No abstract available
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Τετάρτη 16 Αυγούστου 2017
Morbidity and mortality in children undergoing bronchoscopy for foreign body removal
Objectives/Hypothesis
Analyze morbidity and mortality among children undergoing bronchoscopy for foreign body removal.
Study Design
Multicenter retrospective review using the American College of Surgeons Pediatric National Surgical Quality Improvement Program from 2014 and 2015.
Methods
Patients were identified using Current Procedural Terminology code 31635. Demographics, time to surgery, operative times, hospitalization time, and complications were collected. Multivariate logistic regression was used to identify predictive factors for major adverse events.
Results
Three hundred thirty-four patients were included (mean age 3.7 years, 59.0% male). Preoperative sepsis syndrome was present in 5.7% of patients and 8.1% had asthma. Of the patients, 5.1% percent of patients had a tracheostomy. Bronchoscopy was performed by an otolaryngologist (65.4%) or a pediatric surgeon (33.1%). Mean operative time was 27.4 minutes, whereas mean total operating room time was 54.6 minutes. Airway foreign bodies were located in 269 patients (80.5%), with 62.5% being located in the mainstem bronchus. Operative time was longer when foreign bodies were in the mainstem bronchus or distal to it. Mean time to surgery from admission was 0 days, and mean duration of hospitalization was 1 day. One patient (0.3%) required reoperation for respiratory reasons, and three (0.9%) required readmission for related reasons. No patients remained hospitalized at 30 days. Two (0.6%) had a postoperative pneumonia, and two (0.6%) required reintubation. One patient death (0.3%) occurred within 2 weeks of bronchoscopy. No significant differences were identified in operative time, time to surgery, or hospitalization time based on age, gender, presence of a tracheostomy, or surgical specialty.
Conclusions
Bronchoscopy for identification and removal of airway foreign bodies had minimal morbidity in this group.
Level of Evidence
2b Laryngoscope, 2017
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Antibiofilm properties of model composites containing quaternary ammonium methacrylates after surface texture modification
Source:Dental Materials
Author(s): Guilherme Ferreira Rego, Marina Lermen Vidal, Gil Mendes Viana, Lucio Mendes Cabral, Luis Felipe Jochims Schneider, Maristela Barbosa Portela, Larissa Maria Cavalcante
ObjectiveInvestigate antimicrobial properties and surface texture of model composites with different concentration and alkyl chain length of quaternary ammonium monomers (QAS).MethodsMonomers derived from QAS salts with alkyl chain lengths of 12 carbons ((dimethylaminododecyl methacrylate) DMADDM) and 16 carbons (dimethylaminohexadecyl methacrylate—DMAHDM) were obtained from the reactions of their respective organo-halides with the tertiary amine 2-(dimethylamino)ethyl methacrylate (DMAEMA). DMADDM and DMAHDM were incorporated into model composite in concentrations of 5 or 10%, resulting the following groups: G12.5 (DMADDM 5%), G12.10 (DMADDM 10%), G16.5 (DMAHDM 5%), G16.10 (DMAHDM 10%) and GC (control). Biofilm viability, lactic acid production and surface roughness were analysed 24h after samples preparation (initial), repeated after toothbrush abrasion and after polishing simulation. Data were submitted to ANOVA and Tukey's test (p≤0.05).ResultsThe longer the molecular chain size of QAS and the higher its concentration (G16.10), the lower was the viability and the production of lactic acid by the biofilm. No differences were detected in initial roughness' measurements among groups. However, after abrasion, there was an increase of biofilm viability and lactic acid production. Composites containing QAS presented rougher surfaces compared to the CG. After polishing, biofilm viability and surface roughness were statistically similar for all groups. Nevertheless, DMAHDM at 10% showed reduction in lactic acid production.SignificanceChain length and concentration of QAS influenced biofilm development and production of lactic acid. Longer chains and higher concentrations of QAS promoted better antimicrobial properties. Changes in surface texture caused by abrasion, decreased antibiofilm properties.
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Impact of machining on the flexural fatigue strength of glass and polycrystalline CAD/CAM ceramics
Source:Dental Materials
Author(s): Sara Fraga, Marina Amaral, Marco Antônio Bottino, Luiz Felipe Valandro, Cornelis Johannes Kleverlaan, Liliana Gressler May
ObjectivesTo assess the effect of machining on the flexural fatigue strength and on the surface roughness of different computer-aided design, computer-aided manufacturing (CAD/CAM) ceramics by comparing machined and polished after machining specimens.MethodsDisc-shaped specimens of yttria-stabilized polycrystalline tetragonal zirconia (Y-TZP), leucite-, and lithium disilicate-based glass ceramics were prepared by CAD/CAM machining, and divided into two groups: machining (M) and machining followed by polishing (MP). The surface roughness was measured and the flexural fatigue strength was evaluated by the step-test method (n=20). The initial load and the load increment for each ceramic material were based on a monotonic test (n=5). A maximum of 10,000 cycles was applied in each load step, at 1.4Hz. Weibull probability statistics was used for the analysis of the flexural fatigue strength, and Mann-Whitney test (α=5%) to compare roughness between the M and MP conditions.ResultsMachining resulted in lower values of characteristic flexural fatigue strength than machining followed by polishing. The greatest reduction in flexural fatigue strength from MP to M was observed for Y-TZP (40%; M=536.48MPa; MP=894.50MPa), followed by lithium disilicate (33%; M=187.71MPa; MP=278.93MPa) and leucite (29%; M=72.61MPa; MP=102.55MPa). Significantly higher values of roughness (Ra) were observed for M compared to MP (leucite: M=1.59μm and MP=0.08μm; lithium disilicate: M=1.84μm and MP=0.13μm; Y-TZP: M=1.79μm and MP=0.18μm).SignificanceMachining negatively affected the flexural fatigue strength of CAD/CAM ceramics, indicating that machining of partially or fully sintered ceramics is deleterious to fatigue strength.
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Impact of thio-urethane additive and filler type on light-transmission and depth of polymerization of dental composites
Publication date: Available online 12 August 2017
Source:Dental Materials
Author(s): André Luis Faria-e-Silva, Carmem Silvia Pfeifer
ObjectiveThis study evaluated the effects of filler type and the addition of thio-urethane oligomers on light-transmission, polymerization kinetics and depth of cure of resin composites.MethodsBisGMA:UDMA:TEGMA (5:3:2wt%) were mixed with 0 (control) or 20wt% thio-urethane. Fillers with various sizes and refractive indices were included and refractive index (RI) measured. Unfilled resins were used as controls. The RIs of materials were measured before and after polymerization. The irradiance reaching the bottom of 3-mm thick specimens was measured during the polymerization. Degree of conversion to a depth of 5mm was mapped. An optical bench was used to simultaneously follow conversion and light transmission.ResultsThe addition of thio-urethane increased the RI for all composites. As expected, RI also increased with conversion for all materials. The one exception was for the material filled with OX-50, in which the RI of the composite decreased with conversion. In this case, the irradiance at the bottom of the 3mm specimen was also the lowest among all groups. The addition of thio-urethanes had only minimal effect on light transmission within a filler type, but led to increased conversion in depth for all groups. The filler type itself had a greater effect on light transmission, and that correlated well with the degree of conversion.SignificanceThe effect of the thio-urethane addition on degree of conversion in depth was dependent on filler type. The additive can be tailored to improve the RI match with the filler to optimize light transmission in dental composites.
Graphical abstract
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Different Look in to the Role of Flagella in Pathogenesis of Helicobacter pylori
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'Overdiagnosis epidemic' in thyroid cancer: study - Caledon Enterprise
| 'Overdiagnosis epidemic' in thyroid cancer: study Caledon Enterprise CALGARY — A study by researchers at the University of Calgary suggests there's an overdiagnosis epidemic when it comes to thyroid cancer. Dawnelle Topstad and James Dickinson pored over four decades worth of Canadian data on the disease. |
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Diagnostic performance of unenhanced Computed Tomography and 18F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumors
Summary
Objective
Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and18F-fluorodeoxyglucose(18FDG) positron emission tomography(PET)/CT imaging in a high risk population for adrenal malignancy using an optimal reference standard.
Design
Retrospective cohort study.
Methods
Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy.
Results
Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21to78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72%, and negative predictive value (NPV) of 100%.18FDG-PET/CT was performed in 89 patients; median tumor size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median = 10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median = 3 [0.74-13.4] vs. 1.2 [0.5-6.6], respectively, P<.0001).18FDG-PET/CT ALR > 1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85%, and NPV of 86%.
Conclusion
Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG PET/CT could be considered as a second stage imaging.
This article is protected by copyright. All rights reserved.
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Absorption and tolerability of taste-masked hydrocortisone granules in neonates, infants and children under 6 years of age with adrenal insufficiency
Abstract
Objectives
There is no licensed, dose-appropriate formulation of hydrocortisone for children with adrenal insufficiency (AI) and patients rely on compounded adult medication. The aim of this study was to evaluate the absorption, palatability and safety of Infacort®, an immediate-release, granule formulation of hydrocortisone with taste masking.
Study design
Single site with satellites attended by a "flying" doctor from investigator site.
Open-label, single-dose study in three consecutive child cohorts (n=24) with AI; Cohort 1, children aged 2 to <6 years (n=12); Cohort 2, infants aged 28 days to <2 years (n=6); Cohort 3, neonates aged 1 to <28 days (n=6). <comment> Au: the age ranges quoted are slightly different in each of the abstract, main text, Table 1 and Supplemental table. These have now been unified as shown here.</comment>.
Methods
Fasted children were given a single dose of Infacort® as dry granules administered directly from a capsule or spoon followed by a drink. The primary endpoint was the maximum serum cortisol concentration up to 240 minutes after Infacort® administration. Secondary endpoints were palatability and adverse events (AEs).
Results
All children showed an increase in cortisol above baseline after Infacort® (p<0.0001), with geometric mean ± SD cortisol concentration at 60 min of 575.8 ± 299.5 nmol/L. There was no failure in administration of Infacort®, and 95.5% of parents/carers preferred Infacort® to their child's current medication. In 6 children who completed the palatability questionnaire, 80% of responses were very good or neutral and 20% were adverse. No serious or severe treatment-emergent AEs were reported.
Conclusions
Infacort® is well tolerated, easy to administer to neonates, infants and children and shows good absorption, with cortisol levels at 60 minutes after administration similar to physiological cortisol levels in healthy children.
This article is protected by copyright. All rights reserved.
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Incidental detection of two adult gravid filarial worms in breast: a case report
Microfilaria is a major public health problem in tropical and subtropical countries and is an endemic problem in India. Wuchereria bancrofti is the commonest filarial infection. In some lesions, microfilariae and...
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Gender Similarities and Differences for e-Health Behaviors Among U.S. Adults
Telemedicine and e-Health , Vol. 0, No. 0.
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Analysis of nutritional adequacy of local foods for meeting dietary requirements of children aged 6-23 months in rural central Tanzania
Under nutrition remains a serious problem among children in Sub-Saharan Africa. Analysing how diets composed of local foods could achieve nutritional goals for infants and young children in low-income settings...
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Tissue-Specific Extracellular Matrix Enhances Skeletal Muscle Precursor Cell Expansion and Differentiation for Potential Application in Cell Therapy
Tissue Engineering Part A Aug 2017, Vol. 23, No. 15-16: 784-794.
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Special Issue on Strategic Directions in Musculoskeletal Tissue Engineering
Tissue Engineering Part A Aug 2017, Vol. 23, No. 15-16: 717-718.
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Activation of AMPK to the neuroprotection in the oxidative stress by advanced glycosylation end products in human neural stem cells
Source:Experimental Cell Research
Author(s): Chien-Hung Lin, Yi-Chuan Cheng, Christopher J. Nicol, Kuan-Hung Lin, Chia-Hui Yen, Ming-Chang Chiang
Advanced glycosylation end products (AGEs) formation is correlated with the pathogenesis of diabetic neuronal damage, but its links with oxidative stress are still not well understood. Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK). Once activated, AMPK regulates many pathways central to metabolism and energy balance including, glucose uptake, glycolysis and fatty acid oxidation. AMPK is also present in neurons, but its role remains unclear. Here, we show that AGE exposure decreases cell viability of human neural stem cells (hNSCs), and that the AMPK agonist metformin reverses this effect, via AMPK-dependent downregulation of RAGE levels. Importantly, hNSCs co-treated with metformin were significantly rescued from AGE-induced oxidative stress, as reflected by the normalization in levels of reactive oxygen species. In addition, compared to AGE-treated hNSCs, metformin co-treatment significantly reversed the activity and mRNA transcript level changes ofSOD1/2 and Gpx. Furthermore, hNSCs exposed to AGEs had significantly lower mRNA levels among other components of normal cellular oxidative defenses (GSH, Catalase and HO-1), which were all rescued by co-treatment with metformin. This metformin-mediated protective effect on hNSCs for of both oxidative stress and oxidative defense genes by co-treatment with metformin was blocked by the addition of an AMPK antagonist (Compound C). These findings unveil the protective role of AMPK-dependent metformin signaling during AGE mediated oxidative stress in hNSCs, and suggests patients undergoing AGE-mediated neurodegeneration may benefit from the novel therapeutic use of metformin.
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Extracellular matrix type modulates cell migration on mechanical gradients
Source:Experimental Cell Research
Author(s): Christopher D. Hartman, Brett C. Isenberg, Samantha G. Chua, Joyce Y. Wong
Extracellular matrix composition and stiffness are known to be critical determinants of cell behavior, modulating processes including differentiation, traction generation, and migration. Recent studies have demonstrated that the ECM composition can modulate how cells migrate in response to gradients in environmental stiffness, altering a cell's ability to undergo durotaxis. These observations were limited to single varieties of extracellular matrix, and typically cells are exposed to environments containing complex mixtures of extracellular matrix proteins. Here, we investigate migration of NIH 3T3 fibroblasts on mechanical gradients coated with one or more type of extracellular matrix protein. Our results show that NIH 3T3 fibroblasts exhibit durotaxis on fibronectin-coated mechanical gradients but not on those coated with laminin, demonstrating that extracellular matrix type can act as a regulator of cell response to mechanical gradients. Interestingly, NIH 3T3 fibroblasts were also observed to migrate randomly on gradients coated with a mixture of both fibronectin and laminin, suggesting that there may be a complex interplay in the cellular response to mechanical gradients in the presence of multiple extracellular matrix signals. These findings indicate that specific composition of available adhesion ligands is a critical determinant of a cell's migratory response to mechanical gradients.
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Histochemical and immunohistochemical examination of odontoblasts (petroblasts) in petrodentine formation of lungfish
Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Shunya Oka, Ichiro Sasagawa, Mikio Ishiyama
ObjectivePetrodentine, the core of the lungfish tooth plate, is a well-mineralized tissue similar to mammalian enamel and analogous to enameloid in fish teeth. Petrodentine is formed solely by petroblasts, which are specialized odontoblasts, whereas enameloid is a composite tissue produced by both odontoblasts and dental epithelial cells. To clarify the details of petrodentine formation, petroblasts were investigated using histochemical and immunohistochemical techniques.MethodsExtant lungfish (Lepidosiren paradoxa) were used in this study. Tooth plates during the stage of petrodentine formation were observed by means of histochemistry and immunohistochemistry. Commercial kits were used to detect enzyme activity. Correlative sections were immunostained using antibodies against selected peptides. Routine staining such as periodic acid-Schiff (PAS) reaction to identify glycogen and Elastica van Gieson staining for the detection of elastic fibers in histological sections were performed. In addition, conventional transmission electron microscopy was used for observing the fine structure.ResultsPetroblasts showed marked acid and alkaline phosphatase activities, and positive immunoreactivities against anti-nestin, anti-V-ATPase, and anti-Ca2+-ATPase, during the maturation stage, but in the matrix formation stage, reactions were much weaker than that of the maturation stage. During the maturation stage, petroblasts showed intense PAS reactivity, and glycogen particles were observed in petroblasts by transmission electron microscopy. Glucose transporter 1-immunoreactivity was observed in petroblasts in the matrix formation stage and the initial to mid part of the maturation stage.ConclusionsThe results in this study suggested that petroblasts have two functional stages, matrix formation and maturation, and glycogen plays an important role in the modulation of petroblasts.
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Diabetes increases interleukin-17 levels in periapical, hepatic, and renal tissues in rats
Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Mariane Maffei Azuma, João Eduardo Gomes-Filho, Annelise Katrine Carrara Prieto, Renata Oliveira Samuel, Valéria Marçal Felix de Lima, Dóris Hissako Sumida, Edilson Ervolino, Luciano Tavares Angelo Cintra
ObjectivesThis study aimed to evaluate the association between endodontic infection and diabetes on interleukin-17 levels in periapical, hepatic, and renal tissues of rats.DesignForty male rats were divided into groups: normoglycemic rats (N), normoglycemic rats with apical periodontitis (N-AP), rats with experimental diabetes (ED), and rats with experimental diabetes and apical periodontitis (ED-AP). Diabetes was induced by intravenous streptozotocin injection, and blood sugar levels were monitored to confirm disease development. Apical periodontitis (AP) was induced by pulp exposure to the oral environment during 30days. After 30days, hepatic and renal tissues were obtained, and IL-17 levels were quantified by ELISA. The right hemi-jaw was used to quantify IL-17 levels by immunohistochemistry. The values obtained in parametric tests were tabulated and analyzed statistically by analysis of variance (ANOVA) and Tukey tests, and the values obtained for scores were statistically analyzed by using the Kruskal-Wallis and Dun tests. The level of significance was set at 5%.ResultsED and ED-AP groups expressed significantly higher IL-17 levels in both hepatic and renal tissues (p<0.05), compared to N and N-AP groups. Apical periodontitis (AP) in ED-AP group was significantly more severe than that in N-AP group (p<0.05). Furthermore, there was a significantly larger increase in the IL-17 levels in ED-AP group compared to N group (p<0.05).ConclusionOur results indicate that diabetes increases IL-17 levels in hepatic and renal tissues and also enhances IL-17 production in apical periodontitis area of rats.
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Bioconversion, health benefits, and application of ginseng and red ginseng in dairy products
Abstract
Ginseng and red ginseng are popular as functional foods in Asian countries such as Korea, Japan, and China. They possess various pharmacologic effects, including antioxidant, anti-inflammatory, anti-cancer, anti-obesity, and anti-viral activities. Ginsenosides are a class of pharmacologically active components in ginseng and red ginseng. Major ginsenosides are converted to minor ginsenosides, which have better bioavailability and cellular uptake, by microorganisms and enzymes. Studies have shown that ginseng and red ginseng can affect the physicochemical and sensory properties, ginsenosides content, and functional properties of dairy products. In addition, lactic acid bacteria in dairy products can convert into minor ginsenosides and ginseng and red ginseng improve functionality of products. This review will discuss the characteristics of ginseng and red ginseng, and their bioconversion, functionality, and application in dairy products.
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Energy dense foods may increase cancer risk regardless of obesity status
Diet is believed to play a role in cancer risk. Current research shows that an estimated 30% of cancers could be prevented through nutritional modifications. While there is a proven link between obesity and certain types of cancer, less is known about...
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Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria [Research]
Classical homocystinuria (HCU) is an inborn error of sulfur amino acid metabolism caused by deficient activity of cystathionine β-synthase (CBS), resulting in an accumulation of homocysteine and a concomitant decrease of cystathionine and cysteine in blood and tissues. In mice, the complete lack of CBS is neonatal lethal. In this study, newborn CBS knockout (KO) mice were treated with recombinant polyethyleneglycolylated human truncated CBS (PEG-CBS). Full survival of the treated KO mice, along with a positive impact on metabolite levels in plasma, liver, brain, and kidneys, was observed. The PEG-CBS treatment prevented an otherwise fatal liver disease characterized by steatosis, death of hepatocytes, and ultrastructural abnormalities of endoplasmic reticulum and mitochondria. Furthermore, treatment of the KO mice for 5 mo maintained the plasma metabolite balance and completely prevented osteoporosis and changes in body composition that characterize both the KO model and human patients. These findings argue that early treatment of patients with HCU with PEG-CBS may prevent clinical symptoms of the disease possibly without the need of dietary protein restriction.—Majtan, T., Hůlková, H., Park, I., Krijt, J., Kožich, V., Bublil, E. M., Kraus, J. P. Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria.
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Lipidomic and proteomic analysis of exosomes from mouse cortical collecting duct cells [Research]
Exosomes are endosome-derived nanovesicles that are involved in cellular communication and signaling. Exosomes are produced by epithelial cells and are found in biologic fluids including blood and urine. The packaged material within exosomes includes proteins and lipids, but the molecular comparison within exosome subtypes is largely unknown. The purpose of this study was to investigate differences between exosomes derived from the apical plasma membrane and basolateral plasma membrane of polarized murine cortical collecting duct principal cells. Nanoparticle tracking analysis showed that the size and concentration of apical and basolateral exosomes remained relatively stable across 3 different temperatures (23, 37, and 42°C). Liquid chromatography–tandem mass spectrometry analysis revealed marked differences between the proteins packaged within the 2 types of exosomes from the same cells. Several proteins expressed at the inner leaflet of the plasma membrane including α-actinin-1, moesin, 14-3-3 protein /, annexin A1/A3/A4/A5/A6, clathrin heavy chain 1, glyceraldehyde-3-phosphate dehydrogenase, α-enolase, filamin-A, and heat shock protein 90 were identified in samples of apical plasma membrane–derived exosomes, but not in basolateral plasma membrane exosomes from mouse cortical collecting duct cells. In addition to differences at the protein level, mass spectrometry–based shotgun lipidomics analysis showed significant differences in the lipid classes and fatty acid composition of the 2 types of exosomes. We found higher levels of sphingomyelin and lower levels of cardiolipin, among other phospholipids in the apical plasma membrane compared to the basolateral plasma membrane exosomes. The molecular analyses of exosome subtypes presented herein will contribute to our understanding of exosome biogenesis, and the results may have potential implications for biomarker discovery.—Dang, V. D., Jella, K. K., Ragheb, R. R. T., Denslow, N. D., Alli, A. A. Lipidomic and proteomic analysis of exosomes from mouse cortical collecting duct cells.
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Genome sequencing method can detect clinically relevant mutations using 5 CTCs - Science Daily
| Genome sequencing method can detect clinically relevant mutations using 5 CTCs Science Daily Whole genome sequencing using long fragment read (LFR), a technology that can analyze the entire genomic content of small numbers of cells, detected potentially targetable mutations using only five circulating tumor cells (CTCs) in a patient with ... and more » |
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Cancer detection with sugar molecules - Science Daily
| Science Daily | Cancer detection with sugar molecules Science Daily Galectins are a family of proteins that have become a promising source of cancer research in recent years. A representative thereof is galectin-1. It sits on the surface of all human cells; on tumor cells, however, it occurs in enormous quantities ... and more » |
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Mathematical crystal ball gazes into future of prostate cancer treatment - Science Daily
| Mathematical crystal ball gazes into future of prostate cancer treatment Science Daily The chemotherapy docetaxel is widely accepted as a standard therapy for metastatic castration-resistant prostate cancer. But 10-20 percent of patients will have adverse side effects that force discontinuation of treatment. These patients may have been ... and more » |
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Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol
New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these tre...
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Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer: NORDIC 9
Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little...
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Borse ostaggio di Trump e Kim. I titoli più vulnerabili a Milano - Yahoo Finanza
| Yahoo Finanza | Borse ostaggio di Trump e Kim. I titoli più vulnerabili a Milano Yahoo Finanza Anche l'ultima seduta della settimana viene vissuta in calo dalle Borse europee sulla scia della flessione accusata ieri da Wall Street che ha registrato il peggior ... and more » |
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'Overdiagnosis epidemic' in thyroid cancer: study - Red Deer Advocate (subscription)
| Red Deer Advocate (subscription) | 'Overdiagnosis epidemic' in thyroid cancer: study Red Deer Advocate (subscription) CALGARY — A study by researchers at the University of Calgary suggests most people treated for thyroid cancer have tumours that would never pose any harm. Dawnelle Topstad and James Dickinson, with the university's Cumming School of Medicine, ... and more » |
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Intestinal Dysbiosis and Biotin Deprivation Induce Alopecia through Overgrowth of Lactobacillus murinus in Mice
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Atsushi Hayashi, Yohei Mikami, Kentaro Miyamoto, Nobuhiko Kamada, Toshiro Sato, Shinta Mizuno, Makoto Naganuma, Toshiaki Teratani, Ryo Aoki, Shinji Fukuda, Wataru Suda, Masahira Hattori, Masayuki Amagai, Manabu Ohyama, Takanori Kanai
Metabolism by the gut microbiota affects host physiology beyond the gastrointestinal tract. Here, we find that antibiotic-induced dysbiosis, in particular, overgrowth of Lactobacillus murinus (L. murinus), impaired gut metabolic function and led to the development of alopecia. While deprivation of dietary biotin per se did not affect skin physiology, its simultaneous treatment with vancomycin resulted in hair loss in specific pathogen-free (SPF) mice. Vancomycin treatment induced the accumulation of L. murinus in the gut, which consumes residual biotin and depletes available biotin in the gut. Consistently, L. murinus induced alopecia when monocolonized in germ-free mice fed a biotin-deficient diet. Supplementation of biotin can reverse established alopecia symptoms in the SPF condition, indicating that L. murinus plays a central role in the induction of hair loss via a biotin-dependent manner. Collectively, our results indicate that luminal metabolic alterations associated with gut dysbiosis and dietary modifications can compromise skin physiology.
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Gut microbiota metabolism affects host physiology beyond the gastrointestinal tract. Here, Hayashi et al. find that antibiotic-induced gut dysbiosis leads to the development of alopecia in mice on a biotin-deficient diet.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKo2ED
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Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Alexandra Van Keymeulen, Marco Fioramonti, Alessia Centonze, Gaëlle Bouvencourt, Younes Achouri, Cédric Blanpain
The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER)+ and ER− cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER+ lineage is maintained by multipotent SCs or by lineage-restricted SCs. To this end, we generated doxycycline-inducible ER-rtTA mice that allowed us to perform genetic lineage tracing of ER+ LCs and study their fate and long-term maintenance. Our results show that ER+ cells are maintained by lineage-restricted SCs that exclusively contribute to the expansion of the ER+ lineage during puberty and their maintenance during adult life.
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Van Keymeulen et al. performed lineage tracing of estrogen receptor (ER)-expressing cells in the mammary gland. They show that the ER+ cells are maintained by lineage-restricted stem cells that exclusively contribute to the expansion of the ER+ lineage during puberty and to their maintenance during adult life.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKJEB0
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MicroRNA-9 Couples Brain Neurogenesis and Angiogenesis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Romain Madelaine, Steven A. Sloan, Nina Huber, James H. Notwell, Louis C. Leung, Gemini Skariah, Caroline Halluin, Sergiu P. Paşca, Gill Bejerano, Mark A. Krasnow, Ben A. Barres, Philippe Mourrain
In the developing brain, neurons expressing VEGF-A and blood vessels grow in close apposition, but many of the molecular pathways regulating neuronal VEGF-A and neurovascular system development remain to be deciphered. Here, we show that miR-9 links neurogenesis and angiogenesis through the formation of neurons expressing VEGF-A. We found that miR-9 directly targets the transcription factors TLX and ONECUTs to regulate VEGF-A expression. miR-9 inhibition leads to increased TLX and ONECUT expression, resulting in VEGF-A overexpression. This untimely increase of neuronal VEGF-A signal leads to the thickening of blood vessels at the expense of the normal formation of the neurovascular network in the brain and retina. Thus, this conserved transcriptional cascade is critical for proper brain development in vertebrates. Because of this dual role on neural stem cell proliferation and angiogenesis, miR-9 and its downstream targets are promising factors for cellular regenerative therapy following stroke and for brain tumor treatment.
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The coordination of neuronal and vascular cell development is critical to ensure the proper formation of the vertebrate brain. Madelaine et al. show that the microRNA-9 couples neurogenesis and brain angiogenesis through the inhibition of Tlx and Onecut transcription factors regulating neuronal VEGF-A expression.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2w3uDNh
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Subnuclear Relocalization of Structure-Specific Endonucleases in Response to DNA Damage
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Irene Saugar, Alberto Jiménez-Martín, José Antonio Tercero
Structure-specific endonucleases contribute to the maintenance of genome integrity by cleaving DNA intermediates that need to be resolved for faithful DNA repair, replication, or recombination. Despite advances in the understanding of their function and regulation, it is less clear how these proteins respond to genotoxic stress. Here, we show that the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci following DNA damage and colocalizes with the endonucleases Rad1-Rad10 (XPF-ERCC1) and Slx1-Slx4. Recruitment takes place into a class of stress foci defined by Cmr1/WDR76, a protein involved in preserving genome stability, and depends on the E2-ubiquitin-conjugating enzyme Rad6 and the E3-ubiquitin ligase Bre1. Foci dynamics show that, in the presence of DNA intermediates that need resolution by Mus81-Mms4, Mus81 foci persist until this endonuclease is activated by Mms4 phosphorylation. Our data suggest that subnuclear relocalization is relevant for the function of Mus81-Mms4 and, probably, of the endonucleases that colocalize with it.
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Saugar et al. find that, under conditions of DNA damage, the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci, where it colocalizes with the endonucleases Rad1-Rad10 and Slx1-Slx4. Relocalization takes place to a class of stress-induced foci defined by the Cmr1 protein and correlates with the function of the endonuclease.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2w3AXV3
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The Phage Nucleus and Tubulin Spindle Are Conserved among Large Pseudomonas Phages
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Vorrapon Chaikeeratisak, Katrina Nguyen, MacKennon E. Egan, Marcella L. Erb, Anastasia Vavilina, Joe Pogliano
We recently demonstrated that the large Pseudomonas chlororaphis bacteriophage 201φ2-1 assembles a nucleus-like structure that encloses phage DNA and segregates proteins according to function, with DNA processing proteins inside and metabolic enzymes and ribosomes outside the nucleus. Here, we investigate the replication pathway of the Pseudomonas aeruginosa bacteriophages φKZ and φPA3. Bacteriophages φKZ and φPA3 encode a proteinaceous shell that assembles a nucleus-like structure that compartmentalizes proteins and DNA during viral infection. We show that the tubulin-like protein PhuZ encoded by each phage assembles a bipolar spindle that displays dynamic instability and positions the nucleus at midcell. Our results suggest that the phage spindle and nucleus play the same functional role in all three phages, 201φ2-1, φKZ, and φPA3, demonstrating that these key structures are conserved among large Pseudomonas phages.
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The nucleus and spindle are defining features of eukaryotic cells that separate them from bacteria and archaea. Chaikeeratisak et al. show that a tubulin-based spindle and a nucleus-like structure are conserved among large Pseudomonas phages, providing insight into the evolution of these key cell biological structures.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2w3svVu
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NKX2-1 Is Required in the Embryonic Septum for Cholinergic System Development, Learning, and Memory
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Lorenza Magno, Caswell Barry, Christoph Schmidt-Hieber, Polyvios Theodotou, Michael Häusser, Nicoletta Kessaris
The transcription factor NKX2-1 is best known for its role in the specification of subsets of cortical, striatal, and pallidal neurons. We demonstrate through genetic fate mapping and intersectional focal septal deletion that NKX2-1 is selectively required in the embryonic septal neuroepithelium for the development of cholinergic septohippocampal projection neurons and large subsets of basal forebrain cholinergic neurons. In the absence of NKX2-1, these neurons fail to develop, causing alterations in hippocampal theta rhythms and severe deficiencies in learning and memory. Our results demonstrate that learning and memory are dependent on NKX2-1 function in the embryonic septum and suggest that cognitive deficiencies that are sometimes associated with pathogenic mutations in NKX2-1 in humans may be a direct consequence of loss of NKX2-1 function.
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NKX2-1 is a highly conserved patterning gene in the developing forebrain, mutations in which can lead to a spectrum of disorders including cognitive deficiencies. Using genetic fate mapping and intersectional deletion, Magno et al. demonstrate a requirement for embryonic septal NKX2-1 in forebrain cholinergic system development and learning and memory.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2w3Yvc6
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OCT4 and SOX2 Work as Transcriptional Activators in Reprogramming Human Fibroblasts
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Santosh Narayan, Gene Bryant, Shivangi Shah, Georgina Berrozpe, Mark Ptashne
SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming. We report that, at an early stage of reprogramming, virtually all DNA-bound OCT4, SOX2, and SOX2-VP16 were embedded in putative enhancers, about half of which were created de novo. Those associated with SOX2-VP16 were, on average, stronger than those bearing WT SOX2. Many newly created putative enhancers were transient, and many transcription factor locations on DNA changed as reprogramming progressed. These results are consistent with the idea that, during reprogramming, there is an intermediate state that is distinct from both parental cells and iPSCs.
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Narayan et al. show that substituting SOX2 with the strong activator SOX2-VP16 increases reprogramming efficiency of human fibroblasts, especially those cultured from older donors. Thousands of enhancers are created and destroyed in the course of reprogramming, including many enhancers created at binding sites of OCT4 or SOX2.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2w3Brds
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Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Nathan J. Palpant, Yuliang Wang, Brandon Hadland, Rebecca J. Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L. Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E. Murry
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. Using HOPX reporter and knockout hESCs, we show that HOPX regulates blood formation. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis, acting at least in part through failure to suppress Wnt/β-catenin signaling. Thus, chromatin state analysis permits identification of regulators of mesodermal specification, including a conserved role for HOPX in governing primitive hematopoiesis.
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Palpant et al. analyze gene expression and chromatin dynamics in cardiovascular progenitor cells derived from hPSCs to elucidate genes governing cell fate. HOPX is identified as a regulator of primitive hematopoiesis, providing insight into controlling cell lineages from pluripotency for disease modeling or therapeutic applications.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2w2SJrk
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Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Mohammad Moad, Edouard Hannezo, Simon J. Buczacki, Laura Wilson, Amira El-Sherif, David Sims, Robert Pickard, Nicholas A. Wright, Stuart C. Williamson, Doug M. Turnbull, Robert W. Taylor, Laura Greaves, Craig N. Robson, Benjamin D. Simons, Rakesh Heer
Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1) enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease.
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Moad et al. find that multipotent prostate basal stem cells, marked by delta homolog 1 (DLK1), reside in proximal ducts and generate directed large-scale epithelial flows traversing the entire length of the branching gland network. This work describes mechanisms underlying 3D epithelial homeostasis in a complex branching tissue.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2w3vrBD
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An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Logan A. Walsh, Mariano J. Alvarez, Erich Y. Sabio, Marsha Reyngold, Vladimir Makarov, Suranjit Mukherjee, Ken-Wing Lee, Alexis Desrichard, Şevin Turcan, Martin G. Dalin, Vinagolu K. Rajasekhar, Shuibing Chen, Linda T. Vahdat, Andrea Califano, Timothy A. Chan
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy.
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Aberrantly activated transcriptional networks drive metastatic dissemination. Walsh et al. reverse engineer a breast cancer-specific regulatory network, uncovering a transcriptional hierarchy underlying breast cancer metastasis. Findings suggest that collapsing transcriptional hierarchies by targeting keystone proteins, such as TRIM25, is critical to affect the coordinated transcriptomic reprogramming required for metastasis.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKKOMK
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CD44 Interacts with HIF-2α to Modulate the Hypoxic Phenotype of Perinecrotic and Perivascular Glioma Cells
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Elinn Johansson, Elisa S. Grassi, Vasiliki Pantazopoulou, Bei Tong, David Lindgren, Tracy J. Berg, Elin J. Pietras, Håkan Axelson, Alexander Pietras
Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44. The CD44ICD was sufficient to induce hypoxic signaling at perivascular oxygen tensions, and blocking CD44 cleavage decreased HIF-2α stabilization in CD44-expressing cells. Our data indicate that the stem cell marker CD44 modulates the hypoxic response of glioma cells and that the pseudo-hypoxic phenotype of stem-like glioma cells is achieved by stabilization of HIF-2α through interaction with CD44, independently of oxygen.
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Hypoxia-inducible factors (HIFs) maintain glioma stemness, and stem-like glioma cells have an amplified hypoxic response compared to bulk tumor cells. Johansson et al. show that the glioma stem cell marker CD44 is activated under hypoxia and interacts with HIF-2α to enhance the hypoxic and pseudo-hypoxic phenotype of glioma stem cells.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKaits
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Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Erika M. Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C. Hooper, Wouter H. Lamers, Bart Ghesquière, Daniel W. McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial cell branching or cancer cell motility. Genetic deletion of macrophagic GS in tumor-bearing mice promotes tumor vessel pruning, vascular normalization, accumulation of cytotoxic T cells, and metastasis inhibition. These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis.
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Palmieri et al. show that inhibiting glutamine synthetase activity in M2 macrophages skews their polarization toward an HIF1α-mediated M1 state, which impairs cytotoxic T cell recruitment and angiogenesis. As a consequence of a more pronounced immunostimulatory and antiangiogenic effect, GS ablation in macrophages translates into prevention of metastasis.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKhmGy
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The IL-17F/IL-17RC Axis Promotes Respiratory Allergy in the Proximal Airways
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Antonella De Luca, Marilena Pariano, Barbara Cellini, Claudio Costantini, Valeria Rachela Villella, Shyam Sushama Jose, Melissa Palmieri, Monica Borghi, Claudia Galosi, Giuseppe Paolicelli, Luigi Maiuri, Jan Fric, Teresa Zelante
The interleukin 17 (IL-17) cytokine and receptor family is central to antimicrobial resistance and inflammation in the lung. Mice lacking IL-17A, IL-17F, or the IL-17RA subunit were compared with wild-type mice for susceptibility to airway inflammation in models of infection and allergy. Signaling through IL-17RA was required for efficient microbial clearance and prevention of allergy; in the absence of IL-17RA, signaling through IL-17RC on epithelial cells, predominantly by IL-17F, significantly exacerbated lower airway Aspergillus or Pseudomonas infection and allergic airway inflammation. In contrast, following infection with the upper respiratory pathogen Staphylococcus aureus, the IL-17F/IL-17RC axis mediated protection. Thus, IL-17A and IL-17F exert distinct biological effects during pulmonary infection; the IL-17F/IL-17RC signaling axis has the potential to significantly worsen pathogen-associated inflammation of the lower respiratory tract in particular, and should be investigated further as a therapeutic target for treating pathological inflammation in the lung.
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De Luca et al. reveal the complexity of IL-17 signaling in Aspergillus lung infection and fungal allergy. The authors describe a pathogenic loop under conditions of IL-17RA disruption and pave the way for therapeutic strategies selectively targeting the IL-17F/IL-17RC axis.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKCqN2
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Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Eric Sterner, Megan L. Peach, Marc C. Nicklaus, Jeffrey C. Gildersleeve
Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies. The immunological evolution of antibodies to mammalian glycans has not been studied. Using glycan microarrays, protein microarrays, cell binding studies, and molecular modeling, we demonstrate that therapeutic antibodies to the tumor-associated ganglioside GD2 evolved from highly specific germline precursors. The results have important implications for developing vaccines and monoclonal antibodies that target carbohydrate antigens. In addition, they demonstrate an alternative pathway for antibody evolution within the immune system that is distinct from the polyspecific germline pathway.
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Sterner et al. demonstrate that germline antibodies to the mammalian glycan GD2 have unexpectedly high selectivity. No cross-reactivity was observed on a glycan microarray with 500 components or a human proteome array with 19,000 proteins. Molecular dynamics reveal pre-organized and relatively rigid binding pockets for the germline antibodies.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKKNsa
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The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R. Billiar, Michael T. Lotze, Herbert J. Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis. These findings reveal a direct molecular link between TP53 and DPP4 in the control of lipid metabolism and may provide a precision medicine strategy for the treatment of colorectal cancer by induction of ferroptosis.
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Xie et al. find that TP53 antagonizes ferroptosis in colorectal cancer (CRC) cells by favoring the localization of DPP4 toward a nuclear, enzymatically inactive pool. This pathway is different from the previously identified function of TP53 as a positive regulator of ferroptosis in non-CRC cells.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKn636
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Antibiotics Disrupt Coordination between Transcriptional and Phenotypic Stress Responses in Pathogenic Bacteria
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Paul A. Jensen, Zeyu Zhu, Tim van Opijnen
Bacterial genes that change in expression upon environmental disturbance have commonly been seen as those that must also phenotypically matter. However, several studies suggest that differentially expressed genes are rarely phenotypically important. We demonstrate, for Gram-positive and Gram-negative bacteria, that these seemingly uncoordinated gene sets are involved in responses that can be linked through topological network analysis. However, the level of coordination is stress dependent. While a well-coordinated response is triggered in response to nutrient stress, antibiotics trigger an uncoordinated response in which transcriptionally and phenotypically important genes are neither linked spatially nor in their magnitude. Moreover, a gene expression meta-analysis reveals that genes with large fitness changes during stress have low transcriptional variation across hundreds of other conditions, and vice versa. Our work suggests that cellular responses can be understood through network models that incorporate regulatory and genetic relationships, which could aid drug target predictions and genetic network engineering.
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Jensen et al. interrogate stress responses in bacteria using genome-wide techniques and metabolic modeling. The authors find that phenotypic and transcriptional stress networks are distinct. Moreover, nutrient and antibiotic stresses respectively lead to coordinated and uncoordinated responses. Network models are thus key to understanding cellular responses, thereby aiding in predicting bacterial behavior.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKDz7C
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Uncoupling the Mitogenic and Metabolic Functions of FGF1 by Tuning FGF1-FGF Receptor Dimer Stability
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Zhifeng Huang, Yi Tan, Junlian Gu, Yang Liu, Lintao Song, Jianlou Niu, Longwei Zhao, Lakshmi Srinivasan, Qian Lin, Jingjing Deng, Yang Li, Daniel J. Conklin, Thomas A. Neubert, Lu Cai, Xiaokun Li, Moosa Mohammadi
The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1ΔHBS) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1ΔHBS exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo. Hence, suboptimal FGFR activation by a weak FGF1-FGFR dimer is sufficient to evoke a metabolic response, whereas full FGFR activation by stable and sustained dimerization is required to elicit a mitogenic response. In addition to providing a physical basis for the diverse activities of FGF1, our findings will impact ongoing drug discoveries targeting FGF1 and related FGFs for the treatment of a variety of human diseases.
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Huang et al. report that quantitative differences in FGF-FGFR dimer stability give rise to different thresholds of intracellular signals to determine mitogenic versus metabolic activities of FGFs.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vKn37q
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Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Daniel Mauvoisin, Florian Atger, Loïc Dayon, Antonio Núñez Galindo, Jingkui Wang, Eva Martin, Laetitia Da Silva, Ivan Montoliu, Sebastiano Collino, Francois-Pierre Martin, Joanna Ratajczak, Carles Cantó, Martin Kussmann, Felix Naef, Frédéric Gachon
Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD)+ level-dependent, we show that NAD+ is orchestrated by both feeding rhythms and the circadian clock through the NAD+ salvage pathway but also via the nicotinamide riboside pathway. Hence, the diurnal acetylome relies on a functional circadian clock and affects important diurnal metabolic pathways in the mouse liver.
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Mauvoisin et al. provide a rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases with an over-representation of SIRT3 targets. Feeding rhythms and the circadian clock regulate NAD+ synthesis through the salvage and nicotinamide riboside pathways, affecting metabolite accumulation.from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vJTHWV
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Overdiagnosis, ethics, and trolley problems: why factors other than outcomes matter—an essay by Stacy Carter
BiographyStacy Carter is associate professor at Sydney Health Ethics, a centre for theoretical and empirical ethics research at the University of Sydney. She specialises in the ethics of public...
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wbYN0X
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A systematic review of molecular responses to cancer therapy in normal human mucosa
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Mette Marcussen, Conni Skrubbeltrang, Julie Støve Bødker, Ilse Christiansen, Martin Bøgsted, Karen Dybkær, Olav Jonas Bergmann, Hans Erik Johnsen
ObjectiveCancer therapy-induced inflammation of oral and gastrointestinal mucosa affects patients non-uniformly. Preventive strategies are limited; no biomarker exists for pretreatment identification of patients likely to be severely affected. Animal models are preferred for studying molecular responses in mucosa during chemotherapy, but translation into clinical practice is difficult. We performed a systematic review to retrieve papers that described molecular changes in human mucosa during cancer therapy.Study DesignWe searched MEDLINE and Ovid Embase searches for English-language literature from January 1990 to November 2016 and studies referenced in selected papers, that analyzed human mucosa from patients at risk of developing mucositis during cancer therapy. Two authors extracted data according to predefined data fields, including study quality indicators.ResultsWe identified 17 human studies on chemotherapy (n=9) and radiotherapy (n=8), but no targeted therapy studies. Studies were heterogeneous regarding patient cohort, analysis methods, cancer treatment, biopsy timing, and correlations to clinical mucositis. Consequently, meta-analysis was not feasible.ConclusionsFew human studies described the molecular responses of normal mucosa to cancer therapy. Studies were heterogeneous with sparse correlations to clinical mucositis. We proposed a model for acquiring data on treatment- and disease-specific phenotypes and transcriptomes for predictive or preventive initiatives.
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Are facial injuries really different? An observational cohort study comparing appearance concern and psychological distress in facial trauma and non-facial trauma patients
Facial injuries are widely assumed to lead to stigma and significant psychosocial burden. Experimental studies of face perception support this idea, but there is very little empirical evidence to guide treatment. This study sought to address the gap.Data were collected from 193 patients admitted to hospital following facial or other trauma. Ninety (90) participants were successfully followed up eight months later. Participants completed measures of appearance concern and psychological distress (post-traumatic stress symptoms, depressive symptoms, anxiety symptoms).
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Patient Rated Long-Term Results after Complete Denervation of the Wrist
The aim of this study was to examine the long-term results after the denervation of the wrist. Between 1977 and 2001 we treated 375 patients in our clinic. The mean age was 43.5 years, 81% were male and 19% female. The long-term results were assessed by a questionnaire assessing pain on a visual analogue scale and patient satisfaction and by the DASH questionnaire. After a mean follow-up of 12.23 years, we found an overall pain reduction of 52.1%. In 67.7% of the patients we found a relief of pain; of these patients, 44% are free of pain until today, and 56% were temporarily asymptomatic.
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Subungual Melanoma – Management in the Modern Era
Subungual melanoma is a rare subtype of cutaneous melanoma that arises from the structures of the nail apparatus. It presents most commonly in older patients and at an advanced stage.A retrospective review of all patients with subungual melanoma in a single institution over a 15-year period was performed. 54 patients were included (26 males, average age 62.9 years). 28 cases involved the upper limb. Median tumour thickness was 4.5mm. 18 patients had lymph node metastasis at diagnosis, including 11 of 36 patients with positive sentinel lymph node biopsy.
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Reconstructive microsurgical approach for treatment of pyoderma gangrenosum
Pyoderma gangrenosum (PG) is a rare type of autoimmune disease that results in progressive ulcers with or without previous trauma. PG is not well understood to date, and its treatment therefore remains a challenge. Because of the disease's systemic characteristic and the unpredictability of the clinical course, no gold standard treatment is available, especially concerning surgical procedures to treat pyodermic lesions. Often, PG is not recognized during routine clinical practice, and standard ulcer treatment (conservative wound care, debridement, skin grafting, and local flap coverage) is started; this induces an autoinflammatory response, resulting in disastrous ulcers, thereby making free flap coverage necessary.
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Anatomic and high resolution computed tomographic angiography study of the lateral femoral condyle flap: implications for surgical dissection
The Lateral femoral condyle (LFC) flap is a vascularized bone flap based on the superior lateral genicular artery (SLGA). Harvest technique for this flap has not yet been demonstrated. The purpose of this study was to better delineate the blood supply to the bone and skin to allow for a safe and effective harvest.
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Does videoendoscopy provide three-dimensional vision in closed rhinoplasty?
Rhinoplasty is a common procedure in cosmetic surgery all over the world. Patients desire enhancement of their facial beauty by the correction of preexisting nasal deformities. Precisely performed operations lead to better results, and, enhancing technical accuracy accordingly results in more successful outcomes.Endoscopy helps us to visualize the closed parts of the body with the aid of an illuminated optical device. The objective behind present case series was bringing the advantages of open and closed rhinoplasty together by using endoscopic vision systems.
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An implant for autologous soft tissue reconstruction based on an adipose-derived stem cell colonized alginate scaffold
Adipose-derived stem cells represent an interesting option for soft tissue replacement since they are easy to procure and can generate their own blood supply through the production of angiogenic factors. We seeded adipose-derived stem cells on a bioresorbable, biocompatible polymer alginate scaffold to generate autologous soft tissue constructs for repair.
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Does self-consciousness of appearance influence postoperative satisfaction in rhinoplasty?
Facial plastic surgeons and patients benefit from knowledge about how psychological aspects can influence the outcome of cosmetic surgery. The influence of pre-operative self-consciousness of appearance and its effect on benefit after surgery in rhinoplasty patients has not been explored before in other studies.
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Starting a sentinel node service for melanoma: is there a role for predictive nomograms?
A letter to author regarding predictive nomograms for sentinel node status in melanoma.
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Antibiotic Prophylaxis in Breast Reduction Surgery: A Systematic Review and Meta-analysis
To determine the effectiveness and harm of using antibiotic prophylaxis versus placebo or no intervention in patients undergoing breast reduction surgery to prevent surgical site infection.
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Cox16 protein is physically associated with Cox1p assembly intermediates and with cytochrome oxidase [Membrane Biology]
Mitochondrial cytochrome oxidase (COX) catalyzes the last step in the respiratory pathway. In Saccharomyces cervisiae this inner membrane complex is composed of 11 protein subunits. Expression of COX is assisted by some 2 dozen ancillary proteins that intercede at different stages of the assembly pathway. One such protein, Cox16p, encoded by COX16, was shown to be essential for activity and assembly of COX. The function of Cox16p, however, has not been determined. We present evidence that Cox16p is present in Cox1p assembly intermediates and in COX. This is based on the finding that Cox16p, tagged with a dual poly-histidine and protein C tag, co-immunopurified with Cox1p assembly intermediates. The pull-down assays also indicated the presence of Cox16p in mature COX and in supercomplexes consisting of COX and the bc1 complex. From the Western signal strengths, Cox16p appears to be substoichiometric with Cox1p and Cox4p, which could indicate that Cox16p is only present in a fraction of COX. In conclusion, our results indicate that Cox16p is a constituent of several Cox1p assembly intermediates and of COX.
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Syndecan-2 cytoplasmic domain upregulates Matrix Metalloproteinase-7 expression via Protein KinaseC{gamma} mediated FAK/ERK signaling pathway in colon cancer [Signal Transduction]
The syndecan family of heparan sulfate proteoglycans contribute to cell adhesion and communication by serving as co-receptors for cell signaling and extracellular matrix molecules. Syndecan-2 is located at the cell surface, and we previously reported that it induces matrix metalloproteinase-7 (MMP-7) expression in colon cancer cells. However, the underlying regulatory mechanisms are unknown. Here, we report that over-expression of syndecan-2 in HT-29 colon cancer cells increases the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) in parallel with upregulated MMP-7 expression, but a syndecan-2 mutant lacking the cytoplasmic domain showed significant reductions in these effects. Consistent with this observation, FAK inhibition via FAK-related nonkinase expression or inhibition of ERK with the ERK1/2 inhibitor SCH772984 diminished the syndecan-2-mediated upregulation of MMP-7. Activation of protein kinase C (PKC) enhanced syndecan-2-mediated MMP-7 expression, whereas inhibition of PKC had the opposite effect. Of note, the exogenous expression of syndecan-2 triggered localization of PKCγ to the membrane. Expression of syndecan-2 harboring a phospho-mimetic (S198E) mutation of the variable region of the cytoplasmic domain enhanced MMP-7 expression and FAK phosphorylation. Finally, experimental supression of shedding of the syndecan-2 extracellular domain did not significantly affect the syndecan-2-mediated upregulation of MMP-7 in the early period after syndecan-2 over-expression. Taken together, these findings suggest that syndecan-2's cytoplasmic domain upregulates MMP-7 expression in colon cancer cells via PKCγ-mediated activation of FAK/ERK signaling.
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A screen for kinase inhibitors identifies antimicrobial imidazopyridine aminofurazans as specific inhibitors of the Listeria monocytogenes PASTA kinase PrkA [Signal Transduction]
Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial Penicillin-binding-protein And Serine/Threonine kinase-Associated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy. Despite this interest, only limited progress has been made in identifying functional inhibitors of the PASTA kinases that have both activity against the intact microbe and high kinase specificity. Here, we report the results of a small-molecule screen that identified GSK690693, an imidazopyridine aminofurazan-type kinase inhibitor that increases the sensitivity of the intracellular pathogen Listeria monocytogenes to various β-lactams by inhibiting the PASTA kinase PrkA. GSK690693 potently inhibited PrkA kinase activity biochemically and exhibited significant selectivity for PrkA relative to the Staphylococcus aureus PASTA kinase Stk1. Furthermore, other imidazopyridine aminofurazans could effectively inhibit PrkA and potentiate β-lactam antibiotic activity to varying degrees. The presence of the 2-methyl-3-butyn-2-ol (alkynol) moiety was important for both biochemical and antimicrobial activity. Finally, mutagenesis studies demonstrated residues in the back pocket of the active site are important for GSK690693 selectivity. These data suggest that targeted screens can successfully identify PASTA kinase inhibitors with both biochemical and antimicrobial specificity. Moreover, the imidazopyridine aminofurazans represent a family of PASTA kinase inhibitors that have the potential to be optimized for selective PASTA kinase inhibition.
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Change in protein production essential to muscle function - Science Daily
| Change in protein production essential to muscle function Science Daily ... during muscle postnatal development; it is the type of protein produced that changes," said Cooper, who also is the S. Donald Greenberg and R. Clarence and Irene H. Fulbright Professor and a member of the Dan L Duncan Comprehensive Cancer Center ... |
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Cancer-fighting T cells are smarter, stronger than experts thought ... - Science Daily
| Science Daily | Cancer-fighting T cells are smarter, stronger than experts thought ... Science Daily It takes a minuscule amount of force to make T cells behave in the lab as they behave in the body. That finding is a leap in cancer therapy research. and more » |
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Blood biopsy test reads platelets to detect human lung cancer - Science Daily
| Blood biopsy test reads platelets to detect human lung cancer Science Daily However, platelets also respond to a range of inflammatory events and cancer. Because platelet cells don't have a nucleus of their own, all RNA found in platelets either comes from megakaryocytes (the cells that form platelets in bone marrow) or from ... and more » |
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miR-4443 Regulates Mast Cell Activation By T Cell - Derived Microvesicles
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EASI p-EASI: Utilising a combination of serum biomarkers offers an objective measurement tool for disease severity in atopic dermatitis patients.
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Atypical presentation of anti-N-methyl-D-aspartate receptor encephalitis: two case reports
Anti-N-methyl-D-aspartate receptor encephalitis is a rare autoimmune disease characterized by severe neurological and psychiatric symptoms and a difficult diagnosis.
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Impact of sedation technique on the diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration
Daniel Franzen, Didier Schneiter, Walter Weder, Malcolm Kohler
Endoscopic Ultrasound 2017 6(4):257-263
Background and Objectives: There is a paucity of data concerning the impact of the sedation technique used for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on diagnostic accuracy. The aim of this retrospective study was to compare the diagnostic accuracy of EBUS-TBNA in deep and moderate sedations, and to investigate other possible determinants of diagnostic accuracy in three lymph node locations (mediastinal, subcarinal, and hilar). Materials and Methods: The first consecutive patients at our institution undergoing EBUS-TBNA for selective sampling in deep sedation were compared with the first consecutive patients in moderate sedation between 2006 and 2014. Diagnoses based on EBUS-TBNA were compared with those on surgical or radiological follow-up. Results: In a total of 232 patients, the overall diagnostic accuracy for correct diagnosis at the mediastinal, subcarinal, and hilar locations irrespective of the sedation technique was 91%, 93%, and 92%, respectively. At the three mentioned lymph node locations, overall diagnostic accuracy of EBUS-TBNA in deep sedation compared to moderate sedation was 88.5% and 95.5% (P = 0.3), 93.2 and 93.6% (P = 0.9), and 88.6 and 94.0% (P = 0.4), respectively. Conclusions: The sedation technique does not seem to influence the diagnostic accuracy of EBUS-TBNA.
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Endoscopic Ultrasound 2017 6(4):257-263
Background and Objectives: There is a paucity of data concerning the impact of the sedation technique used for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on diagnostic accuracy. The aim of this retrospective study was to compare the diagnostic accuracy of EBUS-TBNA in deep and moderate sedations, and to investigate other possible determinants of diagnostic accuracy in three lymph node locations (mediastinal, subcarinal, and hilar). Materials and Methods: The first consecutive patients at our institution undergoing EBUS-TBNA for selective sampling in deep sedation were compared with the first consecutive patients in moderate sedation between 2006 and 2014. Diagnoses based on EBUS-TBNA were compared with those on surgical or radiological follow-up. Results: In a total of 232 patients, the overall diagnostic accuracy for correct diagnosis at the mediastinal, subcarinal, and hilar locations irrespective of the sedation technique was 91%, 93%, and 92%, respectively. At the three mentioned lymph node locations, overall diagnostic accuracy of EBUS-TBNA in deep sedation compared to moderate sedation was 88.5% and 95.5% (P = 0.3), 93.2 and 93.6% (P = 0.9), and 88.6 and 94.0% (P = 0.4), respectively. Conclusions: The sedation technique does not seem to influence the diagnostic accuracy of EBUS-TBNA.
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Chinese expert consensus statement on issues related to small specimen sampling of lung cancer
Chinese Thoracic Society, Chinese Alliance against Lung Cancer
Endoscopic Ultrasound 2017 6(4):219-230
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Endoscopic Ultrasound 2017 6(4):219-230
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Endoscopic ultrasound for the diagnosis of an uncommon cause of obstructive jaundice masquerading as malignancy
Filippo Antonini, Giampiero Macarri
Endoscopic Ultrasound 2017 6(4):276-277
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Endoscopic Ultrasound 2017 6(4):276-277
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Seagulls of endoscopic ultrasound
Amit Pathak, Abid Shoukat, NS Thomas, Divij Mehta, Malay Sharma
Endoscopic Ultrasound 2017 6(4):231-234
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Endoscopic Ultrasound 2017 6(4):231-234
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Extramedullary plasmacytoma mimicking pancreatic cancer: A case report and literature review
Jae Hyung Kim, Woo Hyun Paik, Mee Joo, Jung Gon Kim, Jong Wook Kim, Won Ki Bae, Nam-Hoon Kim, Kyung-Ah Kim, June Sung Lee
Endoscopic Ultrasound 2017 6(4):269-272
Pancreatic adenocarcinoma may account for more than 80% of all pancreatic neoplasms. Occasionally, other rare tumors such as lymphoma, metastatic tumor, and solid pseudopapillary neoplasm can be considered in the differential diagnosis. We report the case of an 82-year-old man with a pancreatic solid mass. This case suggests that endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with biopsy, that is, EUS-FNA is recommended in the differential diagnosis of the pancreatic solid mass apart from pancreatic adenocarcinoma. In particular, the histologic core obtained by EUS-guided biopsy is helpful for the immunostaining of molecular markers to confirm the final diagnosis.
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Endoscopic Ultrasound 2017 6(4):269-272
Pancreatic adenocarcinoma may account for more than 80% of all pancreatic neoplasms. Occasionally, other rare tumors such as lymphoma, metastatic tumor, and solid pseudopapillary neoplasm can be considered in the differential diagnosis. We report the case of an 82-year-old man with a pancreatic solid mass. This case suggests that endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with biopsy, that is, EUS-FNA is recommended in the differential diagnosis of the pancreatic solid mass apart from pancreatic adenocarcinoma. In particular, the histologic core obtained by EUS-guided biopsy is helpful for the immunostaining of molecular markers to confirm the final diagnosis.
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Endorectal fusion imaging: A description of a new technique
Andre Ignee, Yi Dong, Gudrun Schuessler, Ulrich Baum, Christoph F Dietrich
Endoscopic Ultrasound 2017 6(4):241-244
Background: Fusion imaging is an accepted method in abdominal imaging allowing a simultaneous display of reference imaging with a live ultrasound (US) investigation. For prostate cancer, promising results have been published for endorectal US (ERUS)-guided biopsy of suspicious lesions in magnetic resonance imaging (MRI). To our knowledge, no other indication for the fusion of ERUS with MRI has been reported so far. Methods: We report on three patients scheduled for ERUS due to anorectal fistulae after treatment (n = 2) or rectal carcinoma (n = 1), which were scheduled for real-time virtual onography (RVS), a method for the fusion of MRI imaging with US. Results: In all patients, RVS was successful. The course of the fistulae could be defined and the success of the treatment could be confirmed. In the patient with rectal carcinoma, the lymph nodes suspicious in MRI could be identified. Conclusions: MRI/ERUS fusion has the potential for follow-up of anorectal fistulae and abscesses, and staging of anal and rectal tumors.
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Endoscopic Ultrasound 2017 6(4):241-244
Background: Fusion imaging is an accepted method in abdominal imaging allowing a simultaneous display of reference imaging with a live ultrasound (US) investigation. For prostate cancer, promising results have been published for endorectal US (ERUS)-guided biopsy of suspicious lesions in magnetic resonance imaging (MRI). To our knowledge, no other indication for the fusion of ERUS with MRI has been reported so far. Methods: We report on three patients scheduled for ERUS due to anorectal fistulae after treatment (n = 2) or rectal carcinoma (n = 1), which were scheduled for real-time virtual onography (RVS), a method for the fusion of MRI imaging with US. Results: In all patients, RVS was successful. The course of the fistulae could be defined and the success of the treatment could be confirmed. In the patient with rectal carcinoma, the lymph nodes suspicious in MRI could be identified. Conclusions: MRI/ERUS fusion has the potential for follow-up of anorectal fistulae and abscesses, and staging of anal and rectal tumors.
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Colon carcinoma staging by endoscopic ultrasonography miniprobes
Fernando M Castro-Poças, Mário Dinis-Ribeiro, Anabela Rocha, Marisa Santos, Tarcísio Araújo, Isabel Pedroto
Endoscopic Ultrasound 2017 6(4):245-251
Background and Objectives: Due to the increasing use of endoscopic techniques for colon cancer resection, pretreatment locoregional staging may gain critical interest. The use of endoscopic ultrasonography (EUS) miniprobes in this context has been seldom reported. Our aim was to determine the accuracy of EUS miniprobes for colon cancer staging. Materials and Methods: Forty patients with colon cancer (2 in the cecum, 9 in the ascending colon, 5 in the transverse colon, 5 in the descending colon, and 19 in the sigmoid colon) were submitted to staging using 12 MHz EUS miniprobes. EUS and the anatomopathological results were compared with regard to the T and N stages. It was assessed if the location, longitudinal extension, or circumferential extension of the tumor had any influence on the accuracy in EUS staging. Results: Tumor staging was feasible in 39 (98%) patients except in one case with a stenosing tumor (out of 6). Globally, T stage was accurately determined in 88% of the cases. In the assessment of the presence or absence of lymph node metastasis, miniprobes presented an accuracy of 82% with a sensitivity of 67%. These results were neither affected by the location nor by the longitudinal or circumferential extension of the tumor. Conclusions: EUS miniprobes may play an important role in assessing T and N stages in colon cancer and may represent an incentive to the research of new therapeutic areas for this disease.
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Endoscopic Ultrasound 2017 6(4):245-251
Background and Objectives: Due to the increasing use of endoscopic techniques for colon cancer resection, pretreatment locoregional staging may gain critical interest. The use of endoscopic ultrasonography (EUS) miniprobes in this context has been seldom reported. Our aim was to determine the accuracy of EUS miniprobes for colon cancer staging. Materials and Methods: Forty patients with colon cancer (2 in the cecum, 9 in the ascending colon, 5 in the transverse colon, 5 in the descending colon, and 19 in the sigmoid colon) were submitted to staging using 12 MHz EUS miniprobes. EUS and the anatomopathological results were compared with regard to the T and N stages. It was assessed if the location, longitudinal extension, or circumferential extension of the tumor had any influence on the accuracy in EUS staging. Results: Tumor staging was feasible in 39 (98%) patients except in one case with a stenosing tumor (out of 6). Globally, T stage was accurately determined in 88% of the cases. In the assessment of the presence or absence of lymph node metastasis, miniprobes presented an accuracy of 82% with a sensitivity of 67%. These results were neither affected by the location nor by the longitudinal or circumferential extension of the tumor. Conclusions: EUS miniprobes may play an important role in assessing T and N stages in colon cancer and may represent an incentive to the research of new therapeutic areas for this disease.
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Impact of introduction of endoscopic ultrasound on volume, success, and complexity of endoscopic retrograde cholangiopancreatography in a tertiary referral center
Harathi Yandrapu, Sherif Elhanafi, Farhanaz Chowdhury, Jiayang Liu, Eduardo J Onate, Alok Dwivedi, Mohamed O Othman
Endoscopic Ultrasound 2017 6(4):252-256
Background and Objectives: Endoscopic ultrasound (EUS) is commonly used to examine pancreaticobiliary disorders. We hypothesize that the introduction of EUS service may change the pattern and the complexity of endoscopic retrograde cholangiopancreatographies (ERCPs) performed. The aim of this study is to assess the impact of introducing EUS on the volume, success, and complexity of ERCP. Materials and Methods: This is a single-center retrospective data review of ERCP procedures done "before" and "after" the introduction of EUS (before EUS and after EUS). Patients' demographics, ERCP indications, types of sedation, therapeutic interventions, outcomes, complications, and complexity of ERCP were collected. The categorical and continuous variables were compared using Fisher's exact test and the unpaired t-test, respectively. Multivariable logistic regression analysis was used to compare ERCP outcomes. Results: A total of 945 ERCPs performed over a 3-year period between January 2010 and January 2013 (411 and 534 in the "before EUS" and "after EUS" time periods, respectively) were included in this study. There was a 30% relative increase in the volume of ERCPs after the introduction of EUS. ERCP success rate was higher after the introduction of EUS, even after adjusting the complexity grade [odds ratio (OR) = 4.54, P = 0.001]. Significant increase in the complexity of ERCP was observed after the introduction of EUS service. The OR of performing grade 4 ERCP was 4.44 (P = 0.0005) after the introduction of EUS. Conclusions: The introduction of a new EUS service in our tertiary referral university medical center is associated with an increase in the volume, success, and complexity of ERCP procedures. EUS expertise may be valuable for better ERCP outcomes.
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Endoscopic Ultrasound 2017 6(4):252-256
Background and Objectives: Endoscopic ultrasound (EUS) is commonly used to examine pancreaticobiliary disorders. We hypothesize that the introduction of EUS service may change the pattern and the complexity of endoscopic retrograde cholangiopancreatographies (ERCPs) performed. The aim of this study is to assess the impact of introducing EUS on the volume, success, and complexity of ERCP. Materials and Methods: This is a single-center retrospective data review of ERCP procedures done "before" and "after" the introduction of EUS (before EUS and after EUS). Patients' demographics, ERCP indications, types of sedation, therapeutic interventions, outcomes, complications, and complexity of ERCP were collected. The categorical and continuous variables were compared using Fisher's exact test and the unpaired t-test, respectively. Multivariable logistic regression analysis was used to compare ERCP outcomes. Results: A total of 945 ERCPs performed over a 3-year period between January 2010 and January 2013 (411 and 534 in the "before EUS" and "after EUS" time periods, respectively) were included in this study. There was a 30% relative increase in the volume of ERCPs after the introduction of EUS. ERCP success rate was higher after the introduction of EUS, even after adjusting the complexity grade [odds ratio (OR) = 4.54, P = 0.001]. Significant increase in the complexity of ERCP was observed after the introduction of EUS service. The OR of performing grade 4 ERCP was 4.44 (P = 0.0005) after the introduction of EUS. Conclusions: The introduction of a new EUS service in our tertiary referral university medical center is associated with an increase in the volume, success, and complexity of ERCP procedures. EUS expertise may be valuable for better ERCP outcomes.
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Measurement of total Transcobalamin employing a commercially available assay for Active B12
Publication date: Available online 16 August 2017
Source:Clinical Biochemistry
Author(s): Pieter H. Griffioen, Dianne H.K. van Dam-Nolen, Jan Lindemans, Sandra G. Heil
IntroductionVitamin B12 deficiency is mostly caused by insufficient gastro-intestinal absorption and in rare conditions by Transcobalamin (TC) deficiency. Unsaturated Transcobalamin (apoTC) can be measured by a binding assay using radiolabeled cobalamin. The Active B12 test analyzes saturated Transcobalamin (holoTC) and we hypothesize that this test can be used to measure total TC by additional in vitro saturation with cobalamin.MethodsSerum was saturated in vitro (16 times dilution) with a cyanocobalamin solution and total TC was selectively measured with the Abbott Active B12 test. ApoTC was calculated by subtracting endogenous holoTC from total TC after correction for dilution. Linearity was determined with a pool serum dilution series. Precision was investigated according to the CLSI EP15 protocol. Method comparison was performed against a binding assay using radiolabeled cobalamin. Reference values were determined in 100 healthy controls.ResultsThe method was linear in the range of 240 to 1933pmol/L (R2=0.997, lack of fit F=1.61). Precision of low- and high-pool total TC in serum were; 5.2% and 4.3% respectively. Method comparison against a radiolabeled cobalamin binding assay showed a proportional bias of 30% (y=0.70x+126). Total TC reference values were determined at 500–1276pmol/L.ConclusionWe describe a rapid method to quantify total TC, which can be implemented on routine platforms using commercial Active B12 tests. In addition, apoTC can be assessed by subtracting endogenous holoTC concentration which can be measured in the same run, securing the same calibration level for all three parameters (holoTC, apoTC and total TC). This method is applicable in clinical diagnostics and in larger epidemiological studies.
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Experimental Validation of Fly-Wheel Passive Launch and On-Orbit Vibration Isolation System by Using a Superelastic SMA Mesh Washer Isolator
On-board appendages with mechanical moving parts for satellites produce undesirable micro-jitters during their on-orbit operation. These micro-jitters may seriously affect the image quality from high-resolution observation satellites. A new application form of a passive vibration isolation system was proposed and investigated using a pseudoelastic SMA mesh washer. This system guarantees vibration isolation performance in a launch environment while effectively isolating the micro-disturbances from the on-orbit operation of jitter source. The main feature of the isolator proposed in this study is the use of a ring-type mesh washer as the main axis to support the micro-jitter source. This feature contrasts with conventional applications of the mesh washers where vibration damping is effective only in the thickness direction of the mesh washer. In this study, the basic characteristics of the SMA mesh washer isolator in each axis were measured in static tests. The effectiveness of the design for the new application form of the SMA mesh washer proposed in this study was demonstrated through both launch environment vibration test at qualification level and micro-jitter measurement test which corresponds to on-orbit condition.
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