Context:
Cushing's syndrome (CS) is challenging to diagnose. Increased prevalence of CS in specific patient populations has been reported, but routine screening for CS remains questionable. To ...decrease the diagnostic delay and improve disease outcomes, simple new screening methods for CS in at-risk populations are needed.
Objective:
To develop and validate a simple scoring system to predict CS based on clinical signs and an easy-to-use biochemical test.
Design:
Observational, prospective, multicenter.
Setting:
Referral hospital.
Patients:
A cohort of 353 patients attending endocrinology units for outpatient visits.
Interventions:
All patients were evaluated with late-night salivary cortisol (LNSC) and a low-dose dexamethasone suppression test for CS.
Main Outcome Measures:
Diagnosis or exclusion of CS.
Results:
Twenty-six cases of CS were diagnosed in the cohort. A risk scoring system was developed by logistic regression analysis, and cutoff values were derived from a receiver operating characteristic curve. This risk score included clinical signs and symptoms (muscular atrophy, osteoporosis, and dorsocervical fat pad) and LNSC levels. The estimated area under the receiver operating characteristic curve was 0.93, with a sensitivity of 96.2% and specificity of 82.9%.
Conclusions:
We developed a risk score to predict CS in an at-risk population. This score may help to identify at-risk patients in non-endocrinological settings such as primary care, but external validation is warranted.
A prediction model for Cushing's syndrome diagnosis in at-risk populations was developed based on clinical variables and late night salivary cortisol levels.
ABSTRACT In order to search for evidence of hydration on M-type asteroid (16) Psyche, we observed this object in the 3 m spectral region using the long-wavelength cross-dispersed (LXD: 1.9-4.2 m) ...mode of the SpeX spectrograph/imager at the NASA Infrared Telescope Facility. Our observations show that Psyche exhibits a 3 m absorption feature, attributed to water or hydroxyl. The 3 m absorption feature is consistent with the hydration features found on the surfaces of water-rich asteroids, attributed to OH- and/or H2O-bearing phases (phyllosilicates). The detection of a 3 m hydration absorption band on Psyche suggests that this asteroid may not be a metallic core, or it could be a metallic core that has been impacted by carbonaceous material over the past 4.5 Gyr. Our results also indicate rotational spectral variations, which we suggest reflect heterogeneity in the metal/silicate ratio on the surface of Psyche.
The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the ...differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets.
Background
The use of 3D laparoscopic systems is expanding. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference with the aim of creating evidence-based ...statements and recommendations for the surgical community.
Methods
Systematic reviews of the PubMed and Embase libraries were performed to identify evidence on potential benefits of 3D on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by an international surgical and engineering expert panel which were presented and voted at the EAES annual congress, London, May 2018.
Results
9967 abstracts were screened with 138 articles included. 18 statements and two recommendations were generated and approved. 3D significantly shortened operative time (mean difference 11 min (8% 95% CI 20.29–1.72, I
2
96%)). A significant reduction in complications was observed when 3D systems were used (RR 0.75, 95 CI% 0.60–0.94, I
2
0%) particularly for cases involving laparoscopic suturing (RR 0.57 95% CI 0.35–0.90, I
2
0%). In 69 box trainer or simulator studies, 64% concluded trainees were significant faster and 62% performed fewer errors when using 3D.
Conclusion
We recommend the use of 3D vision in laparoscopy to reduce the operative time (grade of recommendation: low). Future robust clinical research is required to specifically investigate the potential benefit of 3D laparoscopy system on complication rates (grade of recommendation: high).
Proinflammatory cytokines contribute to renal injury, but the downstream effectors within kidney cells are not well understood. One candidate effector is Klotho, a protein expressed by renal cells ...that has antiaging properties; Klotho-deficient mice have an accelerated aging-like phenotype, including vascular injury and renal injury. Whether proinflammatory cytokines, such as TNF and TNF-like weak inducer of apoptosis (TWEAK), modulate Klotho is unknown. In mice, exogenous administration of TWEAK decreased expression of Klotho in the kidney. In the setting of acute kidney injury induced by folic acid, the blockade or absence of TWEAK abrogated the injury-related decrease in renal and plasma Klotho levels. TWEAK, TNFα, and siRNA-mediated knockdown of IκBα all activated NFκB and reduced Klotho expression in the MCT tubular cell line. Furthermore, inhibition of NFκB with parthenolide prevented TWEAK- or TNFα-induced downregulation of Klotho. Inhibition of histone deacetylase reversed TWEAK-induced downregulation of Klotho, and chromatin immunoprecipitation showed that TWEAK promotes RelA binding to the Klotho promoter, inducing its deacetylation. In conclusion, inflammatory cytokines, such as TWEAK and TNFα, downregulate Klotho expression through an NFκB-dependent mechanism. These results may partially explain the relationship between inflammation and diseases characterized by accelerated aging of organs, including CKD.
Introduction
The EVA (Endoscopic Video Analysis) tracking system is a new system for extracting motions of laparoscopic instruments based on nonobtrusive video tracking. The feasibility of using EVA ...in laparoscopic settings has been tested in a box trainer setup.
Methods
EVA makes use of an algorithm that employs information of the laparoscopic instrument’s shaft edges in the image, the instrument’s insertion point, and the camera’s optical center to track the three-dimensional position of the instrument tip. A validation study of EVA comprised a comparison of the measurements achieved with EVA and the TrEndo tracking system. To this end, 42 participants (16 novices, 22 residents, and 4 experts) were asked to perform a peg transfer task in a box trainer. Ten motion-based metrics were used to assess their performance.
Results
Construct validation of the EVA has been obtained for seven motion-based metrics. Concurrent validation revealed that there is a strong correlation between the results obtained by EVA and the TrEndo for metrics, such as path length (
ρ
= 0.97), average speed (
ρ
= 0.94), or economy of volume (
ρ
= 0.85), proving the viability of EVA.
Conclusions
EVA has been successfully validated in a box trainer setup, showing the potential of endoscopic video analysis to assess laparoscopic psychomotor skills. The results encourage further implementation of video tracking in training setups and image-guided surgery.
ABSTRACT
Asteroid families are cosmic puzzles that help us understand the true nature of their original parent body. Ordinary chondrites are the most common types of meteorites that arrive to Earth ...and are composed of three subtypes: H, L, and LL chondrites. The Gefion Asteroid Family (GAF) has been proposed to be the source asteroids for the L chondrites. In this work, we present the results of a spectroscopic campaign of six dynamically defined members of the GAF to test the hypothesis if L chondrites come from this family. Our compositional analysis of these six asteroids shows a range of meteorite analogues from L- to LL chondrites. Combining these results with our previous work, we note that GAF asteroids span the entire ordinary chondrite range of H-, L-, and LL. The observed compositional heterogeneity in the GAF is likely due to largest members of the GAF consisting of interlopers. A more detailed spectroscopic survey of a large subset of asteroids in the GAF region is needed to further isolate true family members.
The conserved transcription factor Myc regulates cell growth, proliferation and apoptosis, and its deregulation has been associated with human pathologies. Although specific miRNAs have been ...identified as fundamental components of the Myc tumorigenic program, how Myc regulates miRNA biogenesis remains controversial. Here we showed that Myc functions as an important regulator of miRNA biogenesis in Drosophila by influencing both miRNA gene expression and processing. Through the analysis of ChIP-Seq datasets, we discovered that nearly 56% of Drosophila miRNA genes show dMyc binding, exhibiting either the canonical or non-canonical E-box sequences within the peak region. Consistently, reduction of dMyc levels resulted in widespread downregulation of miRNAs gene expression. dMyc also modulates miRNA processing and activity by controlling Drosha and AGO1 levels through direct transcriptional regulation. By using in vivo miRNA activity sensors we demonstrated that dMyc promotes miRNA-mediated silencing in different tissues, including the wing primordium and the fat body. We also showed that dMyc-dependent expression of miR-305 in the fat body modulates Dmp53 levels depending on nutrient availability, having a profound impact on the ability of the organism to respond to nutrient stress. Indeed, dMyc depletion in the fat body resulted in extended survival to nutrient deprivation which was reverted by expression of either miR-305 or a dominant negative version of Dmp53. Our study reveals a previously unrecognized function of dMyc as an important regulator of miRNA biogenesis and suggests that Myc-dependent expression of specific miRNAs may have important tissue-specific functions.
The effects of the partial replacement of maltodextrin by native agave fructans on the characteristics of spray-dried pineapple and mango powder were evaluated in this study. An experimental 33 ...design, three concentrations of maltodextrin (5, 7, and 10%), three concentrations of native agave fructans (0, 2, and 4%), and three feed temperatures (110, 115, and 120 ℃) were used. The results using the treatment in which only maltodextrin was used as a reference indicated that an increment in the inlet temperature decreases the moisture content, aw, and solubility. Likewise, an increase (more than 2%) in fructans concentration generates products with increased aw, moisture, hygroscopicity, wettability, and greater solubility. Additionally, no modification of storage stability was observed. Mango and pineapple powder color were affected mainly by the inlet temperature, causing an increase in luminosity (L*) and a decrease in parameter (a*). A scanning electron microscopy showed spherical powder particles with certain contractions; powder stability in treatments with native agave fructans was not modified in the treatment at 2%. Finally, the addition of 2% agave fructans as carrier material was able to reduce the maltodextrin concentration of the spray drying process.
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