The burden and impact of vertigo: findings from the REVERT patient registry

Objective: Despite the high prevalence of vertigo globally and an acknowledged, but under-reported, effect on an individual's wellbeing, few studies have evaluated the burden on healthcare systems and society. This study was aimed to quantitatively determine the impact of vertigo on healthcare resource use and work productivity. Methods: The economic burden of vertigo was assessed through a multi-country, non interventional, observational registry of vertigo patients: the Registry to Evaluate the Burden of Disease in Vertigo. Patients included were those with a new diagnosis of Meniere's disease, benign paroxysmal positional vertigo, other vertigo of peripheral vestibular origin, or peripheral vestibular vertigo of unknown origin. Results: A total of 4,294 patients at 618 centers in 13 countries were included during the registry. Of the 4,105 patients analyzed, only half were in employment. Among this working patient population, 69.8% had reduced their workload, 63.3% had lost working days, and 4.6% had changed and 5.7% had quit their jobs, due to vertigo symptoms. Use of healthcare services among patients was high. In the 3 months preceding Visit 1, patients used emergency services 0.4 +/- 0.9 times, primary care consultations 1.6 +/- 1.8 times, and specialist consultations 1.4 +/- 2.0 times (all mean +/- SD). A mean of 2.0 +/- 5.4 days/patient was also spent in hospital due to vertigo. Conclusion: In addition to the negative impact on the patient from a humanistic perspective, vertigo has considerable impact on work productivity and healthcare resource use

Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis

RNA/Protein & Protein/Protein-Interaktionen innerhalb des U11/U12 di-snRNP Partikels des U12-abhängigen Spleißosoms aus HeLa-Zellen

Im U12-abhängigen Spleißosom interagieren die Ribonukleoproteine (snRNPs) U11 und U12 in Form eines di-Partikels mit der prä-mRNA, wobei die Erkennung und die Paarung der Spleißstellen simultan erfolgen. Die vorliegende Arbeit liefert wichtige Einblicke in die Bildung und die Architektur des humanen U11/U12 di-Partikels. So konnte gezeigt werden, dass das U11/U12-65K Protein über das C-terminale RNA-Erkennungsmotiv direkt an die 3'-Hälfte der U12 snRNA bindet. In diesem Kontext wird ein alternatives Modell zur Sekundärstruktur der U12 snRNA bezüglich der 3'-Hälfte vorgestellt. Über den Aminoterminus interagiert das 65K Protein mit dem U11-assoziierten 59K Protein. Aufgrund dieser dualen Bindungsaktivität stellt das 65K Protein vermutlich eine Hauptkomponente der molekularen Brücke dar, welche zur Paarung der Spleißstellen von U12-Introns führt. Darüber hinaus beschreibt diese Arbeit neue Erkenntnisse bezüglich der evolutionären Beziehung zwischen den U2- und U12-abhängigen Spleißosomen

Expression and distribution of the intermediate filament protein nestin and other stem cell related molecules in the human olfactory epithelium

The olfactory epithelium (OE) is unique inregenerating throughout life and thus is an attractivetarget for examining neurogenesis. The nestin proteinwas shown to be expressed in the OE of rodents and issuggested to be essentially involved in the process ofregeneration. Here we report the expression anddistribution of nestin in the human OE at RNA andprotein level. Moreover, we analysed the expressionprofiles in dependence on age and olfactory capacity.After sinus surgery, biopsies were taken from theolfactory epithelium of 16 patients aged 20-80 yearswith documented differences in their olfactory function.Our studies revealed that nestin is constantly detectablein the apical protuberances of sustentacular cells withinthe human OE of healthy adults. Its expression is notdependent on age, but rather appears to be related to theolfactory function, as a comparison with specimensobtained from patients suffering either from persistentanosmia or hyposmia suggests. Particularly, in thecourse of dystrophy, often accompanied with impairedolfaction, nestin expression was occasionally decreased.Contrarily, the expression of the p75-NGFR protein, amarker for human OE basal cells, was not altered,indicating that at least in the tested samples olfactoryimpairment is not connected with abnormalities at thebasal cell level. These observations emphasize anessential role of nestin for the process of regeneration,and also highlight this factor as a candidate marker forsustentacular cells in the human olfactory epitheliu

Expression and distribution of the intermediate filament protein nestin and other stem cell related molecules in the human olfactory epithelium

The original publication is available at http://pubs.acs.org/page/jnprdf/Smoke plays an intriguing role in promoting the germination of seeds of many species following a fire. Recently, a bicyclic compound containing a condensed butenolide moiety, 3-methyl-2H-furo[2,3-c]pyran-2-one (1), was reported as a potent germination promoter from plant-derived smoke. In this study, a related butenolide, 3,4,5-trimethylfuran- 2(5H)-one (2), which inhibits germination and significantly reduces the effect of 1 when applied simultaneously, was also isolated from plant-derived smoke. The interaction of these compounds with opposing actions on seed germination may have important ecological implications in a post-fire environment and could be useful molecules for understanding the events involved in breaking seed dormancy and promoting seed germination

A Synthetic Sandalwood Odorant Induces Wound-Healing Processes in Human Keratinocytes via the Olfactory Receptor OR2AT4

As the outermost barrier of the body, the skin is exposed to multiple environmental factors, including temperature, humidity, mechanical stress, and chemical stimuli such as odorants that are often used in cosmetic articles. Keratinocytes, the major cell type of the epidermal layer, express a variety of different sensory receptors that enable them to react to various environmental stimuli and process information in the skin. Here we report the identification of a novel type of chemoreceptors in human keratinocytes, the olfactory receptors (ORs). We cloned and functionally expressed the cutaneous OR, OR2AT4, and identified Sandalore, a synthetic sandalwood odorant, as an agonist of this receptor. Sandalore induces strong Ca2+ signals in cultured human keratinocytes, which are mediated by OR2AT4, as demonstrated by receptor knockdown experiments using RNA interference. The activation of OR2AT4 induces a cAMP-dependent pathway and phosphorylation of extracellular signal-regulated kinases (Erk1/2) and p38 mitogen–activated protein kinases (p38 MAPK). Moreover, the long-term stimulation of keratinocytes with Sandalore positively affected cell proliferation and migration, and regeneration of keratinocyte monolayers in an in vitro wound scratch assay. These findings combined with our studies on human skin organ cultures strongly indicate that the OR 2AT4 is involved in human keratinocyte re-epithelialization during wound-healing processes

mRNA of the endothelial isoform of NO-synthase (eNOS) is expressed in olfactory sensory neurons.

<p><i>A,</i> RT-PCR analysis of 1500 purified OSNs with primers specific for eNOS and Gα_olf. <i>B,</i><i> In situ</i> hybridization of eNOS-specific anti-sense and sense probes to cryosections of the murine olfactory epithelium. The scale bars represent 20 µm.</p