Kinematics and eye–head coordination of gaze shifts evoked from different sites in the superior colliculus of the cat

Shifting gaze requires precise coordination of eye and head movements. It is clear that the superior colliculus (SC) is involved with saccadic gaze shifts. Here we investigate its role in controlling both eye and head movements during gaze shifts. Gaze shifts of the same amplitude can be evoked from different SC sites by controlled electrical microstimulation. To describe how the SC coordinates the eye and the head, we compare the characteristics of these amplitude-matched gaze shifts evoked from different SC sites. We show that matched amplitude gaze shifts elicited from progressively more caudal sites are progressively slower and associated with a greater head contribution. Stimulation at more caudal SC sites decreased the peak velocity of the eye but not of the head, suggesting that the lower peak gaze velocity for the caudal sites is due to the increased contribution of the slower-moving head. Eye–head coordination across the SC motor map is also indicated by the relative latencies of the eye and head movements. For some amplitudes of gaze shift, rostral stimulation evoked eye movement before head movement, whereas this reversed with caudal stimulation, which caused the head to move before the eyes. These results show that gaze shifts of similar amplitude evoked from different SC sites are produced with different kinematics and coordination of eye and head movements. In other words, gaze shifts evoked from different SC sites follow different amplitude–velocity curves, with different eye–head contributions. These findings shed light on mechanisms used by the central nervous system to translate a high-level motor representation (a desired gaze displacement on the SC map) into motor commands appropriate for the involved body segments (the eye and the head).     

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.     

Killing of Mycobacterium tuberculosis within human monocytes: activation by cytokines and calcitriol.

Human monocytes were isolated and their ability to harbour growth of virulent tubercle bacilli was assessed, in the presence or absence of various immunomodulators. Calcitriol (1,25(OH2), vitamin D3) alone, at doses of 10(-7)-10(-9) M endowed human monocytes with a significant ability to restrict intracellular growth of the tubercle bacilli. Crude immune lymphokines as well as recombinant interferon-gamma (IFN-gamma) endowed monocytes with no tuberculostatic activity. Similarly, other recombinant cytokines tested, notably colony-stimulating factor-1 (CSF-1), interleukin-1 (IL-1), interleukin-3 (IL-3) and interleukin-6 (IL-6) all failed to stimulate anti-tuberculous properties, and even increased growth of the tubercle bacilli in monocytes, in the case of CSF-1. Conversely, incubation of crude lymphokines in combination with calcitriol led to total stasis of the growth of M. tuberculosis. Experiments with recombinant cytokines and immunologically active vitamins showed that a combination of IFN-gamma tumour necrosis factor-alpha and calcitriol induced a significant amount of intramonocyte killing of M. tuberculosis. Addition of this cocktail of factors to already infected monocytes led to substantial killing of tubercle bacilli. These sets of experiments establish clearly that combinations of recombinant cytokines and vitamins may induce substantial intramonocyte killing of M. tuberculosis. The mechanism involved in this killing activity was not clarified.     

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.     

Mg2+ Transporters in Digestive Cancers

Despite magnesium (Mg²⁺) representing the second most abundant cation in the cell, its role in cellular physiology and pathology is far from being elucidated. Mg²⁺ homeostasis is regulated by Mg²⁺ transporters including Mitochondrial RNA Splicing Protein 2 (MRS2), Transient Receptor Potential Cation Channel Subfamily M, Member 6/7 (TRPM6/7), Magnesium Transporter 1 (MAGT1), Solute Carrier Family 41 Member 1 (SCL41A1), and Cyclin and CBS Domain Divalent Metal Cation Transport Mediator (CNNM) proteins. Recent data show that Mg²⁺ transporters may regulate several cancer cell hallmarks. In this review, we describe the expression of Mg²⁺ transporters in digestive cancers, the most common and deadliest malignancies worldwide. Moreover, Mg²⁺ transporters’ expression, correlation and impact on patient overall and disease-free survival is analyzed using Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Finally, we discuss the role of these Mg²⁺ transporters in the regulation of cancer cell fates and oncogenic signaling pathways.     

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).     

Sex in the Era of COVID-19 in a U.S. National Cohort of Cisgender Men,Transgender Women,and Transgender Men Who Have Sex with Men: April–May 2020

Since the emergence of the COVID-19 pandemic, there has been an increasing body of research focused on the effects that measures like stay-at-home orders and social distancing are having on other aspects of health, including mental health and sexual health. Currently, there are limited extant data on the effects of the pandemic on sexual and gender minorities. Between April 15, 2020, and May 15, 2020, we invited participants in an ongoing U.S. national cohort study (Together 5000) to complete a cross-sectional online survey about the pandemic, and its effects on mental and sexual health and well-being (n?=?3991). Nearly all (97.7%) were living in an area where they were told they should only leave their homes for essentials. Most (70.1%) reported reducing their number of sex partners as a result of the pandemic. Among the 789 participants prescribed HIV pre-exposure prophylaxis (PrEP), 29.9% said they stopped taking their PrEP entirely, and 14.2% started selectively skipping doses. For those who had been taking PrEP, discontinuing PrEP was associated with having no new sex partners (β?=?0.90, 95% CI 0.40–1.40). Among the 152 HIV-positive participants, 30.9% said they were unable to maintain an HIV-related medical appointment because of the pandemic and 13.8% said they had been unable to retrieve HIV medications. Additionally, 35.3% of participants were experiencing moderate to severe anxiety because of the pandemic and 36.7% reported symptoms of depression. In a multivariable logistic regression, reporting a new sex partner in the prior 30 days was significantly associated with being aged 30 or older (vs. not, AOR?=?1.21), being Black (AOR?=?1.79) or Latinx (AOR?=?1.40, vs. white), and being unsure if they had been in close contact with someone diagnosed with COVID-19 (AOR?=?1.32, vs. no contact). It was unassociated with COVID-19-induced anxiety, depression, or knowing someone hospitalized with COVID-19. The pandemic has caused disruptions in sexual behavior (partner reduction) as well as difficulties navigating PrEP and HIV care continua. Findings will guide more comprehensive public health responses to optimize HIV prevention and treatment in the era of COVID-19.