A comparative study of remotely sensed reservoir monitoring across multiple land cover types.

Continuous monitoring of reservoirs and dams is essential for efficient water management. Synthetic Aperture Radar (SAR) imagery offers the potential for continuous monitoring of surface water through all-weather ground observation. The objective of this study is to enhance the accuracy of water body detection and water quantity estimation by applying 64 combinations of speckle filtering and object detection techniques to Sentinel-1 imagery. For speckle filtering, the Median, Gaussian, Lee, and Frost techniques were used with various window sizes (3, 5, 7, and 9). For water body detection, the Otsu, Kittler-Illingworth (KI), Chan-Vese (CV), and K-means methods were employed. The study area included three reservoirs and two dams in Korea, encompassing a variety of water surface sizes and types of land cover. To validate the accuracy of each water body detection combination, manual delineation-based water mask images from Sentinel-2 were employed. Furthermore, a regression equation (y=axb) between water surface area and storage was used to estimate water storage based on SAR imagery, followed by time-series validation using in-situ data. The research results indicate that the optimal detection technique varies significantly depending on the type of surrounding land cover and the size of the water body. The highest performance was observed for the CV technique combination for waterfront pixels, and for the KI technique combination for other land cover pixels. In speckle filtering techniques using a large window size, the false detection rate caused by vegetation and buildings was low; however, the boundaries of water bodies were blurred. Consequently, using smaller window sizes in SAR imagery and leveraging optimal water body detection combinations specific to land cover types, along with post-processing using masking data, would enhance the performance of water surface area and storage estimation.

Zwitterionic polymer on silicone implants inhibits the bacteria-driven pathogenic mechanism and progress of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) occurs in the capsule surrounding breast implants. Malignant transformation of T cells by bacteria-driven chronic inflammation may be underlying BIA-ALCL mechanism. Here, we covalently grafted 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymers on a silicone surface and examined its effects against BIA-ALCL pathogenesis. MPC grafting strongly inhibited the adhesion of bacteria and bacteria-causing inflammation. Additionally, cancer T cell proliferation and capsule-derived fibroblast-cancer cell communication were effectively inhibited by MPC grafting. We further demonstrated the effect of MPC against the immune responses causing BIA-ALCL around human silicone implants in micro-pigs. Finally, we generated a xenograft anaplastic T cell lymphoma mouse model around the silicone implants and demonstrated that MPC grafting could effectively inhibit the lymphoma progression. This study is the first to show that bacteria-driven induction and progression of BIA-ALCL can be effectively inhibited by surface modification of implants. STATEMENT OF SIGNIFICANCE: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a major concern in the field of plastic and reconstructive surgery. In this study, we demonstrate strong inhibitory effect of zwitterionic polymer grafting on BIA-ALCL pathogenesis and progression, induced by bacterial infection and inflammation, both in vitro and in vivo. This study provides a molecular basis for the development of novel breast implants that can prevent various potential complications such as excessive capsular contracture, breast implant illness, and BIA-ALCL incidence, as well as for expanding the biomedical applications of zwitterionic polymers.

Comparison of long-term outcomes in simultaneous pancreas-kidney transplant versus simultaneous deceased donor pancreas and living donor kidney transplant.

Simultaneous deceased donor pancreas and living donor kidney transplant (SPLK) has certain advantages over conventional simultaneous pancreas-kidney transplant (SPK) and may be beneficial for overcoming the paucity of organs needed for diabetic patients requiring transplant. We compared the clinical outcomes of patients who underwent either SPK (n = 149) or SPLK (n = 46) in terms of pre- and post-transplantation variables, development of de novo DSA, occurrence of biopsy-proven acute rejection (BPAR), and graft survival rates. There were no significant differences in the baseline characteristics between the SPK and SPLK groups except for the shorter cold ischemic time of kidney grafts, shorter duration of diabetes, older age of pancreas graft-donors, and younger age of kidney graft-donors in the SPLK group. Our results showed that the death-censored pancreas graft survival rate was lower in the SPLK group. In addition, the incidence of BPAR of the pancreas graft was higher in the SPLK group. There was no significant difference in the presence of de novo DSA and the rates of kidney graft failure, kidney BPAR, and mortality. Our results show that SPLK can be considered an alternative option for SPK although higher incidences of BPAR and graft failure of pancreas after SPLK need to be overcome.

Three-dimensional imaging and analysis of pathological tissue samples with de novo generation of citrate-based fluorophores.

Two-dimensional (2D) histopathology based on the observation of thin tissue slides is the current paradigm in diagnosis and prognosis. However, labeling strategies in conventional histopathology are limited in compatibility with 3D imaging combined with tissue clearing techniques. Here, we present a rapid and efficient volumetric imaging technique of pathological tissues called 3D tissue imaging through de novo formation of fluorophores, or 3DNFC, which is the integration of citrate-based fluorogenic reaction DNFC and tissue clearing techniques. 3DNFC markedly increases the fluorescence intensity of tissues by generating fluorophores on nonfluorescent amino-terminal cysteine and visualizes the 3D structure of the tissues to provide their anatomical morphology and volumetric information. Furthermore, the application of 3DNFC to pathological tissue achieves the 3D reconstruction for the unbiased analysis of diverse features of the disorders in their natural context. We suggest that 3DNFC is a promising volumetric imaging method for the prognosis and diagnosis of pathological tissues.

An Agonistic Monoclonal Antibody Targeting cMet Attenuates Inflammation and Up-Regulates Collagen Synthesis and Angiogenesis in Type 2 Diabetic Mice Wounds.

BACKGROUND: Diabetic wounds account for 25 to 50 percent of total diabetic health care costs annually, and present overall healing rates of less than 50 percent. Because delayed diabetic wound healing is associated with impaired fibroblast function, the authors hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody will promote diabetic wound healing by means of stable activation of hepatocyte growth factor/cMet signaling. METHODS: Two 6-mm dorsal wounds were created in each mouse (6-week-old, male BKS.Cg-Dock7 m +/+Lepr db /J; n = 5). After subcutaneous injections of agonist (20 mg/kg) at 0 and 72 hours, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histologic and immunohistochemical analyses were performed at day 10 (cMet, α-smooth muscle actin, CD68, and transforming growth factor-ß). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with or without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p44/42 mitogen-activated protein kinase, p-mTOR, p-cMet, and ROCK-1 expression. RESULTS: The cMet agonistic monoclonal antibody-treated group showed 1.60-fold lower wound area ( p = 0.027), 1.54-fold higher collagen synthesis ( p = 0.001), and 1.79-fold lower inflammatory cell infiltration ( p = 0.032) than the saline-treated control. The agonist increased cMet (1.86-fold; p = 0.029), α-smooth muscle actin (1.20-fold; p = 0.018), and vascular endothelial growth factor (1.68-fold, p = 0.029) expression but suppressed CD68 (1.25-fold; p = 0.043), transforming growth factor-ß (1.25-fold; p = 0.022), and matrix metalloproteinase-2 (2.59-fold; p = 0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold ( p = 0.029) and activated the hepatocyte growth factor/cMet pathway. CONCLUSIONS: Tyrosine kinase Met agonistic monoclonal antibody treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials. CLINICAL RELEVANCE STATEMENT: Although further clinical studies are necessary to evaluate its therapeutic efficacy, our study suggested that cMet agonistic monoclonal antibody can be the alternative modality in order to improve wound healing cascade in diabetic foot patients.

Novel Chitosan Dermal Filler with Enhanced Moldability and Elasticity.

Currently, dermal fillers are largely based on commercialized cross-linked hyaluronic acid (HA) injections, which require a large injection force. Additionally, HA can be easily decomposed by enzymes, and HA-treated tissues present a risk of developing granuloma. In this study, a chitosan-based dermal filler is presented that operates on a liquid-to-gel transition and allows the injection force to be kept ≈4.7 times lower than that required for HA injections. Evaluation of the physical properties of the chitosan filler indicates high viscoelasticity and recovery rate after gelation at 37 °C. Furthermore, in an in vivo evaluation, the liquid injection-type chitosan filler transitions to a gel state within 5 min after injection into the body, and exhibits a compressive strength that is ≈2.4 times higher than that of cross-linked HA. The filler also exhibits higher moldability and maintains a constant volume in the skin for a longer time than the commercial HA filler. Therefore, it is expected that the chitosan filler will be clinically applicable as a novel material for dermal tissue restoration and supplementation.

A selective small-molecule inhibitor of c-Met suppresses keloid fibroblast growth in vitro and in a mouse model.

Keloids, tumor-like lesions that result from excessive scar formation, have no definitive treatment modality. Activation of c-mesenchymal-epithelial transition factor (c-Met) promotes cell proliferation and survival. Selective c-Met inhibitors, such as PHA-665752, may attenuate the activity of keloid fibroblasts and reduce keloid formation. Here, we aimed to evaluate the effect of PHA-665752, a second-generation selective small-molecule inhibitor of c-Met, on human keloid fibroblasts in vitro and in a mouse model. We performed in vitro cytotoxicity assays, scratch tests, western blotting, and immunofluorescence on human keloid fibroblasts. We also injected human fibroblasts into severe combined immunodeficient mice and measured the degree of nodule formation and skin histologic characteristics. We found that keloid fibroblast migration was inhibited by PHA-665752. Inhibitor treatment was also associated with lower expression of members of the hepatocyte growth factor/c-Met pathway, and lower fibroblast activity and collagen synthesis. In the in vivo experiments, PHA-665752-treated mice had lower nodule volumes and weights, accompanied by less inflammatory cell infiltration and collagen deposition, than those in control mice. These findings showed that although an in vivo model may not accurately represent the pathophysiology of human keloid development, PHA-665752 suppressed keloid fibroblast activity by inhibiting the c-Met-related tyrosine kinase pathway.

Water use efficiency in terrestrial ecosystem over East Asia: Effects of climate regimes and land cover types.

Water use efficiency (WUE) is an environmental factor to account for the metabolism of terrestrial ecosystems using various climate systems and vegetation types. It is estimated by the ratio of gross primary productivity (GPP) to evapotranspiration (ET), the largest carbon and water fluxes with respect to plant respiration. In this study, the WUE was calculated using GPP and ET from the community land model version 4.0 (CLM4.0), inclusive of the prognostic carbon-nitrogen model in the community earth system model (CESM). The estimated WUE in East Asia was analyzed for climate zones, land cover types, and water- and energy-limited zones, with aridity index (AI). Spatial variations from 2001 to 2015 in annual WUE gradually increased as latitude decreased, though small year-to-year differences appeared between monthly GPP and ET. Monthly WUE was lower in summer than fall because the water loss rate in summer was higher than the carbon assimilation increase. The WUE under arid conditions (AI<0.5) was lower than under humid conditions. The GPP, ET, and WUE were higher in the forest, savannas, cropland, and permanent wetland with dense vegetation or abundant water resources than in other land cover types. The WUE was lower in water-limited zones than in energy-limited zones due to the low amount of water to use for the physical processes of GPP and ET. Based on this study, we identified general spatial and temporal variations of carbon fluxes in East Asia with various climate zones and land cover types.

Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing.

Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.

Comparative outcomes between totally laparoscopic total gastrectomy with the modified overlap method for early gastric cancer and advanced gastric cancer: review of 149 consecutive cases.

INTRODUCTION: Totally laparoscopic total gastrectomy (TLTG) for advanced gastric cancer (AGC) has not been conclusively substantiated. AIM: To evaluate TLTG treatment of AGC by comparing its effectiveness and surgical outcomes to those of TLTG treatment of early gastric cancer (EGC). MATERIAL AND METHODS: We performed TLTG with the (modified) overlap method for 149 gastric cancer cases between March 2012 and December 2018. We evaluated clinicopathologic characteristics, complications (including esophagojejunostomy site complications), and surgical outcomes. We also evaluated these variables in terms of their associations with EGC and AGC. RESULTS: Ninety-two males and 57 females, with a mean age of 60.7 years, were included. The mean operation time was 147.7 min. The mean number of harvested lymph nodes was 39.6. Thirteen (8.7%) patients experienced early complications, and 6 (4.0%) experienced late complications (Clavien-Dindo classification ≥ III). Eight (5.4%) patients underwent reoperation, and 8 (5.4%) were readmitted due to complications. There were no statistically significant differences in operation time, hospital stay, or surgical mortality between EGC and AGC. However, there were significant differences in early complications, late complications, rate of reoperation, and rate of readmission between EGC and AGC. CONCLUSIONS: Although it has some limitations, TLTG with the (modified) overlap method for AGC treatment is feasible, safe, and associated with favorable outcomes.

Impact of climate, rising atmospheric carbon dioxide, and other environmental factors on water-use efficiency at multiple land cover types.

Rising atmospheric CO2, changing climate, and other environmental factors such as nitrogen deposition and aerosol concentration influence carbon and water fluxes significantly. Water-use efficiency (WUE) was used to analyze these factors over 3 decades (1981-2010) using the Community Land Model 5.0 (CLM5.0). The study analyzes the effects of climate and other environmental factors on multiple land cover types (forest, grassland, and cropland) with divided study periods (1981-2000 and 2001-2010). Ecosystem WUE (EWUE) and transpiration WUE (TWUE) increased at the forest site due to the CO2 fertilization effect but decreased at the grassland and cropland sites due to lower gross primary production and higher/lower (cropland/grassland) evapotranspiration as consequences of rising temperature and water availability. Inherent WUE confirmed that EWUE and TWUE trends were controlled by the rising temperature and CO2-induced warming through an increase in vapor pressure deficit. In this way, forest and cropland sites showed warming patterns, while the grassland site showed a drier climate. The later period (2001-2010) showed steeper trends in WUE compared with the earlier period at all sites, implying a change in climate. The results showed implications for rising temperature due to increased CO2 concentration at multiple land cover types.

Satellite-based global-scale irrigation water use and its contemporary trends.

Irrigated agriculture is important for satisfying the increasing world food demand, but it interrupts the natural hydrological cycle by applying additional water to crops. Accurate information regarding irrigation water use (IWU) is a prerequisite to exploit land surface modeling and to quantify the uncertainty of climate projections. In this study, the global IWU was estimated for 2000-2015 by combining satellite-based soil moisture (SM) observations from the European Space Agency's Climate Change Initiative (ESA CCI) and the model estimated SM from European ReAnalysis-5 (ERA5). Considering irrigation as an unmodeled hydrological process in ERA5 and the ability of ESA CCI SM to capture the irrigation patterns, the global IWU was estimated by solving the water balance equations for ESA CCI and ERA5 SM. Owing to the global absence of ground-truth data for IWU, the IWU estimates were compared with the reported irrigation water withdrawals (IWWs) provided by Food and Agriculture Organization. The results indicated that satellite-based SM observations have the potential to identify global irrigation. All three ESA CCI products (active, passive, and merged) discerned the global irrigated areas satisfactorily, and the estimated IWU captured the pattern of the country-level IWWs (R = 0.77, 0.72, and 0.81 for active, passive, and merged products, respectively). However, the estimated IWU substantially underestimated the reported IWWs (bias of -76.55, -76.01, and -73.93 km3 for active, passive, and merged products, respectively) due to the coarse spatial resolution (0.25° × 0.25°) of the microwave remote sensing products and the inclusion of supplemental water in the IWWs, which was lost during distribution to crops. Trend analysis of the IWU indicated an increasing trend of the IWU in the first decade of the 21st century. However, in recent years the trend has reversed due to advances in agriculture technology and the adoption of water-efficient irrigation methods.

Impact of Biophysical Mechanisms on Urban Heat Island Associated with Climate Variation and Urban Morphology.

The rapid development of urban areas can potentially alter hydro-meteorological fluxes and lead to the Urban Heat Island (UHI) phenomenon. In this study, UHI intensity and its driving factors were estimated using the Community Land Model (CLM) in cities of Tokyo, Phoenix, Bandung, and Quito, with different landscapes and climates, as a step in risk assessment of urbanization phenomena. The UHI magnitude increased along with the ratio of the height to width (H/W) of urban canyons in cities with the same latitude, especially during the daytime, when Quito (Tokyo) had a higher UHI than Bandung (Phoenix). El Niño-Southern Oscillation (ENSO) events, such as El Niño and La Niña, contributed to UHI variability, during which the cities in the western (eastern) part of Pacific Ocean experienced a higher UHI during El Niño (La Niña). The UHI differences from total biophysical drivers between these events were highest in Tokyo during the daytime as a result of convection process, and in Phoenix during the nighttime due to the hot arid climate of the city. Our results suggest the need to consider climate variation beyond local site characteristics when mitigating heat stress and making decisions regarding urban development.

Influence of Microbiota on Diabetic Foot Wound in Comparison with Adjacent Normal Skin Based on the Clinical Features.

Diabetic foot ulcer (DFU) is a complication experienced by diabetic patients and does not heal well in an altered wound environment. Although diverse microbes in DFU were detected, little is known about their influences on diabetic foot wound (DFW) and the association with the skin microbiota in normal tissue from the same patients according to clinical features. We aimed to analyze the microbiota in normal skin and DFW tissue from the same subject and predict their roles based on clinical features. We analyzed the microbiota in normal skin and DFW tissue from the same subject and compared the associated members of microbiota with clinical parameters. The diversity of skin microbiota was higher than that of DFW tissues, along with compositional differences. In addition, different microbes were associated with clinical features. The proportions of Bacteroidetes, Prevotella, Peptoniphilus, Porphyromonas, and Dialister were higher in the severe groups than of the mild groups, whereas that of Firmicutes was lower in the severe groups. According to wound severity, the microbiota could be related to inflammation, damaging host cell membrane, and pathogenicity through lipopolysaccharide biosynthesis, cellular antigens, and protein digestion metabolism. The predicted DFW microbiota functions according to systemic diabetic status defined by ESRD and HbA1c, differed from those presented by wound severity. Results indicate that the microbiota in normal skin is related to the colonizing microbes in DFW tissue according to clinical features and the different microbes can play important roles in DFW prognosis. This information can be applied to prevent and manage DFW by modulating the microbiota.

Impacts of land use/land cover on runoff and energy budgets in an East Asia ecosystem from remotely sensed data in a community land model.

The impacts of land use/land cover (LULC) conditions on the global water and energy budgets are essential to understanding climate intensification in the 21st century. This study evaluated latent heat flux (LE), sensible heat flux (H), and runoff in four climate regions (temperate, continental, arid, and tropical) in East Asia from 2001 to 2015. Two community land model (CLM) experiments were performed using default LULC data (CLM 4.0) and newly created Moderate Resolution Imaging Spectroradiometer (MODIS) based LULC data from 2010 (CLM 2010) to assess the impact of LULC changes on climate. Anthropogenic LULC changes have considerable impacts on the climate and its extremes. For the whole East Asia region, area-averaged runoff decreased by 2.10%. The temperate region experienced a 3.16% decrease in runoff and a 4.22% increase in LE due to an increase in irrigation activities that could lead to the drying of soil moisture and drought in the future. In contrast, the arid region experienced a 6.30% increase in runoff despite dry conditions and a 5.70% reduction in LE, which ultimately increased H by 2.25% and caused an intensification of the climate in the form of strong heat waves and floods. The continental region followed the same trend as the temperate region with a noticeable decrease in winter H, which caused severe cold weather. The tropical region showed a slight impact of LULC change on energy fluxes due to high precipitation and intense solar radiations. Overall, the results of this research follow the 'dry gets drier and wet gets wetter' paradigm due to LULC changes in the study region.

Detecting global irrigated areas by using satellite and reanalysis products.

Despite the importance of irrigation in meeting the world's food demand and as an essential human modification to water and energy cycles, the reliable extent and distribution of the global irrigated areas remain undefined. In this study, an intuitive method is proposed, based on the aftereffects of irrigation, to detect global irrigated areas by combining satellite and reanalysis datasets. The proposed methodology assumes that irrigation is an unmodeled land surface process, while satellite observations can effectively detect irrigation signals in near real-time. The spatial extents of irrigation were derived by calculating the difference between the remotely sensed and reanalysis datasets. To detect the irrigated areas, three irrigation-dependent variables, soil moisture (SM), land surface temperature (LST), and surface albedo (AL), were used. In the absence of reliable ground truths, the proposed irrigation map was compared to the commonly used global irrigation maps, namely Global Map of Irrigated areas, Global Irrigated Area Map, and recently developed Global Irrigated Areas by Meier et al. (2018). Individual detection by SM, LST, and AL has discrepancies in detecting irrigation signals in highly irrigated, urbanized, and semi-arid regions. However, by combining the individual detection maps, the proposed method showed reasonable agreement with the reference irrigated maps overlapping with approximately 70% of the irrigated areas. We believe that the proposed method, as stand-alone or in combination with the existing irrigation maps, will benefit the studies regarding water and energy balance closure in near-real time for large-scale land surface models by minimizing the uncertainties in model parameterization.

Estimation of health benefits from air quality improvement using the MODIS AOD dataset in Seoul, Korea.

BACKGROUND: Exposure to fine particles in the atmosphere can adversely affect health and even lead to premature death. Recently, South Korea has attracted attention because of its rapid increase in the concentration of Particulate Matter (PM). OBJECTIVES: We estimated the economic benefits of reducing PM10 in Seoul, South Korea, based on MODerate-resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth (AOD). Based on the retrieved PM10 data, we estimated its effects on overall health in each district of Seoul, Korea between 2014 and 2015. METHODS: The relationships between MODIS AOD and ground-based PM10 data were identified in different seasons in South Korea between 2012 and 2013 using the linear regression model. The health benefits were estimated by the Benefits Mapping and Analysis Program (Benmap) using the scenarios from the World Health Organization (WHO). RESULTS: The correlation between MODIS AOD and PM10 concentration differed with the season. There was a higher correlation between MODIS AOD and PM10 concentration in winter (R = 0.57) than there was in other seasons. Based on the MODIS AOD, the average annual PM10 concentration in Seoul was higher in 2014 than it was in 2015, at values of 45.7 µg/m3, and 41.6 µg/m3, respectively. The greatest economic benefit of reducing PM10 concentration (WHO annual standard of 20 µg/m3) was in 2014. This benefit was estimated to be 7022 (95% CI: 599, 20496), 2617 (95% CI: 216, 7750), and 1328 (95% CI: -159, 4679) billion KRW for all-cause, cardiovascular, and respiratory mortalities in 2014 and 2015, respectively. CONCLUSIONS: These results demonstrate that, despite considerable improvements in air quality in recent decades, there is still a need for countermeasures to prevent economic loss due to air pollution in Seoul.

Development of a non-human primate model to support CNS translational research: Demonstration with D-amphetamine exposure and dopamine response.

BACKGROUND: Challenges specific to the discovery and development of candidate CNS drugs have led to implementation of various in silico, in vitro and in vivo approaches to improve the odds for commercialization of novel treatments. NEW METHOD: Advances in analytical methodology and microdialysis probe design have enabled development of a non-human primate model capable of measuring concentrations of drugs or endogenous chemicals in brain extracellular fluid (ECF) and cerebrospinal fluid (CSF). Linking these to population modeling reduces animal numbers to support predictive translational sciences in primates. Application to measure D-amphetamine exposure and dopamine response in ECF and CSF demonstrate the approach. RESULTS: Following a 0.1 mg/kg intravenous bolus dose of D-amphetamine, a population approach was used to build a plasma compartmental-based and brain physiologic-based pharmacokinetic (PK) model linking drug concentrations in plasma to brain ECF and CSF concentrations. Dopamine was also measured in brain ECF. The PK model was used to simulate the relationship between D-amphetamine exposure and dopamine response in ECF over a wide dose range. COMPARISONS WITH EXISTING METHODS: Ability to co-sample and measure drug and endogenous substances in blood, brain ECF and/or CSF, coupled with population modeling, provides an in vivo approach to evaluate CNS drug penetration and effect in non-human primates. CONCLUSIONS: A method to measure drug and endogenous neurochemicals in non-human primate brain fluids is demonstrated. Its basis in non-human primates merits improved confidence regarding predictions of drug exposure and target engagement in human CNS.

Adipose-derived stem cells attenuate atopic dermatitis-like skin lesions in NC/Nga mice.

There is an unmet need in novel therapeutics for atopic dermatitis (AD). We examined the effects of autologous adipose-derived stem cells (ADSCs) on AD-like skin lesions induced by the application of 2,4-dinitrochlorobenzene (DNCB) in NC/Nga mice. Autologous ADSCs and ADSC-conditioned medium (ADSC-CM) were injected intralesionally three times. Clinical severity and histopathologic findings were compared in sham naïve control, saline-treated, ADSC-treated, ADSC-CM-treated and 2.5% cortisone lotion-applied animals. The severity index, skin thickness, mast cell number, as well as expression levels of thymic stromal lymphopoietin, CD45, chemoattractant receptor-homologous molecule, chemokine ligand 9 and chemokine ligand 20 were significantly lower in mice treated with ADSC, ADSC-CM, or 2.5% cortisone lotion. Tissue levels of interferon-γ as well as serum levels of interleukin-33 and immunoglobulin E levels were also decreased in those groups. We conclude that autologous ADSCs improved DNCB-induced AD-like skin lesions in NC/Nga mice by reducing inflammation associated with Th2 immune response and interferon-γ.

Impact of air pollution on cause-specific mortality in Korea: Results from Bayesian Model Averaging and Principle Component Regression approaches.

Health effects related to air pollution are a major global concern. Related studies based on reliable exposure assessment methods would potentially enable policy makers to propose appropriate environmental management policies. In this study, integrated Bayesian Model Averaging (BMA) and Principle Component Regression (PCR) were adopted to assess the severity of air pollution impacts on mortality related to circulatory, respiratory and skin diseases in 25 districts of Seoul, South Korea for the years 2005-2015. These methods were consistent in determining the best regression models and most important pollutants related to mortality in those highly susceptible to poor air quality. Specifically, the results demonstrated that pneumonia was highly associated with air pollution, with a large determination coefficient (BMA: 0.46, PCR: 0.51) and high model's posterior probability (0.47). The most reliable prediction model for pneumonia was indicated by the lowest Bayesian Information Criterion. Among the pollutants, particulate matter with an aerodynamic diameter of 10 µm or less (PM10) was associated with serious health risks on evaluation, with the highest posterior inclusion probabilities (range, 80.20 to 100.00%) and significantly positive correlation coefficients (range, 0.14 to 0.34, p < 0.05). In addition, excessive PM10 concentration (approximately 2.54 times the threshold) and a continuous increase in mortality due to respiratory diseases (approximately 1.50-fold in 10 years) were also exhibited. Overall, the results of this study suggest that currently, socio-environmental policies and international collaboration to mitigate health effects of air pollution is necessary in Seoul, Korea. Moreover, consideration of uncertainty of the regression model, which was verified in this research, will facilitate further application of this approach and enable optimal prediction of interactions between human and environmental factors.