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International audience; Ce récit documente comment des malades sont morts en FaceTime pendant l'épidémie de Covid. À partir d'une enquête de terrain que j'ai commencée en janvier 2020 dans le service de réanimation d'un hôpital de la côte Ouest des États-Unis, je raconte l'apparition de la Covid-19, la séparation des malades de leurs familles, la mort vécue sur l'écran des téléphones mobiles, ainsi que les différentes façons d'agir des soignants face à cette situation que, tous, s'accordèrent à trouver « horrible ».

Background Biological therapies have changed the landscape of pharmacological management of ulcerative colitis (UC). However, a large proportion of patients do not respond to biologics, lose their response over time, or present adverse drug events. This study aims to assess therapeutic response and treatment persistence to adalimumab, infliximab, and vedolizumab, 3 agents widely used in a tertiary referral center of Saguenay–Lac-Saint-Jean (Quebec, Canada). Methods We conducted a retrospective population-based study with a thorough review of patients’ medical charts. Adults at UC diagnosis, with current or past use of adalimumab, infliximab, or vedolizumab, were included in the study. Clinical data were collected in order to assess response phenotypes and persistence to treatment. Kaplan–Meier curves were performed to assess treatment persistence, and predictors for discontinuation were assessed using Cox regression analyses. Results A total of 134 patients were included in this study. For the cases exposed to adalimumab, infliximab, and vedolizumab, 56.9%, 62.5%, and 47.5% were responders, respectively. Mean persistence rates (95% CI) were 5.5 (4.3–6.6), 10.1 (8.7–11.5), and 3.6 (2.9–4.2) years for adalimumab, infliximab, and vedolizumab, respectively. Increased persistence rates were observed in biologic-naïve patients treated with infliximab in comparison to those with the previous exposition to 2 biologics, but no such effect was observed for adalimumab or vedolizumab. Overall, 61.9% of cases had adverse drug events and of these, 6 led to treatment discontinuation. Conclusion This study presents long-term treatment persistence data with adalimumab, infliximab, and vedolizumab, showing that more than half of cases treated with these biologics remained on treatment at least 24 months after initiation.

Angoisse. Histoire du parcours d’une mourante (1970) est une illustration de la grounded theory (théorie ancrée) déjà travaillée par les sociologues Anselm Strauss et Barney Glaser dans Awareness of Dying (1965) et Time for Dying (1968). Plus rarement citée que ces deux derniers, Angoisse est le récit des deux derniers mois de vie de Mme Abel, mourant d’un cancer dans un service hospitalier entre la fin de l’automne 1963 et l’hiver 1964. Nous nous intéressons particulièrement à deux aspects de ce texte. Comme un document d’abord, qui nous offre de précieux détails sur un moment historique caractérisé par une réflexion nouvelle de la part de cliniciens et de chercheurs sur la manière dont la mort arrive à l’hôpital. Nous soulignons ensuite les problèmes méthodologiques et éthiques soulevés par le récit d’Angoisse dans lequel Glaser et Strauss nous racontent l’histoire de Mme Abel à partir des discussions que Strauss a eues avec les deux infirmières chercheuses Shizuko Fagerhaugh et Shirley Teale, qui ont pris soin de la patiente. L’écart qui existe entre, d’une part, l’expérience effective du « cas » par les deux infirmières et, d’autre part, le récit et l’analyse qu’en font les deux sociologues pose des questions aux chercheurs en sciences sociales sur la manière d’aborder l’angoisse et la mort qui arrive comme objets d’observation et de réflexion. Anguish: The Case History of a Dying Trajectory (1970) is an exemplification of the grounded theory approach already developed by the sociologists Anselm Strauss and Barney Glaser in Awareness of Dying (1965) and Time for Dying (1968). A work less commonly cited than the two earlier books, Anguish tells the story of the last two months in the life of Mrs. Abel, dying of cancer on a hospital ward between late autumn in 1963 and the first months of 1964. We take a particular interest in two aspects of the work: first as a document that offers precious details of a historical juncture characterised by medical practitioners and researchers thinking in a new way about the occurrence of death in hospitals. Secondly, we underline the methodological and ethical issues raised by the narrative of Anguish, in which Glaser and Strauss tell us Mrs. Abel’s story based on a series of interviews between Strauss and the two nurse researchers, Shizuko Fagerhaugh and Shirley Teale, who took care of her. The distance of Glaser and Strauss from the case, mediated through a ready-made theoretical apparatus, and the thoughtful interpretations of the two nurse researchers pose questions for social science researchers about how to approach anguish and dying as objects of observation and thought.

This article explores how clinicians in a U.S. specialist center for the diagnosis of dementia probe, interpret and mistrust the “loved ones” who accompany patients during their consultation. Drawing on observations of clinical consultations and team meetings, I ask how trust in these “informants” is challenged. The informant is thus sometimes transformed from being a routine means of gathering information about the patient into an object of diagnosis. The article shows how mistrust towards the informant is actually a tool, rather than an obstacle, for the making of clinical knowledge. Faced with a “bad informant”, rather than merely bracketing or discounting what the informant says, clinicians use what they understand of the affective relationships between the patient and the “bad informant” in order to make a diagnosis. The diagnosis of dementia in an individual is thus shown to draw on and inquire into “relational dimensions” in the patient’s life, made visible and enunciable only when they pose a problem.

The Salivary Scavenger and Agglutinin (SALSA) protein is an innate immune protein with various alleged functions, including the regulation of inflammation and tissue remodeling. Transcriptomic studies of severe equine asthma (SEA) showed downregulation of the gene encoding SALSA in bronchial epithelium of asthmatic compared to non-asthmatic horses. This study aimed to characterize expression of SALSA in equine tissues by immunohistochemistry (IHC), corroborate potential differences in epithelial gene expression between asthmatic and non-asthmatic horses, and assess the structure of equine SALSA. An antibody against SALSA was validated through immunoprecipitation followed by mass spectrometry and Western blotting to recognize the equine protein. This antibody was applied to tissue microarrays (TMAs) containing 22 tissues each from four horses. A quantitative PCR assay was designed to compare gene expression for SALSA between six asthmatic and six non-asthmatic horses, before and after an asthmatic challenge, using cDNA from endoscopic bronchial biopsies as source material. The SALSA gene from bronchial cDNA samples of 10 horses, was amplified and sequenced, and translated to characterize the protein structure. Immunostaining for SALSA was detected in the mucosal surfaces of the trachea, bronchi, bronchioles, stomach, small intestine and bladder, in pancreatic and salivary gland ducts, and in uterine gland epithelium. Staining was strongest in the duodenum, and the intercalated ducts and Demilune cells of the salivary gland. SALSA was concentrated in the apical regions of the epithelial cell cytoplasm, suggestive of a secreted protein. Gene expression was significantly lower (p = 0.031) in asthmatic compared to non-asthmatic horses. Equine SALSA consisted of three to five scavenger receptor cysteine-rich (SRCR) domains, two CUB (C1r/C1s, uegf, bmp-1) domains and one Zona Pellucida domain. These domains mediate the binding of ligands involved in innate immunity. Varying numbers of SRCR domains were identified in different horses, indicating different isoforms. In summary, equine SALSA has a predilection for mucosal sites, has multiple isoforms, and has decreased expression in asthmatic horses, suggesting alterations in innate immunity in equine asthma.

Cet article est base sur une enquete ethnographique de dix-huit mois a la clinique de la memoire, un centre de renommee mondiale situe aux Etats-Unis et specialise dans le diagnostic des maladies neurodegeneratives (telles que la maladie d’Alzheimer ou la demence frontotemporale). Il prend pour point de depart le contexte d’indecidabilite qui caracterise le diagnostic de ces affections ; contexte qui pose parfois la question de la realite du diagnostic neurologique aux medecins, aux patients, a leurs proches et a l’ethnographe. J’aborde cette question a partir de la description des interactions de l’equipe medicale lorsqu’elle delibere au sujet de deux cas complexes de patients. Pour ces deux patients, les discussions en equipe aboutiront a l’attribution d’une categorie diagnostique au statut d’entre-deux qui se nomme la phenocopie. Cette curieuse categorie decrit une maladie neurodegenerative qui ne degenere pas, ou alors tres peu, tres lentement (comme on me l’expliquera). En decrivant les conditions de l’attribution de la categorie de phenocopie, son fonctionnement et ses effets, cet article s’interesse aux rapports hesitants qu’entretient le savoir medical avec les notions de realite et de simulation, de verite et de mensonge. A partir des echanges de l’equipe au sujet de ces deux patients, je documente les tensions qui emergent relativement a la realite de ce qui est donne a voir et a defendre, ainsi que la maniere dont la phenocopie permet de surmonter l’opacite d’une situation pour laquelle on ne sait plus vraiment dire ce qui est reel et ce qui ne l’est pas.

This article describes how today in the United States neurologists diagnose forms of dementia, such as Alzheimer's disease and frontotemporal dementia. Taking as a starting-point the pervasive context of uncertainty in the diagnosis of neurodegenerative diseases, it examines how uncertainty is not merely an epistemological obstacle to the making of knowledge. On the contrary, the article analyses how uncertainty positively incites the use of clinicians’ ‘feelings’ in diagnostic work. Drawing on observations of clinical consultations and team meetings, it studies how, alongside contemporary instruments of objectification, clinicians use, share, and discuss their ‘feelings’ to ultimately renew knowledge about brain diseases. In documenting the manner in which medical expertise is bound to a concrete experience of the world, this article further explores how experts’ ‘intuition’ can be grasped as a conscious and effortful process, rather than as something ineffable, resisting analysis, and confined to an unconscious background.

Background Severe equine asthma is a chronic inflammatory disease of the lung in horses similar to low-Th2 late-onset asthma in humans. This study aimed to determine the utility of RNA-Seq to call gene sequence variants, and to identify sequence variants of potential relevance to the pathogenesis of asthma. Methods RNA-Seq data were generated from endobronchial biopsies collected from six asthmatic and seven non-asthmatic horses before and after challenge (26 samples total). Sequences were aligned to the equine genome with Spliced Transcripts Alignment to Reference software. Read preparation for sequence variant calling was performed with Picard tools and Genome Analysis Toolkit (GATK). Sequence variants were called and filtered using GATK and Ensembl Variant Effect Predictor (VEP) tools, and two RNA-Seq predicted sequence variants were investigated with both PCR and Sanger sequencing. Supplementary analysis of novel sequence variant selection with VEP was based on a score of Results RNA-Seq variant calling and filtering correctly identified substitution variants in PACRG and RTTN. Sanger sequencing confirmed that the PACRG substitution was appropriately identified in all 26 samples while the RTTN substitution was identified correctly in 24 of 26 samples. These variants of uncertain significance had substitutions that were predicted to result in loss of function and to be non-neutral. Amino acid substitutions projected no change of hydrophobicity and isoelectric point in PACRG, and a change in both for RTTN. For PACRG, no difference in allele frequency between the two groups was detected but a higher proportion of asthmatic horses had the altered RTTN allele compared to non-asthmatic animals. Discussion RNA-Seq was sensitive and specific for calling gene sequence variants in this disease model. Even moderate coverage (

Background. Severe equine asthma is a chronic inflammatory disease of the lung in horses similar to low-Th2 late-onset asthma in humans. The disease in horses has complex inheritance including both dominant and recessive patterns that are ill defined. This study aimed to determine the utility of RNA-Seq to call gene variants and identify mutations potentially linked to disease. Methods. RNA-Seq data were generated from endobronchial biopsies collected from 6 asthmatic and 7 non-asthmatic horses before and after challenge (26 samples total). Sequences were aligned to the equine genome with Spliced Transcripts Alignment to Reference software. Read preparation for variant calling was performed with Picard tools and Genome Analysis Toolkit (GATK). Coverage was visualized using Integrative Genomic Viewer software and variants were called and filtered using GATK and Ensembl Variant Effect Predictor (VEP) tools. Novel variant selection by VEP was based on score of Results. Level of expression across the genome was similar in all individuals. RNA-Seq variant calling and filtering identified with highest confidence mutations in PACRG and RTTN. Sanger sequencing confirmed that the PACRG variant was appropriately identified in all 26 samples while the RTTN variant was identified correctly by RNA-Seq in 24 of 26 samples. SIFT and PolyPhen2 indicated both mutations would result in loss of function, and SNAP2 that they would be non-neutral. Amino acid substitutions projected no change of hydrophobicity and isoelectric point in PACRG, a change in both for RTTN; and a slight change in 3D structure for PACRG and RTTN. For PACRG, samples from additional individuals confirmed higher frequency of the heterozygous genotype in asthmatics, while the RTTN homozygous mutant phenotype was more prevalent in the asthmatic compared to non-asthmatic group. Discussion. RNA-Seq was sensitive and specific for calling gene variants in this disease model. Even moderate coverage (

Severe equine asthma is a chronic inflammatory condition of the lower airways similar to adult-onset asthma in humans. Exacerbations are characterized by bronchial and bronchiolar neutrophilic inflammation, mucus hypersecretion and airway constriction. In this study we analyzed the gene expression response of the bronchial epithelium within groups of asthmatic and non-asthmatic animals following exposure to a dusty hay challenge. After challenge we identified 2341 and 120 differentially expressed genes in asthmatic and non-asthmatic horses, respectively. Gene set enrichment analysis of changes in gene expression after challenge identified 587 and 171 significantly enriched gene sets in asthmatic and non-asthmatic horses, respectively. Gene sets in asthmatic animals pertained, but were not limited, to cell cycle, neutrophil migration and chemotaxis, wound healing, hemostasis, coagulation, regulation of body fluid levels, and the hedgehog pathway. Furthermore, transcription factor target enrichment analysis in the asthmatic group showed that transcription factor motifs with the highest enrichment scores for up-regulated genes belonged to the E2F transcription factor family. It is postulated that engagement of hedgehog and E2F pathways in asthmatic horses promotes dysregulated cell proliferation and abnormal epithelial repair. These fundamental lesions may prevent re-establishment of homeostasis and perpetuate inflammation.

Background Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined. Results Paired endobronchial biopsies were obtained pre- and post-challenge from asthmatic and non-asthmatic animals. The transcriptome, determined by RNA-seq and analyzed with edgeR, contained 111 genes differentially expressed (DE) after challenge between horses with and without asthma, and 81 of these were upregulated. Genes involved in neutrophil migration and activation were in central location in interaction networks, and related gene ontology terms were significantly overrepresented. Relative abundance of specific gene products as determined by immunohistochemistry was correlated with differential gene expression. Gene sets involved in neutrophil chemotaxis, immune and inflammatory response, secretion, blood coagulation and apoptosis were overrepresented among up-regulated genes, while the rhythmic process gene set was overrepresented among down-regulated genes. MMP1, IL8, TLR4 and MMP9 appeared to be the most important proteins in connecting the STRING protein network of DE genes. Conclusions Several differentially expressed genes and networks in horses with asthma also contribute to human asthma, highlighting similarities between severe human adult and equine asthma. Neutrophil activation by the bronchial epithelium is suggested as the trigger of the inflammatory cascade in equine asthma, followed by epithelial injury and impaired repair and differentiation. Circadian rhythm dysregulation and the sonic Hedgehog pathway were identified as potential novel contributory factors in equine asthma. Electronic supplementary material The online version of this article (10.1186/s12864-017-4107-6) contains supplementary material, which is available to authorized users.

This article takes up the neuroscientific assumption of our brains as “solitary” and contrasts this understanding with the description of actual clinical practices. Drawing on observations of clinical consultations and team meetings in a world famous US center for the diagnosis of dementia, I examine how the “informant”, a member of the patient’s family, participates in the diagnosis process. Based on specific situations in which the informant is judged to be a “bad” one, I inquire as to how clinicians use what they understand of the affective relationships between the patient and the bad informant in order to make a diagnosis. The diagnosis of dementia in an individual is shown to draw on relational dimensions in the patient’s life, made visible and enunciable only when problematic. This inquiry therefore brings out how these neurologists, even though they are engaged in a neuroscientific paradigm that conceives the brain as a self-sufficient cognitive machinery, nevertheless do consider what links us to the brains sharing our lives, in order to make sense of our networks of neurons.

Colonization of plant roots by Bacillus subtilis is mutually beneficial to plants and bacteria. Plants can secrete up to 30% of their fixed carbon via root exudates, thereby feeding the bacteria, and in return the associated B. subtilis bacteria provide the plant with many growth-promoting traits. Formation of a biofilm on the root by matrix-producing B. subtilis is a well-established requirement for long-term colonization. However, we observed that cells start forming a biofilm only several hours after motile cells first settle on the plant. We also found that intact chemotaxis machinery is required for early root colonization by B. subtilis and for plant protection. Arabidopsis thaliana root exudates attract B. subtilis in vitro, an activity mediated by the two characterized chemoreceptors, McpB and McpC, as well as by the orphan receptor TlpC. Nonetheless, bacteria lacking these chemoreceptors are still able to colonize the root, suggesting that other chemoreceptors might also play a role in this process. These observations suggest that A. thaliana actively recruits B. subtilis through root-secreted molecules, and our results stress the important roles of B. subtilis chemoreceptors for efficient colonization of plants in natural environments. These results demonstrate a remarkable strategy adapted by beneficial rhizobacteria to utilize carbon-rich root exudates, which may facilitate rhizobacterial colonization and a mutualistic association with the host., IMPORTANCE Bacillus subtilis is a plant growth-promoting rhizobacterium that establishes robust interactions with roots. Many studies have now demonstrated that biofilm formation is required for long-term colonization. However, we observed that motile B. subtilis mediates the first contact with the roots. These cells differentiate into biofilm-producing cells only several hours after the bacteria first contact the root. Our study reveals that intact chemotaxis machinery is required for the bacteria to reach the root. Many, if not all, of the B. subtilis 10 chemoreceptors are involved in the interaction with the plant. These observations stress the importance of root-bacterium interactions in the B. subtilis lifestyle.

During their transit along the epididymis, mammalian spermatozoa acquire new proteins that are necessary for their acquisition of forward motility and fertility. By using the bovine model, we previously showed that small membranous vesicles named epididymosomes are secreted in the epididymal intraluminal compartment. Epididymosomes from caput and cauda are different, and interact sequentially with the transiting spermatozoa. In fact, selected proteins of epididymosomes are transferred to different subcompartments of the maturing spermatozoa. In this study, we investigate the possibility that different subpopulations of epididymosomes are present in the caudal portion of the epididymis. Through the use of discontinuous sucrose gradient ultracentrifugation, we isolated two distinct populations that differ in their protein and lipid compositions. Although they have similar diameters, the ultrastructural appearance of these two populations was very different. The low-density (Ld) vesicles are enriched in cholesterol, sphingomyelin, and ganglioside M1, suggesting the existence of detergent-resistant membrane domains or rafts. The high-density (Hd) vesicles show a high protein concentration, including ACTB and VAMP8. When each subpopulation of biotinylated cauda epididymosomes was coincubated with caput spermatozoa, a subset of biotinylated proteins was transferred to the sperm; the Ld and Hd vesicles transferring the same pattern of proteins. In vitro competition assays of protein transferred from Ld or Hd epididymosomes to sperm confirm the similarity in the selected transferred proteins. Electrospray tandem mass spectrometry (ES-MS/MS) analysis of proteins associated with the two populations of vesicles confirm the epididymal origin of some of them, the possible involvement of others in transmembrane signaling systems, and the identification of proteins for which functions in sperm physiology remain to be determined. Mass spectrometry analysis also revealed that ELSPBP1 and GBB2 were transferred from epididymosomes to spermatozoa. Results are discussed with regard to the functions of these two cauda epididymosome populations in sperm physiology.

Multipotent mesenchymal stromal cells (MSC) have attracted interest for their cytotherapeutic potential, partly due to their immunomodulatory abilities. The aim of this study was to test the robustness of our equine cord blood (CB) MSC isolation protocol, to characterize the CB-MSC before and after cryopreservation, and to evaluate their immunosuppressive phenotype. We hypothesized that MSC can be consistently isolated from equine CB, have unique and reproducible marker expression and in vitro suppress lymphoproliferation. Preliminary investigation of constitutive cytoplasmic Toll-like receptor (TLR) 3 and 4 expression was also preformed due to their possible association with anti- or pro-inflammatory MSC phenotypes, respectively. Surface markers were assessed for antigen and mRNA expression by flow cytometry and quantitative polymerase chain reaction (qPCR). Immunomodulatory properties were evaluated in mixed lymphocyte reaction assays, and TLR3 and TLR4 expression were measured by qPCR and immunocytochemistry (ICC). CB-MSC were isolated from each off nine cord blood samples. CB-MSC highly expressed CD29, CD44, CD90, and lacked or had low expression of major histocompatibility complex (MHC) class I, MHC-II, CD4, CD8, CD11a/18 and CD73 before and after cryopreservation. CB-MSC suppressed in vitro lymphoproliferation and constitutively expressed TLR4. Our findings confirmed CB as a reliable MSC source, provides an association of surface marker phenotype and mRNA expression and suggest anti-inflammatory properties of CB-MSC. The relationship between TLRs and lymphocyte function warrants further investigation.

Grey zones, lasting crises and forgotten conflicts are typical of our times. Even though certain conflicts come to an end, many do not because no solution is found for the underlying causes. The great majority of these conflicts are internal and involve non-State entities; they are civil wars. Such complex and interminable crises are a challenge not only for statesmen and diplomats but also for “humanitarians”, in particular the international organizations in charge of humanitarian action. The authors examine the causes and characteristics of such conflicts. They particularly highlight the fact that unending wars not only create short-term humanitarian problems but in the long run destroy civil society. What are the solutions to such conflicts? The authors call for a change of attitudes and a new approach to lasting crises and suggest various forms of action to be taken by the international community. While adequate measures for dealing with humanitarian issues have been found for traditional wars, lasting crises and forgotten conflicts are still awaiting a response by the humanitarian community.

During their transit along the epididymis, mammalian spermatozoa acquire new proteins that are necessary for their acquisition of forward motility and fertility. By using the bovine model, we previously showed that small membranous vesicles named epididymosomes are secreted in the epididymal intraluminal compartment. Epididymosomes from caput and cauda are different, and interact sequentially with the transiting spermatozoa. In fact, selected proteins of epididymosomes are transferred to different subcompartments of the maturing spermatozoa. In this study, we investigate the possibility that different subpopulations of epididymosomes are present in the caudal portion of the epididymis. Through the use of discontinuous sucrose gradient ultracentrifugation, we isolated two distinct populations that differ in their protein and lipid compositions. Although they have similar diameters, the ultrastructural appearance of these two populations was very different. The low-density (Ld) vesicles are enriched in cholesterol, sphingomyelin, and ganglioside M1, suggesting the existence of detergent-resistant membrane domains or rafts. The high-density (Hd) vesicles show a high protein concentration, including ACTB and VAMP8. When each subpopulation of biotinylated cauda epididymosomes was coincubated with caput spermatozoa, a subset of biotinylated proteins was transferred to the sperm; the Ld and Hd vesicles transferring the same pattern of proteins. In vitro competition assays of protein transferred from Ld or Hd epididymosomes to sperm confirm the similarity in the selected transferred proteins. Electrospray tandem mass spectrometry (ES-MS/MS) analysis of proteins associated with the two populations of vesicles confirm the epididymal origin of some of them, the possible involvement of others in transmembrane signaling systems, and the identification of proteins for which functions in sperm physiology remain to be determined. Mass spectrometry analysis also revealed that ELSPBP1 and GBB2 were transferred from epididymosomes to spermatozoa. Results are discussed with regard to the functions of these two cauda epididymosome populations in sperm physiology.