Disulfide-Mediated Elongation of Amyloid Fibrils of α-Synuclein For Use in Producing Self-Healing Hydrogel and Dye-Absorbing Aerogel.

Due to their mechanical robustness, biocompatibility, and nanoscale size, amyloid fibrils (AFs) have been considered as a potential nanomaterial for biological applications. Unfortunately, however, AFs are usually not fully extended because of their pre-mature breakage, which hampers their use to generate biocompatible suprastructures, although the amounts of AFs could be amplified via their self-propagation property. Here, we have demonstrated the full extension of AFs of α-synuclein (αS) by introducing a cysteine residue to its C-terminus which prevents the shear-induced fragmentation of AFs via site-directed disulfide bond formation on the exposed surface of AFs. These heat- and cold-resistant elongated AFs were entangled into self-healable hydrogels through a mild disulfide-exchange process in the presence of tris(2-carboxyethyl) phosphine, which subsequently developed into dye-absorbing aerogels upon freeze-drying without collapsing the three-dimensional internal fibrillar network. The resulting αS aerogel with high porosity and increased surface area was shown to be capable of absorbing both hydrophilic and hydrophobic substances. In addition, the aerogel was further engineered with 8-arm polyethylene glycol containing a sulfhydryl group to increase its drug loading capacity and protease susceptibility for drug unloading. The elongated AFs, therefore, have been suggested to play a pivotal component for the development of bio-nano-matrix for diverse biological applications including drug delivery, tissue engineering, and environmental remediation. STATEMENT OF SIGNIFICANCE: Due to accurate protein self-assembly process, α-synuclein forms an amyloid fibril which are the major component of Lewy bodies. In general, α-synuclein amyloid fibrils break under thermal fluctuations as these nanofibrils elongate to reach certain length. In this study, we have demonstrated the full extension of α-synuclein amyloid fibrils by introducing a cysteine residue to its C-terminus by forming site-directed disulfide bonds on the exposed surface of amyloid fibrils for the first time. The resulting elongated amyloid fibrils were mechanically robust and stable. By using elongated amyloid fibrils, we have made self-healable amyloid fibril hydrogel and dye-absorbing aerogel.

Fabrication of a Dual Stimuli-Responsive Assorted Film Comprising Magnetic- and Gold-Nanoparticles with a Self-Assembly Protein of α-Synuclein.

Development of sensing elements for controllable soft materials is crucial to improve their responsiveness toward remotely provided external stimuli. Magnetic nanoparticles (MNPs) and gold nanoparticles (AuNPs) have been coassembled into a flexible free-floating 2D film to produce a shape deformable mobile structure in the presence of magnetic field and light irradiation by employing a self-assembly protein of α-synuclein (αS). αS was demonstrated to be essential for the preparation of a multisensory system because the intrinsically disordered protein led to a complete dispersion of MNPs to an average size of 10 nm in aqueous solution, pH-dependent closely packed single layer adsorption of αS-MNPs, and α-helix-mediated free-floating MNP monolayer film formation upon dissolving the underlying polycarbonate substrate with chloroform. As AuNPs were incorporated into the assorted hybrid film in the presence of MNPs, however, the ß-sheet component became prominent. By placing the assorted film between a spin-coated thin layer of thermoresponsive P(AAc-co-NIPAAm) hydrogel comprising acrylic acid and N-isopropylacrylamide and a passive layer of silicone elastomer, the resulting triply structure exhibited not only magnet-induced locomotion but also shape deformation due to asymmetric contraction of the sandwiching two layers caused by the heat generated by AuNPs upon near IR irradiation. In fact, two adjoining planar layers of another triply structure were shown to form a three-dimensional lotus flower with the light. This multisensory system is suggested to be further functionalized by modifying the αS molecules and incorporating additional nanoparticles to react to diverse stimuli, which would make the system be utilized in the areas of not only soft robotics but also foldable electronics, high-performance sensors/actuators, and medical/wearable applications.

Variability in body weight precedes diagnosis in dementia: A nationwide cohort study.

BACKGROUND: While there have been disagreements concerning whether obesity and increase in body weight elevate the risk of dementia, variability in body weight has been recently recognized as a new biometric associated with a high risk for a number of diseases. This nationwide, population-based cohort study examined the association between body weight variability and dementia. METHODS: A total of 2,812,245 adults (mean age, 51.7 years; standard deviation, 8.6) without a history of dementia who underwent at least three health examinations between 2005 and 2012 in a nationwide cohort were followed-up until the date of dementia diagnosis (based on prescribed drugs and disease code) or until 2016 (median follow-up duration, 5.38 years; interquartile range, 5.16-5.61). Cox regression models were used to evaluate the risk of Alzheimer's disease and vascular dementia according to body weight variability. RESULTS: The hazard ratios (95% confidence intervals) of the highest quartiles of variability were 1.42 (1.35-1.49) for Alzheimer's disease and 1.47 (1.32-1.63) for vascular dementia compared to the lowest quartile group as a reference. This association was consistent in various subgroup analyses and sensitivity analyses. CONCLUSIONS: Body weight variability could predict Alzheimer's disease and vascular dementia, which may provide new insights into the prevention and management of dementia.

Usefulness of diffusion tensor imaging findings as biomarkers for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. However, no reliable biomarkers have been identified to represent the clinical status. This study aimed to investigate whether diffusion tensor imaging (DTI) findings are useful imaging biomarkers to indicate the clinical status of ALS patients. Ninety-six probable or definite ALS cases and 47 age- and sex-matched, normal controls were enrolled. Demographic and clinical data were collected at the time of DTI. DTI data were acquired using a 3-Tesla magnetic resonance imaging scanner and analysed by voxel-wise statistical analyses for fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy. Compared with the healthy control group, the ALS group had significant differences in DTI scalars in the diffuse tracts of the brain, which was predominant in the corticospinal tract at the brainstem and cerebellar peduncle area. Furthermore, the DTI values correlated with the ALS functional rating scale-revised (ALSFRS-R) scores and the delta ALSFRS-R score representing the rate of disease progression. The subgroup analysis revealed a more severe and widespread brain degeneration was observed in rapidly progressive ALS. Therefore, our results suggest that DTI findings are useful as imaging biomarkers for evaluating the clinical severity and rate of disease progression in ALS.

A Routine Activity Approach to Understand Cybergrooming Victimization Among Adolescents from Six Countries.

Little attention has been given academically to empirically tested theoretical frameworks that aim at measuring the risk of adolescents falling victim to cybergrooming. To this end, we have applied the routine activity theory (RAT) to investigate whether exposure to motivated offenders (PC/laptop ownership and Internet access in one's own bedroom), capable guardianship (parental mediation strategies of Internet use), and target suitability (adolescents' online disclosure of private information) might predict cybergrooming victimization among adolescents. Using data from a cross-sectional survey of 5,938 adolescents from Germany, India, South Korea, Spain, Thailand, and the United States, ranging in age from 12 to 18 (M = 14.77, SD = 1.60), we found that PC/laptop ownership and Internet access in one's own bedroom, parental mediation, and online disclosure are all directly associated with cybergrooming victimization. Although instructive parental mediation is negatively related to online disclosure and cybergrooming victimization, restrictive mediation is positively related to both. In addition, online disclosure partially mediated the relationship between parental mediation and cybergrooming victimization. The analyses confirm the effectiveness of applying RAT to cybergrooming. Moreover, this study highlights the need for prevention programs, including lessons on age-appropriate information and communication technology usage and access, to educate parents on using instructive strategies of Internet mediation, and inform adolescents about how to avoid disclosing too much private information online. RAT could function as a theoretical framework for these programs.

The Utility of Facial Nerve Ultrasonography in Bell's Palsy.

OBJECTIVE: This study aimed to investigate the utility of facial nerve ultrasonography in the functional and structural assessment of early-stage Bell's palsy and the prognostic value of facial nerve ultrasonography in Bell's palsy. STUDY DESIGN: Prospective longitudinal study. SETTING: Single center, a university-affiliated neurology clinic. SUBJECTS AND METHODS: Patients with unilateral Bell's palsy who had visited our clinic within 3 days of symptom onset were enrolled in this study. Demographic information and House-Brackmann grade were collected. Electrophysiologic studies and facial nerve ultrasonography were then performed. The facial nerves on each side were scanned longitudinally with a 5- to 12-MHz probe. The diameter of the facial nerves with and without the sheath was measured at the proximal and distal portions. Follow-up examinations, including House-Brackmann grade analysis, electrophysiologic studies, and facial nerve ultrasonography, were performed after 2 months. RESULTS: Fifty-four patients with unilateral Bell's palsy were enrolled, and 22 underwent the follow-up examinations. The diameters of the facial nerves were larger on the affected side than on the unaffected side at the proximal and distal portions (P < .01). On the affected side, the enlarged facial nerve at the proximal portion had decreased in size after 2 months (P < .05). The initial ultrasonography findings were positively correlated with the initial severity of Bell's palsy, but they did not predict prognosis. CONCLUSION: Ultrasonography could be a useful tool for evaluating the facial nerve in Bell's palsy. Nevertheless, further studies are needed to demonstrate its prognostic value.

Puffing of Rehmannia glutinosa enhances anti-oxidant capacity and down-regulates IL-6 production in RAW 264.7 cells.

The roots of Rehmannia glutinosa (RG) have been widely used for medicinal purposes in Asia. The traditional processing of RG involves repetitive steaming and drying, and 9-time-steamed RG (NSRG) is the most commonly consumed form. For a development of a convenient processing method, RG was puffed at various pressures resulting in significantly increased solid extraction yield by up to 14%. The amount of the Maillard reaction product 5-hydroxymethylfurfural and the antioxidant capacities determined by the ABTS and DPPH radical scavenging assays were enhanced at increasing puffing pressure. Treatment of lipopolysaccharide-stimulated RAW 264.7 macrophages with RG extracts revealed that puffing of RG enhanced its suppression of the pro-inflammatory cytokine IL-6 by up to 37%. The 5-hydroxymethylfurfural contents, ABTS/DPPH radical scavenging capacities, and IL-6 regulatory effects of puffed RG samples were greater than those of the NSRG control, indicating that puffing is a desirable processing technique for development of nutraceuticals using RG.

Inflammasomes and autoimmune and rheumatic diseases: A comprehensive review.

Inflammasomes are a multi-protein platform forming a part of the innate immune system. Inflammasomes are at standby status and can be activated when needed. Inflammasome activation is an important mechanism for the production of active interleukin (IL)-1ß and IL-18, which have important roles to instruct adaptive immunity. Active forms of inflammasomes trigger a series of inflammatory cascades and lead to the differentiation and polarization of naïve T cells and secretion of various cytokines, which can induce various kinds of autoimmune and rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), gout, Sjögren's syndrome, Behçet's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and IgA vasculitis (former Henoch-Schönlein purpura ). In this review, we summarize studies published on inflammasomes and review their roles in various autoimmune diseases. Understanding of the role of inflammasomes may facilitate the diagnosis of autoimmune diseases and the development of tailored therapies in the future.

Transorbital ultrasonography in acute optic neuritis: Can it be a supportive diagnostic tool?

BACKGROUND: Because of limitations of conventional tools for diagnosing optic neuritis (ON), transorbital ultrasonography (TOUS) was introduced as a promising tool to evaluate the optic nerve. However, studies demonstrating its utility are scarce. OBJECTIVE: To assess the practical diagnostic value of TOUS in patients with ON along with other diagnostic tools such as visual evoked potential (VEP), MRI, and optical coherence tomography (OCT). METHODS: Seventeen patients with first-attack unilateral acute ON were enrolled. Clinical characteristics, visual acuity, TOUS, MRI, VEP, and OCT results were evaluated. Bilateral optic nerves were scanned using TOUS to obtain axial images showing the optic nerve and the disc in the longitudinal plane. RESULTS: TOUS revealed thickening of the optic nerve sheath and optic nerve diameter with sheath on the affected side compared with the unaffected side (p = 0.002 and p = 0.003, respectively). Time since onset of initial symptoms was inversely correlated with optic nerve diameter (ρ = -0.517, p = 0.040) and retinal nerve fiber layer thickness (ρ = -0.831, p < 0.001). CONCLUSION: TOUS could be a cost-effective tool for morphologically evaluating acute ON showing a significant thickening of the optic nerve and sheath, although only a limited retrobulbar area could be explored.

Differences in Friendship Networks and Experiences of Cyberbullying Among Korean and Australian Adolescents.

Cyberbullying is one of the negative consequences of online social interaction. The digital environment enables adolescents to engage in online social interaction beyond the traditional physical boundaries of families, neighborhoods, and schools. The authors examined connections to friendship networks in both online and offline settings are related to their experiences as victims, perpetrators, and bystanders of cyberbullying. A comparative face-to-face survey of adolescents (12-15-year-olds) was conducted in Korea (n = 520) and Australia (n = 401). The results reveal that online networks are partially related to cyberbullying in both countries, showing the size of social network sites was significantly correlated with experience cyberbullying among adolescents in both countries. However there were cultural differences in the impact of friendship networks on cyberbullying. The size of the online and offline networks has a stronger impact on the cyberbullying experiences in Korea than it does in Australia. In particular, the number of friends in cliques was positively related to both bullying and victimization in Korea.

Robot versus laparoscopic gastrectomy for cancer by an experienced surgeon: comparisons of surgery, complications, and surgical stress.

BACKGROUND: No previous robotic studies present an equivalent surgical quality comparison in an experienced setting for gastric cancer. In addition, a reliable postoperative complication assessment is needed to accurately evaluate surgical outcomes. METHODS: After 20 cases of robotic-assisted gastrectomy (RAG), a total of 121 consecutive gastric cancer patients underwent gastrectomy (38 RAG vs 83 laparoscopic-assisted gastrectomy [LAG]) from February 2009 to November 2010 at the Department of Surgery, Korea University Anam Hospital, Seoul, Korea. The Clavien-Dindo (C-D) classification was used to classify surgical complications. The granulocyte-to-lymphocyte (G:L) ratio was analyzed to evaluate surgical stress. RESULTS: The baseline characteristics, with the exception of age, were similar. The mean total operation time for RAG (234.4 ± 48.0 min) was not significantly different than that for LAG (220.0 ± 60.6 min; P = 0.198). However, in obese patients, fewer lymph nodes were harvested by RAG (23.4 ± 7.0) than by LAG (32.2 ± 12.5, P = 0.006). Overall C-D complications were more common for RAG (47.3 vs 38.5 %), but the difference was not significant (P = 0.361). The mean hospital stay was similar for the 2 groups. Surgical stress as estimated by the G:L ratio was comparable between the 2 groups. CONCLUSIONS: RAG performed by an experienced surgeon resulted in similar postoperative outcomes and complications to those of LAG. Assessment of operation time, C-D complication grade, and G:L ratio revealed that RAG is a practical and feasible alternative to LAG, with the possible exception of obese patients.

Deciding laparoscopic approaches for wedge resection in gastric submucosal tumors: a suggestive flow chart using three major determinants.

BACKGROUND: The aim of this study was to determine the optimal laparoscopic approach for wedge resection of gastric submucosal tumors (SMTs) based on tumor characteristics. STUDY DESIGN: Between March 2008 and June 2010, 57 patients underwent laparoscopic wedge resection for suspected gastric SMT. Of these 57 patients, 40 underwent exogastric wedge resection (EWR), with the remaining undergoing transgastric wedge resection (TWR). RESULTS: Fifty-seven consecutive patients undergoing surgical resection of gastric SMT were reviewed, with 40 and 17 tumors treated with EWR and TWR, respectively. The average tumor size was significantly greater in the EWR group (p = 0.004). A circular tumor location was a decisive factor for selecting the laparoscopic approach (p = 0.011). Tumors presenting with exophytic growths were predominantly found in the EWR group, and those with endophytic growth were dominant in the TWR group (p < 0.001). A multivariate analysis to determine the independent factors influencing the choice for EWR or TWR revealed that tumor size (95% CI, 1.1 to 20.0; p = 0.033) and circular location of tumor (95% CI, 1.4 to 106.9; p = 0.021) were statistically significant factors. CONCLUSIONS: These data suggest a strategy for selection of appropriate laparoscopic wedge resection strategies based on tumor characteristics. This decision is affected by tumor size, location, and growth pattern.