Large-Scale Traveling Atmospheric and Ionospheric Disturbances Observed in GUVI With Multi-Instrument Validations.

This study presents multi-instrument observations of persistent large-scale traveling ionosphere/atmospheric disturbances (LSTIDs/LSTADs) observed during moderately increased auroral electrojet activity and a sudden stratospheric warming in the polar winter hemisphere. The Global Ultraviolet Imager (GUVI), Gravity field and steady-state Ocean Circulation Explorer, Scanning Doppler Imaging Fabry-Perot Interferometers, and the Poker Flat Incoherent Scatter Radar are used to demonstrate the presence of LSTIDs/LSTADs between 19 UT and 5 UT on 18-19 January 2013 over the Alaska region down to lower midlatitudes. This study showcases the first use of GUVI for the study of LSTADs. These novel GUVI observations demonstrate the potential for the GUVI far ultraviolet emissions to be used for global-scale studies of waves and atmospheric disturbances in the thermosphere, a region lacking in long-term global measurements. These observations typify changes in the radiance from around 140 to 180 km, opening a new window into the behavior of the thermosphere.

Multiresolution Modeling of High-Latitude Ionospheric Electric Field Variability and Impact on Joule Heating Using SuperDARN Data.

The most dynamic electromagnetic coupling between the magnetosphere and ionosphere occurs in the polar upper atmosphere. It is critical to quantify the electromagnetic energy and momentum input associated with this coupling as its impacts on the ionosphere and thermosphere system are global and major, often leading to considerable disturbances in near-Earth space environments. The current general circulation models of the upper atmosphere exhibit systematic biases that can be attributed to an inadequate representation of the Joule heating rate resulting from unaccounted stochastic fluctuations of electric fields associated with the magnetosphere-ionosphere coupling. These biases exist regardless of geomagnetic activity levels. To overcome this limitation, a new multiresolution random field modeling approach is developed, and the efficacy of the approach is demonstrated using Super Dual Auroral Radar Network (SuperDARN) data carefully curated for the study during a largely quiet 4-hour period on February 29, 2012. Regional small-scale electrostatic fields sampled at different resolutions from a probabilistic distribution of electric field variability conditioned on actual SuperDARN LOS observations exhibit considerably more localized fine-scale features in comparison to global large-scale fields modeled using the SuperDARN Assimilative Mapping procedure. The overall hemispherically integrated Joule heating rate is increased by a factor of about 1.5 due to the effect of random regional small-scale electric fields, which is close to the lower end of arbitrarily adjusted Joule heating multiplicative factor of 1.5 and 2.5 typically used in upper atmosphere general circulation models. The study represents an important step toward a data-driven ensemble modeling of magnetosphere-ionosphere-atmosphere coupling processes.

Prospective trial for the clinical efficacy of anogenital skin care with miconazole nitrate-containing soap for diaper candidiasis.

Anogenital skin care for the elderly remains an umbrella term concerning protective and non-interventional regimens, particularly for ordinary diaper users. Our recent investigation has demonstrated the preventive effect of daily anogenital washing with miconazole nitrate-containing soap to the development of diaper candidiasis. We extended this work to cover our hypothesis as to whether the miconazole soap has a therapeutic benefit in genital candidiasis. The study outline includes: (i) the enrollment of 21 bedridden inpatients (84 ± 9 years; eight men and 13 women) who were diagnosed clinically and mycologically with genital candidiasis, and who had never received topical and/or systemic antifungal agents; (ii) administration of anogenital washing with 0.75% miconazole-containing soap once daily for 4 weeks; and (iii) assessment of clinical symptoms and detection of Candida materials by culture and microscopic examination. As assessed by clinical symptom scoring for incontinence-associated dermatitis (IAD), the ratio of patients with severe to moderate symptoms dramatically decreased by 2 weeks and 10 of 21 patients became symptom-free at 4 weeks. The IAD clinical severity score was significantly decreased at 4 weeks. Compared with the baseline positivity, both microscopic and cultured Candida-positive rates were significantly decreased at 4 weeks after washing. All culture-detected fungi were Candida albicans. Severe adverse events did not occur in all participants. Individual medical and risk factors had no significant correlation with clinical severity and duration of candidiasis on variance analysis. In conclusion, topical washing with miconazole soap is a safe and reliable non-medical approach for soothing diaper-associated genital candidiasis in bedridden inpatients in whom it is difficult to perform prompt medical examination.

Pharmacological characteristics of hemokinin-1-derived peptides in rat pruriceptive processing.

Hemokinin-1 (HK-1) is a member of mammalian tachykinin peptide family, and [Leu11]-HK-1 has an antagonistic effect on HK-1. The attenuation of pruritogen-induced scratching behavior by pretreatment with [Leu11]-HK-1 indicates the involvement of HK-1 in pruriceptive processing. However, it remains unclear whether the intrathecal or intranasal administration of HK-1-derived peptides, such as [D-Trp7,9]-[Leu11]-HK-1 or [D-Trp7]-[Leu11]-HK-1, elicits the effects different from [Leu11]-HK-1. The induction of scratching by intrathecal administration of HK-1 was attenuated 30 min, 4 h and 24 h after pretreatment with [Leu11]-HK-1, [D-Trp7,9]-[Leu11]-HK-1 and [D-Trp7]-[Leu11]-HK-1 or [D-Trp9]-[Leu11]-HK-1, respectively. Similarly, the scratching induced by subcutaneous injection of pruritogens as chloroquine and histamine was ameliorated 30 min and 24 h after pretreatment with [Leu11]-HK-1 and these three HK-1-derived peptides, respectively. Moreover, the effective minimum concentrations of intrathecal administrations of [D-Trp9]-[Leu11]-HK-1 on scratching induced by chloroquine and histamine were 10-6 M, while the effective minimum concentrations of intranasal administration of this peptide on scratching induced by chloroquine and histamine were 10-5 M and 10-4 M, respectively. Thus, the present results indicate that the intrathecal administration of HK-1-derived peptides with D-Trp extends its effective time on scratching induced by intrathecal administration of HK-1 and pruritogens such as chloroquine and histamine. Similarly, the induction of scratching by pruritogens was attenuated by intranasal administration of HK-1-derived peptide, although the effective minimum concentration of this peptide was slightly lower than that of intrathecal administration, indicating that intranasal administration is an effective tool for carrying peptides into the brain.

Alleviation of thalamic pain by cilostazol administration: a case report.

Thalamic pain is severe and treatment-resistant; however, there are few available options for improving thalamic pain. This study demonstrated that thalamic pain was alleviated by administration of cilostazol, suggesting that cilostazol may be a candidate for treating thalamic pain.

Space-Based Sentinels for Measurement of Infrared Cooling in the Thermosphere for Space Weather Nowcasting and Forecasting.

Infrared radiative cooling by nitric oxide (NO) and carbon dioxide (CO2) modulates the thermosphere's density and thermal response to geomagnetic storms. Satellite tracking and collision avoidance planning require accurate density forecasts during these events. Over the past several years, failed density forecasts have been tied to the onset of rapid and significant cooling due to production of NO and its associated radiative cooling via emission of infrared radiation at 5.3 µm. These results have been diagnosed, after the fact, through analyses of measurements of infrared cooling made by the Sounding of the Atmosphere using Broadband Emission Radiometry instrument now in orbit over 16 years on the National Aeronautics and Space Administration Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics satellite. Radiative cooling rates for NO and CO2 have been further shown to be directly correlated with composition and exospheric temperature changes during geomagnetic storms. These results strongly suggest that a network of smallsats observing the infrared radiative cooling of the thermosphere could serve as space weather sentinels. These sentinels would observe and provide radiative cooling rate data in real time to generate nowcasts of density and aerodynamic drag on space vehicles. Currently, radiative cooling is not directly considered in operational space weather forecast models. In addition, recent research has shown that different geomagnetic storm types generate substantially different infrared radiative response, and hence, substantially different thermospheric density response. The ability to identify these storms, and to measure and predict the Earth's response to them, should enable substantial improvement in thermospheric density forecasts.

A MULTI-RESOLUTION MODEL FOR NON-GAUSSIAN RANDOM FIELDS ON A SPHERE WITH APPLICATION TO IONOSPHERIC ELECTROSTATIC POTENTIALS.

Gaussian random fields have been one of the most popular tools for analyzing spatial data. However, many geophysical and environmental processes often display non-Gaussian characteristics. In this paper, we propose a new class of spatial models for non-Gaussian random fields on a sphere based on a multi-resolution analysis. Using a special wavelet frame, named spherical needlets, as building blocks, the proposed model is constructed in the form of a sparse random effects model. The spatial localization of needlets, together with carefully chosen random coefficients, ensure the model to be non-Gaussian and isotropic. The model can also be expanded to include a spatially varying variance profile. The special formulation of the model enables us to develop efficient estimation and prediction procedures, in which an adaptive MCMC algorithm is used. We investigate the accuracy of parameter estimation of the proposed model, and compare its predictive performance with that of two Gaussian models by extensive numerical experiments. Practical utility of the proposed model is demonstrated through an application of the methodology to a data set of high-latitude ionospheric electrostatic potentials, generated from the LFM-MIX model of the magnetosphere-ionosphere system.

Ergonomic evaluation of a mechanical anastomotic stapler used by Japanese surgeons.

PURPOSE: The satisfaction rating of currently available mechanical staplers for Japanese surgeons with small hands is low. To identify the issue, we examined the relationship of hand dimensions and grip force with the operation force of a mechanical circular stapler. METHODS: Hand dimensions and grip force were measured in 113 Japanese surgeons (52 men and 61 women). We then evaluated the relationship between grip width and the operation force required to push the lever of the stapler, at three points on the lever, using a digital force gauge. RESULTS: The optimal grip width of the dominant hand was 62.5 ± 8.5 mm for men and 55.5 ± 5.9 mm for women (p < 0.001). The maximum grip force of the dominant hand was 44.2 ± 6.1 kg for men and 29.7 ± 4.5 kg for women (p < 0.001) and the maximum operation force required to push the lever 7.0, 45.0, and 73.0 mm from the end of the lever was 21.8, 28.6, and 42.4 kg, respectively. CONCLUSIONS: To our knowledge, this is the first ergonomic study of a surgical stapler to be conducted in Asia. Firing the stapler by gripping the proximal side of the lever is physically impossible for most Japanese women surgeons since the required operation force exceeds the maximum grip force, which probably accounts for the stress perceived by these women.

Efficacy and safety of sitagliptin as add-on therapy on glycemic control and blood glucose fluctuation in Japanese type 2 diabetes subjects ongoing with multiple daily insulin injections therapy.

To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). HbA1c, 1,5-anhydroglucitol (1,5-AG), body mass index (BMI), insulin doses, six-point self-measured plasma glucose (SMPG) profiles were assessed before, after 12 weeks, and after 24 weeks of MDI with 50 mg/day of sitagliptin in 40 subjects with type 2 diabetes. Safety endpoints included hypoglycemia and any adverse events. HbA1c significantly decreased during the first 12 weeks ( -0.64±0.60%), and was sustained over 24 weeks ( -0.69±0.85%). 1,5-AG increased significantly from 7.5±4.5 µg/mL at baseline to 9.6±5.5 µg/mL after 24 weeks. The bolus insulin dose at 12 weeks was decreased, and the mean plasma glucose, the SD of daily glucose, M-value, and the mean amplitude of glycemic excursions (MAGE) also decreased significantly as compared with baseline values. BMI and frequency of hypoglycemia were not changed significantly. Univariate linear regression analyses revealed that % change in HbA1c was significantly associated with BMI, and % changes in the indexes of glycemic instability (SD of daily glucose and MAGE) were significantly associated with age. In conclusion, adding sitagliptin to MDI significantly improved glycemic control and decreased the daily glucose fluctuation in subjects with type 2 diabetes inadequately controlled with MDI, without weight gain or an increase in the incidence of hypoglycemia. This trial was registered with UMIN (no. UMIN000010157).

Rating and issues of mechanical anastomotic staplers in surgical practice: a survey of 241 Japanese gastroenterological surgeons.

PURPOSE: Commercially available mechanical devices for gastrointestinal anastomosis are mostly made in overseas. Japanese female surgeons have described these devices as being too large and difficult to handle. This study investigated the degree of satisfaction and problems experienced by Japanese surgeons in using various staplers for mechanical anastomosis. METHODS: A questionnaire was prepared and sent via email to 5,537 members of the Japanese Society of Gastroenterological Surgery. The questionnaire included sex, age, surgical glove size, degree of satisfaction with various mechanical staplers, stress felt when using the staplers in anastomosis, and problems regarding the devices. RESULTS: Valid responses were received from 241 respondents (167 males, 74 females, response rate 4.9 %). The satisfaction rate ranged from 0 to 100 %. The average glove size in males was significantly larger than that in females (median: 7.0 versus 6.0; P < 0.0001). Surgeons with glove size 6.0 or smaller felt stress more frequently than those with size 6.5 or larger (median: 40 vs. 20 %; P < 0.0001). Surgeons with glove size 6.0 and smaller experienced more difficulties during firing and releasing. CONCLUSION: The satisfaction rates with currently available mechanical staplers were low. Japanese surgeons with small hands felt more stress when using the staplers. Ergonometric consideration is necessary in stapler design.

Troglitazone inhibits oxidized low-density lipoprotein-induced macrophage proliferation: impact of the suppression of nuclear translocation of ERK1/2.

Thiazolidinediones (TZDs), which were known as novel insulin-sensitizing antidiabetic agents, have been reported to inhibit the acceleration of atherosclerotic lesions. Macrophages play important roles in the development of atherosclerosis. We previously reported that oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation through ERK1/2-dependent GM-CSF production. In the present study, we investigated the effects of two TZDs, troglitazone and ciglitazone on Ox-LDL-induced macrophage proliferation. Troglitazone significantly inhibited Ox-LDL-induced increases in [(3)H]thymidine incorporation into and proliferation of mouse peritoneal macrophages, whereas ciglitazone had no effects. Troglitazone and ciglitazone both significantly induced PPARgamma activity, suggesting that the inhibitory effect of troglitazone was not mediated by PPARgamma. Ox-LDL-induced production of GM-CSF was significantly inhibited by troglitazone, but not by ciglitazone. Troglitazone inhibited Ox-LDL-induced production of intracellular reactive oxygen species, whereas ciglitazone had no effect. The antioxidant reagents NAC and NMPG each inhibited phosphorylation of ERK1/2, whereas troglitazone and ciglitazone had no effects. However, troglitazone, NAC and NMPG all inhibited nuclear translocation of ERK1/2. In conclusion, troglitazone inhibited Ox-LDL-induced GM-CSF production by suppressing nuclear translocation of ERK1/2, thereby inhibiting macrophage proliferation. This suppression of macrophage proliferation by troglitazone may, at least in part, explain its antiatherogenic effects.

Statins suppress oxidized low density lipoprotein-induced macrophage proliferation by inactivation of the small G protein-p38 MAPK pathway.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) ameliorate atherosclerotic diseases. Macrophages play an important role in the development and subsequent stability of atherosclerotic plaques. We reported previously that oxidized low density lipoprotein (Ox-LDL) induced macrophage proliferation through the secretion of granulocyte/macrophage colony-stimulating factor (GM-CSF) and the consequent activation of p38 MAPK. The present study was designed to elucidate the mechanism of the inhibitory effect of statins on macrophage proliferation. Mouse peritoneal macrophages were used in our study. Cerivastatin and simvastatin each inhibited Ox-LDL-induced [(3)H]thymidine incorporation into macrophages. Statins did not inhibit Ox-LDL-induced GM-CSF production, but inhibited GM-CSF-induced p38 MAPK activation. Farnesyl transferase inhibitor and geranylgeranyl transferase inhibitor inhibited GM-CSF-induced macrophage proliferation, and farnesyl pyrophosphate and geranylgeranyl pyrophosphate prevented the effect of statins. GM-CSF-induced p38 MAPK phosphorylation was also inhibited by farnesyl transferase inhibitor or geranylgeranyl transferase inhibitor, and farnesyl pyrophosphate and geranylgeranyl pyrophosphate prevented the suppression of GM-CSF-induced p38 MAPK phosphorylation by statins. Furthermore, we found that statin significantly inhibited the membrane translocation of the small G protein family members Ras and Rho. GM-CSF-induced p38 MAPK activation and macrophage proliferation was partially inhibited by overexpression of dominant negative Ras and completely by that of RhoA. In conclusion, statins inhibited GM-CSF-induced Ras- or RhoA-p38 MAPK signal cascades, thereby suppressing Ox-LDL-induced macrophage proliferation. The significant inhibition of macrophage proliferation by statins may also explain, at least in part, their anti-atherogenic action.

Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase mediate macrophage proliferation induced by oxidized low-density lipoprotein.

We previously reported that oxidized low-density lipoprotein (Ox-LDL)-induced expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) via PKC, leading to activation of phosphatidylinositol-3 kinase (PI-3K), was important for macrophage proliferation [J Biol Chem 275 (2000) 5810]. The aim of the present study was to elucidate the role of extracellular-signal regulated kinase 1/2 (ERK1/2) and of p38 MAPK in Ox-LDL-induced macrophage proliferation. Ox-LDL-induced proliferation of mouse peritoneal macrophages assessed by [3H]thymidine incorporation and cell counting assays was significantly inhibited by MEK1/2 inhibitors, PD98059 or U0126, and p38 MAPK inhibitors, SB203580 or SB202190, respectively. Ox-LDL-induced GM-CSF production was inhibited by MEK1/2 inhibitors but not by p38 MAPK inhibitors in mRNA and protein levels, whereas recombinant GM-CSF-induced macrophage proliferation was inhibited by p38 MAPK inhibitors but enhanced by MEK1/2 inhibitors. Recombinant GM-CSF-induced PI-3K activation and Akt phosphorylation were significantly inhibited by SB203580 but enhanced by PD98059. Our results suggest that ERK1/2 is involved in Ox-LDL-induced macrophage proliferation in the signaling pathway before GM-CSF production, whereas p38 MAPK is involved after GM-CSF release. Thus, the importance of MAPKs in Ox-LDL-induced macrophage proliferation was confirmed and the control of MAPK cascade could be targeted as a potential treatment of atherosclerosis.

15d-PGJ2 inhibits oxidized LDL-induced macrophage proliferation by inhibition of GM-CSF production via inactivation of NF-kappaB.

Macrophage-derived foam cells play an important role in atherosclerotic lesions. Oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation via production of GM-CSF in vitro. This study investigated the effects of 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a natural ligand for peroxisome proliferator-activated receptor gamma, on macrophage proliferation. Mouse peritoneal macrophages and RAW264.7 cells were used for proliferation study and reporter gene assay, respectively. Twenty microgram per milliliter of Ox-LDL induced [3H]thymidine incorporation in mouse peritoneal macrophages, and 15d-PGJ(2) inhibited Ox-LDL-induced [3H]thymidine incorporation in a dose-dependent manner. Ox-LDL increased GM-CSF release and GM-CSF mRNA expression, and activated GM-CSF gene promoter, all of which were prevented by 15d-PGJ(2) or 2-cyclopenten-1-one, a cyclopentenone ring of 15d-PGJ(2). The suppression of GM-CSF promoter activity by 15d-PGJ(2) and 2-cyclopenten-1-one was mediated through reduction of NF-kappaB binding to GM-CSF promoter. These results suggest that 15d-PGJ(2) inhibits Ox-LDL-induced macrophage proliferation through suppression of GM-CSF production via NF-kappaB inactivation.

Reactive oxygen species from mitochondria induce cyclooxygenase-2 gene expression in human mesangial cells: potential role in diabetic nephropathy.

Hyperglycemia increases the production of reactive oxygen species (ROS) from the mitochondrial electron transport chain in bovine endothelial cells. Because several studies have postulated a role for prostaglandins (PGs) in the glomerular hyperfiltration seen in early diabetes, we evaluated the effect of mitochondrial ROS on expression of the inducible isoform of cyclooxygenase (COX-2) in cultured human mesangial cells (HMCs). We first confirmed that incubation of HMC with 30 mmol/l glucose significantly increased COX-2 mRNA but not COX-1 mRNA, compared with 5.6 mmol/l glucose. Similarly, incubation of HMCs with 30 mmol/l glucose significantly increased mitochondrial membrane potential, intracellular ROS production, COX-2 protein expression, and PGE2 synthesis, and these events were completely suppressed by thenoyltrifluoroacetone or carbonyl cyanide m-chlorophenylhydrazone, inhibitors of mitochondrial metabolism, or by overexpression of uncoupling protein-1 or manganese superoxide dismutase. Furthermore, increased expression of COX-2 mRNA and protein was confirmed in glomeruli of streptozotocin-induced diabetic mice. In addition, hyperglycemia induced activation of the COX-2 gene promoter, which was completely abrogated by mutation of two nuclear factor kappaB (NF-kappaB) binding sites in the promoter region. Our results suggest that hyperglycemia increases mitochondrial ROS production, resulting in NF-kappaB activation, COX-2 mRNA induction, COX-2 protein production, and PGE2 synthesis. This chain of events might contribute to the pathogenesis of diabetic nephropathy.

Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes.

OBJECTIVE: To evaluate urinary 8-hydroxydeoxyguanosine (8-OHdG) as a marker for the progression of diabetic macroangiopathic complications. RESEARCH DESIGN AND METHODS: The content of urinary 8-OHdG, common carotid intima-media thickness (IMT), the coronary heart disease (CHD) risk score, the severity of diabetic retinopathy, and urinary albumin excretion were examined in 96 patients with type 2 diabetes, including 32 patients who had been nominated for the Kumamoto Study [Shichiri M, et al. Diabetes Care 23 (Suppl 2):B21-B29, 2000]. In addition, the patients from the Kumamoto Study were further evaluated regarding the effect of intensive insulin therapy on urinary 8-OHdG excretion. RESULTS: The urinary 8-OHdG:creatinine ratio (U8-OHdG) was 2.5-fold higher in patients with increased HbA(1c) than in those with normal HbA(1c) (P < 0.05). In addition, U8-OHdG was 2.3-fold higher in patients with increased IMT (P < 0.005). A similar result was observed between U8-OHdG and CHD risk score (P < 0.01). U8-OHdG was significantly higher in patients with simple retinopathy (P < 0.05) and those with advanced retinopathy (P < 0.01) than in patients without retinopathy. Similarly, U8-OHdG was significantly higher in patients with albuminuria (P < 0.01). Furthermore, in the Kumamoto Study, U8-OHdG was significantly lower in the multiple insulin injection therapy group compared with the conventional insulin injection therapy group (P < 0.01). CONCLUSIONS: Hyperglycemia independently increases 8-OHdG in patients with type 2 diabetes. 8-OHdG is a useful biomarker of not only microvascular but also macrovascular complications in patients with type 2 diabetes.