Heat health risk assessment analysing heatstroke patients in Fukuoka City, Japan.

BACKGROUND: Climate change, as a defining issue of the current time, is causing severe heat-related illness in the context of extremely hot weather conditions. In Japan, the remarkable temperature increase in summer caused by an urban heat island and climate change has become a threat to public health in recent years. METHODS: This study aimed to determine the potential risk factors for heatstroke by analysing data extracted from the records of emergency transport to the hospital due to heatstroke in Fukuoka City, Japan. In this regard, a negative binomial regression model was used to account for overdispersion in the data. Age-structure analyses of heatstroke patients were also embodied to identify the sub-population of Fukuoka City with the highest susceptibility. RESULTS: The daily maximum temperature and wet-bulb globe temperature (WBGT), along with differences in both the mean temperature and time-weighted temperature from those of the consecutive past days were detected as significant risk factors for heatstroke. Results indicated that there was a positive association between the resulting risk factors and the probability of heatstroke occurrence. The elderly of Fukuoka City aged 70 years or older were found to be the most vulnerable to heatstroke. Most of the aforementioned risk factors also encountered significant and positive associations with the risk of heatstroke occurrence for the group with highest susceptibility. CONCLUSION: These results can provide insights for health professionals and stakeholders in designing their strategies to reduce heatstroke patients and to secure the emergency transport systems in summer.

Effects of neuromuscular electrical stimulation on pulmonary alveola and cytokines in chronic obstructive pulmonary disease (COPD) and skeletal muscle atrophy model mice.

[Purpose] It has been reported that exercise affects skeletal muscle in the chronic obstructive pulmonary disease (COPD) disease model. In this study, we examined the effects of neuromuscular electrical stimulation (NMES) in skeletal muscle on alveoli and cytokines. [Materials and Methods] We used twenty wild-type mice, randomly divided into three groups: Group A: Control (non-COPD, non-amyotrophia, non-NMES), Group B: COPD, amyotrophia with NMES and Group C: COPD, amyotrophia without NMES. Among those, a group of mice with ages from 12 to 14 weeks were used to create a chronic obstructive pulmonary disease (COPD) model, a group of mice with ages from 15 to 16 weeks was used to create a disuse syndrome by hind limb suspension, and a group of mice with ages from 17 to 28 weeks (12 weeks) were used to implement NMES. In this study, we used the real-time PCR method to assess the mRNA expression levels. We also conducted morphological analysis, assessed macrophage expression level by staining (general staining and immunostaining), and employed spirometry. [Results] Our study results showed significant decreases in Interleukin-6 (IL-6) levels in the lungs and muscle RING-finger protein-1 (MuRF1) in the muscles. Moreover, the pulmonary stromal macrophage marker (F4/80) and the protease marker (MMP12) showed significantly decreased expression, while no change was observed in the morphological of the alveolar spaces (mean linear intercept). [Conclusion] On the basis of these findings, our study reveals that NMES affects cytokines and macrophages in COPD skeletal muscle atrophy.

The correlation of salivary telomere length and single nucleotide polymorphisms of the ADIPOQ, SIRT1 and FOXO3A genes with lifestyle-related diseases in a Japanese population.

BACKGROUND: It has been reported that genetic factors are associated with risk factors and onset of lifestyle-related diseases, but this finding is still the subject of much debate. OBJECTIVE: The aim of the present study was to investigate the correlation of genetic factors, including salivary telomere length and three single nucleotide polymorphisms (SNPs) that may influence lifestyle-related diseases, with lifestyle-related diseases themselves. METHODS: In one year at a single facility, relative telomere length and SNPs were determined by using monochrome multiplex quantitative polymerase chain reaction and TaqMan SNP Genotyping Assays, respectively, and were compared with lifestyle-related diseases in 120 Japanese individuals near our university. RESULTS: In men and all participants, age was inversely correlated with relative telomere length with respective p values of 0.049 and 0.034. In men, the frequency of hypertension was significantly higher in the short relative telomere length group than in the long group with unadjusted p value of 0.039, and the difference in the frequency of hypertension between the two groups was of borderline statistical significance after adjustment for age (p = 0.057). Furthermore, in men and all participants, the sum of the number of affected lifestyle-related diseases, including hypertension, was significantly higher in the short relative telomere length group than in the long group, with p values of 0.004 and 0.029, respectively. For ADIPOQ rs1501299, men's ankle brachial index was higher in the T/T genotype than in the G/G and G/T genotypes, with p values of 0.001 and 0.000, respectively. For SIRT1 rs7895833, men's body mass index and waist circumference and all participants' brachial-ankle pulse wave velocity were higher in the A/G genotype than in the G/G genotype, with respective p values of 0.048, 0.032 and 0.035. For FOXO3A rs2802292, women's body temperature and all participants' saturation of peripheral oxygen were lower in the G/T genotype than in the T/T genotype, with respective p values of 0.039 and 0.032. However, relative telomere length was not associated with physiological or anthropometric measurements except for height in men (p = 0.016). ADIPOQ rs1501299 in men, but not the other two SNPs, was significantly associated with the sum of the number of affected lifestyle-related diseases (p = 0.013), by genotype. For each SNPs, there was no significant difference in the frequency of hypertension or relative telomere length by genotype. CONCLUSION: Relative telomere length and the three types of SNPs determined using saliva have been shown to be differentially associated with onset of and measured risk factors for lifestyle-related diseases consisting mainly of cardiovascular diseases and cancer.

Application of Single Prolonged Stress Induces Post-traumatic Stress Disorder-like Characteristics in Mice.

We tried to clarify the applicability of a single prolonged stress (SPS) protocol as post-traumatic stress disorder (PTSD) model in mice. To investigate PTSD pathophysiology, we conducted hypothalamo-pituitary-adrenal (HPA) negative feedback testing at 1, 4, 8 and 12 weeks after the SPS by administrating a dexamethasone (DEX) suppression test. The SPS induced over-suppression of the HPA system by DEX treatment at 8 and 12 weeks. To investigate PTSD-like behavioral characteristics, we subjected mice to testing in a light/dark box (to assess anxiety), a Y-maze (working memory), a cliff avoidance (visual cognition), and an open field (locomotor activity) at 1, 4, 8 and 12 weeks after the SPS. In the light/dark box test, the SPS-applied mice spent significantly less time in the light box at 8 or 12 weeks. In the cliff avoidance test, the SPS-applied mice spent significantly less time in the open area at 1 week. However, in both the Y-maze test and the open field test, SPS-applied mice tended toward slight decreases in a time-dependent manner until 12 weeks. Therefore, SPS-applied mice may thus be useful for assessing characteristics relevant to PTSD that coincide with changes in the HPA axis.

Study on Formation Process and Models of Linear Fe Cluster Structure on a Si(111)-7 × 7-CH3OH Surface.

STM results showed that Fe atoms were deposited on a Si(111)-7 × 7 reconstructed surface, which was saturated with CH3OH molecules. Fe atomic linear structure was composed of stable clusters and in-situ observed by the scanning tunneling microscopy (STM). The aim to improve its application of magnetic memory material, both formation process and models, has been explored in this paper. By combining surface images and mass spectrometer data, an intermediate layer model was established. In terms of thermal stability, the most favorable adsorption sites of CH3OH were further explored. After that, Fe atoms were deposited on the Si(111)-7 × 7-CH3OH surface, forming a linear cluster structure. On the one hand, a new Fe cluster model was put forward in this paper, which was established with height measurement and 3D surface display technology. This model is also affected by the evaporation temperature, which can be consistent with the atomic stacking pattern of face centered cubic structures. On the other hand, the slight height change suggested the stability of linear structures. Even in the condition of thin air introduction, Fe cluster showed a good performance, which suggested the possibility of magnetic memory application in the future. These investigations are believed to have, to a certain extent, increased the probability of forming Fe linear clusters on the surface of silicon substrate, especially according to the models and surface technology we adjusted.

Effects of Nonsteroidal Anti-inflammatory Drugs on the Self-renewal Capacity of Blast Progenitors in Hematological Malignancies.

BACKGROUND: With our newly established long-term suspension culture, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the self-renewal capacity of blast progenitors in seven hematological malignant cell lines. MATERIALS AND METHODS: Cyclo-oxygenase inhibitors NS-398 (NS) or indomethacin heptyl ester (indomethacin) at 30 µM was added to the cell culture. In U-937 cells, indomethacin was added at 0.3 or 3 µM. RESULTS: In all cell lines, the agents significantly and markedly inhibited blast colony formation (BCF) and telomerase activity, respectively. Significant exponential clonogenic cell growth was noted under all 23 conditions with or without the agent. The relative slope (SLP) of the line (SLPagent/SLPcontrol) reflects the level of self-renewal induced by the agent and self-renewal was inhibited (relative SLP at 0.9 or below) in four out of 16 conditions, including in U-937 cells treated with 0.3 or 3 µM indomethacin, in Daudi cells treated with indomethacin and in U-266 cells treated with NS. Indomethacin enhanced senescence, necrosis and apoptosis in U-937 and Daudi cells, whereas NS reduced apoptosis in U-937 cells and had no effect on senescence, necrosis and apoptosis in Daudi cells. In U-266 cells, NS enhanced senescence and necrosis, whereas indomethacin reduced apoptosis. There was no significant correlation between the control of BCF and relative SLP. CONCLUSION: NSAIDs enhance or reduce stress responses, inhibit telomerase activity and differentially regulate BCF and self-renewal.

Dialyzer-related Thrombocytopenia due to a Polysulfone Membrane.

A 72-year-old Japanese woman was admitted to our hospital with rapidly progressive glomerulonephritis associated with anti-glomerular basement membrane antibody. Hemodialysis (HD) therapy was initiated on the day of admission using a biocompatible polysulfone (PS) membrane. Her platelet count (PLT; ×10(4)/µL) decreased gradually from 58.7 (day 1) to 5.8 (day 25). Considering the possibility of dialyzer-related thrombocytopenia (DRT), we measured her PLT count before and after the HD session on day 72, which revealed a dramatic decrease of 7.5 to 4.3. This finding suggested that the PS dialyzer caused PLT depletion. After discontinuation of the PS dialyzer, DRT was resolved.

Spinal Functions of B-Type Natriuretic Peptide, Gastrin-Releasing Peptide, and Their Cognate Receptors for Regulating Itch in Mice.

B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPRA) and gastrin-releasing peptide (GRP)-GRP receptor (GRPR) systems contribute to spinal processing of itch. However, pharmacological and anatomic evidence of these two spinal ligand-receptor systems are still not clear. The aim of this study was to determine the spinal functions of BNP-NPRA and GRP-GRPR systems for regulating scratching activities in mice by using pharmacological and immunohistochemical approaches. Our results showed that intrathecal administration of BNP (0.3-3 nmol) dose dependently elicited scratching responses, which could be blocked by the NPRA antagonist (Arg6,ß-cyclohexyl-Ala8,D-Tic16,Arg17,Cys18)-atrial natriuretic factor(6-18) amide (A71915). However, A71915 had no effect on intrathecal GRP-induced scratching. In contrast, pretreatment with a GRPR antagonist (D-Tpi6,Leu13ψ(CH2-NH)-Leu14)bombesin(6-14) (RC-3095) inhibited BNP-induced scratching. Immunostaining revealed that NPRA proteins colocalize with GRP, but not GRPR, in the superficial area of dorsal horn, whereas BNP proteins do not colocalize with either GRP or GRPR in the dorsal horn. Intradermal administration of ligands including endothelin-1, U-46619, bovine adrenal medulla 8-22, and Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL) increased scratching bouts at different levels of magnitude. Pretreatment with intrathecal A71915 did not affect scratching responses elicited by all four pruritogens, whereas pretreatment with RC-3095 only inhibited SLIGRL-induced scratching. Interestingly, immunostaining showed that RC-3095, but not A71915, inhibited SLIGRL-elicited c-Fos activation in the spinal dorsal horn, which was in line with behavioral outcomes. These findings demonstrate that: 1) BNP-NPRA system may function upstream of the GRP-GRPR system to regulate itch in the mouse spinal cord, and 2) both NPRA and GRPR antagonists may have antipruritic efficacy against centrally, but not peripherally, elicited itch.

Formation of linearly linked Fe clusters on Si(111)-7 × 7-C2H5OH surface.

The Fe atoms were deposited on the Si(111)-7 × 7 surface, which has been saturated with the C2H5OH molecules. Then, the Fe clusters were formed on Si(111)-7 × 7-C2H5OH surface and in situ observed by the scanning tunneling microscopy (STM). The STM images showed that with the increase of Fe clusters, the size of clusters was about 5 nm and they self-assembled in straightly linked chain crossing the step to lower or upper terrace. X-ray photoelectron spectroscopy (XPS) was in situ carried out on the surface of Fe/Si(111)-7 × 7-C2H5OH samples before and after the introduction of thin air (4.5 × 10(-2) Langmuir) into the STM chamber. The XPS results showed that the Fe clusters are stable in the abovementioned thin air condition at room temperature. Based on the STM and XPS results, the driving force making one-dimensional straightly linked chain structure might be the magnetic force of the Fe clusters. The formation of straightly linked Fe clusters chains suggests the formation of single magnetic domain Fe clusters. PACS: 07.79.Cz, 81.15.-z, 75.75.Fk.

Dipeptidyl compounds ameliorate the serum-deprivation-induced reduction in cell viability via the neurotrophin-activating effect in SH-SY5Y cells.

OBJECTIVES AND METHODS: We have searched for low-molecular-weight compounds as potent new non-immunosuppressive immunophilin ligands (NI-IPLs) that are stronger than existent NI-IPLs such as GPI1046 and/or V10367 from the perspective of neuroprotective efficacy. We selected six dipeptidyl compounds as new NI-IPL candidates, and first examined the effects of each of these compounds on the serum-deprivation-induced reduction in the viability of SH-SY5Y cells. In addition, we clarified the effects of these compounds on neurotrophin release into medium in SH-SY5Y cells. RESULTS: Pre-treatment with Leu-Ile and Ile-Ile prevented the serum deprivation-induced reduction in cell viability in SH-SY5Y cells. In naive SH-SY5Y cells, treatment with Leu-Ile and Ile-Ile for 24 hours significantly increased both brain-derived neurotrophic factor and glial cell-line-derived neurotrophic factor releases in comparison with relative vehicle treatments. Moreover, none of the dipeptidyl compounds could prevent the concanavalin A-induced enhancement in interleukin-2 and interleukin-4 release in mouse spleen cells. DISCUSSION: The immunosuppressive effect is not essential to the neuroprotective properties of dipeptidyl compounds, and Leu-Ile and Ile-Ile have neurotrophin-activating effects, like FK506 and its existing non-immunosuppressive derivatives.

Embedding of computer-generated hologram in a dithered image.

We have developed an encryption method using a computer-generated hologram (CGH) embedded in a dithered image. First, confidential information is converted into a CGH. Next, the CGH data undergo two separate dithering processes in parallel: one corresponding to CGH white pixels and one corresponding to CGH black pixels. The results from both processes are used to form a dither matrix for creating the final dithered and encoded image. In this way, confidential information can be embedded into the image. The confidential information can be extracted using a technique similar to CGH optical reconstruction.

Ventricular repolarization lability in children with Kawasaki disease.

Kawasaki disease (KD) is an acute febrile disease of unknown etiology that develops in children and is sometimes accompanied by myocardial dysfunction and systemic vasculitis. However, myocardial repolarization lability has not yet been fully investigated. Thus, the objective of this study was to evaluate myocardial repolarization lability (QT variability index-QTVI) based on the body surface electrocardiograms in the acute and recovery phases. The subjects were 25 children with acute KD who were hospitalized for treatment. An equal number of age-matched healthy children were selected as controls. The RR-intervals and QT-intervals were measured based on a body surface electrocardiogram of 120 consecutive heartbeats to calculate the QTVI. The QTVI values were then compared with the acute and recovery phases. The relationships between blood biochemistry data and QTVI values were also examined. QTVI was significantly decreased from the acute phase to the recovery phase (P < 0.05) and then recovered to the same level as that of the control. QTVI in the acute phase showed a significant positive relationship with body temperature and C-reactive protein (P <0.05). QTVI was high in the acute phase and was correlated with an inflammatory reaction and became normalized during the recovery phase.

[S-1-based chemotherapy for recurrent gastric cancer with peritoneal dissemination resulting in long-term survival--report of a case].

A 52-year-old man underwent distal gastrectomy for gastric cancer in July 2000. In July 2005, abdominal CT and barium study of the colon revealed peritoneal recurrence, and chemotherapy of S-1 was started. Within 2 courses, the serum CEA level increased, so combination chemotherapy of S-1 and cisplatin (CDDP) was begun. After 7 courses, the regimen was switched to S-1+paclitaxel (PTX). However, the patient developed digital numbness within 8 courses and single-agent chemotherapy with S-1 was restarted. In July 2007, he developed abdominal distension, and abdominal CT showed a large amount of ascites. S-1+CDDP was administered again, however, and we had to change the regimen within 3 courses due to fatigue and appetite loss. S-1 was restarted, but soon severe fatigue and appetite loss restricted the use of chemotherapeutic agents, and he died in December. This patient had been alive for 2 years and 5 months since peritoneal recurrence was diagnosed. We concluded that S-1-based sequential chemotherapy was effective for recurrent gastric cancer.

A chiral wedge molecule inhibits telomerase activity.

In addition to the Watson-Crick double helix, secondary DNA structures are thought to play important roles in a variety of biological processes. One important example is the G-quadruplex structure that is formed at the chromosome ends, which inhibits telomerase activity by blocking its access to telomeres. G-quadruplex structures represent a new class of molecular targets for DNA-interactive compounds that may be useful to target telomeres. Here, we reported the first example of enantioselective recognition of quadruplex DNA by a chiral cyclic helicene. We propose a new ligand-binding cleft between two telomeric human G-quadruplexes linked by a TTA linker. We found that the cyclic helicene M1 exhibited potent inhibitory activity against telomerase.

Surface Nano-Structuring by Adsorption and Chemical Reactions.

Nano-structuring of the surface caused by adsorption of molecules or atoms and by the reaction of surface atoms with adsorbed species are reviewed from a chemistry viewpoint. Self-assembly of adsorbed species is markedly influenced by weak mutual interactions and the local strain of the surface induced by the adsorption. Nano-structuring taking place on the surface is well explained by the notion of a quasi-molecule provided by the reaction of surface atoms with adsorbed species. Self-assembly of quasi-molecules by weak internal bonding provides quasi-compounds on a specific surface. Various nano-structuring phenomena are discussed: (i) self-assembly of adsorbed molecules and atoms; (ii) self-assembly of quasi-compounds; (iii) formation of nano-composite surfaces; (iv) controlled growth of nano-materials on composite surfaces. Nano-structuring processes are not always controlled by energetic feasibility, that is, the formation of nano-composite surface and the growth of nano-particles on surfaces are often controlled by the kinetics. The idea of the "kinetic controlled molding" might be valuable to design nano-materials on surfaces.

Effects of galantamine on L-NAME-induced behavioral impairment in Y-maze task in mice.

Nitric oxide (NO) may play a role in the established processes of learning and memory. We examined the effects of N(omega)-nitro-L-arginine methylester (L-NAME), a nonselective inhibitor of NO synthase (NOS), on the performance of mice in a Y-maze task. L-NAME (100 mg/kg) markedly impaired spontaneous alternation behavior. However, galantamine (0.5 mg/kg) significantly attenuated this l-NAME-induced impairment. To clarify the molecular basis underlying galantamine's protective effects against L-NAME-induced impairment of spontaneous alternation behavior, we tested the ability of mecamylamine, an antagonist of nicotinic ACh receptor (nAChR), and scopolamine, an antagonist of muscarinic ACh receptor, to reduce galantamine's protective effects, and found that only the former had such an ability. Galantamine significantly also reduced L-NAME-induced decreases in NOx levels. However, mecamylamine cancelled galantamine's efficacy in countering the L-NAME-induced decrease in NOx levels. In the present study, we have determined that galantamine's protection against L-NAME-induced impairment of spontaneous alternation behavior in the Y-maze task might be mediated mainly by NOergic activation via the nAChR-related pathway.

Conversion of 4-oxoproline esters to 4-substituted pyrrole-2-carboxylic acid esters.

The Grignard, Wittig, Tebbe, Horner-Emmons, and Reformatsky reactions of the 4-oxoproline esters gave the corresponding 4-alylated or 4-alkylidenated products, respectively. The products were properly treated with bases to cause aromatization, giving 4-substituted pyrrole-2-carboxylic acid esters such as methyl 4-methylpyrrole-2-carboxylate, which is a trail pheromone of Atta texana.

In vivo anti-tumor effect of PEG liposomal doxorubicin (DOX) in DOX-resistant tumor-bearing mice: Involvement of cytotoxic effect on vascular endothelial cells.

We evaluated the in vivo anti-tumor effect of polyethylene glycol-modified liposomal doxorubicin (PEG liposomal DOX) in the DOX-resistant Colon-26 cancer cells (C26/DOX)-bearing mice model. IC(50) value of DOX to C26/DOX in vitro (40.0 microM) was about 250 times higher than that to control C26 (C26/control) (0.15 microM). However, in vivo anti-tumor effect of PEG liposomal DOX was similar in both C26/control- and C26/DOX-bearing mice, suggesting that the in vivo anti-tumor effect of PEG liposomal DOX was not directly reflecting the sensitivity of these tumor cells to DOX. IC(50) value (0.10 microM) of DOX to HUVEC, a model vascular endothelial cell, was similar to that of C26/control. Double immunohistochemical staining of vascular endothelial cells and apoptotic cells within the tumor tissue after intravenous administration of PEG liposomal DOX showed that the extent of co-localization of apoptotic cells with endothelial cells was significantly higher for C26/DOX tumors (60%) than C26/control ones (20%), suggesting that the apoptosis is caused preferentially for vascular endothelial cells in C26/DOX tumor. From these results, it was suggested that the cytotoxic effect of DOX on vascular endothelial cells in the tumor would be involved in the in vivo anti-tumor effect of PEG liposomal DOX in C26/DOX-bearing mice.

DRIFTS investigation and DFT calculation of the adsorption of CO on Pt/TiO2, Pt/CeO2 and FeOx/Pt/CeO2.

Molecular structures and vibrational spectra of the CO species adsorbed on the Pt/TiO2, Pt/CeO2 and FeOx/Pt/CeO2 have been investigated by means of density functional theory (DFT) calculation and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The geometrical structures and vibrational frequencies were obtained at the MPW1PW91/SDD level. Theoretical calculation shows that the calculated IR spectra were in good agreement with the experimental results. The calculated results clarify the assignment of the adsorbed CO species on the surface of Pt/TiO2, Pt/CeO2 and FeOx/Pt/CeO2.