Paroxysmal Extreme Pain Disorder (PEPD): clinical and genetic investigation

Objectifs 1) Caractériser une famille avec PEPD aux plans clinique, généalogique et génétique. 2) Identifier la cause génétique de la maladie dans cette famille, et en démontrer la pathogénicité. Introduction Le "Paroxysmal Extreme Pain Disorder " (PEPD) est une maladie génétique de transmission autosomique dominante caractérisée par des douleurs paroxystiques rectales, oculaires, maxillaires ou dans les membres inférieurs, qui peuvent être accompagnées d'un érythème. Les épisodes sont déclenchés par le contact cutané, les traumatismes mineurs et l'exposition au chaud. Leur intensité est telle qu'elle en est invalidante. PEPD est causé par des mutations du gène SCN9A, qui code pour la sous-unité alpha du canal sodique Nav1.7. Ce canal est distribué dans des cellules nerveuses périphériques appelées "nocicepteurs" qui sont impliquées dans la transmission du signal lié à la douleur. Méthode et Résultats Résultats Cliniques La partie clinique s'est déroulée à l'aide d'interviews structurées par visite directe, entretiens téléphoniques ou par correspondance. L'anamnèse, les données généalogiques et l'examen clinique ont été étudiés de façon extensive et tabulée. Résultats Génétiques Suite à l'identification de la mutation, un génotypage a été effectué à l'aide de techniques standards, afin de démontrer la co-ségrégation de la mutation avec la maladie. En outre, un groupe contrôle de 92 sujets suisses sans maladie connue ont été génotypés pour exclure la possibilité d'un polymorphisme rare. Grâce aux techniques de PCR et de séquençage, nous avons pu démontrer la présence d'une nouvelle mutation hétérozygote dans l'exon 27 du gène SCN9A, ce dernier étant impliqué dans plusieurs maladies dont PEPD. Cette mutation est codante, et conduit à un changement d'acide aminé dans le canal sodique Nav1.7 (mutation p.L1612P). Conclusions L'étude démontre la présence d'une nouvelle mutation du gène SCN9A permettant d'expliquer les symptômes décrits dans la famille investiguée. En effet, le groupe contrôle et tous les individus non symptomatiques de la famille n'ont pas la mutation, ce qui soutient fortement sa pathogénicité. En outre, il s'agit d'une mutation codante non-synonyme, localisée à proximité d'autres mutations causales précédemment étudiées au plan électrophysiologique

Observational study of suicide in Switzerland: comparison between psychiatric in- and outpatients.

In Switzerland, suicide is a major cause of years of potential life lost. Among people who died by suicide, a significant number suffered from mental illness and were treated by psychiatric care institutions. Psychiatric patients are thus a specific target for suicide prevention. Based on data from a clinical committee reviewing every death by suicide of psychiatric patients in the Canton of Vaud (Switzerland), this observational study aimed to gain knowledge on sociodemographic and clinical characteristics of psychiatric patients who died by suicide by comparing in- and outpatients. Sociodemographic and clinical characteristics of patients who died by suicide in our department from January 2007 to December 2019 were analysed. In- and outpatients were compared. The sample included 153 patients (64.7% males, n = 99). Three quarters (76.4%, n = 81) of the patients had at least one previous suicide attempt. In- and outpatients did not differ significantly in terms of sociodemographics data, psychiatric diagnosis or method of suicide. Almost all (97.2%) of the outpatients had at least one past psychiatric hospitalisation. We found gender disparities for several variables and a lower male/female suicide ratio than in the general Swiss population. Seventy-two percent of the outpatients (n = 49) had a last personal contact with clinicians less than a week before their suicide and 38.8 % of those less than 24 hours (28% of outpatients, n = 19). Patients dying by suicide present most of the time a serious psychiatric history. In- and outpatients seem to have a similar clinical and sociodemographic profile and suicide prevention should thus not be addressed differently in these two groups. The time between death of outpatients and last contact with a therapist was shorter than expected

Priority themes for swiss sustainability research

With this report, the Swiss Academies of Arts and Sciences contribute to achieving the SDGs: With a view to meeting Switzerland‘s commitments under the 2030 Agenda as a whole, it identifies our country‘s most urgent research needs

Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation

Background: Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR. Methods: We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation. Results: PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration. Conclusion: Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity

Crowdsourced Mapping in Crisis Zones: Collaboration, Organisation and Impact

Crowdsourced mapping has become an integral part of humanitarian response, with high profile deployments of platforms following the Haiti and Nepal earthquakes, and the multiple projects initiated during the Ebola outbreak in North West Africa in 2014, being prominent examples. There have also been hundreds of deployments of crowdsourced mapping projects across the globe, that did not have a high profile. This paper, through an analysis of 51 mapping deployments between 2010–2016, complimented with expert interviews, seeks to explore the organisational structures that create the conditions for effective mapping actions, and the relationship between the commissioning body, often a Non-Governmental Organisation (NGO) and the volunteers who regularly make up the team charged with producing the map. The research suggests that there are three distinct areas that need to be improved in-order to provide appropriate assistance through mapping in humanitarian crisis; regionalise; prepare; and research. The paper concludes, based on the case studies, how each of these areas can be handled more effectively, concluding that failure to implement one area sufficiently can lead to overall project failure

Validity and test-retest reliability of manual goniometers for measuring passive hip range of motion in femoroacetabular impingement patients.

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to evaluate the construct validity (known group), concurrent validity (criterion based) and test-retest (intra-rater) reliability of manual goniometers to measure passive hip range of motion (ROM) in femoroacetabular impingement patients and healthy controls.</p> <p>Methods</p> <p>Passive hip flexion, abduction, adduction, internal and external rotation ROMs were simultaneously measured with a conventional goniometer and an electromagnetic tracking system (ETS) on two different testing sessions. A total of 15 patients and 15 sex- and age-matched healthy controls participated in the study.</p> <p>Results</p> <p>The goniometer provided greater hip ROM values compared to the ETS (range 2.0-18.9 degrees; <it>P </it>< 0.001); good concurrent validity was only achieved for hip abduction and internal rotation, with intraclass correlation coefficients (ICC) of 0.94 and 0.88, respectively. Both devices detected lower hip abduction ROM in patients compared to controls (<it>P </it>< 0.01). Test-retest reliability was good with ICCs higher 0.90, except for hip adduction (0.82-0.84). Reliability estimates did not differ between the goniometer and the ETS.</p> <p>Conclusions</p> <p>The present study suggests that goniometer-based assessments considerably overestimate hip joint ROM by measuring intersegmental angles (e.g., thigh flexion on trunk for hip flexion) rather than true hip ROM. It is likely that uncontrolled pelvic rotation and tilt due to difficulties in placing the goniometer properly and in performing the anatomically correct ROM contribute to the overrating of the arc of these motions. Nevertheless, conventional manual goniometers can be used with confidence for longitudinal assessments in the clinic.</p