Expression of amyloid-β in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception

Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer''s disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-β (Aβ), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the Aβ-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor Aβ-induced neuronal dysfunction quantitatively over time.     

A comparative study on the accuracy of the devices for measuring the implant stability

STATEMENT OF PROBLEM

How the ISQ values measured by Osstell™ and Osstell™ Mentor are related, and whether the ISQ values acquired from the two machines changes in accordance with changes in implant stability are not yet fully understood.

PURPOSE

The aim of this study was to find out correlation between the ISQ values acquired from Osstell™ and Osstell™ Mentor, and to evaluate the clinical effectiveness and accuracy of two devices.

MATERIAL AND METHODS

Sixty two implants were inserted into 47 patients, and their ISQ values were measured using Osstell™ and Osstell™ Mentor. In the first stage surgery, the ISQ values of forty four implants inserted into thirty five patients were measured. In the second stage surgery, the values of fifty implants inserted into thirty seven patients were measured. The values were analyzed to determine the difference between the mean ISQ values of Osstell™ and Osstell™ Mentor. In addition, the correlation between implants used in the first and second stage of surgery with regard to their types and areas of insertion were analyzed. The difference between the ISQ values of 32 implants in each patient during the first and second stage was analyzed. The statistical assessment was carried out using SPSS V. 12.0 for Win. (SPSS Inc., Chicago, USA). The Pearson correlation coefficient was used to examine the correlation between Osstell™ and Osstell™ Mentor in the first and second stages of surgery, whereas the difference between their ISQ values was evaluated using a paired t-test.

RESULTS

In the first stage, the mean ISQ value for Osstell™ and Osstell™ Mentor was 70.84 and 75.09, respectively, showing a significant difference (P < .01). In the second stage, the mean ISQ value of Osstell™ and Osstell™ Mentor was 71.76 and 75.94, respectively, also showing a significant difference (P < .01). The difference between the ISQ values in patients in the first and the second stages was significant with both instruments.

CONCLUSION

The significant difference in the values obtained using the Osstell™ and Osstell™ Mentor between the first and second stages of implant surgery indicates that these values can be a convenient and precise way for evaluating the implant stability in clinical practice.     

Comparison of culture screening protocols for methicillin-resistant Staphylococcus aureus (MRSA) using a chromogenic agar (MRSA-Select)

To compare the culture screening protocols for methicillin-resistant Staphylococcus aureus (MRSA), a total of 300 duplicate nasal swabs (233 initial cultures and 67 weekly follow-up cultures) were collected consecutively from 233 patients in the Intensive Care Unit (ICU). One swab was plated directly on MRSA-Select agar (D-MRSA-Select) and observed at 24 hr. The duplicate swab was incubated in tryptic soy broth (TSB) with 6.5% NaCl for 24 hr, and then subcultured on MRSA-Select (B-MRSA-Select), BAP (B-BAP), and mannitol salt agar with 4 mg/L oxacillin (B-MSA(OXA)), and observed at 24 hr. MRSA was detected in 13.7% (32/233) of the initial and 22.4% (15/67) of the follow-up specimens. A patient was classified as MRSA-positive if any of the media grew colonies that were tested and confirmed to be MRSA. In the initial screening samples, the sensitivities of D-MRSA-Select, B-MRSA-Select, B-BAP, and B-MSA(OXA) were 78.1%, 84.4%, 78.1%, and 65.6%, respectively, and the specificities were 100%, 98.0%, 83.1%, and 93.5%, respectively. The sensitivities of all but the B-MRSA-Select protocol were significantly lower (p <0.05). In follow-up screening, the sensitivities of D-MRSA-Select, B-MRSA-Select, B-BAP, and B-MSA(OXA) were 66.7%, 86.7%, 66.7%, and 53.3%, respectively, and the specificities were 100%, 98.1%, 90.4%, and 90.4%, respectively. D-MRSA-Select protocol was considered useful in screening for MRSA because it was fast, highly specific, and showed sensitivity comparable to B-BAP. Salt-containing enrichment broth in conjunction with MRSA-Select (B-MRSA-Select) provides a promising way to increase sensitivity in initial and follow-up screening for MRSA.     

Highly conserved surface proteins of oral spirochetes as adhesins and potent inducers of proinflammatory and osteoclastogenic factors

Oral spirochetes include enormously heterogeneous Treponema species, and some have been implicated in the etiology of periodontitis. In this study, we characterized highly conserved surface proteins in four representative oral spirochetes (Treponema denticola, T. lecithinolyticum, T. maltophilum, and T. socranskii subsp. socranskii) that are homologs of T. pallidum Tp92, with opsonophagocytic potential and protective capacity against syphilis. Tp92 homologs of oral spirochetes had predicted signal peptides (20 to 31 amino acids) and molecular masses of 88 to 92 kDa for mature proteins. They showed amino acid sequence identities of 37.9 to 49.3% and similarities of 54.5 to 66.9% to Tp92. The sequence identities and similarities of Tp92 homologs of oral treponemes to one another were 41.6 to 71.6% and 59.9 to 85.6%, respectively. The tp92 gene homologs were successfully expressed in Escherichia coli, and the recombinant proteins were capable of binding to KB cells, an epithelial cell line, and inhibited the binding of the whole bacteria to the cells. Antiserum (the immunoglobulin G fraction) raised against a recombinant form of the T. denticola Tp92 homolog cross-reacted with homologs from three other species of treponemes. The Tp92 homologs stimulated various factors involved in inflammation and osteoclastogenesis, like interleukin-1beta (IL-1beta), tumor necrosis factor alpha, IL-6, prostaglandin E(2), and matrix metalloproteinase 9, in host cells like monocytes and fibroblasts. Our results demonstrate that Tp92 homologs of oral spirochetes are highly conserved and may play an important role in cell attachment, inflammation, and tissue destruction. The coexistence of various Treponema species in a single periodontal pocket and, therefore, the accumulation of multiple Tp92 homologs may amplify the pathological effect in periodontitis.     

Neuroprotection of adenoviral-vector-mediated GDNF expression against kainic-acid-induced excitotoxicity in the rat hippocampus

Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for several types of neurons. In the present study, we examined the protective roles of adenoviral-vector-delivered GDNF (Ad-GDNF) in the hippocampus damaged by kainic-acid (KA)-induced excitotoxicity using GAD-67 immunoreactivity, immunoblot analysis, behavioral test, 5-bromo-2-deoxyuridine (BrdU) and TUNEL assay. Ad-GDNF was pre-inoculated into the KA-treated rat hippocampus 7 days before KA injection. Ad-GDNF resulted in the suppression of KA-induced tonic-clonic convulsions. In situ apoptosis assay demonstrated a significant reduction in apoptotic cells in the CA3 and dentate hilus regions of the Ad-GDNF-pre-inoculated rats (Ad-GDNF-KA), compared to the KA rats. Striking reductions in the density of GAD-67 neurons were also observed in the CA3 and dentate hilus regions of the KA rats. On the other hand, the number of GAD-67-positive cells was recovered to the control levels in the Ad-GDNF-KA rats. Immunoblot analysis further confirmed that GAD-67 and Bcl-2 expression increased in the Ad-GDNF-KA rats compared to KA rats. Taken together, these results suggest that Ad-GDNF may serve to control KA-induced hippocampal cell loss and behavioral seizure.     

Prevalence of anticholinergic burden and risk factors amongst the older population: analysis of insurance claims data of Korean patients

Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the geriatric population nationally. Objective To evaluate the prevalence of high anticholinergic burden using the newly developed Korean Anticholinergic Burden Scale in comparison with previous tools and to identify associated factors. Setting National insurance data from a cross section (20%) of older Koreans (2016). Methods Anticholinergic burden was measured using the Korean scale in comparison to the Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, and Anticholinergic Risk Scale. High anticholinergic burden was defined as a summed score of ≥?3 for concurrent medications or a dose-standardized average daily score of ≥?3, using each anticholinergic scale. Main outcomes measured Prevalence and predictors of high anticholinergic burden. Results Data of 1,292,323 patients were analyzed. According to the Korean scale, the prevalence of high anticholinergic burden was 25.5%. This result was similar to that from the Anticholinergic Drug Scale (24.9%) and Anticholinergic Cognitive Burden (22.2%). Factors associated with an increased likelihood of anticholinergic burden include: age, gender (female), high Charlson comorbidity index score, polypharmacy, medical aid beneficiary, co-morbidities (such as schizophrenia, depression, urinary incontinence, and Parkinson’s disease), frequent healthcare visits, various healthcare facilities utilized, and predominantly visiting hospital-level facilities. According to the Korean Anticholinergic Burden Scale, the major drugs contributing to the anticholinergic burden were ranitidine, chlorpheniramine, tramadol, and dimenhydrinate. Conclusion This study showed that 1 in 4 older Koreans are exposed to high anticholinergic burden. The predictors identified in this research might assist pharmacists in early interventions for their patients.

     

N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent

Non-collagenous (NC-1) fragments at the C-terminus of basement membrane collagen IV, XV and XIII have been implicated as negative regulators of angiogenesis. Endostatin is an endogenous carboxyl-terminal fragment of collagen XVIII/NC-1, suppressing endothelial cell proliferation, migration in vitro and tumor growth in mouse models. Endostatin can bind zinc through N- and C-terminal residues. Here we demonstrate that N-/C-terminal deleted derivative of human endostatin, H5, effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs). Also, tube formation in vitro was comparably inhibited either by H5 or endostatin. The anti-angiogenic and anti-tumorigenic activities of H5 and endostatin were confirmed by an in vivo assay using chick chorioallantoic membrane (CAM) and mouse models, respectively. Treatment of 30 ng of H5 inhibited the capillary formation in CAM by 50%. In addition, H5 exhibited more potent anti-tumor activity than wild-type endostatin in in vivo mouse metastasis assay. These results indicate that the N-/C-terminal deletion mutant would be a strong candidate of anti-cancer agent against spontaneous tumor development and growth.     

Physicochemical properties of heme iron products in the Korean market

Since absorption efficacy of heme iron (HI) is critically dependent on its solubility in aqueous solution, we investigated the physicochemical properties of two HI products available in the Korean market. The two HI products did not differ in ingredients and color. However, HI polypeptide (HIP), produced in Korea, was fairly soluble over a wide pH range in water-based solutions, whereas HI imported from Japan was insoluble except in strong acid and base solutions. Analysis using an ultraviolet-visible spectrophotometer showed that the chromophore of HIP was shifted to the red compared with that of HI. Fourier transform-infrared analysis revealed that HIP contained mainly amide (NH) groups, while HI largely contained amine (NH(2)) groups. With regard to constituents, between HIP and HI, their major components were different from each other according to their ratio of fronts obtained by thin-layer chromatography. These results suggest that determination of solubility should be included in the quality control process of HI products.     

Inhibitory effect on TNF-α-induced IL-8 production in the HT29 cell of constituents from the leaf and stem ofWeigela subsessilis

Twelve compounds were isolated from the MeOH extract of the leaf and stem of the Korean endemic plant Weigela subsessilis L. H. Bailey. Their chemical structures were elucidated on the basis of physicochemical and spectroscopic data and by comparison with those of published literatures. These compounds were identified as three sterols, beta-sitosterol acetate (2), betasitosterol (3), daucosterol (11), eight triterpenoids, squalene (1), ursolic acid (4), ilekudinol A (5), corosolic acid (6), ilekudinol B (7), esculentic acid (8), pomolic acid (9), asiatic acid (10), and one iridoid glycoside, alboside I (12). This is the first report pertaining to the isolation of these compounds from Weigela subsessilis L. H. Bailey. In addition, three compounds 7, 9, and 12 were found to display a strong inhibitory effect on the production of IL-8 in the HT29 cells stimulated by TNF-alpha.