular compartments within transfected fibroblasts. The endogenous HEL constructs were either present in the cytosol (HELc), secreted (HELs), or linked to the mammalian (KDEL C-terminal sequence that causes retention of HEL in the endoplasmic reticulum (ER)/pre-Golgi recycling compartment (HELr). Using Ii-negative antigen-presenting cells, the presentation of HELr to a HEL 46-61 specific T cell hybridoma was far less efficient than the presentation of the HELs. High levels of Ii expression enhanced drastically the presentation of the HEL 46-61 determinant derived from both HELr and HELs. HELr and HELs presentation was fully sensitive to lysosomotropic agents such as chloroquine, indicating that the formation of complexes between major histocompatibility complex (MHC) class II molecules and determinants derived from endogenous antigens entering the secretory pathway is taking place in an acidic compartment. The degradation and dissociation of Ii might be a prerequisite for the efficient presentation of endogenously derived determinants by MHC class II molecules, as for the presentation of most exogenous antigens. All our results are compatible with the notion that endogenous molecules being translocated into the lumen of the ER could be presented by class II molecules through a processing pathway involving an acidic compartment in which Ii chains dissociate from class II molecules.     

Production of a monoclonal antibody with specificity for deoxynivalenol, 3‐acetyldeoxynivalenol and 15‐acetyldeoxynivalenol

Monoclonal antibodies reactive with deoxynivalenol were generated following the immunization of mice with a deoxynivalenol‐mouse serum albumin conjugate. One of the anti‐deoxynivalenol monoclonal antibodies, designated C6–1, exhibited cross‐reactivity with 3‐acetyldeoxynivalenol and 15‐acetyldeoxynivalenol but not with nivalenol, T‐2 tetraol or scirpentriol. An indirect competitive ELISA based on this monoclonal antibody gave 50% inhibition values of 0–6 μg ml^‐1 for deoxynivalenol, 0–2 μg ml^‐1 for 15‐acetyldeoxynivalenol and 10 μg ml^‐1 for 3‐acetyldeoxynivalenol.     

Posttraumatic Stress Disorder Following Myocardial Infarction: A Systematic Review

The objective of the present review is to provide an overview of existing research that has reported on the association between posttraumatic stress disorder (PTSD) and ischemic heart disease. Specific focus is given to the incidence of PTSD following myocardial infarction (MI). A systematic review using Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA) guidelines was performed by searching four bibliographic databases: PubMed, PsychINFO, ScienceDirect, and ProQuest Dissertations and Theses. A total of 39 articles were included in this literature review. The results of these studies suggest that the occurrence of an acute cardiac event is likely to contribute to the development of PTSD. Not only is this type of psychiatric disorder associated with significant suffering and impaired quality of life, but it is also a predictor of an increased risk of recurrent adverse cardiovascular events and mortality. Screening, assessment, and treatment of PTSD and posttraumatic stress symptoms following a major cardiac event are critical for offsetting potential deleterious psychological and physical consequences.     

Decision-making in pediatric blunt solid organ injury: A deep learning approach to predict massive transfusion,need for operative management,and mortality risk

BackgroundThe principal triggers for intervention in the setting of pediatric blunt solid organ injury (BSOI) are declining hemoglobin values and hemodynamic instability. The clinical management of BSOI is, however, complex. We therefore hypothesized that state-of-art machine learning (computer-based) algorithms could be leveraged to discover new combinations of clinical variables that might herald the need for an escalation in care. We developed algorithms to predict the need for massive transfusion (MT), failure of non-operative management (NOM), mortality, and successful non-operative management without intervention, all within 4 hours of emergency department (ED) presentation.MethodsChildren (≤ 18 years) who sustained a BSOI (liver, spleen, and/or kidney) between 2009 and 2018 were identified in the trauma registry at a pediatric level 1 trauma center. Deep learning models were developed using clinical values [vital signs, shock index-pediatric adjusted (SIPA), organ injured, and blood products received], laboratory results [hemoglobin, base deficit, INR, lactate, thromboelastography (TEG)], and imaging findings [focused assessment with sonography in trauma (FAST) and grade of injury on computed tomography scan] from pre-hospital to ED settings for prediction of MT, failure of NOM, mortality, and successful NOM without intervention. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were used to evaluate each model's performance.ResultsA total of 477 patients were included, of which 5.7% required MT (27/477), 7.2% failed NOM (34/477), 4.4% died (21/477), and 89.1% had successful NOM (425/477). The accuracy of the models in the validation set was as follows: MT (90.5%), failure of NOM (83.8%), mortality (91.9%), and successful NOM without intervention (90.3%). Serial vital signs, the grade of organ injury, hemoglobin, and positive FAST had low correlations with outcomes.ConclusionDeep learning-based models using a combination of clinical, laboratory and radiographic features can predict the need for emergent intervention (MT, angioembolization, or operative management) and mortality with high accuracy and sensitivity using data available in the first 4 hours of admission. Further research is needed to externally validate and determine the feasibility of prospectively applying this framework to improve care and outcomes.Level of EvidenceIIIStudy TypeRetrospective comparative study (Prognosis/Care Management).     

The Pichia pastoris HIS4 gene: nucleotide sequence,creation of a non-reverting his4 deletion mutant,and development of HIS4-based replicating and integrating plasmids

We have obtained a clone of the Pichia pastoris HIS4 gene and have determined its nucleotide sequence. Based upon its deduced amino-acid sequence, the product of the P. pastoris HIS4 gene has the same structural organization as the Saccharomyces cerevisiae His4 protein and appears to encode a trifunctional enzyme catalyzing the second (phosphoribosyl-ATP pyrophosphohydrolase), third (phosphoribosyl-AMP cyclohydrolase), and tenth (histidinol dehydrogenase) steps in histidine biosynthesis. The chromosomal copy of the HIS4 gene was disrupted by homologous recombination, creating the strain SGY58. The his4 deletion mutation in this strain lacks the entire coding region of this gene and has a reversion rate that is undetectable. A set of complementary plasmids that carry the HIS4 gene was also developed. Among these are nine E. coli-P. pastoris shuttle vectors that transform the His4 deletion mutant at high efficiency and an integration vector for creating site-specific alterations of the P. pastoris genome.     

Ginkgo biloba extract EGb761 reduces the development of amphetamine-induced behavioral sensitization: effects on hippocampal type II corticosteroid receptors

Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the behavioral sensitization induced by successive -amphetamine administrations (0.5 mg/kg) as estimated by increasing values of locomotor activity. EGb761 pretreatment also prevented the reduced density of [³H]dexamethasone binding sites in the dentate gyrus and the CA1 hippocampal regions of -amphetamine treated animals. These observations suggest that EGb761, by reducing glucocorticoid levels, could modulate the activity of the neuronal systems involved in the expression of the behavioral sensitization.     

Dose related response to clozapine in a state psychiatric hospital population: A naturalistic study

After noting a striking difference in the dosing practices of two treating psychiatrists, each responsible for the operation of a clozapine unit in a state psychiatric hospital, the authors conducted a retrospective chart review to assess the clinical efficacy of low dose mg. per day) versus high dose ( mg. per day) clozapine treatment for a cohort of 31 inpatients. Levels of psychopathology, behavior, and social functioning were assessed six months pre and during clozapine treatment for 16 patients who received low dose clozapine treatment and 15 patients who received high dose clozapine treatment. Patients on both units demonstrated significant reductions in their levels of psychopathology, improved social functioning and improvement in their behavior following six months clozapine treatment. This naturalistic study suggests that the use of low dose clozapine provides effective treatment for chronic, severely treatment resistant inpatients with schizophrenia or schizo-affective illness, at the same time reducing the potential for significant side effects.