Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210.

BACKGROUND: Establishing the genetic basis of phenotypes such as skeletal dysplasia in model organisms can provide insights into biologic processes and their role in human disease. METHODS: We screened mutagenized mice and observed a neonatal lethal skeletal dysplasia with an autosomal recessive pattern of inheritance. Through genetic mapping and positional cloning, we identified the causative mutation. RESULTS: Affected mice had a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210); the affected mice lacked this protein. Golgi architecture was disturbed in multiple tissues, including cartilage. Skeletal development was severely impaired, with chondrocytes showing swelling and stress in the endoplasmic reticulum, abnormal cellular differentiation, and increased cell death. Golgi-mediated glycosylation events were altered in fibroblasts and chondrocytes lacking GMAP-210, and these chondrocytes had intracellular accumulation of perlecan, an extracellular matrix protein, but not of type II collagen or aggrecan, two other extracellular matrix proteins. The similarities between the skeletal and cellular phenotypes in these mice and those in patients with achondrogenesis type 1A, a neonatal lethal form of skeletal dysplasia in humans, suggested that achondrogenesis type 1A may be caused by GMAP-210 deficiency. Sequence analysis revealed loss-of-function mutations in the 10 unrelated patients with achondrogenesis type 1A whom we studied. CONCLUSIONS: GMAP-210 is required for the efficient glycosylation and cellular transport of multiple proteins. The identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia underscores the value of screening for abnormal phenotypes in model organisms and identifying the causative mutations.

Moro-Giafferi, [Jean] Erlich [16-1-20, cour du Sénat, vote préliminaire pour l'élection du président de la République] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57661

Impact of infection on the prognosis of critically ill cirrhotic patients: results from a large worldwide study.

BACKGROUND: Infections are a leading cause of death in patients with advanced cirrhosis, but there are relatively few data on the epidemiology of infection in intensive care unit (ICU) patients with cirrhosis. AIMS: We used data from the Extended Prevalence of Infection in Intensive Care (EPIC) II 1-day point-prevalence study to better define the characteristics of infection in these patients. METHODS: We compared characteristics, including occurrence and types of infections in non-cirrhotic and cirrhotic patients who had not undergone liver transplantation. RESULTS: The EPIC II database includes 13,796 adult patients from 1265 ICUs: 410 of the patients had cirrhosis. The prevalence of infection was higher in cirrhotic than in non-cirrhotic patients (59 vs. 51%, P < 0.01). The lungs were the most common site of infection in all patients, but abdominal infections were more common in cirrhotic than in non-cirrhotic patients (30 vs. 19%, P < 0.01). Infected cirrhotic patients more often had Gram-positive (56 vs. 47%, P < 0.05) isolates than did infected non-cirrhotic patients. Methicillin-resistant Staphylococcus aureus (MRSA) was more frequent in cirrhotic patients. The hospital mortality rate of cirrhotic patients was 42%, compared to 24% in the non-cirrhotic population (P < 0.001). Severe sepsis and septic shock were associated with higher in-hospital mortality rates in cirrhotic than in non-cirrhotic patients (41% and 71% vs. 30% and 49%, respectively, P < 0.05). CONCLUSIONS: Infection is more common in cirrhotic than in non-cirrhotic ICU patients and more commonly caused by Gram-positive organisms, including MRSA. Infection in patients with cirrhosis was associated with higher mortality rates than in non-cirrhotic patients.

Els apareguts i el culte de les ànimes del Purgatori (segles XIV-XVII). Estudi i edició de textos catalans

Report for the scientific sojourn carried out at the Institut National d'Histoire de l'Art (INHA), France, from 2010 to 2012. It has focused on the analysis and editing of tales of human apparitions from the other world belonging to the Catalan culture or referring to it. We have studied and edited different versions of the process of Esperança Alegre (Lleida, 1500) and the Peregrinació del Venturós Pelegrí. These medieval works have been preserved in sources of the late sixteenth century or later. We have located a manuscript of the Esperança Alegre's tale, unknown to us at the beginning of this research (Biblioteca Nacional de España, ms. 1701), which differs from the version of ms. Baluze 238 of the Bibliothèque Nationale de France. The scribe of the ms. 1701 adds several paragraphs where considers the case as a diabolical phantasmagoria. About the Venturós Pelegrí, we have tried to establish firm criteria for the classification of many editions from the seventeenth to nineteenth centuries. We have been looking for printed books in the libràries of the world and we have made several requests for photographic reproductions, in order to classify undated editions by comparing woodcuts and other decorative elements. In the legend of Prince Charles of Viana (1421-1461), the appearances of his ghost are accompanied by rumors of his poisoning and of his sanctity. In addition, we have studied the cycles of masses for the souls in Purgatory linked to the hagiographies of St. Amadour and St. Vincent Ferrer, as well as the appearances described in L'Ànima d’Oliver of Francesc Moner, in the Carmelite chronicles of Father John of St. Joseph (1642-1718) and in some folktales collected from the eighteenth to the twentieth century. All this have allowed us to verify the evolution of certain cultural paradigms since the Middle Ages to the present.

How to assess prognosis after cardiac arrest and therapeutic hypothermia.

The prognosis of patients who are admitted in a comatose state following successful resuscitation after cardiac arrest remains uncertain. Although the introduction of therapeutic hypothermia (TH) and improvements in post-resuscitation care have significantly increased the number of patients who are discharged home with minimal brain damage, short-term assessment of neurological outcome remains a challenge. The need for early and accurate prognostic predictors is crucial, especially since sedation and TH may alter the neurological examination and delay the recovery of motor response for several days. The development of additional tools, including electrophysiological examinations (electroencephalography and somatosensory evoked potentials), neuroimaging and chemical biomarkers, may help to evaluate the extent of brain injury in these patients. Given the extensive literature existing on this topic and the confounding effects of TH on the strength of these tools in outcome prognostication after cardiac arrest, the aim of this narrative review is to provide a practical approach to post-anoxic brain injury when TH is used. We also discuss when and how these tools could be combined with the neurological examination in a multimodal approach to improve outcome prediction in this population.