Nationwide Surveillance of Azole Resistance in Aspergillus Diseases.

Aspergillus disease affects a broad patient population, from patients with asthma to immunocompromised patients. Azole resistance has been increasingly reported in both clinical and environmental Aspergillus strains. The prevalence and clinical impact of azole resistance in different patient populations are currently unclear. This 1-year prospective multicenter cohort study aimed to provide detailed epidemiological data on Aspergillus resistance among patients with Aspergillus disease in Belgium. Isolates were prospectively collected in 18 hospitals (April 2011 to April 2012) for susceptibility testing. Clinical and treatment data were collected with a questionnaire. The outcome was evaluated to 1 year after a patient's inclusion. A total of 220 Aspergillus isolates from 182 patients were included. The underlying conditions included invasive aspergillosis (n = 122 patients), allergic bronchopulmonary aspergillosis (APBA) (n = 39 patients), chronic pulmonary aspergillosis (n = 10 patients), Aspergillus bronchitis (n = 7 patients), and aspergilloma (n = 5 patients). The overall azole resistance prevalence was 5.5% (95% confidence interval [CI] 2.8 to 10.2%) and was 7.0% (4/57; 95% CI, 2.3 to 17.2%) in patients with APBA, bronchitis, aspergilloma, or chronic aspergillosis and 4.6% in patients with invasive aspergillosis (5/108; 95% CI, 1.7 to 10.7%). The 6-week survival in invasive aspergillosis was 52.5%, while susceptibility testing revealed azole resistance in only 2/58 of the deceased patients. The clinical impact of Aspergillus fumigatus resistance was limited in our patient population with Aspergillus diseases.

Current definition, diagnosis, and treatment of canine and feline idiopathic vestibular syndrome.

Idiopathic vestibular syndrome (IVS) is one of the most common neurological disorders in veterinary medicine. However, its diagnosis and treatment varies between publications. The aim of the current study was to gather experts' opinion about IVS definition, diagnosis, and treatment. An online-survey was used to assess neurology specialists' opinion about the definition, diagnosis and treatment of IVS. The study demonstrated that the definition, diagnosis, and treatment of IVS are largely consistent worldwide, with the EU prioritising less frequently advanced imaging and more often otoscopy to rule out other diseases. IVS was defined by most specialists as an acute to peracute, improving, non-painful peripheral vestibular disorder that often affects cats of any age and geriatric dogs. Regarding diagnosis, a detailed neurological examination and comprehensive blood tests, including thyroid values, blood pressure, and otoscopic examination, was seen as crucial. A thorough workup may also involve MRI and CSF analysis to rule out other causes of vestibular dysfunction. Treatment of IVS typically involved intravenous fluid therapy and the use of an antiemetic, with maropitant once daily being the preferred choice among specialists. Antinausea treatment was considered, however, only by a handful specialists. This survey-based study provides valuable insights from neurology experts and highlights areas that require further research to bridge the gap between theory and practice.

The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes.

The very large G protein-coupled receptor (VLGR1, ADGRV1) is the largest member of the adhesion GPCR family. Mutations in VLGR1 have been associated with the human Usher syndrome (USH), the most common form of inherited deaf-blindness as well as childhood absence epilepsy. VLGR1 was previously found as membrane-membrane adhesion complexes and focal adhesions. Affinity proteomics revealed that in the interactome of VLGR1, molecules are enriched that are associated with both the ER and mitochondria, as well as mitochondria-associated ER membranes (MAMs), a compartment at the contact sites of both organelles. We confirmed the interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented by in situ proximity ligation assays in cells. Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs. The absence of VLGR1 in tissues and cells derived from VLGR1-deficient mouse models resulted in alterations in the MAM architecture and in the dysregulation of the Ca2+ transient from ER to mitochondria. Our data demonstrate the molecular and functional interaction of VLGR1 with components in MAMs and point to an essential role of VLGR1 in the regulation of Ca2+ homeostasis, one of the key functions of MAMs.