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.     

Highly Pathogenic Avian Influenza A(H5N8) Virus Spread by Short- and Long-Range Transmission,France, 2016–17

We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds.     

Seminal cell-free DNA and sperm characteristic’s: An added biomarker for male infertility investigation

Cell-free DNA (Cf-DNA) fragments may constitute an easy-to-measure molecular tool for guiding the choice of care provided to infertile couples who benefit assisted reproductive technology (ART) programmes. Data on Cf-DNA levels in the seminal plasma of men with sperm alterations are scarce. The objective of the present study was to quantify the presence of Cf-DNA in semen by using a quantitative real-time PCR. We compared men with abnormal sperm characteristics (n = 21) with normospermic controls (n = 21). The PCR assay evidenced significantly higher mean Cf-DNA levels in patients with sperm abnormalities than in controls (2.09 versus 1.18 µg/ml, respectively; p = .0003). The Cf-DNA levels were notably higher in men with azoospermia (3.65 µg/ml, versus 1.34 µg/ml in matched controls; p = .03) and men with teratozoospermia (1.80 µg/ml, versus 1.29 µg/ml in matched controls; p = .008). Our data report a significant association between elevated Cf-DNA levels and sperm abnormalities. These results may open up new diagnostic and prognostic perspectives in male infertility.     

Treating acute colonic diverticulitis with extraluminal pericolic air: An Acute Care Surgery in the Netherlands (ACCSENT) multicenter retrospective cohort study

BackgroundOwing to improved quality of computed tomography, a new category of complicated acute diverticulitis, including patients with pericolic air but without abscess formation, can be defined (Hinchey 1a). Recent studies question whether this new category of acute diverticulitis could be treated as uncomplicated cases. The aim of our study is to report on the clinical course of acute diverticulitis Hinchey 1a in current clinical practice.MethodsFor this multicenter retrospective cohort study, patients presenting at the emergency department with Hinchey 1a acute diverticulitis as demonstrated by computed tomography scan, were identified. The primary outcome measure was successful conservative treatment with observation alone, antibiotics, and/or hospital admission. Readmissions, percutaneous drainage of abscesses, and emergency operations were considered as failure.ResultsBetween October 2016 and October 2018, 1,199 patients were clinically suspected for acute diverticulitis, of whom 101 (8.4%) were radiologically diagnosed to have type 1a acute diverticulitis (average age 57 (±13) years, 45% female) and started with conservative treatment. This was successful in 86 (85%) patients. One of the 15 unsuccessfully treated patients (1%) received percutaneous drainage of an abdominal abscess. Surgery was required in 9 cases (9%) after a median time of 6 days (range, 3 to 69 days). Although a difference in the volume of extraluminal air on computed tomography scan was found, this was not shown to be a risk factor for the clinical course.ConclusionPatients with type 1a acute diverticulitis can be treated successfully by conservative therapy in the majority of cases (85%). More research is required to define predictive factors for successful conservative management.     

Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.     

Viscoelastic properties of human arteries methodology and preliminary results

In order to study the biomechanical properties of the arterial wall and to compare arteries with different histologic structures, we designed a device that allows testing of arterial segments under near-physiologic conditions. A hydrodynamic generator simulates systolo-diastolic pressures in an open loop. An intraarterial pressure sensor and a sonomicrometer connected to two piezoelectric crystals placed in diametric opposition on the arterial wall allow computer calculation of compliance, stiffness, midwall radial arterial stress, Young modulus, and incremental modulus for a given arterial segment at a given pressure setting. Seven healthy common carotid artery (CCA) segments and seven healthy (superficial) femoral artery (FA) segments were studied immediately after removal from brain-dead donors between the ages of 18 and 35 years. Histologic examination was performed to determine the density of elastic fibers in the arterial wall. Hysteresis was observed in all segments regardless of pressure settings. Compliance was greater and modulus values and stiffness were lower in CCA than in FA. No evidence of structural change was noted after testing in the circulation loop. These preliminary results open the way to a wide variety of applications for our hydrodynamic circulation loop. Experiments will be undertaken to compare the mechanical properties of arteries before and after cryopreservation.

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Propriétés visco-élastiques des artères humaines. Méthodologie et résultats préliminaires

Résumé Dans le but d'étudier les propriétés mécaniques de la paroi artérielle et de pouvoir établir des comparaisons entre des segments artériels de structure histologique différente, nous avons mis au point un banc d'essai hydrodynamique permettant de tester des segments artériels dans des conditions voisines de la réalité physiologique. Un générateur hydrodynamique permettait d'obtenir dans un circuit ouvert un régime de pressions de type systolo-diastolique. Un capteur de pression intra-artériel, ainsi qu'un sonomicromètre relié à des cristaux piézo-électriques placés de façon diamétralement opposée sur la paroi artérielle, permettaient de calculer, pour un régime de pressions donné et grâce à l'acquisition de données dans un système informatique, la compliance, la rigidité, la contrainte trans-pariétale, le module de Young, le module incrémentiel d'un segment artériel. Nous avons étudié sept artères carotides communes (CC), et sept artères fémorales (superficielles) (F) fraîchement prélevées chez des sujets sains âgés de 18 à 35 ans. Des corrélations avec la richesse en fibres élastiques de la paroi artérielle ont été établies. Nous avons mis en évidence un phénomène d'hystérésis pour chaque artère testée quel que soit le niveau de pression considéré. La compliance des artères CC a été plus importante, les modules et la rigidité ont été moins importants et ce de façon significative par rapport aux artères F. Aucune altération histologique n'a été mise en évidence après passage des segments artériels au banc d'essai. Ces résultas préliminaires nous permettent d'envisager de nombreuses applications à ce travail dont l'une d'entre elles sera la mesure comparative des propriétés mécaniques des artères avant et après cryopréservation.

     

1p36 deletion syndrome: Review and mapping with further characterization of the phenotype,a new cohort of 86 patients

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype–phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.     

Effects of morphine and naloxone on behaviour in the hot plate test: an ethopharmacological study in the rat

The objectives of this study were: i) to analyse the effects of morphine and naloxone on the rat's behaviour in the hot plate test using an ethological approach, and ii) to compare the effectiveness of repeated versus single test paradigms. Animals received either morphine (0, 3, 6 or 9 mg/kg SC) or naloxone (0, 0.01, 0.1 or 1 mg/kg SC). For repeated hot plate measures, rats were tested before and 60, 120, 180 and 240 min following morphine treatment, as well as 30, 60, 90 and 120 min after naloxone injection. For the single test schedule, rats were tested only once 60 min after morphine or 30 min after naloxone administration, or at 60, 120, 180, 240 and 300 min after 9 mg/kg morphine treatment. Behaviour was videotaped and analysed by an ethogram and ethological techniques. A cluster analysis revealed that the most frequently displayed patterns could be categorised into exploratory sniffing reactions (walk-sniff, immobile-sniff) and noxious-evoked elements, including primary (paw-licking, stamping), escape (jumping, leaning posture) and independent (hindleg-withdrawal) patterns. During repeated tests, morphine treatment induced: i) a maximum hypoalgesic effect 60 min post-injection (noxious-evoked patterns were significantly reduced), and ii) an unexpected thermal hyperreactivity rebound effect after 120 min (paw-licking and hindleg-withdrawal were enhanced), although changes in hindpaw-licking are more indicative of a hyperalgesic rebound effect. Most changes were quite similar during the single test schedule at 60 and 120 min after morphine injection. With regard to naloxone treatment, jumping latency was significantly decreased during the repeated test schedule, but not on single exposure to the plate. Other elements were facilitated, however, in the single test (stamping, leaning posture, hindleg-withdrawal). The results indicated that both repeated and single tests paradigms are of value for testing the effects of morphine and naloxone on rats. However, under our conditions the single test paradigm gave a better picture of the overall effects of the drug. Learning as well as habituation and sensitization may mask certain effects during repeated tests. In conclusion, an ethological analysis of the rat's behaviour in the hot plate test following administration of morphine and naloxone has been validated in this study.