Sleep status of older adults with sleep apnoea syndrome may vary by body mass index.

Obesity and ageing are the most important risk factors for sleep apnoea syndrome (SAS); however, the role of body mass index (BMI) on sleep status in healthy older adults is unclear. To explore sleep parameters according to BMI among active older adults, we cross-sectionally examined the relationship between sleep-related parameters and BMI in 32 Japanese adults aged from 83 to 95 years without long-term care who were unaware of having SAS. Correlation and linear regression analyses were performed. Moderate or severe SAS prevalence was high in both those with low (68.8%) and high (68.8%) BMI. A higher increase in apnoea-hypopnoea index (AHI) was negatively correlated with sleep depth in the high-BMI group. In the low-BMI group, the number of awakenings and age were positively correlated with AHI. Older adults may have SAS regardless of their BMI, and the sleep status of patients with SAS may vary by BMI.

Super-multifactorial survey YHAB revealed high prevalence of sleep apnoea syndrome in unaware older adults and potential combinatorial factors for its initial screening.

Study Objectives: Aging is a risk factor for sleep apnoea syndrome (SAS), which is associated with lower quality of life and sudden mortality. However, SAS is often overlooked in older adults without suspicions. Therefore, this study aimed to evaluate SAS incidence and 48 other general factors in older adults. Methods: This cross-sectional study included all non-caregiver-certified, healthy individuals (N = 32) who survived during the long-term cohort study and agreed to participate in apnoea-hypopnoea index (AHI) measurement (aged 83-95 years). AHI and 48 other general factors were evaluated, and simple linear regression analysis was used to identify potential AHI-related factors. Stepwise evaluation was further performed using multiple linear regression analyses. Results: Although no individuals were previously diagnosed with SAS, 30 (93.75%) participants had some degree of SAS (AHI > 5/h), and 22 (68.75%) had severe or moderate SAS (AHI > 15/h). Compared with typical single risk factors represented by body mass index, combining daily steps and other factors improved the fit to the multiple linear regression. Combining daily steps and body mass index improved the fit for males and combining daily steps and red blood cell count improved the fit for females. Conclusion: SAS was highly prevalent in unaware healthy Japanese older adults; combinations of daily steps and body mass index, and daily steps and red blood cell count may predict AHI in such individuals without the need for a specific AHI test.

Establishment of Synergistic Chemoimmunotherapy for Head and Neck Cancer Using Peritumoral Immature Dendritic Cell Injections and Low-Dose Chemotherapies.

The lack of available tumor antigens with strong immunogenicity, human leukocyte antigen restriction, and immunosuppression via regulatory T-cells (Tregs) and myeloid-derived suppressor cells are limitations for dendritic cell (DC)-based immunotherapy in patients with advanced head and neck cancer (HNC). We sought to overcome these limitations and induce effective antitumor immunity in the host. The effect of low-dose docetaxel (DTX) treatment on DC maturation was examined in an ex vivo study, and a phase I clinical trial of combination therapy with direct peritumoral immature DC (iDC) injection with OK-432 and low-dose cyclophosphamide (CTX) plus DTX was designed. Low-dose DTX did not negatively affect iDC viability and instead promoted maturation and IL-12 production. Five patients with metastatic or recurrent HNC were enrolled for the trial. All patients experienced grade 1 to 3 fevers. Intriguingly, elevated CD8+ effector T-cells and reduced Tregs were observed in four patients who completed two treatment cycles. All patients were judged to have progressive disease, but tumor regressions were observed in a subset of targeted metastatic lesions in two of five patients. Our results show that the combination of direct peritumoral iDC injection with OK-432 and low-dose CTX plus DTX is well tolerated and should give rise to changing the immune profile of T-cell subsets and improvement of immunosuppression in advanced HNC patients. Additionally, our ex vivo data on the effect of low-dose DTX treatment on DC maturation may contribute to developing new combination therapies with low-dose chemotherapy and immunotherapy.

The Efficacy of Sublingual Immunotherapy for Allergic Rhinitis May Vary with the Time of Day.

BACKGROUND: Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR). However, many issues regarding SLIT remain to be resolved, including the optimal timing of administration. This study investigated the effect of time of day on SLIT efficacy with the goal of optimizing the therapeutic outcome. METHODS: We performed prophylactic SLIT at different times of day (10 a.m. or 10 p.m.) in 2 mouse models of AR: an ovalbumin (OVA)-induced AR model and Cry j 1-induced AR model, and compared the effects. RESULTS: In the OVA-induced AR model, mice sublingually receiving OVA at 10 a.m. exhibited a greater decrease in total and OVA-specific IgE levels than mice treated at 10 p.m. In addition, mice treated at 10 a.m. exhibited reductions in OVA-specific IL-4, IL-10, and IL-13 production by splenocytes relative to mice treated at 10 p.m. Furthermore, we observed a more efficient capture of sublingually administered OVA in submandibular lymph nodes at 10 a.m. than at 10 p.m. in mice. Similar results were observed in the Cry j 1-induced AR model using Japanese cedar pollen extract for SLIT. CONCLUSIONS: Given the allergen-specific antibody and T cell responses, we suggest that SLIT may be more effective in the resting phase than in the active phase (note that mice are nocturnal animals). Thus, we propose that a chronotherapeutic approach should be considered for SLIT to maximize its effectiveness.

Effects of the nuclear disaster on marine products in Fukushima: An update after five years.

Original data (134Cs and 137Cs, and sampling location) of marine products in Fukushima Prefecture monitored during 2011-2015 (n = 32,492) were analyzed to present an updated detailed description of radiocesium contamination after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident and to examine taxon/habitat-specific decreasing trends in different areas. Furthermore, marine species data presented by the Tokyo Electric Power Company (TEPCO) during 2012-2015 (n = 5458) were analyzed to evaluate the decreasing trends of 137Cs inside and outside (within a 20 km radius) of the FDNPP port. Monitoring results by Fukushima Prefecture show that percentages of samples higher than the Japanese regulatory limit of 100 Bq kg-1-wet (>RL%) were higher, whereas those below the detection limit (RL% and

Radiological impact of TEPCO's Fukushima Dai-ichi Nuclear Power Plant accident on invertebrates in the coastal benthic food web.

Radioactive cesium ((134)Cs and (137)Cs) concentrations in invertebrates of benthic food web (10 taxonomic classes with 46 identified families) collected from wide areas off Fukushima Prefecture (3-500 m depth) were inspected from July 2011, four months after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, to August 2013 to elucidate time-series trends among taxa and areas. Cesium-137 was detected in seven classes (77% of 592 specimens). Higher (137)Cs concentrations within detected data were often found in areas near or south of the FDNPP, which is consistent with the reported spatial distribution of (137)Cs concentrations in highly contaminated seawater and sediments after the FDNPP accident. Overall (137)Cs concentrations in invertebrates, the maxima of which (290 Bq kg(-1)-wet in the sea urchin Glyptocidaris crenularis) were lower than in many demersal fishes, had decreased exponentially with time, and exhibited taxon-specific decreasing trends. Concentrations in Bivalvia and Gastropoda decreased clearly with respective ecological half-lives of 188 d and 102 d. In contrast, decreasing trends in Malacostraca and Polychaeta were more gradual, with longer respective ecological half-lives of 208 d and 487 d. Echinoidea showed no consistent trend, presumably because of effects of contaminated sediments taken into their digestive tract. Comparison of (137)Cs concentrations in the invertebrates and those in seawater and sediments suggest that contaminated sediments are the major source of continuing contamination in benthic invertebrates, especially in Malacostraca and Polychaeta.

Effects of the nuclear disaster on marine products in Fukushima.

After the release of huge amounts of radionuclides into the ocean from the devastated Fukushima Dai-ichi Nuclear Power Plant (FDNPP), safety concerns have arisen for marine products in Fukushima Prefecture. As of October 2012, we had inspected the radionuclide ((131)I, (134)Cs and (137)Cs) concentrations in 6462 specimens within 169 marine species collected off the coast of Fukushima Prefecture from April 2011. Only two species exceeded the Japanese provisional regulatory limit for (131)I (2000 Bq/kg-wet) immediately after the FDNPP accident. In 2011 and 2012, 63 and 41 species respectively exceeded the Japanese regulatory limit for radioactive Cs (100 Bq/kg-wet). The overall radioactive Cs concentrations of the total marine products have decreased significantly. However, the time-series trends of radioactive Cs concentrations have differed greatly among taxa, habitats (pelagic/demersal), and spatial distributions. Higher concentrations were observed in shallower waters south of the FDNPP. Radioactive Cs concentrations decreased quickly or were below detection limits in pelagic fishes and some invertebrates, and decreased constantly in seaweed, surf clams, and other organisms. However, in some coastal demersal fishes, the declining trend was much more gradual, and concentrations above the regulatory limit have been detected frequently, indicating continued uptake of radioactive Cs through the benthic food web. The main continuing source of radioactive Cs to the benthic food web is expected to be the radioactive Cs-containing detritus in sediment. Trial fishing operations for several selected species without radioactive Cs contamination were commenced in Soma area, 50 km north of the FDNPP, from June 2012. Long-term and careful monitoring of marine products in the waters off Fukushima Prefecture, especially around the FDNPP, is necessary to restart the coastal fishery reliably and to prevent harmful rumors in the future.

Substituent effects on core structures and heterogeneous catalytic activities of Mn(III)(µ-O)2Mn(IV) dimers with 2,2':6',2″-terpyridine derivative ligands for water oxidation.

[(OH(2))(R-terpy)Mn(µ-O)(2)Mn(R-terpy)(OH(2)) ](3+) (R-terpy = 4'-substituted 2,2':6',2″-terpyridine, R = butoxy (BuO), propoxy (PrO), ethoxy (EtO), methoxy (MeO), methyl (Me), methylthio (MeS), chloro (Cl)) have been synthesized as a functional oxygen-evolving complex (OEC) model and characterized by UV-vis and IR spectroscopic, X-ray crystallographic, magnetometric, and electrochemical techniques. The UV-vis spectra of derivatives in water were hardly influenced by the 4'-substituent variation. X-ray crystallographic data showed that Mn centers in the Mn(III)(µ-O)(2)Mn(IV) cores for derivatives with R = H, MeS, Me, EtO, and BuO are crystallographically indistinguishable, whereas the derivatives with R = MeO and PrO gave the significantly distinguishable Mn centers in the cores. The indistinguishable Mn centers could be caused by rapid electron exchange between the Mn centers to result in the delocalized Mn(µ-O)(2)Mn core. The exchange integral values (J = -196 to -178 cm(-1)) for delocalized cores were lower than that (J = -163 to -161 cm(-1)) for localized cores, though the Mn···Mn distances are nearly the same (2.707-2.750 Å). The half wave potential (E(1/2)) of a Mn(III)-Mn(IV)/Mn(IV)-Mn(IV) pair of the derivatives decreased with an increase of the electron-donating ability of the substituted groups for the delocalized core, but it deviated from the correlation for the localized cores. The catalytic activities of the derivatives on mica for heterogeneous water oxidation were remarkably changed by the substituted groups. The second order rate constant (k(2)/mol(-1) s(-1)) for O(2) evolution was indicated to be correlated to E(1/2) of a Mn(III)-Mn(IV)/Mn(IV)-Mn(IV) pair; k(2) increased by a factor of 29 as E(1/2) increased by 28 mV.

A cyclic tetranuclear Ni(2)Gd(2) complex bridged by amino acidato ligands, with an S = 9 ground state, derived from ferromagnetic spin-coupling between nickel(ii) and gadolinium(iii) ions.

Synthesis and structure of a cyclic tetranuclear Ni(2)Gd(2) complex bridged by amino acidato ligands, with an S = 9 spin ground state, derived from ferromagnetic spin-coupling between S(Gd) = 7/2 and S(Ni) = 1 are reported.

[Estimation of collimator scatter factor, S(c), of rectangular fields by a saturation model].

We estimated collimator scatter factor, S(c), of symmetric rectangular fields of any size by applying a two-component scatter model to measured in-air output data in width and length directions of measured rectangles. The in-air output was measured for symmetric rectangles with combined width and length sizes of 7 x 7 and 6 x 6 using 10 MV and 4 MV X-rays of Varian's Clinac 2100 C/D, respectively. The model consists of scatter components from the primary collimator and flattening filter and from the collimator jaws: the former shows a saturation curve and the latter increases linearly with enlarging field size. This model was fitted to the measured dataset firstly in the width and secondly in the length directions of rectangles; then, by compiling interpolated matrix data, the S(c) table of symmetric rectangles was constructed. In addition, using this S(c) table, values of S(c) were calculated for a few asymmetric rectangles by Day's method, and were in good agreement with measured values. Therefore, we think that our method is practical and precise for constructing the S(c) table of symmetric rectangles from measured data, and that using this table, the S(c) of any asymmetric rectangles may be calculated.

[Estimation of collimator scatter factor, S(c), of small field sizes using long-SCD method and two saturation models].

To estimate the collimator scatter factor, S(c) of small field sizes in which a mini-phantom cannot be fully included at the nominal treatment distance (NTD=100 cm), we measured the in-air output of 4 MV and 10 MV X-rays of a Varian's Clinac 2100 C/D using a mini-phantom at NTD and at a long source-to-chamber distance (SCD=200 cm) with field-size defined at the isocenter down to 4.6 x 4.6 cm(2) and 2.3 x 2.3 cm(2), respectively. We then compared the fitted curve to the NTD dataset by a cumulative exponential distribution model with that by a cumulative Gaussian distribution (error function) model containing a zero-field extrapolated term derived from the long SCD dataset. The results showed that the zero-field extensions of two fitted curves coincided for a 4 MV X-ray, but a large discrepancy was seen between them for a 10 MV X-ray. Therefore, the S(c) of small field sizes not measurable using a mini-phantom at the NTD can be well estimated by applying the cumulative exponential model to the NTD dataset in the case of a 4 MV X-ray beam filtrated with a cone-shaped flattener. However, to estimate the S(c) of such small field sizes in the case of a 10 MV X-ray beam filtrated with a bell-shaped flattener, we consider it preferable to also measure in-air output at a long SCD and to apply the cumulative Gaussian model as described here.

Micro-patterned nanofibrous biomaterials.

Nanofibrous materials made from bioabsorbable and biocompatible polymers have promising applications as tissue-engineered scaffolds. Genetic analysis of human umbilical vein endothelial cells (HUVEC) that attached to Poly(glycolide) (PGA) nanofibrous materials prepared via electrospinning methods demonstrated high expression of Integrin v and VEGF receptor genes, which are known angiogenesis markers. In order to improve the function of the PGA nanofibrous materials for tissue engineering applications, we used a micro-patterned template instead of a flat collector in the electrospinning process. "Micro-patterned nanofibrous material" demonstrated uniformly sized dents with diameters of 200 micrometers and depths of 36 micrometers. The dents were regularly spaced, with a 250 micrometer space between two dents. These sizes are similar to that of the template. We will discuss further applications of this designable micro-patterned nanofibrous biomaterial.

W-motif exchange between beta-propeller proteins.

The similarity between the structural scaffold of PQQGDH and that of sialidase in the absence of any similarity in the primary structure, catalytic function and substrate recognition encouraged us to attempt a W-motif exchange between these enzymes. By substituting one W-motif in PQQGDH with one from sialidase, a chimeric PQQGDH was constructed, and its enzymatic properties were investigated. The overexpression of the chimeric enzyme resulted in the formation of an inclusion body. However, the refolding procedure resulted in a soluble chimeric enzyme with PQQGDH activity showing similar secondary-structure components as native PQQGDH. In contrast to native PQQGDH, the chimeric PQQGDH showed thermal instability and sensitivity to EDTA; this difference might have been due to the incomplete compatibility of the inserted W-motif. The potential of W-motif replacement was also discussed in view of the possible molecular evolution/engineering of beta-propeller structures.

[Approximation of collimator scatter factor Sc by a saturation model].

To more easily estimate accurate values of collimator scatter facor, S(c), we suggest a two-component saturation model that accounts for scatter from the primary collimator and flattening filter and from the collimator jaws. This model, which assumes an exponential distribution of scatter intensity, was tested by in-air measurements using a mini-phantom for 4 MV and 10 MV X-rays of a Clinac 2100 C/D linear accelerator. The results showed a good fit of this model to our measured data (R(2)>0.9993). When the measured value was divided into the primary collimator/flattening filter component and the collimator jaw component, as expected, the former component showed a rapid and full saturation curve with increased field size, while the latter showed an almost linearly increasing curve. Therefore, we think that this saturation model is useful for the estimation of S(c) and is applicable to monitor unit calculation for an asymmetric field.

Preparation of platinum(IV) complexes with dipeptide and diimine. X-ray crystal structure and 195Pt NMR spectra.

We prepared platinum(IV) complexes containing dipeptide and diimine or diamine, the [PtCl(dipeptide-N,N,O)(diimine or diamine)]Cl complex, where -N,N,O means dipeptide coordinated as a tridentate chelate, dipeptide=glycylglycine (NH(2)CH(2)CON(-)CH(2)COO(-), digly, where two protons of dipeptide are detached when the dipeptide coordinates to metal ion as a tridentate chelate), glycyl-L-alanine (NH(2)CH(2)CON(-)CHCH(3)COO(-), gly-L-ala), L-alanylglycine (NH(2)CH CH(3)CON(-)CH(2)COO(-), L-alagly), or L-alanyl-L-alanine (NH(2)CHCH(3)CON(-)CHCH(3)COO(-), dil-ala), and diimine or diamine=bipyridine (bpy), ethylenediamine (en), N-methylethylenediamine (N-Me-en), or N,N'-dimethylethylenediamine (N,N'-diMe-en). In the complexes containing gly-L-ala or dil-ala, two separate peaks of the (195)Pt NMR spectra of the [PtCl(dipeptide-N,N,O)(diimine or diamine)]Cl complexes appeared in, but in the complexes containing digly or L-alagly, one peak which contained two overlapped signals appeared. One of the two complexes containing gly-L-ala and bpy, [PtCl(gly-L-ala-N,N,O)(bpy)]NO(3), crystallized and was analyzed. This complex has the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions of a=9.7906(3)A, b=11.1847(2)A, c=16.6796(2)A, Z=4. The crystal data revealed that this [PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) complex has the near- (Cl, CH(3)) configuration of two possible isomers. Based on elemental analysis, the other complex must have the near- (Cl, CH(3))-[PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) configuration. The (195)Pt NMR chemical shifts of the near- (Cl, CH(3))-[PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) complex and the far- (Cl, CH(3))-[PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) complex are 0 ppm and -19 ppm, respectively (0 ppm for the Na(2)[PtCl(6)] signal). The additive property of the (195)Pt NMR chemical shift is discussed. The (195)Pt NMR chemical shifts of [PtCl(dipeptide-N,N,O)(bpy)]Cl appeared at a higher field when the H attached to the dipeptide carbon atom was replaced with a methyl group. On the other hand, the (195)Pt NMR chemicals shifts of [PtCl(dipeptide-N,N,O)(diamine)] appeared at a lower field when the H attached to the diamine nitrogen atom was replaced with a methyl group, in the order of [PtCl(digly-N,N,O)(en)]Cl, [PtCl(digly-N,N,O)(N-Me-en)]Cl, and [PtCl(digly-N,N,O)(N,N'-diMe-en)]Cl.

Diversity of epidermal growth factor receptor-mediated activation of downstream molecules in human lung carcinomas.

The correlations among epidermal growth factor receptor (EGFR) gene amplification, gene mutation, overexpression/phosphorylation of EGFR protein and activation of its downstream molecules, signal transducers and activators of transcription 3 (Stat-3), Akt and extracellular signal-related protein kinase 1/2 (Erk1/2) were investigated in 28 cases of human lung carcinomas. In five cases of carcinomas with EGFR amplification, EGFR expression and phosphorylation levels were higher than other cases, and Stat-3 was activated in all five cases. Point mutations in the tyrosine kinase domain of EGFR were detected in five cases, one of which was also associated with gene amplification. In these five cases, both EGFR expression and phosphorylation were enhanced, and Akt was activated in four cases. In the remaining 19 cases, EGFR protein expression was upregulated in eight cases and phosphorylated in four cases, but neither EGFR nor phosphorylated-EGFR expression levels specifically correlated with activation of particular downstream molecules. In general, either Stat-3 or Akt, but not both, was activated reciprocally and complementarily to each other, as indicated by their phosphorylation. However, Erk1/2 was activated regardless of the status of Stat-3, Akt or EGFR proteins. The current data suggest that persistent Stat-3 activation may be a critical event downstream of EGFR that has been overexpressed by gene amplification. In contrast, tumor cells harboring the EGFR mutation may persistently activate a cascade via Akt. Finally, in the majority of cases that have no aberration of the EGFR, its downstream molecules function in reciprocal and/or complementary manner in the maintenance and/or progression of carcinomas. These overall results could provide novel insights into potential chemotherapeutic regimens for lung carcinomas, such as inhibitors of Stat-3, Akt and Erk1/2.

Development of a novel glucose enzyme fuel cell system employing protein engineered PQQ glucose dehydrogenase.

Glucose dehydrogenase harboring pyrroloquinoline quinone as the prosthetic group (PQQGDH) from Acinetobacter calcoaceticus is an ideal enzyme for the anode of biofuel cell, because of its oxygen insensitivity and high catalytic efficiency. However, the application of PQQGDH for the bioanode is inherently limited because of its instability. Using Ser415Cys mutant whose stability was greatly improved, we constructed the biofuel cell system employing the engineered PQQGDH as the bioanode enzyme and bilirubin oxidase (BOD) as the biocathode, and compared the stability of the biofuel cell with that employing wild-type PQQGDH. The maximum power density was 17.6 microW/cm2 at an external optimal load of 200 k omega. Using Ser415Cys mutant, the lifetime of the biofuel cell system was greatly extended to 152 h, more than six times as that of the biofuel cell employing the wild-type.