Insights into molecular mechanisms of disease in Neurodegeneration with Brain Iron Accumulation; unifying theories.

Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterised by dystonia, parkinsonism and spasticity. Iron accumulates in the basal ganglia and may be accompanied by Lewy bodies, axonal swellings and hyperphosphorylated tau depending on NBIA subtype. Mutations in 10 genes have been associated with NBIA that include Ceruloplasmin (Cp) and Ferritin Light Chain (FTL), both directly involved in iron homeostasis, as well as Pantothenate Kinase 2 (PANK2), Phospholipase A2 group 6 (PLA2G6), Fatty acid hydroxylase 2 (FA2H), Coenzyme A synthase (COASY), C19orf12, WDR45 and DCAF17 (C2orf37). These genes are involved in seemingly unrelated cellular pathways, such as lipid metabolism, Coenzyme A synthesis and autophagy. A greater understanding of the cellular pathways that link these genes and the disease mechanisms leading to iron dyshomeostasis is needed. Additionally, the major overlap seen between NBIA and more common neurodegenerative diseases may highlight conserved disease processes. In this review, we will discuss clinical and pathological findings for each NBIA-related gene, discuss proposed disease mechanisms such as mitochondrial health, oxidative damage, autophagy/mitophagy and iron homeostasis and speculate potential overlap between NBIA subtypes

Subcutaneous Emphysema of the Orbit after Nose-Blowing

Orbital emphysema after nose-blowing is an uncommon condition and can appear without a trigger. Herein, we reported a case of orbital emphysema after nose-blowing and performed a literature review. A 68-year-old man fell and sustained an injury near his left orbit. No symptoms were noted. He noticed a left periorbital swelling after blowing his nose. Through computed tomography examination, he was diagnosed with subcutaneous emphysema. There are no previous reports that have reviewed the clinical features, need for surgery, and severity of symptoms of subcutaneous emphysema after nasal swallowing due to different factors. We retrospectively analyzed a cohort of 48 cases by searching PubMed to clarify these issues. Regarding the emphysema trigger, 21 cases had an injury or had previously undergone surgery. In 34 cases, conservative treatment was required, while surgery was selected in the acute phase in 6 cases and after the acute phase as a radical cure in 8 cases. Reduced visual acuity, diplopia, exophthalmos, facial hypoesthesia, and color disorders were noted and were more common among surgical cases. The literature review revealed no association between fracture location and the need for surgery; furthermore, surgery was less required in non-trauma cases, excluding osteoma, than in trauma cases (p = 0.0169). Our study reveals that a strict follow-up examination of visual symptoms is necessary for the first 2 days in cases of subcutaneous emphysema caused by nose blowing after facial trauma

Anti-influenza activity of c60 fullerene derivatives.

The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs