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Purpose: To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD). Methods: We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system. Results: Male patients with PVOD had a larger OB volume (β = 0.284, P < 0.05). OB volume was smaller in patients with a longer course of olfactory dysfunction (β = − 0.254, P < 0.05). According to the LM scoring system, patients with a higher anterior ethmoidal sinus score had smaller OB volume (β = − 0.476, P < 0.05). Conclusions: The study revealed that gender, disease course, and the score of anterior ethmoidal sinusitis can affect the OB volume in patients with PVOD. [ABSTRACT FROM AUTHOR]

Purpose: Impaired brain cortices contribute significantly to the pathophysiological mechanisms of post-traumatic olfactory dysfunction (PTOD). This study aimed to use 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to measure cerebral cortices' metabolism activity and then to explore their associations with olfaction in patients with PTOD. Methods: Ethics committee-approved prospective studies included 15 patients with post-traumatic anosmia and 11 healthy volunteers. Olfactory function was assessed using the Sniffin' Sticks. Participants underwent 18F-FDG PET/CT scan and the image data were collected for the voxel-based whole brain analysis. Furthermore, the standardized uptake value ratio (SUVR) of the whole brain regions was measured and correlated with olfactory function. Results: Patients with post-traumatic anosmia showed significantly reduced glucose metabolism in bilateral rectus, bilateral superior and medial orbitofrontal cortex (OFC), bilateral thalamus, left hippocampus and parahippocampus and left superior temporal pole (all p < 0.001). In contrast, patients with post-traumatic anosmia had significantly increased glucose metabolism in the bilateral insula (all p < 0.001). SUVR values among a total of 17 cerebral cortices including frontal, limbic, and temporal regions were significantly and positively correlated with olfactory function. The cerebral cortices with the top three correlations were the right middle frontal OFC (r = 0.765, p = 0.001), right caudate (r = 0.652, p = 0.010) and right putamen (r = 0.623, p = 0.002). Conclusion: Patients with post-traumatic anosmia presented with distinct patterns of brain metabolism and key cortices that highly associated with the retained olfactory function were identified. The preliminary results further support the potential use of PET imaging for precisely assessing brain metabolism in patients with PTOD. [ABSTRACT FROM AUTHOR]

Purpose: Prognostic assessment of patients with post-infectious olfactory dysfunction (PIOD) poses a challenge for clinicians. While there have been some studies on the prognostic factors of PIOD focusing on demographic factors, the aim of this study was to investigate whether event-related potentials (ERPs) could be used as a new predictor of olfactory recovery in PIOD. Methods: This was a retrospective study involving patients who underwent olfactory examinations using Sniffin' Sticks test before treatment and after 1 year of follow-up. The responder group was defined by an increase of threshold–discrimination–identification (TDI) score of ≥ 6 points. All patients underwent ERP examination and the amplitude and latency of each wave of ERPs were recorded before treatment. Results: A total of 61 patients (age 47.50 ± 11.04 years, 27 males) were analyzed. The presence of olfactory ERPs (oERPs) was greater in the responder group than in the non-responder group (P = 0.007), while that of trigeminal ERPs (tERPs) did not differ between the two groups (P = 0.346). Logistic-regression analyses showed that factors associated with improvement of subjective olfactory function were duration (OR, 1.604; 95% CI, 1.062–2.423; P = 0.025), initial threshold (odds ratio [OR], 0.043; 95% confidence interval [CI], 0.004–0.439; P = 0.008), and latency of N1 in oERPs (OR, 1.007; 95% CI, 1.001–1.013; P = 0.021). Conclusion: Our study shows that duration of OD, initial threshold, and latency of N1 in oERPs were associated with olfactory improvement in PIOD patients, which may provide guidance for clinicians. [ABSTRACT FROM AUTHOR]

The odorant arrives at nasal olfactory epithelium ortho- and retronasally. This experiment aimed to study the potential different olfactory habituation in orthonasal and retronasal pathways. 68 subjects were stimulated by constant airflow with an odor (50% phenethyl alcohol, PEA or 5% n-butyl acetate, BA) presented ortho- or retronasally. Participants rated the perceived odor intensity (0–10 points) per minute until the odor sensation disappeared. We also investigated the cross-habituation: when the subjects achieved full habituation, continue to rate odor intensity in a different pathway after instantly switching the odor stimulation pathway. The olfactory habituation curve was drawn. The differences of ratings between the orthonasal and retronasal olfaction at different time points and between male and female subjects were analyzed. The two odor intensity ratings decreased as the time extended, share the same “fast followed by slow” type. The ratings of orthonasal olfaction decreased faster than that of retronasal. The intensity rating of PEA of male retronasal approach was lower than that of female at the 5th min (p = 0.018). When orthonasal full habituation achieved, there was significant difference between the intensity ratings and the initial ratings of the retronasal stimulation pathway (p < 0.0001), and vice versa. We found obvious habituation as well as cross-habituation in both orthonasal and retronasal olfaction. The habituation of orthonasal olfaction was faster than that of retronasal olfaction. These different habituations were related to the gender. [ABSTRACT FROM AUTHOR]

Introduction: Brain activation in response to olfactory stimuli has been studied using functional magnetic resonance imaging (fMRI), but there is little knowledge about processing repeated olfactory information which is usual in daily life. Methods: This fMRI study was designed to investigate brain response to repeated odorant stimulation with positive and negative valences in 12 healthy right-handed volunteers. There was a 25-min rest interval between two fMRI runs with identical stimulation paradigms with two odors, as phenylethyl alcohol (PEA) and isovaleric acid (IVA), and the two odors were released alternately. Results: There was a similar activation pattern in regions of primary and secondary olfactory cortex induced by odors of both valences, especially by negative odor. Weakened activation of the brain is responsive to repeated both pleasant and unpleasant smell. Nevertheless, the repeated unpleasant odor has a more intimate relationship with the piriform cortex, amygdala, and hippocampus. Conclusion: We conclude that asymmetric brain activation in response to repeated odorant stimulation depended on valences and that the unpleasant odor can evoke more negative emotion and profound memory. Implications: We explore the central processing about repeated olfactory information applied fMRI for the first time, revealing asymmetric brain activation in response to repeated odors of pleasantness and unpleasantness. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation of tissue eosinophil count and chemosensory functions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS). Methods: This was a cross-sectional study including 40 patients with a history of ESS for CRSwNP recruited consecutively. Visual analog scale score and the Lund–Kennedy endoscopic score were recorded. Biopsies of the ethmoidal sinus mucosal were performed and evaluated. Chemosensory functions were measured by Sniffin' Sticks and chemosensory event-related potentials (CSERP). The associations between chemosensory functions and tissue eosinophil count were analyzed using Spearman correlation and partial correlation after adjusting the confounding factors. Kendall's tau-b correlation was performed between sneezing score and CSERP with ethyl alcohol (EAL) stimulation. Results: Olfactory and trigeminal nerve function was successfully evaluated using CSERP. Postoperative tissue eosinophil count was correlated with threshold (T) score (partial correlation coefficient r = − 0.460, p = 0.012) and CSERP peak latency for olfactory (N1: partial r = 0.471, p = 0.010; P2: partial r = 0.487, p = 0.007) and mixed olfactory–trigeminal (N1: partial r = − 0.516, p = 0.008; P2: partial r = − 0.590, p = 0.002). There were also correlations between T score and N1 latency with phenyl ethyl alcohol (PEA) (partial r = − 0.560, p < 0.001), between sneezing score and N1 latency with EAL (Kendall's tau-b = − 0.40, p = 0.005). Conclusions: Postoperative tissue eosinophilia is significantly associated with postoperative olfactory disorders as assessed by Sniffin' Sticks and CSERP peak latency. Furthermore, olfaction as measured by T score correlates with olfactory ERP latency in inflammation-associated olfactory dysfunction. Trigeminal sensitivity also appears to relate to tissue eosinophilia, indicating mucosal inflammation can affect both sensory systems in the nose. [ABSTRACT FROM AUTHOR]

To determine the effects of single nucleotide polymorphisms (SNPs) identified in a genome-wide association study of progressive supranuclear palsy (PSP), we tested their association with brain gene expression, CpG methylation and neuropathology. In 175 autopsied PSP subjects, we performed associations between seven PSP risk variants and temporal cortex levels of 20 genes in- cis, within ±100 kb. Methylation measures were collected using reduced representation bisulfite sequencing in 43 PSP brains. To determine whether SNP/expression associations are due to epigenetic modifications, CpG methylation levels of associated genes were tested against relevant variants. Quantitative neuropathology endophenotypes were tested for SNP associations in 422 PSP subjects. Brain levels of LRRC37A4 and ARL17B were associated with rs8070723; MOBP with rs1768208 and both ARL17A and ARL17B with rs242557. Expression associations for LRRC37A4 and MOBP were available in an additional 100 PSP subjects. Meta-analysis revealed highly significant associations for PSP risk alleles of rs8070723 and rs1768208 with higher LRRC37A4 and MOBP brain levels, respectively. Methylation levels of one CpG in the 3′ region of ARL17B associated with rs242557 and rs8070723. Additionally, methylation levels of an intronic ARL17A CpG associated with rs242557 and that of an intronic MOBP CpG with rs1768208. MAPT and MOBP region risk alleles also associated with higher levels of neuropathology. Strongest associations were observed for rs242557/coiled bodies and tufted astrocytes; and for rs1768208/coiled bodies and tau threads. These findings suggest that PSP variants at MAPT and MOBP loci may confer PSP risk via influencing gene expression and tau neuropathology. MOBP, LRRC37A4, ARL17A and ARL17B warrant further assessment as candidate PSP risk genes. Our findings have implications for the mechanism of action of variants at some of the top PSP risk loci. [ABSTRACT FROM AUTHOR]

To characterize the sequence variation and the potential implication of the Epstein-Barr virus (EBV) oncogene in lymphoma, BamHI-C fragment rightward reading frame 1 (BCRF1) was sequenced in different types of EBV-positive lymphoma in northern China, and polymorphisms were compared with previous variation data from other malignancies. The dominate subtype of BCRF1 in EBV-positive lymphoma was the B95-8 prototype, and a mutation in the signal peptide was more strongly associated with Hodgkin's lymphoma. The high conservation of BCRF1 in EBV-positive lymphoma suggests its important role in maintaining the basic biological activity and immunosuppressive functions of the virus. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to determine the prognostic value of BCAR1 expression and its associations with clinical-demographical characteristics in multiple centers of non-small cell lung cancer (NSCLC) patients. Methods: Gene expression microarray (mRNA) of 77 adenocarcinomas from Mayo Clinic, RNA-sequencing of 508 NSCLC from The Cancer Genome Atlas (TCGA), and immunohistochemistry stain of BCAR1-protein expression in 150 cases from Daping Hospital were included in the study. The association of mRNA or protein expression with patient clinical characteristics and overall survival was assessed in each dataset. We also predicted microRNAs (miRNA) that target BCAR1 using bioinformatics prediction tools and evaluated miRNA expression patterns with BCAR1 expression in miRNA-sequencing data of 74 lung cancer cases from TCGA dataset. Results: In the Mayo Clinic dataset, a higher BCAR1-mRNA level correlated significantly with more advanced tumor-stage and lymphatic metastasis. Similar changes were observed in the TCGA RNA-seq dataset. Additionally, higher BCAR1-mRNA levels predicted poorer survival in adenocarcinoma and squamous carcinoma from the TCGA dataset. The protein levels in the adenocarcinoma cases with lymphatic metastasis were significantly higher than of those without metastasis. Tumor tissues demonstrated remarkably higher levels of protein compared with matched normal tissues although there was no significant difference in BCAR1-mRNA expression between tumor and matched normal tissues was detected. In miRNAs that were downregulated in the tumors, Let-7f-2 and miR-22 differed the most ( P < 0.001 and P = 0.007, respectively). Conclusions: We confirmed that increased BCAR1 expression predicts poorer prognosis in NSCLC. We postulate that mRNA-protein decoupling of BCAR1 may be a result of reduced inhibition of specific miRNAs in tumor tissues, which warrants further study. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) nuclear antigen protein 3A (EBNA-3A), a protein of 944 amino acids, is one of five EBNAs (EBNA-1, -2, -LP, -3A and -3C) essential for conversion of primary B lymphocytes to lymphoblastoid cell lines. To characterize the variations of the EBNA-3A gene and explore the association between EBNA-3A gene variations and EBV-associated diseases, we sequenced the key regions of EBNA-3A in the isolates of 30 EBV-associated gastric carcinomas (EBVaGCs), 44 nasopharyngeal carcinomas (NPCs) and 48 samples from healthy donors in northern China. We found that EBNA-3A shares a common evolutionary origin with isolates from southern China and Japan but has the character of a geographical variant. Based on a phylogenetic tree, all of the samples can be subdivided into three patterns, named 3A-8, 3A-5 and B95-8-like. The distribution of EBNA-3A subtypes among EBVaGC, NPC and healthy donors is not significantly different. The subtype 3A-8 is predominant not only in northern China but also in southern China; it is a geographically associated polymorphism in China. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is responsible for the development of multiple tumors, including EBV-associated gastric carcinoma (EBVaGC), but little is known about its mechanisms in EBVaGC. WNT5A expression and promoter methylation were measured in 5 EBV-positive and 15 EBV-negative GC cell lines. The methylation status of 23 EBV-positive and 25 EBV-negative paired tumor/normal tissue samples was also examined. EBV-positive GC had no or very low expression of WNT5A but a high level of methylation in the promoter region. In contrast, EBV-negative GC had higher WNT5A expression and a lower level of promoter methylation. The reduced WNT5A expression could be restored by treatment with Aza, a methyltransferase inhibitor. Increased expression of WNT5A in vitro inhibited β-catentin expression in EBVaGC cells (SNU719). These results suggest that hypermethylation of WNT5A induced by EBV may contribute to the development of EBVaGC. Ectopic introduction of WNT5A may have preventive/therapeutic potential for tumors with silenced WNT5A. [ABSTRACT FROM AUTHOR]

To characterize the sequence variation of the gp350/220 and explore its potential association with EBV-associated tumors, the gp350/220 gene was sequenced from 41 EBV-associated gastric carcinoma (EBVaGC) and 81 nasopharyngeal carcinoma (NPC) biopsies as well as 35 throat washing (TW) samples from healthy donors. Preferential linkages between variants of the N-terminus of gp350/220 and EBNA3C variants were detected, and type A/BLLF1-a was the dominant variant in this study. The dominant variant in the C-terminal region of gp350/220 was 9P. The similar distribution of gp350/220 variants in NPC, EBVaGC and healthy donors suggest that gp350/220 variations are geographically restricted rather than tumor-specific polymorphisms. [ABSTRACT FROM AUTHOR]

High-energy shot peening (HESP), a method to produce severe plastic deformation by high velocity flying balls, was applied on die cast magnesium alloy AZ91D. Effects of surface nanocrystallization by HESP and heat treatment at different temperatures were investigated. The microstructure evolution was conducted using X-ray diffraction (XRD) and field emission scanning electronic microscopy (FESEM). The hardness was measured by microhardness tester. The experimental results show that surface nanocrystrallization of AZ91D obtained by HESP would lead to the increase of microhardness. Low temperature heated at 100 °C for 1 h do not change the property obviously. However, both the microstructure and microhardness vary greatly after heat treatment at 400 °C for 1 h. [ABSTRACT FROM AUTHOR]

Lung adenocarcinomas from never smokers account for approximately 15 to 20% of all lung cancers and these tumors often carry genetic alterations that are responsive to targeted therapy. Here we examined mutation status in 10 oncogenes among 89 lung adenocarcinomas from never smokers. We also screened for oncogene fusion transcripts in 20 of the 89 tumors by RNA-Seq. In total, 62 tumors had mutations in at least one of the 10 oncogenes, including EGFR (49 cases, 55%), K-ras (5 cases, 6%), BRAF (4 cases, 5%), PIK3CA (3 cases, 3%), and ERBB2 (4 cases, 5%). In addition to ALK fusions identified by IHC/FISH in four cases, two previously known fusions involving EZR- ROS1 and KIF5B-RET were identified by RNA-Seq as well as a third novel fusion transcript that was formed between exons 1-9 of SND1 and exons 2 to 3′ end of BRAF. This in-frame fusion was observed in 3/89 tested tumors and 2/64 additional never smoker lung adenocarcinoma samples. Ectopic expression of SND1-BRAF in H1299 cells increased phosphorylation levels of MEK/ERK, cell proliferation, and spheroid formation compared to parental mock-transfected control. Jointly, our results suggest a potential role of the novel BRAF fusion in lung cancer development and therapy. [ABSTRACT FROM AUTHOR]