Maysin and Its Flavonoid Derivative from Centipedegrass Attenuates Amyloid Plaques by Inducting Humoral Immune Response with Th2 Skewed Cytokine Response in the Tg (APPswe, PS1dE9) Alzheimer\u27s Mouse Model

Alzheimer\u27s disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models. Here, we examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9) AD mouse model. We have investigated the EA-CG efficacy as novel anti-AD likely preventing amyloid plaques using immunofluorescence staining to visually analyze Aβ40/42 and fibril formation with Thioflavin-S or 6E10 which are the profile of immunoreactivity against epitope Aβ1-16 or neuritic plaque, the quantitation of humoral immune response against Aβ, and the inflammatory cytokine responses (Th1 and Th2) using ELISA and QRT-PCR. To minimize the toxicity of the extracted CG, we addressed the liver toxicity in response to the CG extract treatment in Tg mice using relevant markers, such as aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) measurements in serum. The EA-CG extract significantly reduced the Aβ burden, the concentration of soluble Aβ40/42 protein, and fibril formation in the hippocampus and cortex of the Tg mice treated with EA-CG (50 mg/kg BW/day) for 6 months compared with the Tg mice treated with a normal diet. Additionally, the profile of anti-inflammatory cytokines revealed that the levels of Th2 (interleukin-4 (IL-4) and interleukin-10 (IL-10)) cytokines are more significantly increased than Th1 (interferon-γ (IFN-γ), interleukin-2(IL-2)) in the sera. These results suggest that the EA-CG fraction induces IL-4/IL-10-dependent anti-inflammatory cytokines (Th2) rather than pro-inflammatory cytokines (Th1), which are driven by IL-2/IFN-γ. With regard to the immune response, EA-CG induced an immunoglobulin IgG and IgM response against the EA-CG treatment in the Tg mice. Furthermore, EA-CG significantly ameliorated the level of soluble Aβ42 and Aβ40. Similarly, we observed that the fibril formation was also decreased by EA-CG treatment in the hippocampus and cortex after quantitative analysis with Thioflavin-S staining in the Tg brain tissues. Taken together, our findings suggested that Maysin and its derivative flavonoid compounds in the EA-CG fraction might be beneficial therapeutic treatments or alternative preventative measures to adjuvant for boosting humoral and cellular include immune response and anti-inflammation which may lead to amyloid plaque accumulation in Alzheimer\u27s patients\u27 brains

Benefit From Directional Microphone Hearing Aids: Objective and Subjective Evaluations

ObjectivesThe aims of this study were to find and compare the effect of directional (DIR) processing of two different hearing aids via both subjective and objective methods, to determine the association between the results of the subjective and objective evaluations, and to find out individual predictive factors influencing the DIR benefit.MethodsTwenty-six hearing aid users fitted unilaterally with each two different experimental hearing aid performed modified Korean Hearing in Noise Test (K-HINT) in three DIR conditions; omnidirectional (OMNI) mode, OMNI plus noise reduction feature, fixed DIR mode. In order to determine benefits from DIR benefit within a hearing aid and compare performance of the DIR processing between hearing aids, a subjective questionnaire was administrated on speech quality (SQ) and discomfort in noise (DN) domain. Correlation analysis of factors influencing DIR benefit was accomplished.ResultsBenefits from switching OMNI mode to DIR mode within both hearing aids in K-HINT were about 2.8 (standard deviation, 3.5) and 2.1 dB SNR (signal to ratio; SD, 2.5), but significant difference in K-HINT results between OMNI and OMNI plus noise reduction algorithm was not shown. The subjective evaluation resulted in the better SQ and DN scores in DIR mode than those in OMNI mode. However, the difference of scores on both SQ and DN between the two hearing aids with DIR mode was not statistically significant. Any individual factors did not significantly affect subjective and objective DIR benefits.ConclusionDIR benefit was found not only in the objective measurement performed in the laboratory but also in the subjective questionnaires, but the subjective results was failed to have significant correlation with the DIR benefit obtained in the K-HINT. Factors influencing individual variation in perceptual DIR benefit were still hard to explain

Long-term outcome of vertebral artery origin stenosis in patients with acute ischemic stroke

BACKGROUND: Vertebral artery origin (VAO) stenosis is occasionally observed in patients who have acute ischemic stroke. We investigated the long-term outcomes and clinical significance of VAO stenosis in patients with acute ischemic stroke. METHODS: We performed a prospective observational study using a single stroke center registry to investigate the risk of recurrent stroke and vascular outcomes in patients with acute ischemic stroke and VAO stenosis. To relate the clinical significance of VAO stenosis to the vascular territory of the index stroke, patients were classified into an asymptomatic VAO stenosis group and a symptomatic VAO stenosis group. RESULTS: Of the 774 patients who had acute ischemic stroke, 149 (19.3%) of them had more than 50% stenosis of the VAO. During 309 patient-years of follow-up (mean, 2.3 years), there were 7 ischemic strokes, 6 hemorrhagic strokes, and 2 unknown strokes. The annual event rates were 0.97% for posterior circulation ischemic stroke, 4.86% for all stroke, and 6.80% for the composite cardiovascular outcome. The annual event rate for ischemic stroke in the posterior circulation was significantly higher in patients who had symptomatic VAO stenosis than in patients who had asymptomatic stenosis (1.88% vs. 0%, p = 0.046). In a multivariate analysis, the hazard ratio, per one point increase of the Essen Stroke Risk Score (ESRS) for the composite cardiovascular outcome, was 1.46 (95% CI, 1.02-2.08, p = 0.036). CONCLUSIONS: Long-term outcomes of more than 50% stenosis of the VAO in patients with acute ischemic stroke were generally favorable. Additionally, ESRS was a predictor for the composite cardiovascular outcome. Asymptomatic VAO stenosis may not be a specific risk factor for recurrent ischemic stroke in the posterior circulation. However, VAO stenosis may require more clinical attention as a potential source of recurrent stroke when VAO stenosis is observed in patients who have concurrent ischemic stroke in the posterior circulation

Comparative Evaluation of Nanofibrous Scaffolding for Bone Regeneration in Critical-Size Calvarial Defects

In a previous study we found that nanofibrous poly(l-lactic acid) (PLLA) scaffolds mimicking collagen fibers in size were superior to solid-walled scaffolds in promoting osteoblast differentiation and bone formation in vitro. In this study we used an in vivo model to confirm the biological properties of nanofibrous PLLA scaffolds and to evaluate how effectively they support bone regeneration against solid-walled scaffolds. The scaffolds were implanted in critical-size defects made on rat calvarial bones. Compared with solid-walled scaffolds, nanofibrous scaffolds supported substantially more new bone tissue formation, which was confirmed by micro-computed tomography measurement and von Kossa staining. Goldner's trichrome staining showed abundant collagen deposition in nanofibrous scaffolds but not in the control solid-walled scaffolds. The cells in these scaffolds were immuno-stained strongly for Runx2 and bone sialoprotein (BSP). In contrast, solid-walled scaffolds implanted in the defects were stained weakly with trichrome, Runx2, and BSP. These in vivo results demonstrate that nanofibrous architecture enhances osteoblast differentiation and bone formation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78127/1/ten.tea.2008.0433.pd

Effects of Electrode Position on Spatiotemporal Auditory Nerve Fiber Responses: A 3D Computational Model Study

A cochlear implant (CI) is an auditory prosthesis that enables hearing by providing electrical stimuli through an electrode array. It has been previously established that the electrode position can influence CI performance. Thus, electrode position should be considered in order to achieve better CI results. This paper describes how the electrode position influences the auditory nerve fiber (ANF) response to either a single pulse or low- (250 pulses/s) and high-rate (5,000 pulses/s) pulse-trains using a computational model. The field potential in the cochlea was calculated using a three-dimensional finite-element model, and the ANF response was simulated using a biophysical ANF model. The effects were evaluated in terms of the dynamic range, stochasticity, and spike excitation pattern. The relative spread, threshold, jitter, and initiated node were analyzed for single-pulse response; and the dynamic range, threshold, initiated node, and interspike interval were analyzed for pulse-train stimuli responses. Electrode position was found to significantly affect the spatiotemporal pattern of the ANF response, and this effect was significantly dependent on the stimulus rate. We believe that these modeling results can provide guidance regarding perimodiolar and lateral insertion of CIs in clinical settings and help understand CI performance

Effects of Early Surgical Exploration in Suspected Barotraumatic Perilymph Fistulas

ObjectivesTreatment of traumatic perilymph fistula (PLF) remains controversial between surgical repair and conservative therapy. The aim of this study is to analyze the outcomes of early surgical exploration in suspected barotraumatic PLF.MethodsNine patients (10 cases) who developed sudden sensorineural hearing loss and dizziness following barotrauma and underwent surgical exploration with the clinical impression of PLF were enrolled. Types of antecedent trauma, operative findings, control of dizziness after surgery, postoperative hearing outcomes, and relations to the time interval between traumatic event and surgery were assessed retrospectively.ResultsAll patients had sudden or progressive hearing loss and dizziness following trauma. Types of barotrauma were classified by the origin of the trauma: 4 external (car accident, slap injury) and 6 internal traumas (lifting, nasal blowing, straining). Surgical exploration was performed whenever PLF was suspected with the time interval of 2 to 47 days after the trauma. The possible evidence of PLF was found during surgery in 9 cases: a fibrous web around the oval window (n=3), fluid collection in the round window (RW; n=6) and bulging of the RW pseudomembrane (n=1). In every patient, vestibular symptoms disappeared immediately after surgery. The hearing was improved with a mean gain of 27.0±14.9 dB. When the surgical exploration was performed as early as less than 10 days after the trauma, serviceable hearing (≤40 dB) was obtained in 4 out of 7 cases (57.1%).ConclusionSudden or progressive sensorineural hearing loss accompanied by dizziness following barotrauma should prompt consideration of PLF. Early surgical exploration is recommended to improve hearing and vestibular symptoms

Redak slučaj metastatskog spermatocitnog tumora kod psa bez sarkomatoznih i anaplastičnih promena

Spermatocytic tumor is a rare testicular tumor, which is originated from gonocytes. It is characterized by the histological feature of tripartite which is composed of large, medium, and lymphocyte-like small cells. It is well-known that spematocytic tumor is benign, thus a good prognosis is expected after simple resection. Metastatic spermatocytic tumor is extremely rare and usually accompanied by histological variants including sarcomatous changes and anaplastic variants. In this case, however, we report a canine metastatic spermatocytic tumor without prominent sarcomatous changes and anaplastic variants. The mass was composed of three kinds of cells including large, medium, and small cells with high pleomorphism. The neoplastic cells had an indistinct cytoplasmic border and mitotic figures were frequently observed. The primary spermatocytic tumor metastasized to the abdominal organs one month after the resection, and the dog died 13 months after the surgery. Thus, careful follow-up is recommended after surgical resection of canine spermatocytic tumor even though metastasis in spermatocytic tumors is rare.Spermatocitni tumor je redak tumor testisa, koji potiče od gonocita. Karakteriše ga histološki nalaz tri morfološka tipa ćelija, a sastoji se od velikih, srednjih i limfocitima sličnih malih ć elija. Dobro je poznato da je spermatocitni tumor benignog ponašanja pa se očekuje dobra prognoza nakon jednostavne resekcije. Metastatski spermatocitni tumor izuzetno je redak i obično je prać en histološkim varijacijama, uključujuć i sarkomatozne i anaplastične promene. U ovom slučaju, međutim, opisan je metastatski spermatocitni tumor bez izraženih sarkomatoznih promena i anaplastičnih varijanti. Masa se sastojala od tri vrste ć elija, uključujuć i velike, srednje i male ć elije sa visokim pleomorfi zmom. Neoplastične ć elije su imale nejasnu citoplazmatsku granicu i često su primeć ene mitotičke fi gure. Primarni spermatocitni tumor metastazirao je na trbušne organe mesec dana nakon resekcije, a pas je uginuo 13 meseci nakon operacije. Stoga se preporučuje pažljivo prać enje nakon hirurške resekcije spermatocitnog tumora mada su metastaze u spermatocitnim tumorima retke