Polypharmacy of medications and fall-related fractures in older people in Japan: a comparison between driving-prohibited and driving-cautioned medications.

WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is a risk factor for fall-related fractures. However, it is unclear whether polypharmacy itself is a direct risk factor. The aim of this study was to assess the association between the risk of fall-related fractures and polypharmacy of driving-prohibited and driving-cautioned medications in older outpatients. METHODS: We conducted a cross-sectional study of outpatients aged ≥65 years receiving any medication, using two sampling data sets from the October 2011 and October 2012 national insurance claims in Japan. Using logistic regression models, we analysed the association between the numbers of driving-prohibited or driving-cautioned medications administered or dispensed to patients and the occurrence of fall-related fractures. RESULTS AND DISCUSSION: In both analysis populations (n = 303 311 and n = 326 219), the adjusted odds ratio of driving-prohibited medications for the occurrence of fall-related fractures significantly increased as the number of these medications per patient increased (95% confidence interval: 0, 1-2, 3-4, 5-6, 7-8 and ≥9 medications; reference, 0·95-1·24, 1·18-1·79, 1·47-2·96, 1·26-5·21 and 1·50-15·2 in October 2011 and reference, 1·11-1·42, 1·39-2·03, 1·33-2·72, 1·53-5·49 and 1·30-13·0 in October 2012). The association was maintained even for sensitivity analyses restricted to medications administered orally or orally and by injection. However, a similar association was not observed for driving-cautioned medications. WHAT IS NEW AND CONCLUSION: Medication class is a more important risk factor for fall-related fractures rather than polypharmacy alone with no regard to medication class.

h-BN nanosheets as simple and effective additives to largely enhance the activity of Au/TiO2 plasmonic photocatalysts.

The activity of Au nanoparticle-loaded P25 TiO2 (Au/P25) plasmonic photocatalysts, evaluated by the oxidative decomposition of formic acid in water under visible light irradiation, was enhanced up to 3 times by simply mixing Au/P25 with photocatalytically inactive h-BN nanosheets as a result of electron transfer from photoexcited Au/TiO2 to the h-BN nanosheets and retardation of the charge recombination.

A PLK4 mutation causing azoospermia in a man with Sertoli cell-only syndrome.

About 15% of couples wishing to have children are infertile; approximately half these cases involve a male factor. Polo-like kinase 4 (PLK-4) is a member of the polo protein family and a key regulator of centriole duplication. Male mice with a point mutation in the Plk4 gene show azoospermia associated with germ cell loss. Mutational analysis of 81 patients with azoospermia and Sertoli cell-only syndrome (SCOS) identified one man with a heterozygous 13-bp deletion in the Ser/Thr kinase domain of PLK4. Division of centrioles occurred in wild-type PLK4-transfected cells, but was hampered in PLK-4-mutant transfectants, which also showed abnormal nuclei. Thus, this PLK4 mutation might be a cause of human SCOS and nonobstructive azoospermia.

Nerve injury induces the expression of syndecan-1 heparan sulfate proteoglycan in primary sensory neurons.

Heparan sulfate proteoglycans (HSPGs) have important functions in development of the central nervous system; however, their functions in nerve injury are not yet fully understood. We previously reported the expression of syndecan-1, a type of HSPG, in cranial motor neurons after nerve injury, suggesting the importance of syndecan-1 in the pathology of motor nerve injury. In this study, we examined the expression of syndecan-1, a type of HSPG, in primary sensory neurons after nerve injury in mice. Sciatic nerve axotomy strongly induced the expression of syndecan-1 in a subpopulation of injured dorsal root ganglion (DRG) neurons, which were small in size and had CGRP- or isolectin B4-positive fibers. Syndecan-1 was also distributed in the dorsal horn of the spinal cord ipsilateral to the axotomy, and located on the membrane of axons in lamina II of the dorsal horn. Not only sciatic nerve axotomy, infraorbital nerve axotomy also induced the expression of syndecan-1 in trigeminal ganglion neurons. Moreover, syndecan-1 knockdown in cultured DRG neurons induced a shorter neurite extension. These results suggest that syndecan-1 expression in injured primary sensory neurons may have functional roles in nerve regeneration and synaptic plasticity, resulting in the development of neuropathic pain.

YKL-40 level in gingival crevicular fluid from patients with periodontitis and type 2 diabetes.

OBJECTIVE: YKL-40 is a chitin-binding glycoprotein, the level of which increases in inflammatory diseases, diabetes mellitus (DM), cardiovascular diseases, and tumors. Gingival crevicular fluid (GCF) contains many proteins and markers of periodontitis. The purpose of this study was to investigate YKL-40 level in GCF from patients with periodontitis and DM and the association between YKL-40 level and chronic periodontitis (CP) or DM. SUBJECTS AND METHODS: The subjects were 121 patients with DM, CP, DM and periodontitis (DM-P), and healthy subjects (H). GCF was collected using paper strips after the sites for GCF collection were clinically evaluated for probing depth (PD), gingival index (GI), and bleeding on probing (BOP). YKL-40 in GCF was identified by Western blotting, and its level was determined by ELISA. RESULTS: YKL-40 was contained in GCF samples from H, DM, CP, and DM-P sites, and its levels (amount and concentration) in CP and DM-P were significantly higher than those in H and DM. GCF YKL-40 level significantly correlated with PD and GI, and its level in BOP-positive sites was significantly higher than that in BOP-negative ones. CONCLUSIONS: GCF YKL-40 level was elevated in periodontitis, but not DM. YKL-40 in GCF may be an inflammatory marker for periodontitis.

Effects of free fatty acids on human salivary gland epithelial cells.

Obesity and type 2 diabetes (T2D) are characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been proposed to promote inflammatory responses. Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammatory mononuclear cell infiltration and destruction of epithelial cells in the salivary and lacrimal glands. IL-6 production and α-fodrin degradation are increased in salivary gland epithelial cells of patients with primary SS. Although previous studies have shown a link between SS and either dyslipidemia or T2D, little is known about the clinical significance of FFAs in primary SS. Here we report that SFAs, but not unsaturated fatty acids, induced IL-6 production via NF-κB and p38 MAPK activation in human salivary gland epithelial cells. Moreover, palmitate induced apoptosis and α-fodrin degradation by caspase-3 activation. Unlike salivary gland epithelial cells, induction of IL-6 production and the degradation of α-fodrin in response to palmitate were undetectable in squamous carcinoma cells and keratinocytes. Taken together, SFAs induced IL-6 production and α-fodrin degradation in salivary gland epithelial cells, implicating a potential link between the pathogenesis of primary SS and SFAs level in plasma.

Centimeter-long Ta3N5 nanobelts: synthesis, electrical transport, and photoconductive properties.

Centimeter-long Ta3N5 nanobelts were synthesized by a reaction of centimeter-long TaS3 nanobelt templates with flowing NH3 at 800 °C for 2 h. The nanobelts have cross-sections of about 50 × 100 nm(2), and lengths up to 0.5 cm. A field effect transistor (FET) made of a single Ta3N5 nanobelt was fabricated on silica/silicon substrate. The electric transport of the individual nanobelt revealed that the nanobelt is a semiconductor with a room-temperature resistivity of 11.88 Ω m, and can be fitted well with an empirical formula ρ = 10831 exp(-T/43.8) - 22.6, where ρ is resistivity (Ω m) and T is absolute temperature (K). The FET showed decent photoconductive performance under light irradiation in the range 250-630 nm. The photocurrent increased by nearly 10 times the dark current under 450 nm light irradiation at an applied voltage of 5.0 V.

In vivo analysis of kallikrein-related peptidase 6 (KLK6) function in oligodendrocyte development and the expression of myelin proteins.

Oligodendrocytes are important for not only nerve conduction but also central nervous system (CNS) development and neuronal survival in a variety of conditions. Kallikrein-related peptidase 6 (KLK6) is expressed in oligodendrocytes in the CNS and its expression is changed in several physiological and pathological conditions, especially following spinal cord injury (SCI) and experimental autoimmune encephalomyelitis. In this study, we investigated the functions of KLK6 in oligodendrocyte lineage cell development and the production of myelin proteins using KLK6-deficient (KLK6(-/-)) mice. KLK6(-/-) mice were born without apparent defects and lived as long as wild-type (WT) mice. There was no significant difference in the numbers of oligodendrocyte precursor cells and mature oligodendrocytes in the adult naive spinal cord between WT and KLK6(-/-) mice. However, there were fewer mature oligodendrocytes in the KLK6(-/-) spinal cord than in the WT spinal cord at postnatal day 7 (P7). Expression of myelin basic protein (MBP) and oligodendrocyte-specific protein/claudin-11, major myelin proteins, was also decreased in the KLK6(-/-) spinal cord compared with the WT spinal cord at P7-21. Moreover, after SCI, the amount of MBP in the damaged spinal cords of KLK6(-/-) mice was significantly less than that in the damaged spinal cords of WT mice. These results indicate that KLK6 plays a functional role in oligodendrocyte development and the expression of myelin proteins.

Infrared spectroscopic and electron microscopic characterization of gold nanogap structure fabricated by focused ion beam.

Using infrared spectroscopy of plasmonic resonances and mapping of elemental composition and structure, we investigated the correlation between optical and structural properties of nanometre-scale gaps in gold nanorod dimers fabricated by electron beam lithography (EBL) and focused ion beam (FIB) milling. In spite of their very similar scanning electron microscopy (SEM) images, a fully cut nanogap and a shallower cut with slight imperfection near the gap region were clearly distinguished by their strongly different infrared plasmonic resonance behaviour. The differences in the infrared spectra are related to different structural and chemical results from elaborated cross-sectional transmission electron micrographs and energy dispersive x-ray spectrometry (EDX) mapping of the gap region.

Sb(2)O(3) nanobelt networks for excellent visible-light-range photodetectors.

Excellent photoconductive properties have been found in Sb(2)O(3) nanobelts synthesized by a surfactant-assisted solvothermal method. Visible-light photodetectors have been designed from Sb(2)O(3) nanobelt networks using micrometer-wide gold wires as masks. Photodetectors show high sensitivity to visible light, high stability, and reproducibility. Fast response and decay times (<0.3 s) are comparable or even better than these parameters in many other metal oxide nanoscale photodetectors. The dominant mechanism of excellent photoconductivity is attributed to the barrier height modulations in the nanobelt-to-nanobelt contact regions. These results demonstrate that Sb(2)O(3) nanobelt networks can indeed serve as high-performance photodetectors in the visible light range.

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer.

BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15-4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.

pH sensor based on boron nitride nanotubes.

A submicrometer-sized pH sensor based on biotin-fluorescein-functionalized multiwalled BN nanotubes with anchored Ag nanoparticles is designed. Intrinsic pH-dependent photoluminescence and Raman signals in attached fluorescein molecules enhanced by Ag nanoparticles allow this novel nanohybrid to perform as a practical pH sensor. It is able to work in a submicrometer-sized space. For example, the sensor may determine the environmental pH of sub-units in living cells where a traditional optical fiber sensor fails because of spatial limitations.

[Surgically treated pleomorphic carcinoma of the lung].

We experienced 3 resected cases of pleomorphic carcinoma of the lung. Each cases were 74-year-old man (case 1), 74-year-old woman (case 2) and 69-year-old man (case 3). Two patients (case 1 and 2) were histologically diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with giant cell carcinoma. One patient (case 3) was similarly diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with adenocarcinoma and squamous cell carcinoma. Although lymph nodes metastasis were not recognized in all patients, invasion to vessels were recognized in 2 patients (case 1 and 3). In one patient (case 1), recurrence was recognized at contralateral side 1 month after surgery and he died of other disease 2 months after surgery. The other 2 patients were alive without recurrence 24 and 5 months after surgery. Recently it is reported that recurrence is recognized at early phase after surgery and prognosis is poor in a case with vessel invasions in spite of pathological NO state. Since one patient (case 3) had nonmetastatic lymph nodes with vessel invasions, careful observation is considered to be necessary.

Cyclooxygenase-2-derived prostaglandin E2 is involved in vascular endothelial growth factor production in interleukin-1alpha-stimulated human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Prostaglandin E(2), which exerts its actions via EP receptors (EP1, EP2, EP3 and EP4), is a bioactive metabolite of arachidonic acid produced by cyclooxygenase-1 and/or cyclooxygenase-2. Interleukin-1alpha induces prostaglandin E(2) production via cyclooxygenase-2 in human periodontal ligament cells. Vascular endothelial growth factor is a key regulator of physiologic as well as pathologic angiogenesis and has been indicated to be involved in the pathology of periodontal diseases. In the present study, we investigated whether interleukin-1alpha induced vascular endothelial growth factor production in human periodontal ligament cells and whether cyclooxygenase-2-derived prostaglandin E(2) regulated interleukin-1alpha-induced vascular endothelial growth factor production. MATERIAL AND METHODS: Human periodontal ligament cells were obtained from extracted teeth of periodontally healthy subjects. After pre-incubation with a nonselective cyclooxygenase-1/2 inhibitor, indomethacin or a selective cyclooxygenase-2 inhibitor (NS-398), periodontal ligament cells were treated with or without interleukin-1alpha, prostaglandin E(2), various EP receptor agonists and dibutyryl cAMP (a cAMP analogue). The levels of vascular endothelial growth factor and prostaglandin E(2) in the culture supernatant were measured by enzyme-linked immunosorbent assay. The vascular endothelial growth factor mRNA expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: Interleukin-1alpha induced vascular endothelial growth factor production in a dose-dependent and time-dependent manner. The interleukin-1alpha-induced vascular endothelial growth factor mRNA and protein expression was inhibited to the same extent by indomethacin and NS-398. Indomethacin and NS-398 completely inhibited interleukin-1alpha-induced prostaglandin E(2) production. Exogenous prostaglandin E(2), butaprost (an EP2 receptor agonist) and dibutyryl cAMP abolished the inhibitory effect of indomethacin on interleukin-1alpha-induced vascular endothelial growth factor production. CONCLUSION: We suggest that interleukin-1alpha induced vascular endothelial growth factor production via cyclooxygenase-2-derived prostaglandin E(2) in human periodontal ligament cells. The interleukin-1alpha/prostaglandin E(2) pathway might regulate vascular endothelial growth factor production in periodontal lesions.

Considerable Enhancement of Field Emission of SnO(2) Nanowires by Post-Annealing Process in Oxygen at High Temperature.

The field emission properties of SnO(2) nanowires fabricated by chemical vapor deposition with metallic catalyst-assistance were investigated. For the as-fabricated SnO(2) nanowires, the turn-on and threshold field were 4.03 and 5.4 V/mum, respectively. Considerable enhancement of field emission of SnO(2) nanowires was obtained by a post-annealing process in oxygen at high temperature. When the SnO(2) nanowires were post-annealed at 1,000 degrees C in oxygen, the turn-on and threshold field were decreased to 3.77 and 4.4 V/mum, respectively, and the current density was increased to 6.58 from 0.3 mA/cm(2) at the same applied electric field of 5.0 V/mum.

Oxygen-regulated protein-150 prevents calcium homeostasis deregulation and apoptosis induced by oxidized LDL in vascular cells.

Oxidized LDLs (oxLDLs) induce apoptosis, which contributes to the pathogenesis of atherosclerosis. The 150 kDa oxygen-regulated protein (ORP150), an endoplasmic reticulum (ER)-resident chaperone, is upregulated by hypoxia and prevents ischemia-induced cell death. The aim of this work was to investigate whether and how ORP150 can prevent apoptosis induced by oxLDLs in vascular cells. OxLDLs induced ORP150 expression in the ER of human microvascular endothelial cell line (HMEC-1). ORP150 expression was blocked by antioxidants, by the permeant calcium chelator BAPTA-AM, and by inhibitors of the inositol-1,4,5 trisphosphate (IP3) receptors, 2-aminoethyl diphenylborinate (2-APB) and xestospongin C. ORP150 silencing by siRNA-enhanced oxLDL-induced apoptosis, while forced ORP150 expression increased the resistance of cells via an inhibition of the oxLDL-induced calcium rise, and of subsequent calpain activation, cytochrome c release, caspase 3 activation and apoptosis. A similar protective effect was achieved by BAPTA-AM, 2-APB and xestospongin C. Altogether, these data indicate that (i)ORP150 inhibits oxLDL-induced apoptosis by blocking calcium signaling and subsequent apoptosis, (ii)calcium released from ER stores through IP3 channels is involved in the oxLDL-induced calcium rise and apoptosis, and is inhibited by ORP150. Finally, ORP150 is expressed in advanced atherosclerotic lesions, where it may locally participate to reduce the apoptotic effect of oxLDLs and the subsequent risk of plaque rupture.

Experimental and theoretical studies suggesting the possibility of metallic boron nitride edges in porous nanourchins.

We first describe the synthesis of novel and highly porous boron nitride (BN) nanospheres (100-400 nm o.d.) that exhibit a rough surface consisting of open BN nanocones and corrugated BN ribbons. The material was produced by reacting B2O3 with nanoporous carbon spheres under nitrogen at ca. 1750 degrees C. The BN nanospheres were characterized using scanning electron microscopy, high-resolution electron microscopy, and electron energy loss spectroscopy. The porous BN spheres show relatively large surface areas of ca. 290 m2/g and exhibit surprisingly stable field emission properties at low turn-on voltages (e.g., 1-1.3 V/microm). We attribute these outstanding electron emission properties to the presence of finite BN ribbons located at the surface of the nanospheres (exhibiting zigzag edges), which behave like metals as confirmed by first-principles calculations. In addition, our ab initio theoretical results indicate that the work function associated to these zigzag BN ribbons is 1.3 eV lower when compared with BN-bulk material.

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury.

Previous studies indicated that the expression of neuropsin, a serine protease, is induced in mature oligodendrocytes after injury to the CNS. The pathophysiology of spinal cord injury (SCI) involves primary and secondary mechanisms, the latter contributing further to permanent losses of function. To explore the role of neuropsin after SCI, histochemical and behavioral analyses were performed in wild-type (WT) and neuropsin-deficient (neuropsin(-/-)) mice using a crush injury model, a well-characterized and consistently reproducible model of SCI. In situ hybridization revealed that neuropsin mRNA expression was induced in the spinal cord white matter from WT mice after crush SCI, peaking at day 4. Neuropsin(-/-) mice showed attenuated demyelination, oligodendrocyte death, and axonal damage after SCI. Although axonal degeneration in the corticospinal tract was obvious caudal to the lesion site in both strains of mice after SCI, the number of surviving nerve fibers caudal to the lesion was significantly larger in neuropsin(-/-) mice than WT mice. Behavioral analysis revealed that the recovery at days 10-42 was significantly improved in neuropsin(-/-) mice compared with WT mice in spite of the severe initial hindlimb impairments due to SCI in both strains. These observations suggest that neuropsin is involved in the secondary phase of the pathogenesis of SCI mediated by demyelination, oligodendrocyte death, and axonal degeneration.