Long-term outcomes of hemiarthroplasty using a smaller head combined with rotator cuff reconstruction in patients with cuff-tear arthropathy.

Background: Hemiarthroplasty (HHR) using a smaller head with rotator cuff reconstruction is a treatment option for cuff-tear arthropathy, offering advantages like facilitating rotator cuff-tear closure, increasing the lever arm of deltoid, and restoring function in irreparable cuff tears. This study aimed to evaluate the long-term outcomes of this procedure. Methods: A retrospective analysis was conducted for 91 shoulders undergoing HHR using a smaller head with rotator cuff reconstruction between May 2005 and September 2012. Surgery involved reducing the size of humeral head and performing rotator cuff reconstruction based on the site of the deficient rotator cuff. The study analyzed University of California, Los Angeles shoulder scores, Japanese Orthopaedics Association shoulder scores, range of motion, and postoperative radiographs. Results: Twenty-eight patients, divided into an elderly group (14 women, 2 men, mean age 74.5 ± 3.8 years) and a younger group (6 women, 6 men, mean age 63.5 ± 3.1 years) were followed up for a mean of 133.2 ± 14.1 months. No complications were reported. The clinical scores and range of motion significantly improved postoperatively and remained over 10 years. Radiographs revealed high incidence of glenoid wear (82.1%), bone resorption (43%) and cranial humeral head migration (54%), with no prosthesis loosening. Conclusion: We believe that HHR using a smaller head with rotator cuff reconstruction is a surgical technique that can maintain stable long-term outcomes in both elderly and younger individuals with cuff-tear arthropathy.

Real-Time Monitoring of Adsorption-Induced Scrolling of Colloidal Inorganic Nanosheets.

Inorganic nanotubes have attracted much attention due to their unique physicochemical properties. Nanotubes can be prepared by scrolling exfoliated nanosheets under ambient conditions. However, how the nanosheet scrolled in its colloidal state has not been experimentally visualized. In this paper, we directly observed the scrolling process of nanosheets upon adsorption of organic cations. Exfoliated flat nanosheets of niobate and clay in aqueous colloids were found to scroll by adding organic cations, such as exfoliation reagents, to the colloids. Employment of cationic stilbazolium dye enabled in situ observation of the dye adsorption and scrolling by optical microscopy based on changes in color and morphology of the nanosheets. The scrolling was promoted for nanosheets adsorbed with a stilbazolium dye with a longer alkyl chain, suggesting that the interaction between the hydrophobic parts of the dye cations is the driving force of the scrolling. This finding should encourage research on the formation of nanotubes from nanosheets and also provides important guidelines for the selection of appropriate exfoliation reagents when exfoliating nanosheets from layered crystals.

Differences in incidence rate and onset timing of undiagnosed finger symptom among shoulder surgeries related to complex regional pain syndrome.

The purpose of this study was to clarify the difference in onset timing and incidence of undiagnosed finger symptom (UDFS) between various shoulder surgical procedures. In this study, UDFS symptoms included the following four symptoms in the fingers;edema, limited range-of-motion, skin color changes, and abnormal sensations. UDFS cases were defined as those presenting with at least one UDFS. In result, the incidence rate of UDFS cases was 7.1% overall (58/816 shoulders), 7.4% (32/432) in arthroscopic rotator cuff repair (ARCR), 9.0% (11/122) in open rotator cuff repair (ORCR), 1.4% (2/145) in arthroscopic subacromial decompression (ASD), 13.2% (5/38) in open reduction and internal fixation (ORIF), 11.1% (3/27) in humeral head replacement, 4.8% (1/21) in anatomical total shoulder arthroplasty, and 12.9% (4/31) in reverse total shoulder arthroplasty cases. The Rate was significantly higher with ARCR compared to ASD (p<.01). About onset timing in weeks postoperatively, the ORIF group had a statistically earlier symptom onset than the Rotator cuff repair (ARCR + ORCR) group (2.4 weeks vs. 6.0 weeks, p<.01). When classifying the onset timing into before and after the removal of the abduction pillow, the ORIF group showed a statistically higher rate of onset before brace removal than the Rotator cuff repair groups (p<.01). Differences in UDFS among shoulder surgeries were demonstrated in this study. J. Med. Invest. 70 : 415-422, August, 2023.

Noninvasive Three-dimensional Assessment of Single Molecular Crystals Using Multiphoton Microscopic Observation and Their Deformation-induced Emission Characteristics.

Distinguishing the luminescence contribution from the surface and bulk of a crystal is a long-standing challenge in crystal materials. Herein, three-dimensional, multiphoton, luminescence microscope imaging of the elastic molecular single crystal 1,4-bis(4-methylthien-2-yl)-2,3,5,6-tetrafluorobenzene, was conducted. Further, the luminescence contribution from the surface and bulk of the crystal was experimentally distinguished. Strong luminescence was observed only from the surface of the crystal, while the bulk did not emit strongly. Furthermore, the surface and bulk luminescence behavior responded well to the mechanical shape change of the crystal; i.e., strong luminescence was observed for the elongated side of the crystal.

Relationship between hematoma-like tissue on the footprint and structural outcome of arthroscopic rotator cuff repair with a transosseous technique.

Background: We have tried to create hematoma over the footprint site at the end of arthroscopic rotator cuff repair (ARCR) surgery, expecting to apply biochemical effects of the platelet-related factors. The purpose of this study was to investigate the presence of hematoma-like tissue (HLT) on postoperative magnetic resonance imaging, and to evaluate the relationship between the HLT and the structural outcomes of ARCR. Materials and methods: Twenty-five patients were reviewed with a mean age at surgery of 69.8 years (range, 52-85 years). Postoperative magnetic resonance imaging was performed at 1 week, 6-8 weeks, and >6 months postoperatively. Structural outcomes for the repaired cuff and thickness of HLT were evaluated on coronal T2-weighted images. Signal intensity of HLT was evaluated on coronal T2-weighted fat-suppressed images as the ratio compared to supraspinatus tendon intensity (HLT/SSP ratio). Results: Structural outcomes showed Sugaya type 1 in 12 shoulders, type 2 in 4, and type 3 in 9. HLT thickness was significantly thicker at 1 week and 6-8 weeks postoperatively in Sugaya type 1 patients than in type 3 patients (1 week; P = .014, 6-8 weeks; P < .001). HLT/SSP ratio gradually decreased (at 1 week; 1.9 ± 0.7, 6-8 weeks; 1.6 ± 0.6, >6 months; 1.2 ± 0.5), and differed significantly between >6 months and both 1 week and 6-8 weeks (P < .001 each).

Correlation of suprascapular notch morphology with suprascapular nerve palsy: a 3D-computed tomography study.

Background: The morphology of the suprascapular (SS) notch is a very important factor in treatment of suprascapular nerve (SSN) palsy. Several studies have reported SS notch morphology in cadavers or using a three-dimensional computed tomography (3D-CT); however, none has reported the distribution of SS notch morphology according to the age group. In addition, the correlation between SS notch morphology and SSN palsy remains unclear. The purposes of this study were to investigate the morphological distribution of the SS notch by age group in a large population and to assess the relationship between SS notch morphology and SSN palsy. Methods: We studied the 3D-CT images of 1063 shoulders in 1009 patients (mean age, 60.8 years; age range, 14-96 years). There were 53 shoulders with SSN palsy and 1010 shoulders without SSN palsy. Morphology of the SS notch was classified by Rengachary's classification (types I-VI). Shoulders with types I-IV were classified into the nonossified superior transverse scapular ligament (STSL) group (group N) and those with types V and VI into the ossified STSL group (group O). Results: The Rengachary's classifications of the 1063 shoulders were as follows: type I: n = 113, 10.6%; type II: n = 313, 29.4%; type III: n = 383, 36.0%; type IV: n = 109, 10.3%; type V: n = 107, 10.0%; and type VI: n = 38, 3.6%. Mean age was significantly older in the ossified STSL group, and the age was <40 years for only two shoulders in this group. The Rengachary's classifications of the SSN palsy cases were as follows: type I: 7.5%, II: 24.5%, III: 34.0%, IV: 15.1%, V: 13.2%, and VI: 5.7%. There was no statistical difference in age and sex, Rengachary type, or ossification between SSN palsy and non-SSN palsy cases. Conclusions: Ossification of the STSL was significantly more common in older patients, which suggests age-related change. In addition, no relation was identified between narrow notch or ossification of the STSL with the onset of SSN palsy.

Risk factors for eccentric glenoid wear after humeral head replacement for cuff tear arthropathy.

Background: In our previous report, glenoid wear (GW) after humeral head replacement for cuff tear arthropathy was classified with modified Goya's classification (grade 0-3), and, among 3 subtypes of grade 3 (glenoid bone erosion), grade 3B (superior eccentric erosion) showed significantly more pain and limited active flexion postoperatively compared to grade 3C (concentric erosion). The purpose of this study was to detect individual risk factors for the progression to grade 3B GW. Methods: Seventy-nine shoulders in 70 patients who were followed up for a mean of 8.2 years (range, 5.0-13.2 years), including 29 men and 41 women, with a mean age at the surgery of 71.1 years (range, 54-87 years), were reviewed. Atrophy and fatty degeneration of torn cuff muscle, preoperative humeral head displacement (superior translation ratio [STR], anterior translation ratio, and other several parameters) on preoperative magnetic resonance imaging, and other individual factors were analyzed as possible risk factors. Results: GW at the final follow-up was grade 0: 5 shoulders, grade 1: 17, grade 2: 20, and grade 3: 37 (3A: 4, 3B: 22, and 3C: 11). Preoperative higher STR was defined as a risk factor for grade 3 GW (odds ratio, 35.5; 95% confidence interval, 1.8-693.0; P = .018). Comparison among the three subtypes of grade 3 showed that patients with grade 3B GW had larger STR than 3C (41.4 ± 14.2% vs. 23.5 ± 13.3 % P = .006). Conclusion: Patients with preoperative high STR are considered to have a risk for grade 3B GW, which possibly relates to poor clinical outcome and future revision.

NIR-II-Excitable Dye-Loaded Nanoemulsions for Two-Photon Microscopy Imaging of Capillary Blood Vessels in the Entire Hippocampal CA1 Region of Living Mice.

For in vivo two-photon fluorescence microscopy (2PM) imaging, the development of techniques that can improve the observable depth and temporal resolution is an important challenge to address biological and biomedical concerns such as vascular dynamics in the deep brain (typically the hippocampal region) of living animals. Improvements have been achieved through two approaches: an optical approach using a highly tissue-penetrating excitation laser oscillating in the second near-infrared wavelength region (NIR-II, 1100-1350 nm) and a chemical approach employing fluorescent probes with high two-photon brightness (characterized by the product of the two-photon absorption cross section, σ2, and the fluorescence quantum yield, Φ). To integrate these two approaches, we developed a fluorescent dye exhibiting a sufficiently high σ2Φ value of 68 Goeppert-Mayer units at 1100 nm. When a nanoemulsion encapsulating >1000 dye molecules per particle and a 1100 nm laser were employed for 2PM imaging, capillary blood vessels in almost the entire hippocampal CA1 region of the mouse brain (approximately 1.1-1.5 mm below the surface) were clearly visualized at a frame rate of 30 frames s-1 (averaged over eight frames, practically 3.75 frames s-1). This observable depth and frame rate are much higher than those in previous reports on 2PM imaging. Furthermore, this nanoemulsion allowed for the visualization of blood vessels at a depth of 1.8 mm, corresponding to the hippocampal dentate gyrus. These results highlight the advantage of combining bright probes with NIR-II lasers. Our probe is a promising tool for studying the vascular dynamics of living animals and related diseases.

Glenoid wear and its impact on clinical results after humeral head replacement using a single prosthesis in cuff tear arthropathy with more than 8 years of follow-up.

BACKGROUND: Glenoid wear (GW) is a long-term complication after humeral head replacement (HHR) and is one of the major reasons for revision surgery. This study aimed to evaluate GW at >8 years of follow-up after HHR in patients with cuff tear arthropathy (CTA) by use of a modified classification of GW, to examine the relationship between GW and clinical outcomes, and to identify risk factors for GW progression. METHODS: This retrospective case-series study included 34 shoulders that were monitored for >8 years after HHR in patients with CTA (13 men and 21 women; mean age at surgery, 70.9 years [range, 55-82 years]). Patients were monitored for a mean of 10.3 years (range, 8.1-13.2 years). GW was classified using plain radiographs as follows: grade 0, no remarkable postoperative changes; grade 1, postoperative glenohumeral joint space narrower than preoperative glenohumeral joint space; grade 2, contact between glenoid and humeral head prosthesis; and grade 3, glenoid erosion. Grade 3 cases were further classified into the following subtypes: grade 3A, partial erosion of anterior glenoid; grade 3B, partial erosion of superior glenoid; and grade 3C, concentric erosion of glenoid. Clinical outcomes including range of motion (active flexion and active external rotation) and postoperative pain (Constant score) were compared between grade 0-2 shoulders and grade 3 shoulders, as well as between the grade 3 subtypes. Age, sex, preoperative range of motion, preoperative pain, and number of ruptured tendons were analyzed as possible risk factors for progression to grade 3. RESULTS: The final GW grade was grade 0 in 3 shoulders, grade 1 in 10, grade 2 in 6, and grade 3 in 15 (grade 3A in 2, grade 3B in 6, and grade 3C in 7). The grade 3 group had lower pain scores (10.7 ± 6.2 vs. 14.2 ± 1.9, P = .044) and limited active flexion (108.2° ± 42.3° vs. 140.6° ± 26.7°, P = .041) compared with the grade 0-2 group. Subtype comparison showed that the grade 3B group had lower pain scores (7.0 ± 6.7 vs. 15.0 ± 0.0, P = .007) and limited active flexion (80.0° ± 26.2° vs. 140.8° ± 27.5°, P = .010) compared with the grade 3C group. Limited preoperative active external rotation was an individual risk factor for grade 3 GW (odds ratio, 0.93; 95% confidence interval, 0.88-0.99; P = .009). CONCLUSIONS: In the long term (>8 years) after HHR with tendon transfer in patients with CTA, patients with the development of grade 3C GW ultimately achieve pain relief even without revision surgery whereas grade 3B GW is associated with persistent pain and might require revision surgery.

Formation of a Giant Anisotropically Ordered Assembled Structure of Inorganic Nanosheets through an Optically Induced Stream.

Formation of a desirable submillimeter-scaled assembled structure of particles in the colloid is a difficult subject in colloidal chemistry. Herein, a submillimeter-scaled ordered assembled structure consisting of highly anisotropic two-dimensional plate-like particles, niobate nanosheets, was obtained through an optical manipulation technique that was assisted by a scattering-force-induced stream. A 532 nm continuous wave laser beam with a power of 400 mW was used to illuminate a liquid crystalline niobate nanosheet colloid from the bottom side of a sample cell, inducing the stream of oriented nanosheets toward the upper side of the sample cell. As a result, a 200 µm ordered assembled structure consisting of oriented nanosheets was formed. The assembled structure was also characterized by two-dimensional anisotropy, reflecting that the highly anisotropic morphologies of each nanosheet and the shape of that structure were dependent on the polarization of incident illumination. This study has revealed a new noncontact and on-demand way to obtain submillimeter-scaled ordered anisotropic colloidal assembled structures of nanosized particles such as nanosheets, contributing to fundamental materials science and expanding the utilities of nanosheets.

Morphology of the coracoid process as a predictor of articular-side tear at the upper border of the subscapularis.

BACKGROUND: Articular-side tear at the upper border of the subscapularis (SSC-AST) is often detected during shoulder arthroscopic surgery, although its exact pathology remains unknown. The purpose of this study was to investigate the correlation between various characteristics of the coracoid process, including classification of the morphology of the coracoid process tip, and the presence of SSC-AST. METHODS: This retrospective, case-controlled study included patients who underwent arthroscopic subacromial decompression with or without rotator cuff repair between January 2018 and September 2021. A total of 130 shoulders in 124 patients, including 77 male and 53 female shoulders (mean age at surgery, 64 years [range, 39-88 years]), were included in this study. Three-dimensional (3D) computed tomography examination was performed preoperatively, and the following indices were measured: coracoid proximal length, coracoid distal length, coracoid angle, coracoglenoid angle, offset of the coracoid process and glenoid (anterior, lateral, and superior offset), and coracoid base angle. The morphology of the tip of the coracoid process was classified into 3 types according to 3D reconstructed views: flat type, round type, and beak type. The presence of SSC-AST was intraoperatively evaluated arthroscopically via a posterior glenohumeral portal. Morphologic risk factors for SSC-AST were evaluated between SSC-AST cases (group T) and non-SSC-AST cases (group N) by multivariable logistic analysis. In addition, the correlation between the incidence of SSC-AST and classification of the tip of the coracoid process was analyzed. RESULTS: SSC-AST was present in 53 shoulders (40.8%). Group T patients were significantly older than group N patients (68.4 ± 10.0 years vs. 61.5 ± 11.8 years, P < .001). No sex difference was detected between the 2 groups (28 male and 25 female shoulders in group T vs. 49 male and 28 female shoulders in group N, P = .28). Multivariate analysis of morphologic parameters between the 2 groups detected a smaller superior offset as a risk factor for SSC-AST (odds ratio, 0.91; 95% confidence interval, 0.84-0.98; P = .01). No significant differences were found in the other parameters. Regarding classification of the tip of the coracoid process, round- and beak-type coracoid tips had a significantly higher rate of SSC-AST than flat-type tips (flat type, 21.8%; round type, 64.7%; and beak type, 46.3%) (P < .001). CONCLUSIONS: Evaluation of the correlation between the morphology of the coracoid process on 3D computed tomography and the presence of SSC-AST visualized during arthroscopy indicated a significant association between SSC-AST and the morphology of the coracoid process.

Ferroelectric columnar assemblies from the bowl-to-bowl inversion of aromatic cores.

Organic ferroelectrics, in which the constituent molecules retain remanent polarization, represent an important topic in condensed-matter science, and their attractive properties, which include lightness, flexibility, and non-toxicity, are of potential use in state-of-the-art ferroelectric devices. However, the mechanisms for the generation of ferroelectricity in such organic compounds remain limited to a few representative concepts, which has hitherto severely hampered progress in this area. Here, we demonstrate that a bowl-to-bowl inversion of a relatively small organic molecule with a bowl-shaped π-aromatic core generates ferroelectric dipole relaxation. The present results thus reveal an unprecedented concept to produce ferroelectricity in small organic molecules, which can be expected to strongly impact materials science.

SIRT1 decelerates morphological processing of oligodendrocyte cell lines and regulates the expression of cytoskeleton-related oligodendrocyte proteins.

SIRT1 is involved in the regulation of a variety of biological processes such as metabolism, stress response, autophagy and differentiation. Although progenitor cells of oligodendrocytes (OPCs) express high level of SIRT1, its function on differentiation is unknown. Because we have shown that SIRT1 plays a pivotal role in differentiation of neural precursor cells, we hypothesized that SIRT1 may also participate in the differentiation of oligodendrocytes (OLGs). We examined whether SIRT1 was expressed in two human oligodendrocyte cell lines: KG-1-C and MO 3.13 OLG. Transfection of cell lines with SIRT1-siRNA and SIRT2-siRNA promoted the extension of cellular processes. SIRT1-siRNA and SIRT2-siRNA increased acetyl-α-tubulin level, conversely, over expression of SIRTs resulted in decreased the ratio of acetyl-α-tubulin to α-tubulin. We also found knockdown of SIRT1 and SIRT2 induced overexpression of ßIV-tubulin and tubulin polymerization promoting protein (TPPP) (OLG-specific cytoskeleton-related molecules) that distributed widely in cell bodies. Taken together, SIRT1 may play a role in oligodenroglial differentiation and myelinogenesis.

Hyperemesis-induced Wernicke-Korsakoff Syndrome due to Hypergastrinemia during Long-term Treatment with Proton Pump Inhibitors.

We herein report a patient with Wernicke-Korsakoff syndrome (WKS) who had neither a history of alcoholism or of history of gastric surgery. A 56-year-old woman was transferred to our hospital because of the loss of consciousness and she was diagnosed to have Wernicke encephalopathy. She showed proton pump inhibitor-induced refractory hypergastrinemia with the subsequent development of hyperemesis and a vitamin B1 deficiency.

Systematic Control of Structural and Photophysical Properties of π-Extended Mono- and Bis-BODIPY Derivatives.

A series of π-extended mono- and bis-BODIPY (BODIPY=boron-dipyrromethene) derivatives, namely, benzo[a]phenanthrene-fused BODIPY (Phena-Mono-BDP), benzo[a]anthracene-fused BODIPY (Ant-Mono-BDP), and dibenz[a,h]anthracene (DBA)-bridged bis-BODIPY (Ant-Bis-BDP), were designed and synthesized to examine their structural, electrochemical, and photophysical properties. Single-crystal X-ray crystallographic analyses demonstrated the planar configuration of Ant-Mono-BDP, in contrast to that of nonplanar Phena-Mono-BDP, whereas Ant-Bis-BDP has a DBA-centered planar configuration and two terminal nonplanar units of BODIPYs. The oxidation and reduction potentials agree with the estimated energies obtained through DFT calculations. The localized HOMO and LUMO states suggested the intramolecular charge-transfer characteristics in these BODIPY derivatives. The absorption spectra of these compounds extended up to the near-IR region. Strong redshifted trends of fluorescence spectra were observed in Ant-Bis-BDP with increasing solvent polarity, as supported by the differences in dipole moments estimated from Lippert-Mataga plots. To evaluate the excited-state dynamics of these molecules, the fluorescence quantum yield (ΦFL ) of Ant-Bis-BDP dramatically increased in the range from 0.05 to 0.86, with decreasing solvent polarity. Finally, the efficient two-photon absorption cross section of Ant-Bis-BDP (ca. 1200 GM at λ=1000 nm) was also obtained by considering the large π-extended structure (acceptor-donor-acceptor type).

Transplantation of Mesenchymal Stem Cells Improves Amyloid-ß Pathology by Modifying Microglial Function and Suppressing Oxidative Stress.

Mesenchymal stem cells (MSC) are increasingly being studied as a source of cell therapy for neurodegenerative diseases, and several groups have reported their beneficial effects on Alzheimer's disease (AD). In this study using AD model mice (APdE9), we found that transplantation of MSC via the tail vein improved spatial memory in the Morris water maze test. Using electron paramagnetic resonance imaging to evaluate the in vivo redox state of the brain, we found that MSC transplantation suppressed oxidative stress in AD model mice. To elucidate how MSC treatment ameliorates oxidative stress, we focused on amyloid-ß (Aß) pathology and microglial function. MSC transplantation reduced Aß deposition in the cortex and hippocampus. Transplantation of MSC also decreased Iba1-positive area in the cortex and reduced activated ameboid shaped microglia. On the other hand, MSC transplantation accelerated accumulation of microglia around Aß deposits and prompted microglial Aß uptake and clearance as shown by higher frequency of Aß-containing microglia. MSC transplantation also increased CD14-positive microglia in vivo, which play a critical role in Aß uptake. To confirm the effects of MSC on microglia, we co-cultured the mouse microglial cell line MG6 with MSC. Co-culture with MSC enhanced Aß uptake by MG6 cells accompanied by upregulation of CD14 expression. Additionally, co-culture of MG6 cells with MSC induced microglial phenotype switching from M1 to M2 and suppressed production of proinflammatory cytokines. These data indicate that MSC treatment has the potential to ameliorate oxidative stress through modification of microglial functions, thereby improving Aß pathology in AD model mice.

Early administration of galantamine from preplaque phase suppresses oxidative stress and improves cognitive behavior in APPswe/PS1dE9 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disease that progressively impairs memory and cognition. Deposition of amyloid-ß (Aß) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and known to occur early in the course of AD. Several reports suggest a relationship between change in redox status and AD pathology including progressive Aß deposition, glial cell activation, and inflammation. Galantamine is an acetylcholinesterase inhibitor and has been reported to have an oxidative stress inhibitory function. In the present study, galantamine was administered orally to AD model mice from before the appearance of Aß plaques (preplaque phase), and in vivo change in redox status of the brain was measured using electron paramagnetic resonance (EPR) imaging. Administration of galantamine from the preplaque phase ameliorated memory decline in Morris water maze test and novel object recognition test. Monitoring of the redox status of the brain using EPR imaging showed that galantamine treatment improved the unbalanced redox state. Additionally, galantamine administration enhanced microglial function to promote Aß clearance, reducing the Aß-positive area in the cortex and amount of insoluble Aß in the brain. In contrast, galantamine treatment from the preplaque phase suppressed the production of proinflammatory cytokines through neurotoxic microglial activity. Therefore, galantamine administration from the preplaque phase may have the potential of clinical application for the prevention of AD. In addition, our results demonstrate the usefulness of EPR imaging for speedy and quantitative evaluation of the efficacy of disease-modifying drugs for AD.

Ferroelectric Behavior of a Hexamethylenetetramine-Based Molecular Perovskite Structure.

We report the development of a molecular ferroelectric material inspired by the hexamethylenetetramine (hmta) non-centrosymmetric molecular rotator. The bromide salt of diprotonated hmta (hmtaH2 ) crystalized as (hmtaH2 )(NH4 )Br3 in a metal-free ABX3 perovskite-type structure, in which the A and B sites are occupied by hmtaH2 2+ and ammonium cations, respectively. The compound crystallized in the Pma2 polar space group. A distorted polar perovskite structure formed owing to the distortion of {(NH4 )Br6 } octahedrons that are stabilized through the formation of NH⋅⋅⋅Br hydrogen bonds and the orientational ordering of positive charges on the non-centrosymmetric hmtaH2 molecules. This spontaneous polarization exhibited ferroelectric behavior with a nominally high Curie temperature (>400 K), in which the electrical switching of polarization originates from the rotation of the hmtaH2 unit.

Microscope Observation of Morphology of Colloidally Dispersed Niobate Nanosheets Combined with Optical Trapping.

Although inorganic nanosheets prepared by exfoliation (delamination) of layered crystals have attracted great attention as 2D nanoparticles, in situ real space observations of exfoliated nanosheets in the colloidally dispersed state have not been conducted. In the present study, colloidally dispersed inorganic nanosheets prepared by exfoliation of layered niobate are directly observed with bright-field optical microscopy, which detects large nanosheets with lateral length larger than several micrometers. The observed nanosheets are not strictly flat but rounded, undulated, or folded in many cases. Optical trapping of nanosheets by laser radiation pressure has clarified their uneven cross-sectional shapes. Their morphology is retained under the relation between Brownian motion and optical trapping.

CD14 and Toll-Like Receptor 4 Promote Fibrillar Aß42 Uptake by Microglia Through A Clathrin-Mediated Pathway.

We previously demonstrated that microglia play an essential role in clearance of amyloid-ß (Aß) in Alzheimer's disease (AD)-like pathology. Our prior work also showed that several receptors expressed on microglia participated in Aß phagocytosis. However, clathrin-mediated endocytosis (CME), which is associated with production and release of Aß in neurons, has received much less attention in the context of microglial Aß uptake. To elucidate the detailed mechanisms of microglial Aß uptake pathways, we focused on CD14 and Toll-like receptor 4 (TLR4), which have been shown to mediate fibrillar Aß1 - 42 (fAß42) phagocytosis in microglia. CD14 has also been known to control lipopolysaccharide-induced internalization of TLR4 in a clathrin-dependent manner. However, it remains unclear whether CD14 and TLR4 engage in CME in microglial fAß42 uptake, including whether CD14 interacts with TLR4 in the process. In the present study, we found that CD14-positive microglia increased in an age-dependent manner in the cortex of AD model mice. Immunostaining showed that CD14 interacted with TLR4 to internalize fAß42 in the mouse microglial cell line MG6. Knock-down of CD14 and TLR4 in MG6 cells significantly reduced intracellular fAß42, showing their involvement in fAß42 uptake. We also found that clathrin participated in fAß42 uptake by MG6 cells. Furthermore, CD14 and TLR4 mediated fAß42 uptake via clathrin-dependent mechanisms. These results indicate that CD14 and TLR4 participate not only in phagocytosis but also in clathrin-dependent fAß42 internalization in microglia. These findings provide novel molecular understanding of microglial fAß42 uptake, which could be of therapeutic relevance for AD.