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Idiopathic olfactory loss (IOL) is a common olfactory disorder. Little is known about the pathophysiology of this disease. Previous studies demonstrated decreased olfactory bulb (OB) volume in IOL patients when compared with controls. The aim of our study was to investigate structural brain alterations in areas beyond the OB. We acquired T1-weighted magnetic resonance images from 16 patients with IOL and from 16 age- and sex-matched controls on a 3T scanner. Voxel-based morphometry (VBM) was performed using VBM8 toolbox and SPM8 in a Matlab environment. Psychophysical testing confirmed that patients had higher scores for Toyota and Takagi olfactometer and lower scores for Sniffin' Sticks olfactory test than controls (t = 46.9, P < 0.001 and t = 21.4, P < 0.001, respectively), consistent with olfactory dysfunction. There was a significant negative correlation between the 2 olfactory tests (r = -0.6, P = 0.01). In a volume of interest analysis including primary and secondary olfactory areas, we found patients with IOL to exhibit gray matter volume loss in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal cortex, and the piriform cortex. The present study indicates that changes in the central brain structures proximal to the OB occur in IOL. Further investigations of this phenomenon may be helpful to elucidate the etiology of IOL.

BACKGROUND: Th e impact of OSA treatment with CPAP on percutaneous coronary intervention (PCI) outcomes remains largely unknown.

BackgroundThe management of pediatric recurrent or metastatic soft tissue sarcoma after multimodal treatment remains challenging. We investigated the feasibility, efficacy, and morbidity of permanent interstitial 125I seed implantation under image guidance as a salvage treatment for pediatric patients with recurrent or metastatic soft tissue sarcoma.MethodsThis was a retrospective study of 10 patients who underwent percutaneous ultrasound or computed tomography (CT) guided permanent 125I seed implantation. Postoperative dosimetry was performed for all patients. Actuarial D90 was 121–187.1 Gy (median, 170.3 Gy). The number of 125I seeds implanted was 6–158 (median, 34.5), with a median specific activity of 0.7 mCi per seed (range, 0.62–0.8 mCi); total activity was 4.2–113.76 mCi. Follow-up time was 6–107 months (median, 27.5 months); no patients were lost to follow-up.ResultsThe overall response rate (complete response + partial response) was 8/10 (80 %), including two patients with complete response (CR) (20 %) and five patients with partial response (PR) (60 %). Local control rates after 1 and 2 years were 70.1 and 62.3 %, respectively, with a mean local control time of 70.6 months (95 % confidence interval (CI) 45.1–96.0). Survival rates after 1 and 2 years were 68.6 and 57.1 %, respectively, with a mean survival time of 65.3 months (95 % CI 34.1–96.5). Three patients died from distant metastasis; one died from local recurrence 12 months after seed implantation. Three patients suffered a grade I skin reaction and one developed ulceration. No severe adverse neurologic sequelae or blood vessel damage occurred.ConclusionsImage guided permanent interstitial 125I seed implantation as a salvage treatment appears to have a satisfactory outcome in children with recurrent or metastatic soft tissue sarcoma.

Microbial carbonates commonly flourished following mass extinction events. The end-Devonian (Hangenberg) mass extinction event is a first-order mass extinction on the scale of the ‘Big Five’ extinctions. However, to date, it is still unclear whether global microbial carbonate proliferation occurred after the Hangenberg event. The earliest known Carboniferous stromatolites on tidal flats are described from intertidal environments of the lowermost Tournaisian (Qianheishan Formation) in northwestern China. With other early Tournaisian microbe-dominated bioconstructions extensively distributed on shelves, the Qianheishan stromatolites support microbial carbonate proliferation after the Hangenberg extinction. Additional support comes from quantitative analysis of the abundance of microbe-dominated bioconstructions through the Famennian and early Tournaisian, which shows that they were globally distributed (between 40° latitude on both sides of the palaeoequator) and that their abundance increased distinctly in the early Tournaisian compared to the latest Devonian (Strunian). Comparison of variations in the relative abundance of skeleton- versus microbe-dominated bioconstructions across the Hangenberg and ‘Big Five’ extinctions suggests that changes in abundance of skeletal bioconstructors may play a first-order control on microbial carbonate proliferation during extinction transitions but that microbial proliferation is not a general necessary feature after mass extinctions.

The carbon (δ 13 C org ) and nitrogen (δ 15 N) isotopic compositions of bulk organic matter were analyzed in two high-resolution Permian-Triassic transitional sections containing microbialite in south China. The results from these shallow-marine sections show that an abrupt negative shift in δ 15 N, from ~+3‰ to ~0‰, occurred immediately after the latest Permian mass extinction (LPE) in both sections, concurrent with a distinct negative shift in δ 13 C org . The persistently low values of δ 15 N suggest that, following the LPE, microbial nitrogen fi xation became the main source of biologically available nitrogen in the Nanpanjiang Basin and perhaps over a broader region of the eastern Paleotethys Ocean. Enhanced N fi xation is probably indicative of the prevalence of stratifi ed anoxic water masses characterized by intense denitrifi cation and/or anaerobic ammonium oxidation at the time. Perturbation of the marine nitrogen cycle might have contributed to high temperatures following the main marine mass extinction through the release of the greenhouse gas N 2 O. The sharp declines in δ 15 N and δ 13 C org may be ascribed to an abrupt change in shallow-water microbial communities, which differed in composition from contemporaneous deep-water communities.

*These authors made equal contributions to this paper. BACKGROUND AND PURPOSECytoplasmic retention of β-catenin will lead to its nuclear translocation and subsequent interaction with the transcription factor TCF/LEF that regulates target gene expression. We have previously demonstrated aberrant expression of β-catenin in a model of asthma induced by toluene diisocyanate (TDI). The aim of this study was to examine whether the receptor for advanced glycation end products (RAGE) can regulate β-catenin expression in TDI-induced asthma. EXPERIMENTAL APPROACHMale BALB/c mice were sensitized and challenged with TDI to generate a chemically-induced asthma model. Inhibitors of RAGE, FPS-ZM1 and the RAGE antagonist peptide (RAP), were injected i.p. after each challenge. Airway resistance was measured in vivo and bronchoalveolar lavage fluid was analysed. Lungs were examined by histology and immunohistochemistry. Western blotting and quantitative PCR were also used. KEY RESULTSExpression of RAGE and of its ligands HMGB1, S100A12, S100B, HSP70 was increased in TDI-exposed lungs. These increases were inhibited by FPS-ZM1 or RAP. Either antagonist blunted airway reactivity, airway inflammation and goblet cell metaplasia, and decreased release of Th2 cytokines. TDI exposure decreased level of membrane β-catenin, phosphorylated Akt (Ser 473 ), inactivated GSK3β (Ser 9 ), dephosphorylated β-catenin at Ser 33 / 37 /Thr 41 , which controls its cytoplasmic degradation, increased phosphorylated β-catenin at Ser 552 , raised cytoplasmic and nuclear levels of β-catenin and up-regulated its targeted gene expression (MMP2, MMP7, MMP9, VEGF, cyclin D1, fibronectin), all of which were reversed by RAGE inhibition. CONCLUSION AND IMPLICATIONSRAGE was required for stabilization of β-catenin in TDI-induced asthma, identifying protective effects of RAGE blockade in this model. AbbreviationsBALF, bronchoalveolar lavage fluid; GSK, glycogen synthase kinase; RAGE, receptor for advanced glycation end products; TDI, toluene diisocyanate