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Δευτέρα 27 Φεβρουαρίου 2017

Late latent mucinous syphilis mimicking connective tissue disease

Abstract

As evidenced by the CDC statistics, syphilis is yet again on the rise. It is known as the great mimicker because of its variable symptoms and how frequently it can be confused with other diseases. The different stages of syphilis (primary, secondary, latent, late latent and tertiary) are discussed. We describe a new histopathologic pattern of syphilis, one that mimics connective tissue disease and can represent a diagnostic pitfall. In this time and age when syphilis is rising especially among the men who have sex with men subgroup, it is important to keep a high index of suspicion of syphilis even when clinically and histopathologically the findings on first glance may not appear characteristic.



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Hazards and Incidents: Detection and Learning in Radiation Medicine, A Comparison of Two Educational Interventions

Publication date: Available online 27 February 2017
Source:Practical Radiation Oncology
Author(s): Robert Thompson, Yilan Lu, Marc Potvin, Jordan Holmes, Lisa Di Prospero, Brian Keller, Ewa Szumacher, Brian Liszewski, Pamela Catton, Meredith Giuliani, Bethany Pitcher, Melania Pintilie, Jean-Pierre Bissonnette
PurposeInter-professional, educational live simulations were compared to group discussion-based exercises in terms of their ability to improve Radiation Medicine trainees` ability to detect hazards and incidents and understand behaviors that may prevent them.Methods and MaterialsTrainees and recent graduates of Radiation Therapy, Medical Physics, and Radiation Oncology programs were recruited and randomized to either a simulation-based or group discussion-based training intervention. Participants engaged in hazard and incident detection, analysis, as well as a discussion of potential preventive measures and the concept of the "highly reliable team". A video examination tool modeled on actual incidents, using five-minute videos created by faculty, students, and volunteers, was created to test hazard and incident recognition ability before and after training. Hazard and incident detection sensitivity and specificity analyses were conducted and a survey of the participants' and facilitators' perceptions was conducted.ResultsTwenty-seven participants were assigned to the simulation (n=15) or discussion group (n=12). Hazard and incident-detection sensitivity ranged from 0.04–0.56 before and 0.04–0.35 after training for the discussion and simulation groups, respectively. The pre- and post-training difference in sensitivity between groups was 0.03 (p=0.75) for the minimum and 0.33 (p=0.034) for the maximum reaction time. Participant perceptions of the training's educational value in a variety of domains ranged from a mean score of 6.58–8.17 and 7–8.07 for the discussion and simulation groups, respectively. Differences were not statistically significant. Twenty-six of the 27 participants indicated that they would recommend this event to a colleague.ConclusionsParticipants' ability to detect hazard and incidents as portrayed in 5-minute videos in this study was low both before and after training and simulation-based training was not superior to discussion-based training. However, levels of satisfaction and perceptions of the training's educational value were high, especially with simulation-based training.



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Clinical clues early in the lives of individuals with lipoid proteinosis can determine the course of the disease



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Analysis of a Chinese pedigree with trichorhinophalangeal syndrome derived from a missense mutation in the TRPS1 gene



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Intraoperative dermoscopic features of onychomatricoma: a review of 10 cases

Summary

Background

Amelanotic nail tumours are difficult to diagnose. Dermoscopy is an accessible tool successfully used in diagnosis of amelanotic or melanotic skin tumours. We have previously shown the usefulness of dermoscopy in the preoperative diagnosis of onychomatricoma (OM). In this study, we completed this work by identifying additional intraoperative criteria to better establish the initial diagnosis of this tumour.

Aims

Evaluation of intraoperative dermoscopy in a small series of OM cases in order to define relevant diagnostic criteria.

Methods

In total, 10 patients with OM diagnosed in our centre were enrolled in the study. Six trained dermoscopists individually evaluated each criterion, then the data were compared and a consensus reached after discussion between the observers. For each criterion, we analysed its frequency and its interobserver accordance. We defined three architectural criteria (the 'Sagrada Familia' sign, digitations and the 'mirror sign'), and three vascular criteria (sagittal vessels, dotted vessels and irregular vessels).

Results

The Sagrada Familia sign, digitations and mirror sign were found in 100%, 90% and 70% of the cases, respectively, with high interobserver agreement. The vascular criteria were less regularly observed: sagittal, dotted and irregular vessels were respectively found in 80%, 70% and 50% of the OM cases, and were more difficult to assess, as shown by the lower interobserver agreement rates.

Conclusion

Intraoperative dermoscopy of the nail matrix and bed offers useful information for the diagnosis and management of OM. Larger comparative studies should be performed to evaluate the true benefit of this approach.



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Facial spinulosis caused by Demodex folliculorum: diagnostic assessment by means of reflectance confocal microscopy



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Multiple pilomatrixomas in children: the need for long-term follow-up and aesthetically sensitive incisions

Summary

Pilomatrixomas are benign, calcified epitheliomas of the hair follicle, predominately affecting children and commonly presenting in the head and neck region. The current literature is almost unanimous in recommending surgical excision. Reconstruction of these defects may require the need for a skin graft, resulting in poor cosmetic outcome and donor site morbidity. We present two cases demonstrating the benefits of minimal access incisions for pilomatrixomas in children. We recommend that multiple or recurrent lesions should prompt referral to a specialist for management and long-term follow-up.



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The value of systematic contouring of the bowel for treatment plan optimization in image-guided cervical cancer high-dose-rate brachytherapy

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Publication date: Available online 27 February 2017
Source:Brachytherapy
Author(s): Antonio L. Damato, Ivan Buzurovic, Mandar S. Bhagwat, Robert A. Cormack, Phillip M. Devlin, Scott Friesen, Jorgen Hansen, Larissa J. Lee, Matthias M. Manuel, Linda P. Cho, Desmond O'Farrell, Akila N. Viswanathan
PurposeTo investigate the dose–volume histogram metrics and optimization results of the contoured bowel in cervical cancer brachytherapy.Methods and MaterialsTreatment plans of cervical cancer patients treated with image-guided high dose rate were retrospectively analyzed with institutional review board approval. In addition to the clinical target volume, rectum, bladder, and sigmoid, the bowel was contoured at the time of planning (Group 1) or at the time of this analysis (Group 2).ResultsThirty-two patients treated with 145 insertions were included. Before optimization, mean ± 1 standard deviation overall bowel minimum dose to the most irradiated 2 cm3 volume of an organ (D2cc) was 67.8 Gyα/β3 ± 13.7 Gyα/β3 (Group 1: 72.6 ± 13.2 Gyα/β3; Group 2: 57.3 ± 8.0 Gyα/β3). Before optimization, one patient in Group 1 presented a bowel D2cc metric exceeding 100 Gyα/β3. After optimization, bowel D2cc mean ± 1 standard deviation was 59.4 ± 6.7 Gyα/β3 (Group 1: 61.4 ± 6.0 Gyα/β3, p < 0.001; Group 2: 55.2 ± 6.5 Gyα/β3, p = 0.026).ConclusionsGiven the potentially high doses and the benefit of optimization in reducing dose to the organs at risk, we recommend consideration of systematic contouring of the bowel when bowel is present in the pelvis.



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Microwave ablation in the spleen versus partial splenic artery embolisation: A new technique for hypersplenism in cirrhosis

Publication date: Available online 28 February 2017
Source:Arab Journal of Gastroenterology
Author(s): Fathia Assal, Mohamed El Kassas, Eslam Esmail, Amr A. Elbadry, Sabry Abousaif, Reem Mahdy, Asem Elfert
Background and study aimsSplenectomy has been associated with high perioperative morbidity and mortality. Partial splenic artery embolisation (PSE) was found to be an effective and safer method but with numerous complications. Local thermal ablative techniques such as microwave ablation (MWA) have been tried and were found to be safe and effective alternatives. This randomised controlled study aimed to compare the efficacy and safety of MWA versus PSE in the treatment of hypersplenism in patients with post-hepatitis C cirrhosis.Patients and methodsIn total, 40 patients with post-hepatitis C cirrhosis complicated with hypersplenism were randomised into two groups: Group I: 20 patients treated with percutaneous MWA of splenic parenchyma under ultrasound guidance and Group II: 20 patients treated with PSE using Embosphere.ResultsThere was a significant increase in haemoglobin levels in group I compared with group II after 3months of follow-up. However, White blood cell (WBC) count and platelets significantly increased more in group II than in group I after 1month. Postprocedure significant hyperbilirubinaemia, hypoalbuminaemia, decreased prothrombin concentration, and increased creatinine levels were encountered in group II only. There was a significant increase in postoperative complications in group II compared to group I, and a single case of mortality was reported in group II.ConclusionMWA and PSE were comparably effective; however, MWA was safer than PSE, which caused serious adverse events and mortality. MWA appears to be a good alternative for the treatment of hypersplenism in patients with cirrhosis and portal hypertension.



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Schwannoma of the psoas: An unusual cause of abdominal pain

Publication date: Available online 28 February 2017
Source:Arab Journal of Gastroenterology
Author(s): Elias Makhoul, Ralph Kamel, Naim Hanna
Schwannomas are usually benign tumours arising from Schwann cells of peripheral nerve sheath. Retroperitoneal location is extremely rare compromising 0.5–5% of all schwannomas, except in patients having von Recklinghausen's disease, in whom retroperitoneal location is more frequent and malignant cases are known to occur. Complete surgical excision with negative margins is the definitive treatment on which the diagnosis is usually made due to nonspecific radiologic appearance.In this article we would like to present an unusual cause of recurrent, abdominal pain in an eighty-six-year-old male.



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Adsorption behavior and mechanism of ibuprofen onto BiOCl microspheres with exposed {001} facets

Abstract

BiOCl microspheres with exposed {001} facets have been synthesized through a simple solvothermal method. The adsorption and photocatalytic activities of BiOCl microspheres were evaluated by removal of ibuprofen (IBP) as the model reaction. Parameters including IBP concentration, BiOCl dosage, and inorganic ions were investigated to reveal the role of adsorption in BiOCl-based photocatalysis. We found that the high IBP removal rate by BiOCl is not due to photocatalytic oxidation but to surface adsorption. The combination of ICP/MS, IC, XPS, and FT-IR results directly proved that anion exchange between dissociated IBP and Cl accompanied by the formation of surface complex (O–Bi–OOC–C12H17) onto the BiOCl surface is the main adsorption mechanism. In addition, we also demonstrated that organic compounds with carboxyl group (–COOH) such as diclofenac, benzoic acid, and p-phthalic acid can be adsorbed by BiOCl while organic compounds without carboxyl group such as carbamazepine, nitrobenzene, and p-chloronitrobenzene cannot be adsorbed. We believe that the BiOCl adsorption behavior and mechanism should be considered when discussing its photocatalytic mechanism.



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Heavy metal accumulation in some aquatic insects (Coleoptera: Hydrophilidae) and tissues of Chondrostoma regium (Heckel, 1843) relevant to their concentration in water and sediments from Karasu River, Erzurum, Turkey

Abstract

The objectives of this research were to determine and compare the heavy element concentrations in two study areas in Erzurum, Turkey (Aşkale and Dumlu sites). Assessment of some heavy elements in sediment, water, fish (Chondrostoma regium) tissues, and some aquatic insects (Coleoptera: Hydrophilidae) were carried out in June to August 2014. Heavy element levels in aquatic insect samples and their associated water and sediment were analyzed by energy dispersive X-ray fluorescence (EDXRF) spectrometer. Fish tissues, from the same habitat, were measured by inductively coupled plasma mass spectrometry (ICP-MS). Eleven elements (Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Hg, Pb) were measured in fish tissues, and 14 elements (Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Br, Pb) were measured in insects. According to the results, it can be said that insects were contaminated by water and sediment, thus accumulated higher concentration of some elements than their environment. The fish, which was caught from Aşkale station, accumulates significantly higher level of heavy metals than Dumlu station's fish. The results were compared with national and international standards. The values of some heavy elements were found at higher concentration than the acceptable limits. The possible consequences of these results are briefly discussed from the point of potential hazards to ecology and human health. Element concentrations in fish tissue are below the limits, which are proposed by Turkish Food Codex, FAO/WHO, and EC, and safe for human consumption in the edible parts of fish species in the regions.



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Effects of epiphytic algae on biomass and physiology of Myriophyllum spicatum L. with the increase of nitrogen and phosphorus availability in the water body

Abstract

The disappearance of submerged vascular macrophytes in shallow eutrophic lakes is a common phenomenon in the world. To explore the mechanism of the decline in submerged macrophyte abundance due to the growth of epiphytic algae along a nutrient gradient in eutrophic water, a 2 × 3 factorial experiment was performed over 4 weeks with the submerged macrophyte (Myriophyllum spicatum L.) by determining the plant's biomass and some physiological indexes, such as chlorophyll (Chl) content, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity in the leaves of M. spicatum L. on days 7, 14, 21, and 28, which are based on three groups of nitrogen and phosphorus levels in the water body (N-P [mg L−1]: NP1 0.5–0.05, NP2 2.5–0.25, NP3 4.5–0.45) and two levels of epiphytic algae (the epiphytic algae group and the control group). Epiphytic algal biomass was also assayed. The results indicated that epiphytic algal biomass remarkably enhanced in the course of the experiment with elevated levels of nitrogen and phosphorus in the water. Under the same level of nutrient condition, plants' biomass accumulation and Chl content were higher in the control group than that in the epiphytic algae group, respectively, while MDA content and SOD activity in the former were lower than that in the latter. The influences of epiphytic algae on the biomass accumulation and Chl content and MDA content became greater and greater with elevated levels of nutrients. In general, in this experiment, water nutrients promoted the growth of both epiphytic algae and submerged plants, while the growth of epiphytic algae hindered submerged macrophytes' growth by reducing Chl content and promoting peroxidation of membrane lipids in plants.



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Editorial Board

Publication date: April 2017
Source:Medical Image Analysis, Volume 37





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Dual Discriminative Local Coding for Tissue Aging Analysis

Publication date: Available online 27 February 2017
Source:Medical Image Analysis
Author(s): Yang Song, Qing Li, Fan Zhang, Heng Huang, Dagan Feng, Yue Wang, Mei Chen, Weidong Cai
In aging research, morphological age of tissue helps to characterize the effects of aging on different individuals. While currently manual evaluations are used to estimate morphological ages under microscopy, such operation is difficult and subjective due to the complex visual characteristics of tissue images. In this paper, we propose an automated method to quantify mor- phological ages of tissues from microscopy images. We design a new sparse representation method, namely dual discriminative local coding (DDLC), that classifies the tissue images into different chronological ages. DDLC in- corporates discriminative distance learning and dual-level local coding into the basis model of locality-constrained linear coding thus achieves higher discriminative capability. The morphological age is then computed based on the classification scores. We conducted our study using the publicly avail- able terminal bulb aging database that has been commonly used in existing microscopy imaging research. To represent these images, we also design a highly descriptive descriptor that combines several complementary texture features extracted at two scales. Experimental results show that our method achieves significant improvement in age classification when compared to the existing approaches and other popular classifiers. We also present promising results in quantification of morphological ages.



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Facile control of ZnO nanostructures by varying molar concentration of zinc acetate

Publication date: June 2017
Source:Materials Research Bulletin, Volume 90
Author(s): H.R. Guzmán-Carrillo, E.M. Rivera-Muñoz, N. Cayetano-Castro, R. Herrera-Basurto, Z. Barquera-Bibiano, F. Mercader-Trejo, A. Manzano-Ramírez
This paper reports the synthesis of ZnO nanostructures (nano-bullets, nanorods, nanospheres) by a facile and novel modified polyol method without surfactants, varying only the molar concentration of precursor salt (Zinc acetate dihydrate) using ethylene glycol and deionized water. At a constant temperature of 160°C, nano-bullets were obtained at a concentration of 0.6M, whereas at 0.8M nanorods were observed while at 1.0M only nanospheres appear. X-ray Diffraction, Scanning Electron Microscopy, High-Resolution Transmission Electron Microscopy and Room-Temperature Photoluminescence properties were used to characterize the nanostructures. Based on the results it is suggested a high dependence between morphology and molar concentration of the precursor salt as well as a mechanism of crystallization of the different nanostructures. The nanostructures may be used to produce optoelectronic devices.

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Effect of biochar on cadmium bioavailability and uptake in wheat (Triticum aestivum L.) grown in a soil with aged contamination

Publication date: June 2017
Source:Ecotoxicology and Environmental Safety, Volume 140
Author(s): Tahir Abbas, Muhammad Rizwan, Shafaqat Ali, Muhammad Zia-ur-Rehman, Muhammad Farooq Qayyum, Farhat Abbas, Fakhir Hannan, Jörg Rinklebe, Yong Sik Ok
Cadmium (Cd) is a well-known and widespread toxic heavy metal while the effects of biochar (BC) on Cd bioavailability and toxicity in wheat, especially in soils with aged contamination are largely unknown. In the present study, the effect of rice straw BC on Cd immobilization in soil and uptake by wheat in an agricultural contaminated-soil was investigated. Different levels of rice straw BC (0%, 1.5%, 3.0% and 5% w/w) were incorporated into the soil and incubated for two weeks. After this, wheat plants were grown in the amended soil until maturity. The results show that the BC treatments increased the soil and soil solution pH and silicon contents in the plant tissues and in the soil solution while decreased the bioavailable Cd in soil. The BC application increased the plant-height, spike-length, shoot and root dry mass and grain yield in a dose additive manner when compared with control treatment. As compared to control, BC application increased the photosynthetic pigments and gas exchange parameters in leaves. Biochar treatments decreased the oxidative stress while increased the activities of antioxidant enzymes in shoots compared to the control. The BC treatments decreased the Cd and Ni while increased Zn and Mn concentrations in shoots, roots, and grains of wheat compared to the control. As compared to the control, Cd concentration in wheat grains decreased by 26%, 42%, and 57% after the application of 1.5%, 3.0%, and 5.0% BC respectively. Overall, the application of rice straw BC might be effective in immobilization of metal in the soil and reducing its uptake and translocation to grains.

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U-Pb geochronology and petrogenesis of intrusive rocks: Constraints on the mode of genesis and timing of Cu mineralization in SWSK area, Lut Block

Publication date: June 2017
Source:Journal of Geochemical Exploration, Volume 177
Author(s): A. Hosseinkhani, M.H. Karimpour, A. Malekzadeh Shafaroudi, J.F. Santos
The South-West Sorkh-Kuh (SWSK) area, part of the Tertiary volcanic-plutonic rocks in the Lut Block, eastern Iran, comprises volcanic rocks intruded by intrusive rocks of hornblende diorite and biotite quartz monzonite compositions. Biotite quartz monzonite has been intensively affected by quartz-sericite-pyrite, argillic and silicification alterations and hornblende diorite shows weak propylitic and carbonate alterations. Disseminated, stockwork and vein-type styles of mineralization are associated with intrusive rocks. The vein-type mineralization with NW-SE trend is hosted by hornblende diorite. The ore in vein-type mineralization consist of quartz, chalcopyrite, pyrite, and secondary Cu-Fe minerals. Disseminated and stockwork mineralizations consist of quartz, pyrite, chalcopyrite, and secondary minerals replacing biotite quartz monzonite and hornblende diorite intrusive rocks. The highest grades in terms of Cu (3%), As (1.3%), Mo (150ppm), Pb (362ppm), Zn (743ppm), and Au (278ppb) are associated with vein-type mineralization. Intrusive rocks causing mineralization, are of metaluminous to peraluminous types with calc-alkaline to high-K calc-alkaline affinity formed in a volcanic arc setting. The enrichment of LILE (Ba, K, Cs, Sr), depletion of HFSE (Nb, P, Ti) and enrichment of LREE relative to HREE indicate the formation of source magmas above a subduction zone. The results of zircon U–Pb dating give constraints on the timing of emplacement of biotite quartz monzonite and hornblende diorite bodies at 40.16±0.72 and 20.1±2.1Ma, respectively. The younger date extends the time span of mineralizations in the Lut Block from Middle Eocene to Early Oligocene (42–33Ma.) reported by previous researchers to more recent Early Miocene times. The initial 87Sr/86Sr ratios and εNd values of both biotite quartz monzonite and hornblende diorite reside in the restricted ranges of 0.7055–0.7066 and −0.33 to +1.88, respectively, consistent with an origin above a subduction zone followed by crustal contaminations of the initial magma compositions, especially with regard to biotite quartz monzonite. The zircon U-Pb ages as well as geochemical and radiogenic isotope data for the intrusive bodies associated with mineralization in this study are in accordance with previous studies on intrusive bodies related to porphyry copper deposits in the Lut Block. In contrast to previous studies, this study further extends the span of mineralization events to at least Early Miocene times.



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Grain structure modification of Cu-Sn IMCs by applying Cu-Zn UBM on transient liquid-phase bonding in novel 3D-IC technologies

Publication date: June 2017
Source:Intermetallics, Volume 85
Author(s): Wei-Yu Chen, Rui-Wen Song, Jenq-Gong Duh
This study focuses on the formation mechanism of impinged-grain of Cu6Sn5 and interfolded-grain of Cu6(Sn,Zn)5 in Cu/Sn-3.5Ag/Cu and Cu/Sn-3.5Ag/Cu-15Zn (wt %) transient liquid-phase (TLP) bonding after reflow, respectively. Due to the application of TLP process in 3D-IC technology, the Cu-Sn intermetallic compounds (IMCs) rapidly form from the Cu pads and occupy the entire joint. These Cu-Sn IMCs with large volume fraction weaken the bond reliability resulting from its homogeneous grain structure and brittleness. It is demonstrated that doping Zn into one of the Cu substrates effectively modify the homogeneous grain structure into interfolded structure. The interfolded grain structure of Cu6(Sn,Zn)5 acts as a barrier for crack propagation and therefore enhances the bond reliability. The mechanisms involved are explained in details using thermodynamic related theories, First-principle simulation, FE-SEM observation and electron backscatter diffraction (EBSD) analyses. Owing to the effective modification of grain structure, Cu/Sn-3.5Ag/Cu-15Zn TLP bonding is potentially useful in strengthening the interconnections for novel 3D-IC technologies.

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Effects of chronic waterborne cadmium and zinc interactions on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas)

Publication date: June 2017
Source:Ecotoxicology and Environmental Safety, Volume 140
Author(s): Melissa K. Driessnack, Ankur Jamwal, Som Niyogi
The present study was designed to evaluate the interactive effects of chronic waterborne cadmium (Cd) and zinc (Zn) on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas). Trios (1 male: 2 female; n=6–7) of fish were exposed for 21 days to: (i) control (no added Cd or Zn), (ii) waterborne Cd (7µg/L), (iii) waterborne Zn (170µg/L), and (iv) Cd and Zn in mixture (7 and 170µg/L, respectively). Exposure to Cd or Zn alone did not elicit any significant effect on reproductive output (cumulative egg production) relative to the control, however exposure to Cd and Zn in mixture resulted in a ~50% decrease in fish fecundity. Plasma estradiol in females was reduced by Cd and Zn exposures, both individually and in mixture, with the maximum reduction in the metal mixture exposure. The expression of hepatic estrogen receptor genes (ER-α and ER-β) in females was affected by exposure to Zn, alone and in mixture with Cd, but not to Cd alone, whereas hepatic vitellogenin gene expression was downregulated across all treatments. Increased follicular atresia in the ovary was also recorded, but only in fish exposed to Cd and Zn in mixture. The interactions of Cd and Zn in mixture decreased Cd accumulation in tissues (gill and liver), however no reciprocal reduction in tissue Zn accumulation was observed. In addition, the expression of the hepatic metallothionein gene was upregulated following exposure to Zn, alone and in combination with Cd, with no additive effects in the latter treatment. Overall, our findings suggest that chronic exposure to waterborne Cd and Zn in mixture may induce additive reproductive toxicity, essentially by disrupting estrogen-mediated functions in fish.



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Effects of bamboo charcoal on antibiotic resistance genes during chicken manure composting

Publication date: June 2017
Source:Ecotoxicology and Environmental Safety, Volume 140
Author(s): Haichao Li, Manli Duan, Jie Gu, Yajun Zhang, Xun Qian, Jun Ma, Ranran Zhang, Xiaojuan Wang
Composting is widely used for animal waste disposal, and bamboo charcoal (BC) can be used for nitrogen conservation during composting. However, the effects of BC on antibiotic resistance genes (ARGs) during chicken manure composting are still unclear. This study investigated the effects on ARGs of adding different proportions of BC (0%, 5%, 10%, and 20% w/w) to chicken manure compost. After 26 days, the relative abundances (RAs) of most ARGs (tetC, tetG, tetW, tetX, sul2, drfA1, drfA7, ermB, ermF, ermQ, and ermX) and intI1 declined by 21.6–99.5%, whereas sul1 increased by 7.5–17.7 times. The average RAs reductions with 0%, 5%, 10%, and 20% BC were 0.85, 1.05, 1.08, and 1.15 logs, respectively. The most important environmental factor for the ARG profiles was temperature according to redundancy analysis. Furthermore, BC significantly decreased the bio-Cu and bio-Zn levels, thereby reducing the co-selection pressure from heavy metals. Different proportions of BC had no significant effects on the removal of tetG, tetW, tetX, sul2, drfA1, and ermB. Supplementation with 10% BC was more effective at removing tetC and drfA7 compared with the other treatments. The results suggested that 10% BC supplementation is appropriate for reducing ARGs in chicken manure compost.

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Zinc complexed chitosan/TPP nanoparticles: A promising micronutrient nanocarrier suited for foliar application

Publication date: 1 June 2017
Source:Carbohydrate Polymers, Volume 165
Author(s): Paresh Deshpande, Ashwin Dapkekar, Manoj D. Oak, Kishore M. Paknikar, Jyutika M. Rajwade
Cultivation of cereals in zinc deficient soils leads to declined nutritional quality of grain. Zinc deficiency in humans is a consequence of consumption of micronutrient deficient cereals as staple food. To achieve an increase in zinc density in grain, we evaluated zinc complexed chitosan nanoparticles (Zn-CNP) as a potential 'nanocarrier' suited for foliar fertilization. Zn-CNP were synthesized using tri-polyphosphate as a cross-linker. Spherical Zn-CNP (diameter 250–300nm) were positively charged (zeta potential, +42.34mV) and contained ∼20mg Zn/g (w/w). Plant growth in zinc deficient sand media, followed by foliar application of Zn-CNP (twice-a-week, for 5 weeks) after anthesis resulted in 27 and 42% increase in grain zinc content of MACS 3125 and UC1114 (durum wheat cultivars) respectively. Translocation of zinc ions from foliar applied Zn-CNP into the leaf and seed tissue was demonstrated using zinquin and dithizone stains, respectively. The study indicates the suitability of chitosan-based nanocarriers in agronomic biofortification.



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Editorial Board

Publication date: March 2017
Source:Pathology - Research and Practice, Volume 213, Issue 3





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Usefulness of the Continuous-Wave Doppler-Derived Pulmonary Arterial–Right Ventricular Pressure Gradient Just before Atrial Contraction for the Estimation of Pulmonary Arterial Diastolic and Wedge Pressures

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Publication date: Available online 27 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Michito Murayama, Taisei Mikami, Sanae Kaga, Kazunori Okada, Takuma Hioka, Nobuo Masauzi, Masahiro Nakabachi, Hisao Nishino, Shinobu Yokoyama, Mutsumi Nishida, Hiroyuki Iwano, Mamoru Sakakibara, Satoshi Yamada, Hiroyuki Tsutsui
In our new echocardiographic method, pulmonary regurgitant velocity immediately before right atrial (RA) contraction is used to estimate pulmonary artery diastolic pressure (PADP) and mean PA wedge pressure (MPAWP). Our aim here was to compare the usefulness of this new method with that of the conventional method, which uses pulmonary regurgitant velocity at end diastole. We studied 55 consecutive patients who underwent echocardiography and right-sided heart catheterization. The pulmonary regurgitant velocities just before RA contraction and at end diastole were measured to obtain echocardiographic estimates of PADP (EPADPpreA and EPADPED, respectively) by adding the pressure gradients to the echocardiographically estimated RA pressure. Compared with EPADPED, EPADPpreA correlated better with PADP (r = 0.87) and MPAWP (r = 0.80), and direct fixed biases were detected for EPADPED but not for EPADPpreA. The area under the receiver operating characteristic curve distinguishing patients with MPAWP ≥18 mm Hg was greater for EPADPpreA (0.97) than for E/e′ (0.94) and E/A (0.83). EPADPpreA is thus useful in estimating PADP and MPAWP in patients with heart disease.



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What Help Could Ultrasound Elastography Give to the Diagnosis of Breast Papillary Lesions?

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Publication date: Available online 27 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Lu-Jing Li, Ji-Yi Yao, Xin-Chuan Zhou, Xin-Bao Zhao, Wen-Jing Zhong, Bing Ou, Bao-Ming Luo, Shao-Yun Hao, Hui Zhi
On the basis of results of our previous studies and the findings of other scholars, the most common histologic type of false-positive diagnosis with strain elastography (SE) was papilloma. The objectives of our study were to evaluate whether SE could contribute to conventional ultrasound differentiation between benign and malignant papillary lesions and between papillary lesions and other common benign breast lesions. Data on 89 papillary lesions at our hospital, including 74 benign and 15 malignant papillary lesions, were included in our study. In addition, 198 non-papillary benign tumors were selected as the control group, including 126 fibroadenomas and 72 cases of fibrocystic mastopathy. All patients gave written informed consent. All patients with breast lesions underwent conventional ultrasound and SE examination. Breast Imaging Recording and Data System (BI-RADS) category and SE score were compared with respect to sensitivity, specificity and accuracy in differentiating between benign and malignant papillary lesions. We then explored the possibility of using BI-RADS combined with SE to differentiate papillary lesions from non-papillary benign tumors. For differentiating between benign and malignant papillary lesions, the area under the receiver operating characteristic curve (AUC) of BI-RADS was 0.568, whereas the AUC values of SE score, strain ratio and BI-RADS combined with SE were 0.517, 0.584 and 0.509, respectively (p > 0.05). For differentiating between papillary lesions and non-papillary benign lesions, the AUC of BI-RADS combined with SE was 0.835, which was higher than the values for BI-RADS (0.775) and SE (SE score: 0.648, strain ratio: 0.661) (p < 0.001). The specificity and accuracy of BI-RADS combined with SE were significantly higher than those for BI-RADS alone without a decrease in sensitivity (p < 0.05). SE could not improve the diagnostic efficiency of BI-RADS in differentiating between benign and malignant papillary lesions. However, BI-RADS combined with SE could improve the specificity of BI-RADS without decrease in sensitivity for differentiating breast papillary lesions from non-papillary benign lesions.



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Inhibition of CDK4 sensitizes multidrug resistant ovarian cancer cells to paclitaxel by increasing apoptosiss

Abstract

Purpose

Overexpression of cyclin-dependent kinase (CDK) 4 has been observed in a variety of cancers and has been found to contribute to tumor cell growth and proliferation. However, the effect of inhibition of CDK4 in ovarian cancer is unknown. We investigated the therapeutic effect of the CDK4 inhibitor palbociclib in combination with paclitaxel in ovarian cancer cells.

Methods

Cell viabilities were determined by MTT assay after exposure to different dosages of palbociclib and/or paclitaxel. Western blot, immunofluorescence, and Calcein AM assays were conducted to determine the mechanisms underlying the cytotoxic effects of palbociclib in combination with paclitaxel. CDK4 siRNA was used to validate the outcome of targeting CDK4 by palbociclib in ovarian cancer cells.

Results

We found that combinations of palbociclib and paclitaxel significantly enhanced drug sensitivity in both Rb-positive (SKOV3TR) and Rb-negative (OVCAR8TR) ovarian cancer-derived cells. When combined with paclitaxel, palbociclib induced apoptosis in both SKOV3TR and OVCAR8TR cells. We also found that palbociclib inhibited the activity of P-glycoprotein (Pgp), and that siRNA-mediated CDK4 knockdown sensitized multidrug resistant (MDR) SKOV3TR and OVCAR8TR cells to paclitaxel.

Conclusions

Inhibition of CDK4 by palbociclib can enhance paclitaxel sensitivity in both Rb-positive and Rb-negative MDR ovarian cancer cells by increasing apoptosis. CDK4 may serve as a promising target in the treatment of ovarian cancer.



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Cryptosporidium-contaminated water disinfection by a novel Fenton process

Publication date: May 2017
Source:Free Radical Biology and Medicine, Volume 106
Author(s): Sina Matavos-Aramyan, Mohsen Moussavi, Hedieh Matavos-Aramyan, Sara Roozkhosh
Three novel modified advanced oxidation process systems including ascorbic acid-, pro-oxidants- and ascorbic acid-pro-oxidants-modified Fenton system were utilized to study the disinfection efficiency on Cryptosporidium-contaminated drinking water samples. Different concentrations of divalent and trivalent iron ions, hydrogen peroxide, ascorbic acid and pro-oxidants at different exposure times were investigated. These novel systems were also compared to the classic Fenton system and to the control system which comprised of only hydrogen peroxide. The complete in vitro mechanism of the mentioned modified Fenton systems are also provided. The results pointed out that by considering the optimal parameter limitations, the ascorbic acid-modified Fenton system decreased the Cryptosporidium oocytes viability to 3.91%, while the pro-oxidant-modified and ascorbic acid-pro-oxidant-modified Fenton system achieved an oocytes viability equal to 1.66% and 0%, respectively. The efficiency of the classic Fenton at optimal condition was observed to be 20.12% of oocytes viability. The control system achieved 86.14% of oocytes viability. The optimum values of the operational parameters during this study are found to be 80mgL−1 for the divalent iron, 30mgL−1 for ascorbic acid, 30mmol for hydrogen peroxide, 25mgL−1 for pro-oxidants and an exposure time equal to 5min. The ascorbic acid-pro-oxidants-modified Fenton system achieved a promising complete water disinfection (0% viability) at the optimal conditions, leaving this method a feasible process for water disinfection or decontamination, even at industrial scales.

Graphical abstract

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Editorial Board

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Publication date: March 2017
Source:Free Radical Biology and Medicine, Volume 104





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Effect of shear stress on structure and function of polyplex micelles from poly(ethylene glycol)-poly(l-lysine) block copolymers as systemic gene delivery carrier

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Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Kaori M. Takeda, Yuichi Yamasaki, Anjaneyulu Dirisala, Sorato Ikeda, Theofilus A. Tockary, Kazuko Toh, Kensuke Osada, Kazunori Kataoka
Structural stability of polyplex micelles (PMs), prepared from plasmid DNA (pDNA) and poly(ethylene glycol)-b-poly(l-lysine) block catiomer (PEG−PLys), was evaluated in terms of their resistance against shear stress. When exposed to shear stress at magnitudes typically present in the blood stream, structural deterioration was observed in PMs owing to the partial removal of PEG−PLys strands. Eventually, impaired PEG coverage of the polyplex core led to accelerated degradation by nucleases, implying that structural deterioration by shear stress in blood stream may be a major cause of rapid clearance of PMs from blood circulation. To address this issue, introduction of disulfide crosslinking into the PM core was shown to be an efficient strategy, which successfully mitigated unfavorable effects of shear stress. Furthermore, improved in vivo blood retention profile and subsequently enhanced antitumor efficacy in systemic treatment of pancreatic adenocarcinoma were confirmed for the crosslinked PMs loaded with pDNA encoding an anti-angiogenic protein, suggesting that high stability under the shear stress during blood circulation may be a critical factor in systemically applicable gene delivery systems.



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Evidence-based management of rosacea



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News and Notices



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Anti-melanoma differentiation-associated protein 5 autoantibodies as a marker for dermatomyositis-associated interstitial lung disease



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Induced autoimmune bullous diseases



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Intense pulsed light combined with methyl aminolaevulinate for treating actinic keratoses and photoaged skin of the dorsal hands has considerable advantages. However, is it worth the extra expense?



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Image Gallery: Haemophagocytic lymphohistiocytosis in an adult with Langerhans cell histiocytosis



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Towards personalized modification of microbial imbalances



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Image Gallery: PELVIS syndrome



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The treatment of vulval lichen sclerosus in prepubertal girls: a critically appraised topic

Summary

Lichen sclerosus is one of the dermatoses that specifically affects the anogenital skin. It has peaks of incidence in prepubertal girls and postmenopausal women. The objective of this critical appraisal was to review systematically the evidence for efficacy and safety of different treatments. There are no randomized controlled studies of treatment in prepubertal girls and most studies are small case series or case reports. There is little focus on quality of life.



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Severe systemic juvenile xanthogranuloma is an indication for systemic therapy



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Atopic dermatitis and gut microbiota



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Neuropeptide PACAP promotes sweat secretion



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NICE approval of adalimumab for moderate-to-severe hidradenitis suppurativa: the end of the beginning for hidradenitis suppurativa therapeutics?



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Plain language summaries in Simplified Chinese



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More than skin-deep: is basal cell carcinoma a marker for a cancer-prone phenotype?



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Fumaric acid esters: a new therapeutic option for skin manifestations in lupus erythematosus?



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British Association of Dermatologists’ guidelines for the management of contact dermatitis 2017



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Enhancing Mitofusin/Marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies

Publication date: Available online 27 February 2017
Source:Neurobiology of Aging
Author(s): Bilal Khalil, Marie-Jeanne Cabirol-Pol, Laetitia Miguel, Alexander J. Whitworth, Magalie Lecourtois, Jean-Charles Liévens
TAR DNA-binding protein 43 kDa (TDP-43) is considered a major pathological protein in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The precise mechanisms by which TDP-43 dysregulation leads to toxicity in neurons are not fully understood. Using TDP-43-expressing Drosophila, we examined whether mitochondrial dysfunction is a central determinant in TDP-43 pathogenesis. Expression of human wild-type TDP-43 in Drosophila neurons results in abnormally small mitochondria. The mitochondrial fragmentation is correlated with a specific decrease in the mRNA and protein levels of the Drosophila pro-fusion gene mitofusin/marf. Importantly, overexpression of Marf ameliorates defects in spontaneous walking activity and startle-induced climbing response of TDP-43-expressing flies. Partial inactivation of the mitochondrial pro-fission factor, DRP1, also mitigates TDP-43-induced locomotor deficits. Expression of TDP-43 impairs neuromuscular junction transmission upon repetitive stimulation of the giant fiber circuit that controls flight muscles, which is also ameliorated by Marf overexpression. We show here for the first time that enhancing the pro-fusion gene mitofusin/marf is beneficial in an in vivo model of TDP-43 proteinopathies, serving as a potential therapeutic target.



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AdDRESSing T-cell responses to antituberculous drugs



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APOE e4 status and poor glycaemic control predict white matter hyperintensity growth from 73-76 years

Publication date: Available online 27 February 2017
Source:Neurobiology of Aging
Author(s): Simon R. Cox, Stuart J. Ritchie, David Alexander Dickie, Alison Pattie, Natalie A. Royle, Janie Corley, Benjamin S. Aribisala, Sarah E. Harris, Maria Valdés Hernández, Alan J. Gow, Susana Muñoz Maniega, John M. Starr, Mark E. Bastin, Joanna M. Wardlaw, Ian J. Deary
We examined whether APOE status interacts with vascular risk factors (VRFs) to predict progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when risk of dementia increases. At age 73 years, baseline VRFs were assessed via self-reported history of diabetes, hypertension, smoking and hypercholesterolemia, and via objective measures of blood HbA1c, Body Mass Index, diastolic and systolic blood pressure, and blood HDL ratio. APOE e4 allele was coded as either present or absent. WMH progression was measured on MRI over 3 years in 434 older adults, in a same-year-of-birth cohort. APOE e4 carriers with either a self-reported diagnosis of diabetes (β = 0.160, p = 0.002) or higher glycated haemoglobin levels (β = 0.114, p = 0.014) exhibited greater WMH progression, and the former survived correction for multiple testing. All other APOE-VRF interactions were non-significant (βinteraction < 0.056, p > 0.228). The results suggest that carrying the APOE 'risk' e4 allele increases the risk of greater age-related WMH progression over the early part of the eighth decade of life, when combined with poorer glycaemic control. The interaction effect was robust to co-occurring VRFs, suggesting a possible target for mitigating brain and cognitive ageing at this age.



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Increasing value in research



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Cover Image: Aquagenic wrinkling of the palms: a clue to underlying cystic fibrosis heterozygosity



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Not All Probabilities Are Equivalent: Evidence From Orientation Versus Spatial Probability Learning.

Author: Jabar, Syaheed B.; Anderson, Britt
DOI: 10.1037/xhp0000354
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017


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Weighted Integration Suggests That Visual and Tactile Signals Provide Independent Estimates About Duration.

Author: Ball, Danny M.; Arnold, Derek H.; Yarrow, Kielan
DOI: 10.1037/xhp0000368
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017


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The Onset and Time Course of Semantic Priming During Rapid Recognition of Visual Words.

Author: Hoedemaker, Renske S.; Gordon, Peter C.
DOI: 10.1037/xhp0000377
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017


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Anticipation in Manual Tracking With Multiple Delays.

Author: Stepp, Nigel; Turvey, Michael T.
DOI: 10.1037/xhp0000393
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017


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Contextual Cueing Improves Attentional Guidance, Even When Guidance Is Supposedly Optimal.

Author: Harris, Anthony M.; Remington, Roger W.
DOI: 10.1037/xhp0000394
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017


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Detecting Target Changes in Multiple Object Tracking With Peripheral Vision: More Pronounced Eccentricity Effects for Changes in Form Than in Motion.

Author: Vater, Christian; Kredel, Ralf; Hossner, Ernst-Joachim
DOI: 10.1037/xhp0000376
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017


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Hand hygiene compliance: Social cohesion and role modeling

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Publication date: Available online 27 February 2017
Source:American Journal of Infection Control
Author(s): Deepak Asudani




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Classification of aliphatic-butylene terephthalate copolyesters in relation to aliphatic/aromatic ratio

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Malgorzata Wojtczak, Slawomir Dutkiewicz, Andrzej Galeski, Agnieszka Gutowska
Aliphatic-aromatic copolyesters containing: butylene terephthalate ester and a mixture of butylene esters: adipate, succinate and glutarate, (PBASGT), were synthesized and classified according to their chemical composition and physical performance. Several such mixtures of aliphatic dimethyl esters are available on the market. Structures and properties of PBASGTs were characterized by various techniques including 1H NMR spectrometry, calorimetry, x-ray scattering and diffraction, dynamic mechanical analysis and tensile testing. All copolyesters were nearly random copolymers. Surprisingly, only the aromatic component is able to crystallize in the form characteristic for poly (butylene terephtalate). The increase of aromatic units content did not change the crystallographic form, however, a stronger crystallinity develops. The dramatic changes of thermal and mechanical properties of PBASGT were observed with the increase of aliphatic units content, e.g. from brittle to tough behavior. Copolyesters with aromatic content of 30% and below exhibit single relaxation peak of aliphatic rich amorphous components. At the concentration of 40% and above the aromatic component is segregated while the amorphous aliphatic units form joint pools. A partial segmental miscibility of aromatic and aliphatic components is suggested. It was shown that PBASGT with 40% of aromatic units is biodegradable.

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Block copolymer compatibilized polymer: fullerene blend morphology and properties

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Y. Sun, P. Pitliya, C. Liu, X. Gong, D. Raghavan, A. Karim
Recent studies have shown the role of block copolymer as compatibilizer in tuning the phase separated morphology of the active layer so as to improve the overall photovoltaic efficiency of organic photovoltaic (OPV) devices. Here, we substantiate this observation by investigating the role of a rod-coil block copolymer poly-(3-hexylthiophene)-b-polystyrene (P3HT-b-PS) as compatibilizer in influencing the blend morphology and device performance of several polymer:fullerene blend systems. Fullerene derivatives N-(3-methoxypropyl)-2-(carboxyethyl)-5-(4-cyanophenyl) fulleropyrrolidine (NCPF) and N-(3-methoxypropyl)-2-(carboxyethyl)-5-(5, 5-difluorobenzo-dioxole) fulleropyrrolidine (FFNCPF) were synthesized using Prato reaction, while P3HT-b-PS copolymer was synthesized using the combination of Grignard metathesis, ATRP, and click chemistry. The addition of P3HT-b-PS in P3HT:PCBM blend led to the formation of more homogenous structure compared to the pure P3HT:PCBM blend. Also, a reduction in domain size was observed in P3HT: FFNCPF system upon P3HT-b-PS addition which can be attributed to the compatibilization effect of BCP. Incorporation of P3HT-b-PS block copolymer was found to effectively alter the thin film nanostructure of polymer/fullerene derivative blends and polymer crystalline structure. Maximum enhancement in power conversion efficiency (PCE) of compatabilized P3HT:PCBM blend system was noticed followed by P3HT:FFNCPF and P3HT:NCPF. The moderate improvement in photovoltaic properties can be correlated with face-on orientation of P3HT crystallites and the segregation of the fullerene domains at the bulk heterojunction (BHJ) cathode interface which facilitates the efficient charge collection as respective electrodes.

Graphical abstract

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Nano-voids in epoxy resins: Role in the transport of light gases

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): David Roilo, Pushkar N. Patil, Roberto S. Brusa, Antonio Miotello, Riccardo Checchetto
Epoxy membranes with same chemical structure but different free volumes were prepared using aliphatic epoxide and polyether diamines as cross-linking agents. Their fractional free volume fh(T) was previously evaluated as a function of temperature and cross-linking density [P. N. Patil et al., PhysChemChemPhys18 (2016) 3817–3824]. Original H2 permeation measurements were performed changing sample temperature and network structure and compared with CO2 and N2 transport data. Modelling gas permeability Φ in the framework of the free volume theory we observe that the Arrhenius-type behavior of Φ for test gases is consequence of the fh(T) linear increase with temperature and that at equal fh value membranes exhibit increasing Φ values by decreasing the cross-linking density. Analysis of permeability data on this set of test molecules with different size and condensation properties suggests that increasing the cross-linking between polymer chains limits their thermal fluctuations and the redistribution of the free volume elements where diffusional jumps of penetrant molecules occur.

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Correlation between viscoelastic behavior and morphology of nanocomposites based on SR/EPDM blends compatibilized by maleic anhydride

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Leila Bazli, Alireza Khavandi, Mohammad Ali Boutorabi, Mohammad Karrabi
Silicone rubber (SR)/ethylene-propylene-diene monomer (EPDM)/nanoclay (Cloisite15 A) nanocomposites with various compositions were prepared via melt compounding using a two-roll mill. The maleic anhydride grafted ethylene-propylene-diene monomer (MAH-g-EPDM) was used as a compatibilizer in this immiscible system. The effect of adding the nanoclay and MAH-g-EPDM on the oscillatory shear rheological properties, dynamic mechanical performance, relaxation behavior and morphology of the nanocomposites were studied. Cole-Cole, Van Gurp-Palmen and Han plots revealed a good dispersion of the filler in EPDM and an agglomeration of it in SR, which were also presented in XRD analysis. Furthermore, it was observed that MAH can have a compatibilizing effect on the nanocomposites only in the presence of the nanoclay, which was in agreement with the DMTA results. Based on SEM observations, spherical and elongated droplet structures were observed for the rubber blends and nanocomposites, respectively. In addition, droplets in MAH and the nanoclay-containing samples were more regular than the MAH-free ones, which asserts the synergistic effect of these two components. Moreover, interfacial tensions between the matrix and dispersed phase calculated from the Palierne model provided a good insight for the obtained results.

Graphical abstract

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Novel electrochromic copolymers based on 3-3′-dibromo-2-2′-bithiophene and 3,4 ethylene dioxythiophene

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Buket Bezgin Carbas
A novel electrochromic material of poly(3-3′-dibromo-2-2′-bithiophene) (P(DBT)) and new electrochromic copolymers of 3,4-ethylenedioxythiophene and 3-3′-dibromo-2-2′-bithiophene prepared from different monomer feed ratios were synthesized by using electroanalytical methods. Homopolymerization and copolymerization were achieved in the medium of 0.1 M LiClO4/ACN solvent-electrolyte couple. Cyclic voltammetry (CV), atomic force microscopy (AFM), fourier transform infrared spectroscopy and ultraviolet and visible (UV-Vis) absorption spectroscopy were used to characterize corresponding homopolymer and copolymers. Electrochemical, morphological and optical properties of copolymers were alternated depending on changing the monomer feed ratio in the copolymer structure. Furthermore, electrochromic properties of the all polymers were also investigated.

Graphical abstract

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Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies

Abstract

Purpose

Alectinib, a central nervous system (CNS)-active ALK inhibitor, has demonstrated efficacy and safety in ALK+ non-small-cell lung cancer that has progressed following crizotinib treatment. Other ALK inhibitors have shown concentration-dependent QTc prolongation and treatment-related bradycardia. Therefore, this analysis evaluated alectinib safety in terms of electrophysiologic parameters.

Methods

Intensive triplicate centrally read electrocardiogram (ECG) and matched pharmacokinetic data were collected across two alectinib single-arm trials. Analysis of QTcF included central tendency analysis [mean changes from baseline with one-sided upper 95% confidence intervals (CIs)], categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations. Alectinib effects on other ECG parameters (heart rate, PR interval and QRS duration) were also evaluated.

Results

Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms observed pre-dose at week 2. The upper one-sided 95% CI was <10 ms at all time points. There was no relevant relationship between change in QTcF and alectinib plasma concentrations. Alectinib treatment resulted in a generally asymptomatic exposure-dependent decrease in mean heart rate of ~11 to 13 beats per minute at week 2. No clinically relevant effects were seen on other ECG parameters. Approximately 5% of patients reported cardiac adverse events of bradycardia or sinus bradycardia; however, these were all grade 1–2.

Conclusions

Alectinib does not prolong the QTc interval or cause changes in cardiac function to a clinically relevant extent, with the exception of a decrease in heart rate which was generally asymptomatic.



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Overexpression of ANLN contributed to poor prognosis of anthracycline-based chemotherapy in breast cancer patients

Abstract

Purpose

To investigate the associations of ANLN expression with prognosis of breast cancer and clinical outcome of anthracycline-based chemotherapy.

Methods

This study enrolled 308 breast cancer patients in which 264 of them received anthracycline-based chemotherapy. Immunohistochemistry was used to detect ANLN expression level of the patients. Clinical characteristics of the patients were collected, and associations of ANLN expression with prognosis were analyzed.

Results

Our results showed that ANLN expression was associated with survival of breast cancer patients, and it was also related to clinical outcome of patients received anthracycline-based chemotherapy. Breast cancer patients with high expression of ANLN would have poor prognosis and poor clinical outcome to anthracycline-based chemotherapy.

Conclusion

ANLN could be an independent prognosis predictor for breast cancer, and its expression might be used to predict the anthracycline-based chemotherapy clinical outcome in breast cancer patients.



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An allometric pharmacokinetic/pharmacodynamics model for BI 893923, a novel IGF-1 receptor inhibitor

Abstract

Purpose

BI 893923 is a novel IGF1R/INSR inhibitor with promising anti-tumor efficacy. Dose-limiting hyperglycemia has been observed for other IGF1R/INSR inhibitors in clinical trials. To counterbalance anti-tumor efficacy with the risk of hyperglycemia and to determine the therapeutic window, we aimed to develop a translational pharmacokinetic/pharmacodynamics model for BI 893923. This aimed to translate pharmacokinetics and pharmacodynamics from animals to humans by an allometrically scaled semi-mechanistic model.

Methods

Model development was based on a previously published PK/PD model for BI 893923 in mice (Titze et al., Cancer Chemother Pharmacol 77:1303–1314, 13). PK and blood glucose parameters were scaled by allometric principles using body weight as a scaling factor along with an estimation of the parameter exponents. Biomarker and tumor growth parameters were extrapolated from mouse to human using the body weight ratio as scaling factor.

Results

The allometric PK/PD model successfully described BI 893923 pharmacokinetics and blood glucose across mouse, rat, dog, minipig, and monkey. BI 893923 human exposure as well as blood glucose and tumor growth were predicted and compared for different dosing scenarios. A comprehensive risk–benefit analysis was conducted by determining the net clinical benefit for each schedule. An oral dose of 2750 mg BI 893923 divided in three evenly distributed doses was identified as the optimal human dosing regimen, predicting a tumor growth inhibition of 90.4% without associated hyperglycemia.

Conclusion

Our model supported human therapeutic dose estimation by rationalizing the optimal efficacious dosing regimen with minimal undesired effects. This modeling approach may be useful for PK/PD scaling of other IGF1R/INSR inhibitors.



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Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main and Multivessel Coronary Artery Disease: Do We Have the Evidence?.

Author: Gersh, Bernard J. MB, ChB, DPhil; Stone, Gregg W. MD; Bhatt, Deepak L. MD, MPH
Page: 819-821


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Why NOBLE and EXCEL Are Consistent With Each Other and With Previous Trials.

Author: Ruel, Marc MD, MPH; Farkouh, Michael E. MD, MSc
Page: 822-824


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Role of Diastolic Stress Testing in the Evaluation for Heart Failure With Preserved Ejection Fraction: A Simultaneous Invasive-Echocardiographic Study.

Author: Obokata, Masaru MD, PhD; Kane, Garvan C. MD, PhD; Reddy, Yogesh N. V. MD; Olson, Thomas P. PhD; Melenovsky, Vojtech MD, PhD; Borlaug, Barry A. MD
Page: 825-838


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High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

Author: Ellingsen, Oyvind MD, PhD; Halle, Martin MD; Conraads, Viviane MD, PhD; Stoylen, Asbjorn MD, PhD; Dalen, Havard MD, PhD; Delagardelle, Charles MD; Larsen, Alf-Inge MD, PhD; Hole, Torstein MD, PhD; Mezzani, Alessandro MD, PhD; Van Craenenbroeck, Emeline M. MD, PhD; Videm, Vibeke MD, PhD; Beckers, Paul PhD; Christle, Jeffrey W. PhD; Winzer, Ephraim MD, PhD; Mangner, Norman MD; Woitek, Felix MD; Hollriegel, Robert MD; Pressler, Axel MD; Monk-Hansen, Tea MD, PhD; Snoer, Martin MD, PhD; Feiereisen, Patrick PhD; Valborgland, Torstein MD; Kjekshus, John MD, PhD; Hambrecht, Rainer MD; Gielen, Stephan MD; Karlsen, Trine PhD; Prescott, Eva MD, DMSc; Linke, Axel MD; For the SMARTEX Heart Failure Study (Study of Myocardial Recovery After Exercise Training in Heart Failure) Group
Page: 839-849


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Body Mass Index and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review and Meta-Analysis.

Author: Mariscalco, Giovanni MD, PhD; Wozniak, Marcin J. PhD; Dawson, Alan G. MB ChB, BSc; Serraino, Giuseppe F. MD; Porter, Richard MB ChB; Nath, Mintu MSc; Klersy, Catherine MD, MSc; Kumar, Tracy BSc; Murphy, Gavin J. MD
Page: 850-863


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An Apparent Obesity Paradox in Cardiac Surgery.

Author: Carnethon, Mercedes R. PhD; Khan, Sadiya S. MD, MS
Page: 864-866


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Brain Emboli After Left Ventricular Endocardial Ablation.

Author: Whitman, Isaac R. MD; Gladstone, Rachel A. BA; Badhwar, Nitish MD; Hsia, Henry H. MD; Lee, Byron K. MD; Josephson, S. Andrew MD; Meisel, Karl M. MD; Dillon, William P. Jr. MD; Hess, Christopher P. MD, PhD; Gerstenfeld, Edward P. MD; Marcus, Gregory M. MD, MAS
Page: 867-877


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The Sound of Silence: How Much Noise Should We Make About Postablation Silent Strokes?.

Author: Zei, Paul C. MD, PhD; Vora, Nirali MD
Page: 878-880


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Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure.

Author: Abu-Taha, Issam H. PhD; Heijman, Jordi PhD; Hippe, Hans-Jorg MD; Wolf, Nadine M. PhD; El-Armouche, Ali MD; Nikolaev, Viacheslav O. PhD; Schafer, Marina MSc; Wurtz, Christina M. PhD; Neef, Stefan MD; Voigt, Niels MD; Baczko, Istvan MD, PhD; Varro, Andras MD, PhD, DSc; Muller, Marion MSc; Meder, Benjamin MD; Katus, Hugo A. MD; Spiger, Katharina PhD; Vettel, Christiane PhD; Lehmann, Lorenz H. MD; Backs, Johannes MD; Skolnik, Edward Y. MD; Lutz, Susanne PhD; Dobrev, Dobromir MD; Wieland, Thomas PhD
Page: 881-897


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Meal Timing and Frequency: Implications for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association.

Author: St-Onge, Marie-Pierre PhD, FAHA, Chair; Ard, Jamy MD; Baskin, Monica L. PhD; Chiuve, Stephanie E. ScD; Johnson, Heather M. MD, FAHA; Kris-Etherton, Penny PhD, RD, FAHA; Varady, Krista PhD; On behalf of the American Heart Association Obesity Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Clinical Cardiology; and Stroke Council
Page: e96-e121


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ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Author: Chan, Wiley V. MD, Co-Chair; Pearson, Thomas A. MD, MPH, PhD, FAHA, Co-Chair; Bennett, Glen C. MPH; Cushman, William C. MD, FAHA; Gaziano, Thomas A. MD, MSc; Gorman, Paul N. MD, PhD; Handler, Joel MD; Krumholz, Harlan M. MD, ScM, FACC, FAHA; Kushner, Robert F. MD; MacKenzie, Thomas D. MD, MSPH; Sacco, Ralph L. MD, FAHA; Smith, Sidney C. Jr MD, FACC, FAHA; Stevens, Victor J. PhD; Wells, Barbara L. PhD; Castillo, Graciela MPH; Heil, Susan K.R. PhD; Stephens, Jennifer MPH; Vann, Julie C. Jacobson PhD, MS, RN
Page: e122-e137


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Highlights From the Circulation Family of Journals.

Author:
Page: 898-903


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Wide Complex Tachycardia on Telemetry: What Is the Diagnosis?.

Author: Padala, Santosh K. MD; Kalahasty, Gautham MD; Ellenbogen, Kenneth A. MD
Page: 904-906


http://ift.tt/2l6KUvX

In Vivo Study of Electromagnetic Interference With Pacemakers Caused by Everyday Electric and Magnetic Fields.

Author: Stunder, Dominik MSc; Seckler, Tobias MSc; Joosten, Stephan PhD; Zink, Matthias Daniel MD; Driessen, Sarah PhD; Kraus, Thomas MD; Marx, Nikolaus MD; Napp, Andreas MD
Page: 907-909


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Letter by Nadir Regarding Article, "Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients With Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting)".

Author: Nadir, M. Adnan MD, MBBS, MRCP
Page: e138-e139


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Letter by Vallurupalli and Uretsky Regarding Article, "Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients With Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting)".

Author: Vallurupalli, Srikanth MD; Uretsky, Barry F. MD
Page: e140-e141


http://ift.tt/2lQ08Tu

Response by Meneveau and Ecarnot to Letter Regarding Article, "Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients With Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting)".

Author: Meneveau, Nicolas MD, PhD; Ecarnot, Fiona MSc
Page: e142-e143


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Letter by Crossley Regarding Article, "What I Wish Clinicians Knew About Industry [horizontal ellipsis] and Vice Versa".

Author: Crossley, George H. MD
Page: e144


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Correction to: Apoptosis of Endothelial Cells Precedes Myocyte Cell Apoptosis in Ischemia/Reperfusion Injury.

Author:
Page: e145


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Factors Associated with Early Mortality Among Patients with De Novo Metastatic Breast Cancer: A Population-Based Study

Background.

Although improvements in survival have been achieved for patients with metastatic breast cancer, some patients experience early death after diagnosis.

Patients and Methods.

Using Surveillance, Epidemiology, and End Results data, we identified 26,538 patients with de novo metastatic breast cancer diagnosed between January 1, 2000 and June 30, 2011. We evaluated time trends for deaths at 1 and 6 months after diagnosis. We then restricted the cohort to patients diagnosed between 2010 and 2011 (n = 3,317), when human epidermal growth factor receptor 2 was routinely collected, and examined factors associated with early death.

Results.

In 2000, 15.9% of patients died within 1 month of diagnosis and 33.2% within 6 months. In 2011, the proportion of women dying within 1 month decreased to 13.4% and 26.3% within 6 months (p < .001). Older age and uninsured status were associated with early death (at both time points, age ≥70 [versus age <40] had >8.5 higher odds of dying, and uninsured [versus insured] patients had >2.5 higher odds of death). In addition, in some subgroups (e.g., no insurance and triple negative disease), more than half of patients died within 6 months. Region was also associated with early death.

Conclusion.

Although we observed improvements in the proportion of patients experiencing early death, one quarter of patients with de novo metastatic disease diagnosed in 2011 died within 6 months of diagnosis. In addition to tumor factors and older age, geography and uninsured status were associated with early death. Our findings highlight the need for focused interventions for metastatic patients at highest risk for poor outcomes. The Oncologist 2017;22:1–8

Implications for Practice: With nearly one quarter of patients in our dataset diagnosed in 2011 dying within 6 months of diagnosis, our findings highlight the persistent and critical need of further characterization and identification of patients who are risk for poor outcomes in order to optimize care, impact change, and improve outcomes for all women with metastatic breast cancer. Our data also emphasize the need for interventions among those at highest risk for early death. These interventions would likely promote immediate referral for clinical trial participation, early palliative care referrals, and additional supportive services, optimizing equitable patient access to cancer treatment and care.



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Survival Gains from First-Line Systemic Therapy in Metastatic Non-Small Cell Lung Cancer in the U.S., 1990-2015: Progress and Opportunities

Background.

Approximately 190,000 Americans are diagnosed with non-small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients.

Materials and Methods.

We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990–2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use.

Results.

From 1990–2015, one-year survival proportion increased by 14.1% and mean per-patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively.

Conclusion.

Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per-patient and population-level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. The Oncologist 2017;22:1–7

Implications for Practice: Approximately 93,500 Americans are diagnosed with metastatic non-small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990–2015. Over this period, the one-year survival proportion and mean per-patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care.



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Response to Tyrosine Kinase Inhibitors in Myeloproliferative Neoplasia with 8p11 Translocation and CEP110-FGFR1 Rearrangement

This brief communication reports on a patient with an exceedingly rare "8p11 (eight-p-eleven) myeloproliferative syndrome" (EMS) with CEP110-FGFR1 rearrangement who responded to treatment with the multi-tyrosine kinase inhibitor (TKI) dasatinib. Dasatinib improved quality of life substantially by increasing blood counts and reducing the need for transfusions. This report demonstrates that the second-generation TKI may provide a therapeutic option for elderly and frail EMS patients who cannot be offered aggressive therapy, including allogeneic hematopoietic cell transplantation. The Oncologist 2017;22:1–4



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Cross-cultural consistency and diversity in intrinsic functional organization of Broca's Region

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Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Yu Zhang, Lingzhong Fan, Svenja Caspers, Stefan Heim, Ming Song, Cirong Liu, Yin Mo, Simon B. Eickhoff, Katrin Amunts, Tianzi Jiang
As a core language area, Broca's region was consistently activated in a variety of language studies even across different language systems. Moreover, a high degree of structural and functional heterogeneity in Broca's region has been reported in many studies. This raised the issue of how the intrinsic organization of Broca's region effects by different language experiences in light of its subdivisions. To address this question, we used multi-center resting-state fMRI data to explore the cross-cultural consistency and diversity of Broca's region in terms of its subdivisions, connectivity patterns and modularity organization in Chinese and German speakers. A consistent topological organization of the 13 subdivisions within the extended Broca's region was revealed on the basis of a new in-vivo parcellation map, which corresponded well to the previously reported receptorarchitectonic map. Based on this parcellation map, consistent functional connectivity patterns and modularity organization of these subdivisions were found. Some cultural difference in the functional connectivity patterns was also found, for instance stronger connectivity in Chinese subjects between area 6v2 and the motor hand area, as well as higher correlations between area 45p and middle frontal gyrus. Our study suggests that a generally invariant organization of Broca's region, together with certain regulations of different language experiences on functional connectivity, might exists to support language processing in human brain.



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Amyloid and tau PET demonstrate region-specific associations in normal older people

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Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Samuel N. Lockhart, Michael Schöll, Suzanne L. Baker, Nagehan Ayakta, Kaitlin N. Swinnerton, Rachel K. Bell, Taylor J. Mellinger, Vyoma D. Shah, James P. O'Neil, Mustafa Janabi, William J. Jagust
β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [18F]AV-1451 (for tau) and [11C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant's mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB—AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p<.01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates.



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On the neural basis of sensory weighting: Alpha, beta and gamma modulations during complex movements

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Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Nicolas Lebar, Jérémy Danna, Simon Moré, Laurence Mouchnino, Jean Blouin
Previous studies have revealed that visual and somatosensory information is processed as a function of its relevance during movement execution. We thus performed spectral decompositions of ongoing neural activities within the somatosensory and visual areas while human participants performed a complex visuomotor task. In this task, participants followed the outline of irregular polygons with a pen-controlled cursor. At unpredictable times, the motion of the cursor deviated 120° with respect to the actual pen position creating an incongruence between visual and somatosensory inputs, thus increasing the importance of visual feedback to control the movement as suggested in previous studies. We found that alpha and beta power significantly decreased in the visual cortex during sensory incongruence when compared to unperturbed conditions. This result is in line with an increased gain of visual inputs during sensory incongruence. In parallel, we also found a simultaneous decrease of gamma and beta power in sensorimotor areas which has not been reported previously. The gamma desynchronization suggests a reduced integration of somatosensory inputs for controlling movements with sensory incongruence while beta ERD could be more specifically linked to sensorimotor adaptation processes.



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The global signal in fMRI: Nuisance or Information?

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Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Thomas T. Liu, Alican Nalci, Maryam Falahpour
The global signal is widely used as a regressor or normalization factor for removing the effects of global variations in the analysis of functional magnetic resonance imaging (fMRI) studies. However, there is considerable controversy over its use because of the potential bias that can be introduced when it is applied to the analysis of both task-related and resting-state fMRI studies. In this paper we take a closer look at the global signal, examining in detail the various sources that can contribute to the signal. For the most part, the global signal has been treated as a nuisance term, but there is growing evidence that it may also contain valuable information. We also examine the various ways that the global signal has been used in the analysis of fMRI data, including global signal regression, global signal subtraction, and global signal normalization. Furthermore, we describe new ways for understanding the effects of global signal regression and its relation to the other approaches.



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Early processing in primary visual cortex is necessary for conscious and unconscious vision while late processing is necessary only for conscious vision in neurologically healthy humans

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Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Mikko Hurme, Mika Koivisto, Antti Revonsuo, Henry Railo
The neural mechanisms underlying conscious and unconscious visual processes remain controversial. Blindsight patients may process visual stimuli unconsciously despite their V1 lesion, promoting anatomical models, which suggest that pathways bypassing the V1 support unconscious vision. On the other hand, physiological models argue that the major geniculostriate pathway via V1 is involved in both unconscious and conscious vision, but in different time windows and in different types of neural activity. According to physiological models, feedforward activity via V1 to higher areas mediates unconscious processes whereas feedback loops of recurrent activity from higher areas back to V1 support conscious vision. With transcranial magnetic stimulation (TMS) it is possible to study the causal role of a brain region during specific time points in neurologically healthy participants. In the present study, we measured unconscious processing with redundant target effect, a phenomenon where participants respond faster to two stimuli than one even when one of the stimuli is not consciously perceived. We tested the physiological feedforward-feedback model of vision by suppressing conscious vision by interfering selectively either with early or later V1 activity with TMS. Our results show that early V1 activity (60ms) is necessary for both unconscious and conscious vision. During later processing stages (90ms), V1 contributes selectively to conscious vision. These findings support the feedforward-feedback-model of consciousness.



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Internet use, online information seeking and knowledge among third molar patients attending public dental services

Abstract

Background

While Australians are searching the Internet for third molar (TM) information, the usefulness of online sources might be questioned due to quality variation. This study explored: (1) internet use, online information seeking behavior among TM patients attending public dental services and (2) whether patients' TM knowledge scores are associated with the level of internet use and eHealth Literacy Scale (eHEALS) scores.

Methods

Baseline survey data from the "Engaging Patients in Decision-Making" study were used. Variables included: socio-demographics, internet access status, online information seeking behavior, eHEALS, the Control Preferences Scale (CPS) and TM knowledge.

Results

Participants (n=165) were mainly female (73.8%), aged 19-25 years (42.4%) and had "secondary school or less" education (58.4%). A majority (n=79, 52.7%) had sought online dental information which was associated with active decisional control preference (OR=3.1, P=.034) and higher educational attainment (OR=2.7, P=.040). TM knowledge scores were not associated with either the level of Internet use (F (2, 152) =2.1, P=.094, ƞ2=.031). or the eHEALS scores (r=.147, P=.335).

Conclusion

The internet prepared patient" phenomena exists among public TM patients and was explained by preference for involvement in decision-making. However, Internet use was not associated with better TM knowledge. Providing TM patients with internet guidance might be an opportunity to improve TM knowledge.

This article is protected by copyright. All rights reserved.



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Necrotising fasciitis as a complication of odontogenic infection: a review of management and case series

Abstract

Objective

To establish the incidence of head and neck necrotising fasciitis (NF) in the Adelaide Oral and Maxillofacial Surgery Unit. To review the current literature regarding the management of head and neck NF. To determine the evidence for the role of hyperbaric oxygen therapy in the management of NF.

Method

A retrospective audit of all patients admitted to the Royal Adelaide Hospital Oral and Maxillofacial Surgery Unit 2006-2015 with severe odontogenic infections was carried out. Patient demographics were recorded and treatment details were collected and analysed.

Results

A total of 672 patients were admitted for management of severe odontogenic infections. Of these, three were identified as NF. One case was treated using hyperbaric oxygen as an adjunct to conventional surgical and medical management. Two cases were managed using aggressive surgical management alone. Two patients survived. The incidence of head and neck NF in South Australia is 48 per 100,000 infections per year.

Conclusion

The first line treatment of severe odontogenic infections remains conventional surgical and medical management, however hyperbaric oxygen therapy may have an additional role in the management of NF and other rare severe infections in medically complex patients.

This article is protected by copyright. All rights reserved.



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Referral Patterns of General Dental Practitioners for Bone Grafting and Implant Placement

Abstract

Dental implant rehabilitation is a well-established procedure often conducted in the general dental practice setting. The outcomes for implant placement are reliable when the recipient site is favorable. Our goal has been to assess the accuracy with which general dental practitioners (GDP's) assess the bone volume available for implant placement and their referral patterns for implant sites, which may require bone grafting.

Fifty-three GDP's were surveyed and asked to assess 5 different scenarios and cone beam scans for difficulty (0 no difficulty - 5 the most difficult), and bone grafting requirements (yes/no and who to perform), prior to implant placement.

This article is protected by copyright. All rights reserved.



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Potential application and prevalence of the CD30 (Ki-1) antigen among solid tumors: A focus review of the literature

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Publication date: Available online 27 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Garrett K. Berger, Kevin Gee, Cassandra Votruba, Ali McBride, Faiz Anwer
BackgroundCD30 (Ki-1) is a cell membrane protein derived from the tumor necrosis factor (TNF) receptor family. The CD30 antigen has been associated primarily with Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Brentuximab vedotin (BV) is an antibody-drug conjugate targeting the CD30 antigen. FDA approval for BV includes relapsed and refractory HL and sALCL. The CD30 antigen also has been identified in many solid tumors, predominantly of germ cell origins and early clinical data is promising.ObjectivePerform a focus literature review evaluating the prevalence of the CD30 antigen among nonlymphomatous tumors with a potential correlate for CD30 targeted therapy.Eligibility criteriaInclusion criteria: all retrospective reviews and case reports citing CD30 positivity or negativity in non-lymphomatous malignancies in which data were presented based on location. Exclusion criteria: studies with hematopoetic malignancies, cutaneous malignancies, non-human populations, and non-english publications.Included studiesA total of 119 articles met these criteria and are summarized in this manuscript.ConclusionThe CD30 antigen has shown variable prevalence among non-hematopoetic tumors, most notably among germ cell tumors and mesothelioma. With additional, preclinical and properly powered clinical studies, CD30 targeted therapy such as that of BV, alone or in combination with other agents may prove to be a strong candidate in the treatment of various CD30+ malignancies.



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Role of brain-derived neurotrophic factor and nerve growth factor in the regulation of Neuropeptide W in vitro and in vivo

Publication date: Available online 27 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Rikang Wang, Fengxia Yan, Rifang Liao, Pei Wan, Peter J. Little, Wenhua Zheng
Nerve growth factor (NGF) and Brain-derived neurotrophic factor (BDNF) are neurotrophic factors involved in the growth, survival and functioning of neurons. In addition, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has recently been proposed. Neuropeptide W (NPW) is an endogenous peptide ligand for the GPR7 and GPR8 and a stress mediator in the hypothalamus. It activates the HPA axis by working on hypothalamic corticotrophin-releasing hormone (CRH). No information is available about the interrelationships between neurotrophines like NGF/BDNF and NPW. We studied the effect and underlying mechanisms of NGF/BDNF on the production of NPW in PC12 cells and hypothalamus. NGF time- and concentration-dependently stimulated the expression of NPW in PC12 cells. The effect of NGF was blocked by the inhibition of PI3K/Akt signal pathway with specific inhibitors for PI3K or Akt siRNA for Akt while inhibition of ERK pathway had no effect. Moreover, BDNF concentration-dependently induced the expression of NPW mRNA and decreased the expression of NPY mRNA in primary cultured hypothalamic neurons which was also blocked by a PI3K kinase inhibitor. Finally, in vivo study showed that exogenous BDNF injected icv increased NPW production in the hypothalamus and this effect was reversed by a PI3 kinase inhibitor. These results and the fact that BDNF was able to stimulate the expression of CRH demonstrated that neurotrophines can modulate the expression of NPW in neuronal cells via the PI3K/Akt pathway and suggest that BDNF might be involved in functions of the HPA axis, at least in part by modulating the expression of NPW/NPY and CRH.

Graphical abstract

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Evolution of thyroid hormone distributor proteins

Publication date: Available online 27 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Thomas R. McLean, Michelle M. Rank, Peter M. Smooker, Samantha J. Richardson
Thyroid hormones (THs) are evolutionarily old hormones, having effects on metabolism in bacteria, invertebrates and vertebrates. THs bind specific distributor proteins (THDPs) to ensure their efficient distribution through the blood and cerebrospinal fluid in vertebrates. Albumin is a THDP in the blood of all studied species of vertebrates, so may be the original vertebrate THDP. However, albumin has weak affinity for THs. Transthyretin (TTR) has been identified in the blood across different lineages in adults vs juveniles. TTR has intermediate affinity for THs. Thyroxine-binding globulin has only been identified in mammals and has high affinity for THs. Of these THDPs, TTR is the only one known to be synthesised in the brain and is involved in moving THs from the blood into the cerebrospinal fluid. We analysed the rates of evolution of these three THDPs: TTR has been most highly conserved and albumin has had the highest rate of divergence.

Graphical abstract

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Sex chromosome complement involvement in angiotensin receptor sexual dimorphism

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Publication date: Available online 27 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Florencia M. Dadam, Carla D. Cisternas, Ana F. Macchione, Andrea Godino, José Antunes-Rodrigues, María J. Cambiasso, Laura M. Vivas, Ximena E. Caeiro
This study aimed to define whether sex chromosome complement (SCC) may differentially modulate sex differences in relative gene expression of basal Agtr1a, Agtr2, and Mas1 receptors at fore/hindbrain nuclei and at medulla/cortical kidney.Samples were collected from gonadectomized male (XX and XY) and female (XX and XY) mice of the "four core genotypes" model. At brain level, a SCC effect at the area postrema was demonstrated. An increase in mRNA level of Agtr1a and Agtr1a/Agtr2 ratio in XY-SCC mice was associated with a decrease in Mas1 compared to XX-SCC mice. In the renal cortex, a SCC effect for Agtr2 and Mas1 was observed. Regardless of sex (male or female), XX-SCC mice expressed higher levels of mRNA Agtr2 and Mas1 than XY-SCC mice {F(1,12) = 6,126,p < 0.05; F(1,21) = 5,143,p < 0.05}. Furthermore, XX-female mice showed a significant increase in Mas1 expression compared to XY-female mice.These results reveal a SCC modulatory effect at central and kidney level on angiotensin receptor expression, with an enhancement of the vasodilatory arm in XX-mice and an increase in the vasoconstriction arm in XY-mice, which may underlie sex differences in the regulation of arterial pressure.



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The small RNA miR-375– a pancreatic islet abundant miRNA with multiple roles in endocrine beta cell function

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Publication date: Available online 27 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Lena Eliasson
The pathophysiology of diabetes is complex and recent research put focus on the pancreatic islets of Langerhans and the insulin-secreting beta cells as central in the development of the disease. MicroRNAs (miRNAs), the small non-coding RNAs regulating post-transcriptional gene expression, are significant regulators of beta cell function. One of the most abundant miRNAs in the islets is miR-375. This review focus on the role of miR-375 in beta cell function, including effects in development and differentiation, proliferation and regulation of insulin secretion. It also discusses the regulation of miR-375 expression, miR-375 as a potential circulating biomarker in type 1 and type 2 diabetes, and the need for the beta cell to keep expression of miR-375 within optimal levels. The summed picture of miR-375 is a miRNA with multiple functions with importance in the formation of beta cell identity, control of beta cell mass and regulation of insulin secretion.



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Role of cancer stem-cell marker doublecortin-like kinase 1 in head and neck squamous cell carcinoma

Publication date: April 2017
Source:Oral Oncology, Volume 67
Author(s): Lorenz Kadletz, Dietmar Thurnher, Robert Wiebringhaus, Boban M. Erovic, Ulana Kotowski, Sven Schneider, Rainer Schmid, Lukas Kenner, Gregor Heiduschka
BackgroundSo far, no data is available on the role of the tumor stem cell marker doublecortin-like kinase 1 (DCLK1) in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate DCLK1 expression in HNSCC patients that underwent surgery and postoperative radiotherapy, and to assess its potential as a therapeutic target in vitro.MethodsWe immunohistochemically stained for DCLK1 in 127 sections of HNSCC samples obtained during surgery of HNSCC patients and correlated the expression to patients' overall- and disease-free survival, as well as human papilloma virus (HPV) status. Additionally, we compared our survival data with data obtained from The Cancer Genome Atlas (TCGA). The effects of the DCLK1 inhibitor LRRK-2-in-1 on HNSCC cell lines alone and in combination with irradiation.ResultsExpression of DCLK1 in 127 patients was associated with poor survival. In particular, DCLK1 expression had a significant impact on survival of oropharyngeal carcinoma patients. Specifically, DCLK1+/HPV patients had the worst prognosis after simultaneous assessment of DCLK1 and HPV status in comparison to the other three possible DCLK1/HPV constellations. Higher levels of DCLK1 mRNA were also associated with poor clinical outcome. Inhibition of DCLK1 in our HNSCC cell lines led to growth arrest and induction of apoptosis. The combination of DCLK1 inhibition with irradiation had a synergistic effect.ConclusionFirstly, DCLK1 is a prognostic biomarker for shortened survival. Secondly, through inhibition of DCLK1, it may serve as a therapeutic target as well.



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Functional characterisation of the Drosophila cg6568 gene in host defence against Mycobacterium marinum

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Publication date: Available online 27 February 2017
Source:Microbes and Infection
Author(s): Hyo Sun Jin, Hye-Mi Lee, Da-Hye Lee, Guang-Ho Cha, Kyoung Sang Cho, Ji-Chan Jang, Eun-Kyeong Jo
Mycobacterium marinum is a pathogenic mycobacterial species closely related to Mycobacterium tuberculosis. In this study, we established a mycobacterial infection model of Drosophila melanogaster to characterize the role played by cg6568, a homolog of the human cathelicidin gene, in the innate defense against infection. Drosophila cg6568 was expressed at various levels during all developmental stages, and the expression levels were modulated by M. marinum in a time-dependent manner. 20-hydroxyecdysone induced Drosophila cg6568 transcription both in vitro and in vivo. Using flies expressing cg6568 RNAi, we found that cg6568 was essential both for D. melanogaster survival and the exertion of antimicrobial effects during M. marinum infection. Thus, we named the gene product a cathelicidin-like antimicrobial protein of D. melanogaster (dCAMP). Our results indicate that dCAMP is crucial in terms of the innate D. melanogaster defense during M. marinum infection.



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Nano-grained perovskite LEDs shine more brightly

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Publication date: Available online 24 February 2017
Source:Nano Today





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“La Monstrua Desnuda”: an artistic textbook representation of Prader–Willi syndrome in a painting of Juan Carreño de Miranda (1680)



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Effect of metformin and oral contraceptives on polycystic ovary syndrome and IVF cycles

Abstract

Aim

The aim of this study is to investigate the effect of metformin and/or OC added to the treatment of PCOS patients at our clinic on IVF outcome.

Materials and methods

This study is a retrospective study that assesses the data of PCOS patients who received IVF between 2005 and 2015 at a private IVF center. The study included 496 PCOS cases aged between 24 and 40. Participants diagnosed with PCOS were divided into 4 groups according to the use of metformin and OC prior to the IVF cycle: 11.1% were in the metformin group, 31.3% in the OC group, 14.9% in the Metformin + OC group, and 42.7% in the control group.

Results

No difference was found in the total gonadotropin dose and duration of stimulation between the groups. Clinical pregnancy rates and implantation rates were similar in all groups, although the numbers of oocytes, mature oocytes, fertilized oocytes, and transferred embryos were lower in the treatment groups received metformin compared to the OC group and control group. There was no significant difference in the presence of OHSS and the singleton and multiple pregnancies between the four groups.

Conclusion

The present study established no positive role of metformin and OC use in increasing the treatment success in IVF/ICSI cycles in PCOS patients. It would be appropriate to limit the use of these agents with special indications such as decreasing insulin resistance or synchronizing follicular cohort.



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Pronounced effect of hapten binding on thermal stability of an anti-(4-hydroxy-3-nitrophenyl)acetyl antibody possessing a glycine residue at position 95 of the heavy chain

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Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Yusui Sato, Satomi Inaba, Harumi Fukada, Takachika Azuma, Masayuki Oda
Immune response to T-cell-dependent antigens is highly dynamic; several B-cell clones responsible for antibody production appear alternately during immunization. It was previously shown that at least two-types of antibodies are secreted after immunization with (4-hydroxy-3-nitrophenyl)acetyl (NP); one has Tyr and another has Gly at position 95 of the heavy chain (referred to as Tyr95- and Gly95-type). The former appeared at an early stage, while the latter appeared at a late stage, i.e., after secondary immunization, although Fv domains of these antibodies were encoded by same genes of variable heavy and light chains. We examined whether any biophysical properties of antigen-combing sites relate to this shift in B-cell clones by preparing single-chain Fv (scFv). Thermodynamic and kinetic parameters of the interaction of scFv with various haptens are in accordance with those of intact antibodies, indicating that scFvs are appropriate models for the study on structure and function of antibodies. Next, we measured thermal stability of scFvs using differential scanning calorimetry and found that the apparent melting temperature of free Tyr95-type was 64–66°C,while that of Gly95-type was 47–48°C, indicating that the latter was highly unstable. However, Gly95-type greatly gained thermal stability because of hapten binding. We discussed the relationship between thermal stability resulted by hapten binding and dynamism of antibody response during immunization.



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