Management of peripheral facial nerve palsy

Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell’s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the scull and mastoid, cerebral MRI, or nerve conduction studies. Bell’s palsy may be diagnosed after exclusion of all secondary causes, but causes of secondary FNP and Bell’s palsy may coexist. Treatment of secondary FNP is based on the therapy of the underlying disorder. Treatment of Bell’s palsy is controversial due to the lack of large, randomized, controlled, prospective studies. There are indications that steroids or antiviral agents are beneficial but also studies, which show no beneficial effect. Additional measures include eye protection, physiotherapy, acupuncture, botulinum toxin, or possibly surgery. Prognosis of Bell’s palsy is fair with complete recovery in about 80% of the cases, 15% experience some kind of permanent nerve damage and 5% remain with severe sequelae

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Roles of Ca2+ and secretory pathway Ca2+-ATPase pump type 1 (SPCA1) in intra-Golgi transport

Mechanisms for intra-Golgi transport remain a hotly debated topic. Recently, we published data illuminating a new aspect involved in intra-Golgi transport, namely a release of free cytosolic Ca2+ ([Ca2+]cyt) from the lumen of Golgi cisternae that is fundamental for the secretion and the progression of newly synthesized proteins through the Golgi apparatus (GA). This increase in [Ca2+]cyt during the late stage of synchronous intra-Golgi transport stimulates the fusion of membranes containing cargo proteins and Golgi cisternae, allowing the progression of proteins through the GA. Subsequent restoration of the basal [Ca2+]cyt is also important for the delivery of cargo to the proper final destination. Additionally, the secretory pathway Ca2+-ATPase Ca2+ pump (SPCA1) plays an essential role at this stage. The fine regulation of membrane fusion is also important for the formation and the maintenance of the Golgi ribbon and SPCA1, which regulates [Ca2+]cyt levels, can be considered a controller of trafficking. This evidence contradicts a model of intra-Golgi transport in which permanent membrane continuity allows cargo diffusion and progression