Blast-induced tinnitus and hearing loss in rats: behavioral and imaging assays

Abstract The current study used a rat model to investigate the underlying mechanisms of blast-induced tinnitus, hearing loss, and associated traumatic brain injury (TBI). Seven rats were used to evaluate behavioral evidence of tinnitus and hearing loss, and TBI using magnetic resonance imaging following a single 10-msec blast at 14?psi or 194 dB sound pressure level (SPL). The results demonstrated that the blast exposure induced early onset of tinnitus and central hearing impairment at a broad frequency range. The induced tinnitus and central hearing impairment tended to shift towards high frequencies over time. Hearing threshold measured with auditory brainstem responses also showed an immediate elevation followed by recovery on day 14, coinciding with behaviorally-measured results. Diffusion tensor magnetic resonance imaging results demonstrated significant damage and compensatory plastic changes to certain auditory brain regions, with the majority of changes occurring in the inferior colliculus and medial geniculate body. No significant microstructural changes found in the corpus callosum indicates that the currently adopted blast exposure mainly exerts effects through the auditory pathways rather than through direct impact onto the brain parenchyma. The results showed that this animal model is appropriate for investigation of the mechanisms underlying blast-induced tinnitus, hearing loss, and related TBI. Continued investigation along these lines will help identify pathology with injury/recovery patterns, aiding development of effective treatment strategies.     

Effect of different examination conditions on image quality and quantitative value of amyloid positron emission tomography using 18F-flutemetamol

Annals of Nuclear Medicine - The recommended start time for 18F-flutemetamol amyloid positron emission tomography (PET) examination is 60–120 min after 18F-flutemetamol injection,...     

Effect of Reinsertion of Activated Nucleus Pulposus on Disc Degeneration: An Experimental Study on Various Types of Collagen in Degenerative Discs

We examined the emergence and sequential changes in type I, II, and VI collagen production in an experimental rabbit model of disc degeneration. Type I collagen was minimally present initially and did not change over 24 weeks. Type I collagen seemed to have no effect on the degenerative process in this model. Staining for type II collagen was positive circumferentially in chondrocytelike cells and was mild in the early phase of disc degeneration, when the chondrocytelike cells began to appear in the inner layers of the annulus fibrosus. The stain became stronger during the middle phase when the chondrocytelike cells arranged themselves in cluster. Compared with type II collagen, the staining for type VI collagen was relatively strong early in the degenerative process. These findings led us to speculate that these chondrocytelike cells play an active role in the degenerative process. The reinsertion of nucleus pulposus cells cocultured with annulus fibrosus delayed disc degeneration and the emergence of chondrocytelike cells. Considering that the emergence of chondrocytelike cells which produce type II and type VI collagen is delayed in discs with the injection of cocultured nucleus pulposus cells by annulus fibrosus cells, we conclude that chondrocytelike cells that produce type VI collagen also seems to accelerate degeneration. Type VI collagen is produced at an earlier phase than type II collagen and may be both active agent and a marker for disc degeneration.     

Phylogenetic analysis of porcine epidemic diarrhea virus field strains prevailing recently in China

Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), which is characterized by severe diarrhea, dehydration and high mortality in the affected pigs. Recently, clinical outbreaks of diarrhea in suckling piglets emerged in pig-producing areas of China. In this study, molecular detection of PEDV was conducted using RT-PCR (targeting the M gene) on samples collected from piglets with watery diarrhea from 15 pig farms, and phylogenetic analysis of PEDV field strains was carried out based on their M and S genes. In addition, the complete genome sequence of a PEDV field strain was determined. PEDV was detected in 92.7 % of the samples (267/288). The 15 M genes that were amplified shared 99.6-100 % nucleotide identity and 99.1-100 % amino acid similarity with each other. The 15 S genes exhibited 98.6-99.9 % homology, both at the nucleotide level and at the deduced amino acid level. Phylogenetic analysis showed that all of the amplified M genes grouped in cluster 3, together with some Chinese, Korean and Thai strains, while all of the amplified S genes were in cluster 3 and were closely related to Korean strains. Compared with previous PEDV strains, all of the S genes have common characteristics, namely, a 4-aa (GENQ) insertion between positions 55 and 56, a 1-aa (N) insertion between positions 135 and 136, and a 2-aa (DG) deletion between positions 155 and 156, similar or identical to Korean KNU-serial strains reported in recent years. The genome of the sequenced PEDV field strain is 28,038 nucleotides in length, excluding the poly (A) tail. Our findings suggest that a novel PEDV with a characteristic variant S gene is responsible for recent outbreaks of clinical diarrhea in piglets in China.     

Perivascular abnormalities in pediatric encephalopathy with fulminant brain edema

BackgroundAcute encephalopathy with acute brain swelling (ABS) is a recently proposed disease of unknown etiology, characterized by rapid progression to whole-brain swelling. To our knowledge, we reported the first case of a patient with acute encephalopathy with ABS wherein brain magnetic resonance imaging (MRI) abnormalities were noted prior to the diffuse brain swelling onset.Case presentationAn 11-year-old boy was admitted to our unit owing to prolonged disturbance of consciousness following febrile status epilepticus. At the initial visit, the vital signs were within the normal range, except for the body temperature and consciousness level (Glasgow Coma Scale 6; E1V1M4). The initial laboratory results showed elevated inflammatory marker levels and mild hyponatremia. Cerebrospinal fluid analysis revealed albuminocytologic dissociation, whereas the myelin basic protein level was not elevated. Electroencephalography showed diffuse, high-amplitude slow waves.No abnormalities were detected on the initial brain computed tomography (CT) scan. However, at 11 h after the seizure onset, diffuse hyperintense lesions were observed throughout the cerebrum on T2-weighted brain MRI. The patient was diagnosed with acute encephalopathy and received methylprednisolone-pulse therapy (1 g) with high-dose gamma globulin (1 g/kg) administration. At 14 h after the seizure onset, the patient was declared brain-dead; the brain CT findings revealed whole-brain swelling and herniation.ConclusionOur findings were suggestive of a perivascular pathophysiology and may be used for subtyping acute encephalopathy. In cases where such findings are observed, subsequent development of severe diffuse brain swelling should be considered.     

Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease–like symptoms

Disruption of copper homeostasis has been implicated in Alzheimer's disease (AD) during the last 2 decades; however, whether copper is a friend or a foe is controversial. Within a genetically tractable Drosophila AD model, we manipulated the expression of human high-affinity copper importer orthologous in Drosophila to explore the in vivo roles of copper ions in the development of AD. We found that inhibition of Ctr1C expression by RNAi in Aβ-expressing flies significantly reduced copper accumulation in the brains of the flies as well as ameliorating neurodegeneration, enhancing climbing ability, and prolonging lifespan. Interestingly, Ctr1C inhibition led to a significant increase in higher-molecular-weight Aβ42 forms in brain lysates, whereas it was accompanied by a trend of decreased expression of amyloid-β degradation proteases (including NEP1-3 and IDE) with age and reduced Cu-Aβ interaction-induced oxidative stress in Ctr1C RNAi flies. Similar results were obtained from inhibiting another copper importer Ctr1B and overexpressing a copper exporter DmATP7 in the nervous system of AD flies. These results imply that copper may play a causative role in developing AD, as either Aβ oligomers or aggregates were less toxic in a reduced copper environment or one with less copper binding. Early manipulation of brain copper uptake can have a great effect on Aβ pathology.     

Nonparametric Tests of Associations with Disease Based on U‐Statistics

In case‐control studies, association analysis was designed to test whether genetic variants were associated with human diseases. To evaluate the association, analysing one genetic marker at a time suffered from weak power, because of the correction for multiple testing and possibly small genetic effects. An alternative strategy was to test simultaneous effects of multiple markers, which was believed to be more powerful. However, when the number of markers under investigation was large, they would be subjected to weak power as well, because of the greater degrees of freedom. To conquer these limitations in case‐control studies, we proposed a novel method that could test joint association of several loci (i.e. haplotype), with only a single degree of freedom. In this research, we developed a nonparametric approach, which was based on U‐statistics. We also introduced a new kernel for U‐statistic, which could combine the haplotype structure information, and was expected to enhance the power. Simulations indicated that our proposed approach offered merits in identifying the associations between diseases and haplotypes. Application of our method to a study of candidate genes for internalising disorder illustrated its virtue in utility and interpretation, and provided an excellent result in detecting the associations.     

A Novel PCR-Based Approach to Discover miRNA Target Genes

MiRNAs are potent regulators of gene expression, and most miRNAs have from several to several thousands of gene targets. Validating the numerous gene targets of a given miRNA remains challenging despite the existence of various tools and databases that predict candidate gene-miRNA pairs. In the present study, we present a high-throughput but flexible method that applies a PCR-based application to simulate the binding of miRNAs to their gene targets. Using hsa-miR-377 as an illustrative example, our method was able to identify 13 potential targets of hsa-miR-377. Moreover, our results include 2 genes (SOD2 and PPM1A) that have already been verified as targets of hsa-miR-377. Our method may provide an alternative way of identifying the gene targets of miRNAs for future research.     

Andrographolide Suppresses IL-6/Stat3 Signaling in Peripheral Blood Mononuclear Cells from Patients with Chronic Rhinosinusitis with Nasal Polyps

The mechanisms underlying the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely unknown. CRSwNP has garnered considerable public health concern owing to its high incidence and unsatisfactory treatment outcomes. Herbal remedies are promising candidates for the treatment of CRSwNP. We examined the utility of andrographolide, a diterpenoid lactone extracted from the Chinese herb Andrographis paniculata, an anti-inflammatory agent for CRSwNP treatment by evaluating interleukin (IL)-6 and IL-17 production and monitoring T helper 17 (Th17) differentiation of peripheral blood mononuclear cells (PBMCs) isolated from 20 Chinese CRSwNP patients and 11 control subjects. All CRSwNP patients exhibited clinical features of CRSwNP. Andrographolide significantly inhibited IL-6 and IL-17 production, suppressed p-Stat3 expression, and inhibited Th17 differentiation of PBMCs in vitro. These findings suggested that andrographolide has useful anti-inflammatory properties and could be used for the treatment of CRSwNP.