Αλέξανδρος Γ. Σφακιανάκης
Αναπαύσεως 5 Άγιος Νικόλαος Λασιθίου 72100
2841026182
6948891480
Κυριακή 25 Σεπτεμβρίου 2016
Skin Diseases (full book)
Near-road enhancement and solubility of fine and coarse particulate matter trace elements near a major interstate in Detroit, Michigan
Publication date: November 2016
Source:Atmospheric Environment, Volume 145
Author(s): Michelle M. Oakes, Janet M. Burke, Gary A. Norris, Kasey D. Kovalcik, J. Patrick Pancras, Matthew S. Landis
Communities near major roadways are disproportionately affected by traffic-related air pollution which can contribute to adverse health outcomes. The specific role of particulate matter (PM) from traffic sources is not fully understood due to complex emissions processes and physical/chemical properties of PM in the near-road environment. To investigate the spatial profile and water solubility of elemental PM species near a major roadway, filter-based measurements of fine (PM2.5) and coarse (PM10-2.5) PM were simultaneously collected at multiple distances (10 m, 100 m, and 300 m) from Interstate I-96 in Detroit, Michigan during September–November 2010. Filters were extracted in water, followed by a hot acid extraction, and analyzed by magnetic sector field high resolution inductively coupled plasma mass spectrometry (HR-ICPMS) to quantify water-soluble and acid-soluble trace elements for each PM size fraction. PM2.5 and PM10-2.5 species measured in the near-road samples included elements associated with traffic activity, local industrial sources, and regional pollution. Metals indicative of brake wear (Ba, Cu) were dramatically enriched near the roadway during downwind conditions (factor of 5 concentration increase), with the largest increase within 100 m of the roadway. Moderate near-roadway increases were observed for crustal elements and other traffic-related PM (Fe, Ca), and the lowest increases observed for regional PM species (S). Water solubility varied by PM species and size, and for PM2.5 included highly (S, K, Ca, Mg, Zn, Ba), moderately (Cu, Mn, Sb, Pb), and minimally (Fe, Ti) water-soluble species, with lower water solubility for most species in PM10-2.5. Results from this study indicate that water-soluble PM2.5 and PM10-2.5 metals, particularly from brake/tire wear, were enhanced in the near-roadway environment which may have human health implications.
Graphical abstract
http://ift.tt/2cxoBvb
Validation and optimization of SST k-ω turbulence model for pollutant dispersion within a building array
Source:Atmospheric Environment, Volume 145
Author(s): Hesheng Yu, Jesse Thé
The prediction of the dispersion of air pollutants in urban areas is of great importance to public health, homeland security, and environmental protection. Computational Fluid Dynamics (CFD) emerges as an effective tool for pollutant dispersion modelling. This paper reports and quantitatively validates the shear stress transport (SST) k-ω turbulence closure model and its transitional variant for pollutant dispersion under complex urban environment for the first time. Sensitivity analysis is performed to establish recommendation for the proper use of turbulence models in urban settings. The current SST k-ω simulation is validated rigorously by extensive experimental data using hit rate for velocity components, and the "factor of two" of observations (FAC2) and fractional bias (FB) for concentration field. The simulation results show that current SST k-ω model can predict flow field nicely with an overall hit rate of 0.870, and concentration dispersion with FAC2 = 0.721 and FB = 0.045. The flow simulation of the current SST k-ω model is slightly inferior to that of a detached eddy simulation (DES), but better than that of standard k-ε model. However, the current study is the best among these three model approaches, when validated against measurements of pollutant dispersion in the atmosphere. This work aims to provide recommendation for proper use of CFD to predict pollutant dispersion in urban environment.
http://ift.tt/2cxqnMT
Net global warming potential and greenhouse gas intensity of conventional and conservation agriculture system in rainfed semi arid tropics of India
Source:Atmospheric Environment, Volume 145
Author(s): G. Pratibha, I. Srinivas, K.V. Rao, Arun K. Shanker, B.M.K. Raju, Deepak K. Choudhary, K. Srinivas Rao, Ch. Srinivasarao, M. Maheswari
Agriculture has been considered as one of the contributors to greenhouse gas (GHG) emissions and it continues to increase with increase in crop production. Hence development of sustainable agro techniques with maximum crop production, and low global warming potential is need of the hour. Quantifying net global warming potential (NGWP) and greenhouse gas intensity (GHGI) of an agricultural activity is a method to assess the mitigation potential of the activity. But there is dearth of information on NGWP of conservation agriculture under rainfed conditions. Hence in this study two methods such as crop based (NGWPcrop) and soil based (NGWPsoil) were estimated from the data of the experiment initiated in 2009 in rainfed semiarid regions of Hyderabad, India with different tillage practices like conventional tillage (CT), reduced tillage (RT), zero tillage (ZT) and residue retention levels by harvesting at different heights which includes 0, 10 and 30 cm anchored residue in pigeonpea-castor systems. The results of the study revealed that under rainfed conditions CT recorded 24% higher yields over ZT, but CT and RT were on par with each other. However, the yield gap between the tillage treatments is narrowing down over 5 years of study. ZT and RT recorded 26 and 11% lower indirect GHG emissions (emissions from farm operations and input use) over CT, respectively. The percent contribution of CO2 eq. N2O emission is higher to total GHG emissions in both the crops. Both NGWPcrop, NGWPsoil, GHGIcrop, and GHGIsoil based were influenced by tillage and residue treatments. Further, castor grown on pigeonpea residue recorded 20% higher GHG emissions over pigeonpea grown on castor residues. The fuel consumption in ZT was reduced by 58% and 81% as compared to CT in pigeonpea and castor, respectively. Lower NGWP and GHGI based on crop and soil was observed with increase in crop residues and decrease in tillage intensity in both the crops. The results of the study indicate that, there is scope to reduce the NGWP emissions by reducing one tillage operation as in RT and increase in crop residue by harvesting at 10 and 30 cm height with minimal impact on the crop yields. However, the trade-off between higher yield and soil health versus GHG emissions should be considered while promoting conservation agriculture. The NGWPcrop estimation method indicated considerable benefits of residues to the soil and higher potential of GHG mitigation than by the NGWPsoil method and may overestimate the potential of GHG mitigation in agriculture system.
http://ift.tt/2dabjmn
Long-Term Follow-Up after Phrenic Nerve Reconstruction for Diaphragmatic Paralysis: A Review of 180 Patients
J reconstr Microsurg
DOI: 10.1055/s-0036-1588018
Background Phrenic nerve reconstruction has been evaluated as a method of restoring functional activity and may be an effective alternative to diaphragm plication. Longer follow-up and a larger cohort for analysis are necessary to confirm the efficacy of this procedure for diaphragmatic paralysis. Methods A total of 180 patients treated with phrenic nerve reconstruction for chronic diaphragmatic paralysis were followed for a median 2.7 years. Assessment parameters included: 36-Item Short Form Health Survey (SF-36) physical functioning survey, spirometry, chest fluoroscopy, electrodiagnostic evaluation, a five-item questionnaire to assess specific functional issues, and overall patient-reported outcome. Results Overall, 134 males and 46 females with an average age of 56 years (range: 10–79 years) were treated. Mean baseline percent predicted values for forced expiratory volume in 1 second, forced vital capacity, vital capacity, and total lung capacity, were 61, 63, 67, and 75%, respectively. The corresponding percent improvements in percent predicted values were: 11, 6, 9, and 13% (p ≤ 0.01; ≤ 0.01; ≤ 0.05; ≤ 0.01). Mean preoperative SF-36 physical functioning survey scores were 39%, and an improvement to 65% was demonstrated following surgery (p ≤ 0.0001). Nerve conduction latency, improved by an average 23% (p ≤ 0.005), and there was a corresponding 125% increase in diaphragm motor amplitude (p ≤ 0.0001). A total of 89% of patients reported an overall improvement in breathing function. Conclusion Long-term assessment of phrenic nerve reconstruction for diaphragmatic paralysis indicates functional correction and symptomatic relief.
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Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2cYIQ6i
Memory Consolidation in Sleep Disorders
In recent years sleep-related memory consolidation has become a central topic in the sleep research field. Several studies have shown that in healthy individuals sleep promotes memory consolidation. Notwithstanding this, the consequences of sleep disorders on offline memory consolidation remain poorly investigated. Research studies indicate that patients with insomnia, obstructive sleep apnea, and narcolepsy often exhibit sleep-related impairment in the consolidation of declarative and procedural information.
http://ift.tt/2cUCnpV
Preparing for the unpredictable: The continuing need for pandemic influenza preparedness
Source:Vaccine
Author(s): Bruce G. Gellin, Firdausi Qadri
http://ift.tt/2cYgfy1
Association between Nesfatin-1 levels and Metabolic Improvements in Severely Obese Patients Who Underwent Biliopancreatic Derivation With Duodenal Switch
Source:Peptides
Author(s): David H. St-Pierre, Julie Martin, Hiroyuki Shimizu, Yuko Tagaya, Takahumi Tsuchiya, Simon Marceau, Laurent Biertho, Marjorie Bastien, Sarah-Maude Caron-Cantin, Serge Simard, Denis Richard, Katherine Cianflone, Paul Poirier
CONTEXTNesfatin-1 is a neuroendocrine peptide with potent anorexigenic activity in rodents. The potential role of nesfatin-1 on the regulation of energy balance, metabolic functions and inflammation is currently debated in obese humans. In the present study, nesfatin-1 fluctuations and their associations with metabolic factors were investigated in severely obese patients who underwent biliopancreatic diversion with duodenal switch (BPD/DS) and severely obese controls (SOC).BASIC PROCEDURESSixty severely obese patients who underwent BPD/DS and 15 SOC (matched for BMI and age) were included in the study. Associations between nesfatin-1 levels and body composition, glucose metabolism, lipid profile as well as inflammatory markers were evaluated at baseline and over a post-surgery12-month (12M) period.MAIN FINDINGSBody weight was reduced at 6M and at 12M in BPD/DS patients (P<0.001). Nesfatin-1 levels were reduced at 6M (women: P<0.05) and at 12M (men and women; P<0.001) in BPD/DS patients. At baseline, nesfatin-1 levels negatively correlated with weight, fat (FM) and fat-free mass (FFM) in the whole population (combined BPD/DS and SOC patients). At 12M, nesfatin-1 concentrations positively correlated with weight, FM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, triglyceride and apoB values. At 12M, % changes in nesfatin-1 were positively associated with % changes in weight, FM, FFM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, apoB and C-reactive protein.CONCLUSIONNesfatin-1 levels decrease following BPD/DS-induced weight loss and are significantly associated with parameters of metabolic health.
http://ift.tt/2cuJgLv
Double-hit follicular lymphoma with MYC and BCL2 translocations: a study of 7 cases with a review of literature
Publication date: December 2016
Source:Human Pathology, Volume 58
Author(s): Yuan Miao, Shimin Hu, Xinyan Lu, Shaoying Li, Wei Wang, L. Jeffrey Medeiros, Pei Lin
Follicular lymphoma with MYC and BCL2 translocations, so-called double-hit follicular lymphoma (DH-FL), is rare. Here, we report the clinicopathological features of 7 cases of DH-FL. All neoplasms had a follicular pattern (1 partially diffuse). Five cases were predominantly low grade, 4 of which had focal (≤20%) grade 3A areas, and 2 cases were of grade 3. All cases were positive for pan–B-cell antigens, CD10, and BCL6; 6 cases were positive for BCL2. Ki-67 was less than or equal to 50% in 6 cases and 90% in 1 grade 3 case. Three patients presented with stage IV disease and 3 had a Follicular Lymphoma International Prognostic Index score of greater than 2. Six patients received immunochemotherapy, and 1 is still under induction therapy with rituximab, ibrutinib, and lenalidomide. Four achieved complete remission and two had a partial response with persistent or refractory disease. The median follow-up time was 25 months (range, 8.5-53.7 months). Two patients treated with standard regimen for follicular lymphoma had relapsed or refractory disease, and 1 died from complications of allogeneic stem cell transplant administered for relapse. In contrast, all 4 patients treated with more intensive regimen for double-hit lymphoma achieved complete remission. In summary, despite predominantly low-grade histology, cases of DH-FL in this study were aggressive and responded better to more intensive than standard treatment regimens, suggesting DH-FL is part of the spectrum of double-hit high-grade lymphoma.
http://ift.tt/2cuFT7x
Acoustic softening and stress superposition in ultrasonic vibration assisted uniaxial tension of copper foil: Experiments and modeling
Publication date: 15 December 2016
Source:Materials & Design, Volume 112
Author(s): C.J. Wang, Y. Liu, B. Guo, D.B. Shan, B. Zhang
Ultrasonic vibration is widely utilized in manufacturing processes mainly because acoustic field could significantly affect the metal plasticity leading to stress reduction. However, viewpoints on the influence mechanism have not reached a consensus yet. In this paper, an ultrasonic vibration assisted uniaxial tension experiment with copper foils is carried out using a specially-developed device. The results show that the extent of stress reduction increases with the increase of the vibration amplitude. Acoustic softening and stress superposition are both considered in a developed model to describe the stress reduction due to ultrasonic excitation during metal forming process. Considering that ultrasonic vibration provides the energy for dislocation sliding, acoustic softening is analyzed based on crystal plasticity theory considering ultrasonic intensity. Stress superposition, mostly induced by the additional periodic strain, is included by taking account of its proportional relationship with vibration amplitude. The calculation results from the numerical model show a good agreement with those from the experiment. These findings provide an instructive understanding of mechanism of stress reduction in ultrasonic vibration assisted metal deformation and are especially helpful for pro-actively designing ultrasonic vibration assisted metal forming processes.
Graphical abstract
http://ift.tt/2d9lffD
Investigation on bonding strength of steel/aluminum clad sheet processed by horizontal twin-roll casting, annealing and cold rolling
Publication date: 15 December 2016
Source:Materials & Design, Volume 112
Author(s): G. Chen, J.T. Li, H.L. Yu, L.H. Su, G.M. Xu, J.S. Pan, T. You, G. Zhang, K.M. Sun, L.Z. He
In this work, a stainless steel/aluminum clad sheet was produced successfully by horizontal twin-roll casting. The interface morphology, element distribution and bonding strength of the clad sheets after different annealing and cold rolling processes were investigated using optical microscopy, electron probe micro-analyzer and T-type peel test. The surfaces of the steel and aluminum sheets after peeling were studied using scanning electron microscopy. In the as-cast clad sheet, a 3μm thick diffusional layer exists at the Fe/Al interface. The average peel strength is 12N/mm. Suitable annealing treatment can greatly improve the bonding quality of the interface. The average peel strength increases with increasing annealing temperature, from 12N/mm at 450°C to 21N/mm at 510°C. After annealing at 540°C, the diffusional layer becomes almost three times the original thickness, which results in a sharp drop in the average peel strength to 5N/mm. Cold rolling processing also improves the bonding strength of the clad sheets. The average peel strength of the clad sheet annealed at 510°C increases as the reduction in thickness by cold rolling increases, from 23N/mm for 25% reduction, to 28N/mm for 40% reduction.
Graphical abstract
http://ift.tt/2d9kVhe
Ideal tensile strength and shear strength of ZrO2(111)/Ni(111) ceramic-metal Interface: A first principle study
Publication date: 15 December 2016
Source:Materials & Design, Volume 112
Author(s): Xingye Guo, Yi Zhang, Yeon-Gil Jung, Li Li, James Knapp, Jing Zhang
The ideal mechanical strengths of ZrO2(111)/Ni(111) ceramic-metal (C-M) interface are calculated through simulated tensile and shear deformations using the first principles calculations. The structures of ZrO2(111)/Ni(111) interfaces with 1- and 3-layer Ni thicknesses are optimized and the mechanical properties are investigated. For tensile deformation in [111] direction, the Young's moduli of the 1-layer Ni and 3-layer Ni M-C models are 139.9GPa and 60.2GPa, respectively; and ultimate tensile strengths are 11.6GPa and 7.9GPa, respectively. For shear deformation in {111} 〈110〉 system, the shear moduli of the 1-layer Ni and 3-layer Ni M-C models are 43.9GPa and 30.4GPa, respectively; and ultimate shear strengths are 7.0GPa and 3.0GPa, respectively. For shear deformation in {111} 〈112−〉 system, the shear moduli of the 1-layer Ni and 3-layer Ni M-C models are 30.9GPa and 17.3GPa, respectively; and ultimate shear strengths are 6.0GPa and 1.8GPa, respectively. Overall, 1-layer Ni C-M interface models have better mechanical properties than those of 3-layer models. The observed strengths are explained by using charge distribution, electron localization function, and Bader charge transfer analyses. The results are important for designing robust thermal barrier coating through optimizing bond coat thickness.
Graphical abstract
http://ift.tt/2d9lcAI
Advanced ceramic components with embedded sapphire optical fiber sensors for high temperature applications
Publication date: 15 December 2016
Source:Materials & Design, Volume 112
Author(s): Amir Ghazanfari, Wenbin Li, Ming C. Leu, Yiyang Zhuang, Jie Huang
This paper describes an extrusion-based additive manufacturing process that has been developed to enable embedment of sapphire optical fiber sensors in ceramic components during the part fabrication. In this process, an aqueous paste of ceramic particles is extruded through a moving nozzle to build the part layer-by-layer. In the case of sensor embedment, the fabrication process is halted after a certain number of layers have been deposited; the sensors are placed in their predetermined locations, and the remaining layers are deposited until the part fabrication is completed. Because the sensors are embedded during the fabrication process, they are fully integrated with the part and the problems of traditional sensor embedment can be eliminated. Scanning electron microscopy was used to observe the embedded sensors and to detect any possible flaws in the part or embedded sensor. Attenuation of the sensors was measured in near-infrared region (1500–1600nm wavelength). Standard test methods were employed to examine the effect of embedded fibers on the strength and hardness of the parts. The results indicated that the sapphire fiber sensors with diameters smaller than 250 micrometers were able to endure the freeform extrusion fabrication process and the post-processing without compromising the part properties.
Graphical abstract
http://ift.tt/2d9l988
Acute alcohol exposure increases tyrosine hydroxylase protein expression and dopamine synthesis in zebrafish
Source:Behavioural Brain Research SreeTestContent1, Volume 317
Author(s): Steven Tran, Amanda Facciol, Magda Nowicki, Diptendu Chatterjee, Robert Gerlai
Zebrafish have become a popular animal model for investigating the effects of alcohol on the brain and behaviour. Acute exposure to alcohol has been shown to alter dopaminergic signalling in zebrafish, but the underlying mechanisms have not been well defined. In the current study, we characterize the effects of alcohol on the zebrafish dopaminergic system by focusing on tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Using western blot analysis, we demonstrate that a 60min exposure to 1% alcohol increases tyrosine hydroxylase protein expression in the zebrafish brain. Enzymatic activity assays confirmed that alcohol also increases tyrosine hydroxylase enzymatic activity, whereas HPLC analysis demonstrated increased levels of whole-brain dopamine and its metabolite DOPAC. In addition to activation of the dopaminergic system, behavioural analysis revealed accompanying increase of distance traveled following 1% alcohol exposure. These findings suggest that acute alcohol exposure elevates dopamine synthesis via increased tyrosine hydroxylase protein expression. Our results support the hypothesis that alcohol alters dopaminergic signalling in the zebrafish brain in a similar manner as compared to mammals.
http://ift.tt/2dbz3b9
Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent
Publication date: December 2016
Source:Biomedicine & Pharmacotherapy, Volume 84
Author(s): Pingju Ge, Fugeng Sheng, Yiguang Jin, Li Tong, Lina Du, Lei Zhang, Ning Tian, Gongjie Li
Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd2-diethylenetriaminepentaacetate-bis(alendronate) (Gd2-DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pKa, complex constant, and T1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd2-DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd2-DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r1) of 7.613mM−1s−1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd2-DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd2-DTPA-BA. The signal intensity of Gd2-DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd2-DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd2-DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases.
Graphical abstract
http://ift.tt/2cuv45r
Evaluation of antioxidant and stabilizing lipid peroxidation nature of Solanum xanthocarpum leaves in experimentally diethylnitrosamine induced hepatocellular carcinogenesis
Publication date: December 2016
Source:Biomedicine & Pharmacotherapy, Volume 84
Author(s): Periyannan Velu, Annamalai Vijayalakshmi, Perumal Iyappan, Dhananjayan Indumathi
Solanum xanthocarpum Schrad. & Wendl, is a traditional edible leaves as a form of decoction, extracts used as a herbal medicine, and consumed for health promoting profiles. The present investigation was carried out to evaluate antioxidant status and lipid peroxidation level of anticancer activity of Solanum xanthocarpum (SXC) on Diethylnitrosamine (DEN) induced hepato carcinogenesis in male Wistar albino rats. Hepatic cancer was developed on the liver of Wistar rats treated by DEN or vehicle three times a week for 16 weeks. Tumour incidence, tumour volume, tumour burden, lipid peroxidation, antioxidant, liver marker enzymes and histopathological changes were assessed in DEN alone and in DEN+SXC leaves extract treated rats. Hundred percent tumour incidences with an imbalance in carcinogen metabolizing enzymes and cellular redox status were observed in rats treated with DEN alone. Oral administration of SXC aqueous leaves extract treatment at a dose of 150mg/kg b.w. to DEN treated rats were prevented tumour incidence and restored the elevated activities of liver marker enzymes and antioxidant status to near normal with decreased lipid peroxide levels. The biochemical consistent with histopathological observations suggesting marked hepatoprotective effect of the leaves extract in a dose dependent manner. These results clearly suggest that SXC aqueous leaves extract treatment prevents liver damage, lipid peroxidation, protects the antioxidant defense system and anti-carcinogenic potential in DEN induced hepatic carcinogenesis.
Graphical abstract
http://ift.tt/2cuyeWs
Adalimumab: A Review in Hidradenitis Suppurativa
Abstract
Subcutaneous adalimumab (Humira®) is a tumour necrosis factor-α blocker that is the only approved agent for the treatment of moderate to severe hidradenitis suppurativa (HS) in several countries worldwide. This article reviews the clinical efficacy and safety of subcutaneous adalimumab in patients with moderate to severe HS. In clinical trials (PIONEER I and II), a greater proportion of adalimumab than placebo recipients reached HS clinical response (HiSCR) at week 12. The main secondary endpoints, such as the proportion of patients with an abscess and inflammatory nodule count of ≤2 at week 12, were significantly greater with adalimumab than with placebo in PIONEER II, but not in PIONEER I. In addition, adalimumab showed the potential to reduce the high health-related quality of life burden of HS and increase patient satisfaction. HiSCR rates were generally maintained in the longer term, and the safety profile of adalimumab in patients with moderate to severe HS was consistent with the known safety profile of the drug for other indications, with no new emerging safety signals. Adalimumab is an effective and generally well tolerated treatment for patients with moderate to severe HS, and is the first agent approved for this difficult-to-treat disease.
http://ift.tt/2d1rEsZ
Primary and Secondary Chemoprevention of Malignant Melanoma
Abstract
The incidence of malignant melanoma (MM) continues to rise in the United States. While sun protection and full body skin examinations remain the mainstay of preventative care, chemoprevention of the deadly disease has become an increasingly popular field of study. In this focused review, we discuss current findings and analyze the risks and benefits of various agents investigated for the primary and secondary chemoprevention of MM. Such agents include topical retinoids, vitamins, and supplements, Polypodium leucotomas extracts, non-steroidal anti-inflammatory agents (NSAIDs), statins, sunscreens, and field therapy with topical imiquimod for primary and secondary chemoprevention. We further identify a need for expanded high quality human research on the topic.
http://ift.tt/2dtVCIU
Structural Determinants for NF-Y/DNA Interaction at the CCAAT Box
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Valentina Nardone, Antonio Chaves-Sanjuan, Marco Nardini
The recently determined crystal structures of the sequence-specific transcription factor NF-Y have illuminated the structural mechanism underlying transcription at the CCAAT box. NF-Y is a trimeric protein complex composed by the NF-YA, NF-YB, and NF-YC subunits. NF-YB and NF-YC contain a histone-like domain and assemble on a head-to-tail fashion to form a dimer, which provides the structural scaffold for the DNA sugar-phosphate backbone binding (mimicking the nucleosome H2A/H2B–DNA assembly) and for the interaction with NF-YA. The NF-YA subunit hosts two structurally extended α-helices; one is involved in NF-YB/NF-YC binding and the other inserts deeply into the DNA minor groove, providing exquisite sequence-specificity for recognition and binding of the CCAAT box. The analysis of these structural data is expected to serve as a powerful guide for future experiments aimed at understanding the role of post-translational modification at NF-Y regulation sites and to unravel the three-dimensional architecture of higher order complexes formed between NF-Y and other transcription factors that act synergistically for transcription activation. Moreover, these structures represent an excellent starting point to challenge the formation of a stable hybrid nucleosome between NF-Y and core histone proteins, and to rationalize the fine molecular details associated to the wide combinatorial association of plant NF-Y subunits.
http://ift.tt/2cumLGA
Mitochondria-Associated Membranes Response to Nutrient Availability and Role in Metabolic Diseases
Publication date: Available online 23 September 2016
Source:Trends in Endocrinology & Metabolism
Author(s): Pierre Theurey, Jennifer Rieusset
Metabolic diseases are associated with nutrient excess and metabolic inflexibility. Mitochondria and endoplasmic reticulum are important organelles and nutrient sensors, and their dysfunction has been extensively and independently implicated in metabolic diseases. Both organelles interact at sites known as mitochondria-associated membranes (MAMs), in order to exchange metabolites and calcium. Recent evidence indicates that MAM could be a hub of hepatic insulin signaling and nutrient sensing. In this review, we discuss the roles organelle function and communication play in the cell's adaptation to nutrient availability, in both physiology and metabolic diseases. We highlight how dynamic regulation of MAM affects mitochondria physiology and adaptation of cellular metabolism to nutrient availability, and how chronic MAM disruption participates in the metabolic inflexibility associated with metabolic disorders.
http://ift.tt/2cTR78t
Interstitial lung disease in primary Sjögren's syndrome
Source:Autoimmunity Reviews
Author(s): F. Roca, S. Dominique, J. Schmidt, A. Smail, P. Duhaut, H. Lévesque, I. Marie
Interstitial lung disease (ILD) has been reported in 3 to 11% of patients with primary Sjögren's syndrome (pSS). The aims of this retrospective multicenter study were to: 1) analyze characteristics and outcome of ILD in pSS; and 2) evaluate predictive factors associated with ILD onset and deterioration. Twenty-one of 263 patients with pSS (8%) developed ILD. ILD onset preceded pSS diagnosis (n=5), was concurrently identified in association with pSS (n=6) and developed after pSS onset (n=9). Presenting ILD manifestations were: acute/subacute (n=11) onset of ILD, symptomatic progressive onset of ILD (n=5), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT-scan (n=5). ILD therapy included: steroids (n=21), cyclophosphamide (n=1), azathioprine (n=4) and rituximab (n=1). The course of ILD was as follows: improvement (15.8%), stabilization (47.4%) or deterioration (36.8%). Predictive parameters of ILD onset were: older age (p=0.044), Raynaud's phenomenon (p=0.001) and esophageal involvement (p=0.001). Factors associated with ILD deterioration were: older age (p=0.038) and esophageal involvement (p=0.038). Thus, this study underscores the poor outcome of ILD during pSS; thus, systematic screening of pulmonary involvement is required in pSS patients, resulting in both diagnosis and management at early stage of ILD. We also suggest that patients presenting predictive factors of ILD deterioration may need a closer follow-up and a more aggressive therapy.
http://ift.tt/2cNpfRr
Carbon assimilation in Eucalyptus urophylla grown under high atmospheric CO2 concentrations: A proteomics perspective
Publication date: Available online 24 September 2016
Source:Journal of Proteomics
Author(s): Bruna Marques dos Santos, Tiago Santana Balbuena
Photosynthetic organisms may be drastically affected by the future climate projections of a considerable increase in CO2 concentrations. Growth under a high concentration of CO2 could stimulate carbon assimilation—especially in C3-type plants. We used a proteomics approach to test the hypothesis of an increase in the abundance of the enzymes involved in carbon assimilation in Eucalyptus urophylla plants grown under conditions of high atmospheric CO2. Our strategy allowed the profiling of all Calvin-Benson cycle enzymes and associated protein species. Among the 816 isolated proteins, those involved in carbon fixation were found to be the most abundant ones. An increase in the abundance of six key enzymes out of the eleven core enzymes involved in carbon fixation was detected in plants grown at a high CO2 concentration. Proteome changes were corroborated by the detection of a decrease in the stomatal aperture and in the vascular bundle area in Eucalyptus urophylla plantlets grown in an environment of high atmospheric CO2. Our proteome approach indicates a positive metabolic response regarding carbon fixation in a CO2-enriched atmosphere. The slight but significant increase in the abundance of the Calvin enzymes suggests that stomatal closure did not prevent an increase in the carbon assimilation rates.Biological significanceThe sample enrichment strategy and data analysis used here enabled the identification of all enzymes and most protein isoforms involved in the Calvin-Benson-Bessham cycle in Eucalyptus urophylla. Upon growth in CO2-enriched chambers, Eucalyptus urophylla plantlets responded by reducing the vascular bundle area and stomatal aperture size and by increasing the abundance of six of the 11 core enzymes involved in carbon fixation. Our proteome approach provides an estimate on how a commercially important C3-type plant would respond to an increase in CO2 concentrations. Additionally, confirmation at the protein level of the predicted genes involved in carbon assimilation may be used in plant transformation strategies aiming to increase plant adaptability to climate changes or to increase plant productivity.
Graphical abstract
http://ift.tt/2da3ZF7
Overexpression of OsSPL9 enhances accumulation of Cu in rice grain and improves itsdigestibility and metabolism
Source:Journal of Genetics and Genomics
Author(s): Mingfeng Tang, Chuanshe Zhou, Lu Meng, Donghai Mao, Chengbing Liu, Can Peng, Yuxing Zhu, Dechun Zhang, Daoyou Huang, Zhiliang Tan, Caiyan Chen
http://ift.tt/2dbfyQd
Influence of Pulse Repetition Frequency on 3-D Power Doppler Quantification
Source:Ultrasound in Medicine & Biology
Author(s): Carlos A.M. Soares, Theo Z. Pavaz, Andre H. Miyague, Marek Kudla, Wellington P. Martins
Three-dimensional power Doppler quantification has limited application because of its high dependency on attenuation. The purpose of the study described here was to assess if different degrees of attenuation, depending on pulse repetition frequency (PRF) adjustment, alter 3-D power Doppler quantification in a region of 100% moving blood when using vascularization index, flow index and vascularization flow index (VFI). A cubic-shaped gelatin phantom with a 1.8-mm-internal-diameter silicon tube was used. The tube, placed at 45° to the phantom's surface, was filled with blood-mimicking fluid with as constant maximum velocity of 30 cm/s. Two different attenuation blocks (low and high attenuation) were alternatively placed between the phantom and the transvaginal transducer. One single observer acquired 10 data sets for each PRF level from 0.3 to 7.5 kHz, using the high- and low-attenuation blocks, for a total of 200 3-D power Doppler data sets. We assessed VFI from 1.5-mm-diameter spherical samples, virtually placed inside the tube, always at the same position. No difference was noted between high- and low-attenuation VFI values when using a PRF of 0.3 kHz. As PRF increased, it was observed that VFI quantification progressively differed between low and high attenuation. Also, a slope on VFI values for both high- and low-attenuation models could be observed when increasing PRF, particularly above 4.0 kHz. We concluded that PRF adjustment is very relevant when using VFI to quantify 3-D power Doppler signal.
http://ift.tt/2dtLm37
Influence of Donor Age and Stimulation Intensity on Osteogenic Differentiation of Rat Mesenchymal Stromal Cells in Response to Focused Low-Intensity Pulsed Ultrasound
Source:Ultrasound in Medicine & Biology
Author(s): Regina Puts, Josefine Albers, Anke Kadow-Romacker, Sven Geissler, Kay Raum
A focused low-intensity pulsed ultrasound (FLIPUS) was used to investigate the effects of stimulation period, acoustic intensity and donor age on the osteogenic differentiation potential of rat mesenchymal stromal cells (rMSCs). rMSCs from 3- and 12-mo-old female Sprague Drawly rats were isolated from bone marrow and stimulated 20 min/d with either 11.7 or 44.5 mW/cm2 (spatial average temporal average intensity) for 7 or 14 d. Osteogenic differentiation markers, i.e., Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN) and degree of matrix calcification were analyzed. On day 7 of stimulation, OCN gene expression was enhanced 1.9-fold in cells from young rats when stimulated with low intensity. The low intensity also led to a 40% decrease in RUNX2 expression on day 7 in aged cells, whereas high intensity enhanced expression of RUNX2 on day 14. FLIPUS treatment with low intensity resulted in a 15% increase in extracellular matrix mineralization in young but not old rMSCs. These differences suggest the necessity of a donor-age related optimization of stimulation parameters.
http://ift.tt/2d1fL6s
Langerhans cells are predominant high affinity immunoglobulin E receptor bearing cells in the epidermis of bullous pemphigoid skin
Publication date: Available online 23 September 2016
Source:Journal of Dermatological Science
Author(s): Bartlomiej Kwiek, Anna Leśniewska, Cezary Kowalewski, Katarzyna Woźniak
http://ift.tt/2cD0hGQ
Enzyme-linked immunosorbent assays for detection of anti-transcriptional intermediary factor-1 gamma and anti-Mi-2 autoantibodies in dermatomyositis
Publication date: Available online 23 September 2016
Source:Journal of Dermatological Science
Author(s): Manabu Fujimoto, Akihiro Murakami, Shunsuke Kurei, Naoko Okiyama, Atsushi Kawakami, Michiaki Mishima, Shinji Sato, Mariko Seishima, Takafumi Suda, Tsuneyo Mimori, Kazuhiko Takehara, Masataka Kuwana
BackgroundAutoantibodies against transcriptional intermediary factor 1 (TIF1) and Mi-2 are selectively detected in patients with dermatomyositis (DM). To measure these antibodies readily, the development of reliable ELISA systems has been needed.ObjectiveThis study aimed to establish enzyme-linked immunosorbent assays (ELISAs) for anti-TIF1γ and anti-Mi-2β antibodies (Abs) and to assess their utility.MethodsSerum samples were obtained from 104 patients with classic DM, 68 with clinically amyopathic DM (CADM) and 70 with polymyositis, who were followed up at 8 medical centers across Japan. Serum samples from 190 patients with other connective tissue diseases (CTDs) and 123 healthy individuals were also assessed. Serum antibody levels were examined by ELISAs coated with full-length TIF1γ or Mi-2β proteins produced by a baculovirus expression system. To assess the cross-reactivity, partial-length Mi-2β proteins with or without mutations were produced and examined for reactivity.ResultsWhen compared with immunoprecipitation assay, anti-TIF1γ Ab ELISA showed 100% sensitivity and 100% specificity, while anti-Mi-2β Ab ELISA showed 100% sensitivity and 99.6% specificity. Anti-TIF1γ Ab was positive in 30 (28.8%) with classic DM and 4 (5.9%) with CADM, whereas 14 (13.5%) with classic DM, but none with CADM, were positive for anti-Mi-2β Ab. Of 30 anti-TIF1γ Ab-positive DM patients, 23 (67.6%) had malignancy. Anti-Mi-2β Ab-positive serum samples exhibited modest cross-reactivity with the TIF1γ protein due to the homologous amino acid sequence containing cysteines in their plant homeodomains.ConclusionThe current study demonstrates the utility of newly established ELISAs for anti-TIF1γ and anti-Mi-2β Abs, which can serve as easier detection systems for routine testing.
http://ift.tt/2d9Q41Q
Decrease of versican levels in the follicular dermal papilla is a remarkable aging-associated change of human hair follicles
Publication date: Available online 23 September 2016
Source:Journal of Dermatological Science
Author(s): Seong Jin Jo, Jin Yong Kim, Sunhyae Jang, Soon Jin Choi, Kyu Han Kim, Ohsang Kwon
http://ift.tt/2cCZAx2
PRELIM II(EDI BOARD)
Source:Neuroscience Research, Volume 111
http://ift.tt/2djOcce
Editorial Board/Title Page
Publication date: October 2016
Source:Cortex, Volume 83
http://ift.tt/2cN2rRU
The role of autophagy in the pathogenesis of systemic lupus erythematosus
Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Xiao Liu, Haihong Qin, Jinhua Xu
Autophagy is a highly conserved catabolic process, whereby unwanted cytoplasmic contents are enclosed by the double-membrane autophagosomes and delivered to the lysosomes for degradation. It is responsible for the recycling of nutrients and cellular components, thus playing a pivotal role in maintaining cellular homeostasis as well as cell survival during stress conditions. Perturbations in autophagy are implicated in multiple diseases, such as cancers and neuro-degeneration diseases. Recent studies demonstrate that autophagy may participate in almost every step of immune responses, including pathogen recognition, antigen processing and presentation, immune cell development and function, and immunoregulation. The pathogenesis of some autoimmune diseases, such as multiple sclerosis and Crohn's disease, has been reported to be associated with dysregulated autophagy. Systemic lupus erythematosus (SLE) is a chronic, potentially fatal autoimmune disease, characterized by dysregulation of immune cells and production of autoantibodies that cause widespread tissue and organ damage. The pathogenesis of SLE remains unclear. With several single nucleotide polymorphisms (SNPs) in autophagy-related gene5 (ATG5) being linked to SLE susceptibility, more and more lines of evidence from animal model, cell biology, immunology, and genetics studies show that autophagy contributes to the occurrence, development, and severity of SLE.
Graphical abstract
http://ift.tt/2djroVH
Clinical observation of lymphocyte active immunotherapy in 380 patients with unexplained recurrent spontaneous abortion
Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Jian-Ling Chen, Jian-Ming Yang, Ya-Zhe Huang, Ying Li
PurposeThis study aims to investigate the clinical curative effect of lymphocyte active immunotherapy (LAI) on unexplained recurrent spontaneous abortion (RSA).MethodsA total of 749 RSA patients who received medical service in our hospital from October 2009 to June 2013 were enrolled into this study. These patients were randomly divided into two groups: LAI group (treatment group) and routine progesterone for maintenance tocolysis group (control group). A comparative analysis on the pregnancy outcomes in these two groups was conducted.ResultsAbortion rate was significantly lower in the LAI group than in the control group (P<0.05). Furthermore, pregnancy success rates were 89.7% and 32.2% in patients who received LAI and routine progesterone for maintenance tocolysis, respectively, and the difference was statistically significant (P<0.05).ConclusionOur analysis suggested that LAI can treat RSA effectively and has an excellent clinical effect. Furthermore, the detection of blocking antibodies showed a positive prediction on pregnancy outcome.
http://ift.tt/2djs9Ov
Characterization of Carbonaceous Matter in Xenolithic Clasts from the Sharps (H3.4) Meteorite: Constraints on the Origin and Thermal Processing
Publication date: Available online 25 September 2016
Source:Geochimica et Cosmochimica Acta
Author(s): Yoko Kebukawa, Michael E. Zolensky, Queenie H.S. Chan, Keisuke Nagao, A.L. David Kilcoyne, Robert J. Bodnar, Charles Farley, Zia Rahman, Loan Le, George D. Cody
Primitive xenolithic clasts, often referred to as "dark clasts", are well known in many regolith breccias. The Sharps H3.4 ordinary chondrite contains unusually large dark clasts up to ∼1 cm across. Poorly-graphitized carbon (PGC), with Fe, Ni metal and described as "carbon-rich aggregates", has been reported in these clasts (Brearley, 1990). We report detailed analyses of carbonaceous matter in several identical Sharps clasts using FTIR, Raman, C-XANES, and TEM that provide insight on the extent of thermal processing and possible origin of such clasts. We also prepared acid residues of the clasts using the HCl/HF method and conducted mass spectrometric analysis of the entrained noble gases.Carbonaceous matter is often used to infer thermal history due to its sensitivity to thermal processes. The FTIR spectra of the acid residue from the Sharps clast suggest that carbonaceous matter in the clast contains less hydrogen and oxygen compared to acid residues from typical type 3.4 ordinary chondrites. The metamorphic temperatures obtained by Raman spectroscopy ranges between ∼380 °C to ∼490 °C. TEM observations indicate that the clasts experienced a peak temperature of 300 °C to 400 °C, based on the carbon d002 layer lattice spacing of C-rich aggregates. These estimates are consistent with an earlier estimate of 330 ± 50 °C, that is also estimated by the d002 layer lattice spacing (Brearley, 1990). It should be noted that the lattice spacing thermometer is based on terrestrial metamorphose rocks, and thus temperature was probably underestimated. Meanwhile, the C-XANES spectra of the C-rich aggregates show high exciton intensities, indicative of graphene structures that developed at around 700 °C to 800 °C following an extensive period of time (millions of years), however, the surrounding matrix areas experienced lower temperatures of less than 300 °C to 500 °C. Noble gas analysis of the acid residue from the Sharps clasts shows that the residue is almost identical with some material reported in carbonaceous chondrites, i.e., heavily enriched in the Q-gas component as well as HL-gas from presolar diamonds and Ne-E(H) from presolar SiC.These results indicate that the C-rich aggregates in the Sharps clasts formed under relatively high temperature conditions, up to 800 °C, and were subsequently mixed with lower temperature matrix, probably in a different parent body, before they were incorporated into the final Sharps lithology by collision.
http://ift.tt/2cCGXcD
Targeted multimodal nano-reporters for pre-procedural MRI and intra-operative image-guidance
Source:Biomaterials, Volume 109
Author(s): Joonseok Lee, Andrew C. Gordon, Hacksung Kim, Wooram Park, Soojeong Cho, Byeongdu Lee, Andrew C. Larson, Elena A. Rozhkova, Dong-Hyun Kim
Multimodal-imaging probes offer a novel approach, which can provide detail diagnostic information for the planning of image-guided therapies in clinical practice. Here we report targeted multimodal Nd3+-doped upconversion nanoparticle (UCNP) imaging reporters, integrating both magnetic resonance imaging (MRI) and real-time upconversion luminescence imaging (UCL) capabilities within a single platform. Nd3+-doped UCNPs were synthesized as a core–shell structure showing a bright visible emission upon excitation at the near infrared (minimizing biological overheating and increasing tissue penetration depth) as well as providing strong MRI T2 contrast (high r2/r1 ratio). Transcatheter intra-arterial infusion of Nd3+-doped UCNPs conjugated with anti-CD44-monoclonal antibody allowed for high performance in vivo multimodal UCL and MR imaging of hepatocellular carcinoma (HCC) in an orthotopic rat model. The resulted in vivo multimodal imaging of Nd3+ doped core-shell UCNPs combined with transcatheter intra-arterial targeting approaches successfully discriminated liver tumors from normal hepatic tissues in rats for surgical resection applications. The demonstrated multimodal UCL and MRI imaging capabilities of our multimodal UCNPs reporters suggest strong potential for in vivo visualization of tumors and precise surgical guidance to fill the gap between pre-procedural imaging and intraoperative reality.
http://ift.tt/2dqUoLq
Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo
Source:Biomaterials, Volume 109
Author(s): Kevin J. Kauffman, Faryal F. Mir, Siddharth Jhunjhunwala, James C. Kaczmarek, Juan E. Hurtado, Jung H. Yang, Matthew J. Webber, Piotr S. Kowalski, Michael W. Heartlein, Frank DeRosa, Daniel G. Anderson
mRNA has broad potential for treating diseases requiring protein expression. However, mRNA can also induce an immune response with associated toxicity. Replacement of uridine bases with pseudouridine has been postulated to modulate both mRNA immunogenicity and potency. Here, we explore the immune response and activity of lipid nanoparticle-formulated unmodified and pseudouridine-modified mRNAs administered systemically in vivo. Pseudouridine modification to mRNA had no significant effect on lipid nanoparticle physical properties, protein expression in vivo, or mRNA immunogenicity compared to unmodified mRNA when delivered systemically with liver-targeting lipid nanoparticles, but reduced in vitro transfection levels. Indicators of a transient, extracellular innate immune response to mRNA were observed, including neutrophilia, myeloid cell activation, and up-regulation of four serum cytokines. This study provides insight into the immune responses to mRNA lipid nanoparticles, and suggests that pseudouridine modifications may be unnecessary for therapeutic application of mRNA in the liver.
http://ift.tt/2dqToXV
Should people have a doctor remove a dysplastic nevus or a common mole to prevent it from changing into melanoma?
No. Normally, people do not need to have a dysplastic nevus or common mole removed. One reason is that very few dysplastic nevi or common moles turn into melanoma (1, 3). Another reason is that even removing all of the moles on the skin would not prevent the development of melanoma because melanoma can develop as a new colored area on the skin (2). That is why doctors usually remove only a mole that changes or a new colored area on the skin.
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma: RAPTOR final analysis
Source:European Journal of Cancer
Author(s): Bernard Escudier, Vincent Molinie, Sergio Bracarda, Pablo Maroto, Cezary Szczylik, Paul Nathan, Sylvie Negrier, Claudia Weiss, Camillo Porta, Viktor Grünwald, Laurence Albiges
BackgroundPapillary histology accounts for 10–15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC).MethodsThis phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety.FindingsAnalysis sets included safety (N = 92; 100%), intent-to-treat (ITT) (n = 88), and PP populations (n = 46). In the safety population, most patients were men (78%) and the mean age was 60 years (range 23–84). Papillary histology was confirmed in 78% of patients (type 1, 32%; type 2, 64%; missing information, 4%). PFS rate at 6 months was 34% (80% confidence interval [CI] 25–45). In the ITT population, median PFS was 4.1 months (95% CI 3.6–5.5), 65% of patients achieved stable disease, and median OS was 21.4 months (95% CI 15.4–28.4). Among patients with type 1 or type 2 histology, median PFS was 7.9 months (95% CI 2.1–11.0) and 5.1 months (95% CI 3.3–5.5), respectively, and median OS was 28.0 months (95% CI 7.6–not estimable) and 24.2 months (95% CI 15.8–32.8), respectively. Common grade >2 adverse events were asthenia (13%), anaemia (7%), and fatigue (5%).InterpretationResults of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour.
http://ift.tt/2cSRy32
Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America
Source:European Journal of Cancer, Volume 67
Author(s): Maria A. Karalexi, Margarita Baka, Anton Ryzhov, Anna Zborovskaya, Nadya Dimitrova, Snezana Zivkovic, Sultan Eser, Luis Antunes, Mario Sekerija, Tina Zagar, Joana Bastos, Anna Demetriou, Domenic Agius, Margareta Florea, Daniela Coza, Sophia Polychronopoulou, Eftichia Stiakaki, Maria Moschovi, Emmanuel Hatzipantelis, Maria Kourti, Stelios Graphakos, Maria S. Pombo-de-Oliveira, Hans Olov Adami, Eleni Th. Petridou
AimTo assess trends in survival and geographic disparities among children (0–14 years) with chronic myeloid leukaemia (CML) before and after the introduction of molecular therapy, namely tyrosine kinase inhibitors (TKIs) in Southern-Eastern European (SEE) countries and the USA.MethodsWe calculated survival among children with CML, acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) in 14 SEE (1990–2014) cancer registries and the U.S. Surveillance, Epidemiology and End Results Program (SEER, 1990–2012). We used Kaplan–Meier curves and multivariate Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsAmong 369 CML cases, substantial improvements were noted in 2-year survival during the post-TKI (range: 81–89%) compared to pre-TKI period (49–66%; HR: 0.37, 95% CI: 0.23–0.60). Risk of death was three times higher for <5-year-old children versus those aged 10–14 years (HR: 3.03, 95% CI: 1.85–4.94) and 56% higher for those living in SEE versus SEER (HR: 1.56, 95% CI: 1.01–2.42). Regardless of geographic area and period of TKI administration, however, age seems to be a significant determinant of CML prognosis (pre-TKI period, HR0–4y: 2.71, 95% CI: 1.53–4.79; post-TKI period, HR0–4y: 3.38, 95% CI: 1.29–8.85). Noticeably, post-TKI survival in CML overall approximates that for ALL, whereas therapeutic advancements for AML remain modest.ConclusionRegistry data show that introduction of molecular therapies coincides with revolutionised therapeutic outcomes in childhood CML entailing dramatically improved survival which is now similar to that in ALL. Given that age disparities in survival remain substantial, offering optimal therapy to entire populations is an urgent priority.
http://ift.tt/2dgR6y9
Building a ‘Repository of Science’: The importance of integrating biobanks within molecular pathology programmes
Source:European Journal of Cancer, Volume 67
Author(s): Claire Lewis, Stephen McQuaid, Peter W. Hamilton, Manuel Salto-Tellez, Darragh McArt, Jacqueline A. James
Repositories containing high quality human biospecimens linked with robust and relevant clinical and pathological information are required for the discovery and validation of biomarkers for disease diagnosis, progression and response to treatment. Current molecular based discovery projects using either low or high throughput technologies rely heavily on ready access to such sample collections. It is imperative that modern biobanks align with molecular diagnostic pathology practices not only to provide the type of samples needed for discovery projects but also to ensure requirements for ongoing sample collections and the future needs of researchers are adequately addressed. Biobanks within comprehensive molecular pathology programmes are perfectly positioned to offer more than just tumour derived biospecimens; for example, they have the ability to facilitate researchers gaining access to sample metadata such as digitised scans of tissue samples annotated prior to macrodissection for molecular diagnostics or pseudoanonymised clinical outcome data or research results retrieved from other users utilising the same or overlapping cohorts of samples. Furthermore, biobanks can work with molecular diagnostic laboratories to develop standardised methodologies for the acquisition and storage of samples required for new approaches to research such as 'liquid biopsies' which will ultimately feed into the test validations required in large prospective clinical studies in order to implement liquid biopsy approaches for routine clinical practice. We draw on our experience in Northern Ireland to discuss how this harmonised approach of biobanks working synergistically with molecular pathology programmes is a key for the future success of precision medicine.
http://ift.tt/2cSQmMW
Corrigendum to “Immunohistochemical subtypes predict survival in metastatic breast cancer receiving high-dose chemotherapy with autologous haematopoietic stem cell transplantation” [Eur J Cancer 57 (April 2016) 118–126]
Source:European Journal of Cancer
Author(s): Laurys Boudin, Christian Chabannon, Patrick Sfumato, Renaud Sabatier, François Bertucci, Carole Tarpin, Magali Provansal, Gilles Houvenaeghel, Eric Lambaudie, Agnes Tallet, Michel Resbeut, Emmanuelle Charafe-Jauffret, Boris Calmels, Claude Lemarie, Jean-Marie Boher, Jean-Marc Extra, Patrice Viens, Anthony Gonçalves
http://ift.tt/2cSQyf0
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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