Background Sweet syndrome is a neutrophilic dermatosis with cutaneous tender lesions that can be associated with malignancies, infections, systemic inflammatory disorders, and medications. Although ...numerous studies have described Sweet syndrome, few studies have systematically investigated Sweet syndrome. Objective We sought to describe characteristics and treatments of patients with Sweet syndrome and evaluate clinical differences depending on the underlying cause. Methods A retrospective study was conducted to identify patients with Sweet syndrome evaluated at Mayo Clinic from 1992 to 2010. Results Of 77 patients with Sweet syndrome (mean age of onset 57 years), 43 (56%) were male. Eighteen patients (23%) reported a preceding infection. A total of 41 (53%) patients were classified as having classic Sweet syndrome, 27 (35%) patients had malignancy-associated Sweet syndrome, and in 9 (12%) patients drug-induced Sweet syndrome was considered. In all, 21 patients had a hematologic malignancy or myeloproliferative/myelodysplastic disorder, whereas 6 patients had solid tumors. The mean hemoglobin level, in both male and female patients ( P < .0443 and P < .0035, respectively), was significantly lower in malignancy-associated versus classic and drug-induced Sweet syndrome. Systemic corticosteroids were the most frequently used treatment (70%). Limitations This is a retrospective study and represents patients from a single academic center. Conclusions Sweet syndrome is a distinctive disorder with certain clinical and histologic characteristics, which usually has a complete response to systemic corticosteroids. It is important to evaluate Sweet syndrome patients who have laboratory evidence of anemia for an underlying malignancy.
Concerns over groundwater depletion and ecosystem degradation have led to the incorporation of the concept of groundwater sustainability as a groundwater policy instrument in several water codes and ...management directives worldwide. Because sustainable groundwater management is embedded within integrated, co-evolving hydrological, ecological, and socioeconomic systems, implementing such policies remains a challenge for water managers and the scientific community. The problem is further exacerbated when participatory processes are lacking, resulting in a communication gap among water authorities, scientists, and the broader community. This paper provides a systematic review of the concept of groundwater sustainability, and situates this concept within the calls from the hydrologic literature for more participatory and integrated approaches to water security. We discuss the definition of groundwater sustainability from both a policy and scientific perspective, tracing the evolution of this concept from safe yield, to sustainable groundwater management. We focus on the diversity of societal values related to groundwater sustainability, and the typology of the aquifer performance and governance factors. In addition, we systematically review the main components of an effective scientific evaluation of groundwater sustainability policy, which are multi-process modeling, uncertainty analysis, and participation. We conclude that effective groundwater sustainability policy implementation requires an iterative scientific evaluation that (i) engages stakeholders in a participatory process through collaborative modeling and social learning; (ii) provides improved understanding of the coevolving scenarios between surface water-groundwater systems, ecosystems, and human activities; and (iii) acknowledges and addresses uncertainty in our scientific knowledge and the diversity of societal preferences using multi-model uncertainty analysis and adaptive management. Although the development of such a transdisciplinary research approach, which connects policy, science, and practice for groundwater sustainability evaluation, is still in its infancy worldwide, we find that research towards groundwater sustainability is growing at a much faster rate than groundwater research as a whole.
This paper focuses on a collection of methods that can be used to analyze the water-energy-food (WEF) nexus. We classify these methods as qualitative or quantitative for interdisciplinary and ...transdisciplinary research approaches. The methods for interdisciplinary research approaches can be used to unify a collection of related variables, visualize the research problem, evaluate the issue, and simulate the system of interest. Qualitative methods are generally used to describe the nexus in the region of interest, and include primary research methods such as Questionnaire Surveys, as well as secondary research methods such as Ontology Engineering and Integrated Maps. Quantitative methods for examining the nexus include Physical Models, Benefit-Cost Analysis (BCA), Integrated Indices, and Optimization Management Models. The authors discuss each of these methods in the following sections, along with accompanying case studies from research sites in Japan and the Philippines. Although the case studies are specific to two regions, these methods could be applicable to other areas, with appropriate calibration.
A number of MR-derived quantitative metrics have been suggested to assess the pathophysiology of MS, but the reports about combined analyses of these metrics are scarce. Our aim was to assess the ...spatial distribution of parameters for white matter myelin and axon integrity in patients with relapsing-remitting MS by multiparametric MR imaging.
Twenty-four patients with relapsing-remitting MS and 24 age- and sex-matched controls were prospectively scanned by quantitative synthetic and 2-shell diffusion MR imaging. Synthetic MR imaging data were used to retrieve relaxometry parameters (R1 and R2 relaxation rates and proton density) and myelin volume fraction. Diffusion tensor metrics (fractional anisotropy and mean, axial, and radial diffusivity) and neurite orientation and dispersion index metrics (intracellular volume fraction, isotropic volume fraction, and orientation dispersion index) were retrieved from diffusion MR imaging data. These data were analyzed using Tract-Based Spatial Statistics.
Patients with MS showed significantly lower fractional anisotropy and myelin volume fraction and higher isotropic volume fraction in widespread white matter areas. Areas with different isotropic volume fractions were included within areas with lower fractional anisotropy. Myelin volume fraction showed no significant difference in some areas with significantly decreased fractional anisotropy in MS, including in the genu of the corpus callosum and bilateral anterior corona radiata, whereas myelin volume fraction was significantly decreased in some areas where fractional anisotropy showed no significant difference, including the bilateral posterior limb of the internal capsule, external capsule, sagittal striatum, fornix, and uncinate fasciculus.
We found differences in spatial distribution of abnormality in fractional anisotropy, isotropic volume fraction, and myelin volume fraction distribution in MS, which might be useful for characterizing white matter in patients with MS.
We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. ...However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for producing chimeric mice for use in future long-term studies, including hepatitis virus infection analysis or drug toxicity studies.
Synthetic FLAIR images are of lower quality than conventional FLAIR images. Here, we aimed to improve the synthetic FLAIR image quality using deep learning with pixel-by-pixel translation through ...conditional generative adversarial network training.
Forty patients with MS were prospectively included and scanned (3T) to acquire synthetic MR imaging and conventional FLAIR images. Synthetic FLAIR images were created with the SyMRI software. Acquired data were divided into 30 training and 10 test datasets. A conditional generative adversarial network was trained to generate improved FLAIR images from raw synthetic MR imaging data using conventional FLAIR images as targets. The peak signal-to-noise ratio, normalized root mean square error, and the Dice index of MS lesion maps were calculated for synthetic and deep learning FLAIR images against conventional FLAIR images, respectively. Lesion conspicuity and the existence of artifacts were visually assessed.
The peak signal-to-noise ratio and normalized root mean square error were significantly higher and lower, respectively, in generated-versus-synthetic FLAIR images in aggregate intracranial tissues and all tissue segments (all
< .001). The Dice index of lesion maps and visual lesion conspicuity were comparable between generated and synthetic FLAIR images (
= 1 and .59, respectively). Generated FLAIR images showed fewer granular artifacts (
= .003) and swelling artifacts (in all cases) than synthetic FLAIR images.
Using deep learning, we improved the synthetic FLAIR image quality by generating FLAIR images that have contrast closer to that of conventional FLAIR images and fewer granular and swelling artifacts, while preserving the lesion contrast.
Claudin-1 (CL-1) is responsible for the paracellular barrier function of glomerular parietal epithelial cells (PEC) in kidneys, but the role of CL-1 in proximal tubules remains to be elucidated. In ...this study, to evaluate CL-1 as a potential therapeutic drug target for chronic kidney disease, we investigated change of CL-1 expression in the proximal tubules of diseased kidney and elucidated the factors that induced this change. We established Alport mice as a kidney disease model and investigated the expression of CL-1 in diseased kidney using quantitative PCR and immunohistochemistry (IHC). Compared to wild type mice, Alport mice showed significant increases in plasma creatinine, urea nitrogen and urinary albumin excretion. CL-1 mRNA was increased significantly in the kidney cortex and CL-1 was localized on the adjacent cell surfaces of PECs and proximal tubular epithelial cells. The infiltration of inflammatory cells around proximal tubules and a significant increase in TNF-α mRNA were observed in diseased kidneys. To reveal factors that induce CL-1, we analyzed the induction of CL-1 by albumin or tumor necrosis factor (TNF)-α in human proximal tubular cells (RPTEC/TERT1) using quantitative PCR and Western blotting. TNF-α increased CL-1 expression dose-dependently, though albumin did not affect CL-1 expression in RPTEC/TERT1. In addition, both CL-1 and TNF-α expression were significantly increased in UUO mice, which are commonly used as a model of tubulointerstitial inflammation without albuminuria. These results indicate that CL-1 expression is induced by inflammation, not by albuminuria in diseased proximal tubules. Moreover, we examined the localization of CL-1 in the kidney of IgA nephropathy patients by IHC and found CL-1 expression was also elevated in the proximal tubular cells. Taken together, CL-1 expression is increased in the proximal tubular epithelial cells of diseased kidney. Inflammatory cells around the tubular epithelium may produce TNF-α which in turn induces CL-1 expression.
Hypertension may be related to alterations of the glymphatic system, a waste metabolite drainage system in the brain. We aimed to investigate analysis along the perivascular space index changes in ...elderly subjects with hypertension.
Diffusion-weighted images were acquired from 126 subjects, including 63 subjects with hypertension (25 men and 38 women; mean age, 72.45 years) and 63 age- and sex-matched controls (25 men and 38 women; mean age, 72.16 years). We calculated the analysis along the perivascular space index as a ratio of the mean of x-axis diffusivities in the projection and association areas to the mean of y-axis diffusivity in the projection area and z-axis diffusivity in the association area. The left, right, and mean analysis along the perivascular space indices of both hemispheres were compared between the hypertension and control groups using a Mann-Whitney
test. The Spearman correlation coefficient was used to assess the correlation between the left, right, and mean ALPS indices and blood pressure and pulse pressure.
The left (
= .011) and mean (
= .024) analysis along the perivascular space indices of the hypertension group were significantly lower than that of the control group. The left, right, and mean analysis along the perivascular space indices of all subjects were significantly negatively correlated with blood pressure values (
= -0.200 to -0.278,
= .002-0.046) and pulse pressure values (
= -0.221 to -0.245,
= .006-0.013).
Our results are consistent with a model in which hypertension causes glymphatic dysfunction.
Background. While the clinical validity of Doppler ultrasonography in renal parenchymal disease is still controversial, we have previously reported that the resistive index (RI) and the atrophic ...index (AI) could estimate tubulointerstitial injury. We aimed to determine whether these indices could estimate renal prognosis in chronic kidney disease (CKD). Methods. We performed a 2-year follow-up study with an observational cohort of 311 CKD patients. The patients were examined by Doppler ultrasonography to calculate RI and AI to be calculated. Glomerular filtration rate (GFR) was estimated with the abbreviated MDRD study equation every 6 months. Results. When we divided the patients into three groups by the RI value of 0.65 and 0.70, there were significant differences in the decrease in GFR among the three groups at 24 months. Kaplan–Meier analysis also showed a significant difference among the three groups in the survival rate of worsening renal function, which was defined as a decrease in GFR of at least 20 mL/min 1.73 m2 or the need for long-term dialysis therapy until the end of the 2-year follow-up. Cox proportional-hazard analysis identified overt proteinuria (≥1.0 g/g creatinine), high RI (>0.70) and high systolic blood pressure (≥140 mmHg) as independent predictors of worsening renal function. In contrast, AI was of no significance in evaluating renal prognosis in CKD. Conclusions. This study suggested that RI, and proteinuria and hypertension were independent risk factors for the progression of CKD.
Arterial stiffness is reported to be able to cause axonal demyelination or degeneration. The present study aimed to use advanced MR imaging techniques to examine the effect of arterial stiffness on ...the WM microstructure among older adults.
Arterial stiffness was measured using the cardio-ankle vascular elasticity index (CAVI). The high-CAVI (mean CAVI ≥ 9 points) and the low-CAVI groups (mean CAVI < 9 points) were created. The neuronal fiber integrity of the WM was evaluated by neurite orientation dispersion and density imaging and magnetization transfer saturation imaging. Tract-Based Spatial Statistics and the tracts-of-interest analysis were performed. Specific WM regions (corpus callosum, internal capsule, anterior thalamic radiation, corona radiata, superior longitudinal fasciculus, forceps minor, and inferior fronto-occipital fasciculus) were selected in the tracts-of-interest analysis.
In Tract-Based Spatial Statistics, the high-CAVI group showed a significantly lower myelin volume fraction value in the broad WM and significantly higher radial diffusivity and isotropic volume fraction values in the corpus callosum, forceps minor, inferior fronto-occipital fasciculus, internal capsule, corona radiata, and anterior thalamic radiation than the low-CAVI group. In tracts-of-interest analysis using multivariate linear regression, significant associations were found between the mean CAVI and radial diffusivity in the anterior thalamic radiation and the corona radiata; isotropic volume fraction in the anterior thalamic radiation and the corona radiata; and myelin volume fraction in the superior longitudinal fasciculus (
< .05). Additionally, partial correlation coefficients were observed for the significant associations of executive function with radial diffusivity and myelin volume fraction (
< .05).
Arterial stiffness could be associated with demyelination rather than axonal degeneration.
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