Publication date: Available online 3 February 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Elof Axel Carlson
Scientific disputes are commonly presented and settled in journal publications. Most are resolved by a weighing of evidence and new findings. In some cases the arguments are personal and in the form of ad hominem attacks on the personality or integrity of an author of a journal article. Many famous scientists (e.g., Galileo, Newton, and Hooke) used ad hominem arguments in responding to their critics. William Bateson, W. F. R. Weldon, William Castle, and H. J. Muller used ad hominem arguments in their publications until the end of World War I, when editorial policy of journals changed. Motivating some of the attacks are philosophic differences (such as holistic or reductionist approaches to science), ideological differences (such as Marxist or Capitalist outlooks), politics (such as Cold War depictions by East and West on fallout from nuclear testing), or conflicts of interest (which can be professional or financial such as the debates over nontraditional and orthodox medicine or over tobacco smoking and health). Most of the time, the disputes are motivated by honest disagreements over the interpretation of the data. A recent surge (2009–2016) of ad hominem attacks by Edward Calabrese have appeared disparaging H. J. Muller, E. B. Lewis, other twentieth-century contributors to radiation genetics, and the National Academy of Sciences. They address the mutational effects of low-dose radiation exposure. Calabrese's attacks have led to responses by geneticists in the field of mutagenesis, by agencies criticized by Calabrese, and by students and colleagues of those who have been accused of deception by Calabrese. This article reviews some of the history of ad hominem arguments in science and the background to the attacks by Calabrese. I argue that Calabrese's characterization of Muller and his supporters is unjust, misleading, and hurtful. I also propose some methods for dealing with or preventing ad hominem attacks in professional journals.
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Παρασκευή 3 Φεβρουαρίου 2017
Scientific Feuds, Polemics, and Ad Hominem Arguments in Basic and Special-Interest Genetics
Updating irradiated graphite disposal: Project ‘GRAPA’ and the international decommissioning network
Publication date: May 2017
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): Anthony Wickham, Hans-Jürgen Steinmetz, Patrick O'Sullivan, Michael I. Ojovan
Demonstrating competence in planning and executing the disposal of radioactive wastes is a key factor in the public perception of the nuclear power industry and must be demonstrated when making the case for new nuclear build. This work addresses the particular waste stream of irradiated graphite, mostly derived from reactor moderators and amounting to more than 250,000 tonnes world-wide. Use may be made of its unique chemical and physical properties to consider possible processing and disposal options outside the normal simple classifications and repository options for mixed low or intermediate-level wastes. The IAEA has an obvious involvement in radioactive waste disposal and has established a new project 'GRAPA' – Irradiated Graphite Processing Approaches – to encourage an international debate and collaborative work aimed at optimising and facilitating the treatment of irradiated graphite.
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135Xe measurements with a two-element CZT-based radioxenon detector for nuclear explosion monitoring
Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Lily Ranjbar, Abi T. Farsoni, Eric M. Becker
Measurement of elevated concentrations of xenon radioisotopes (131mXe, 133mXe, 133Xe and 135Xe) in the atmosphere has been shown to be a very powerful method for verifying whether or not a detected explosion is nuclear in nature. These isotopes are among the few with enough mobility and with half-lives long enough to make their detection at long distances realistic. Existing radioxenon detection systems used by the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) suffer from problems such as complexity, need for high maintenance and memory effect. To study the response of CdZnTe (CZT) detectors to xenon radioisotopes and investigate whether it is capable of mitigating the aforementioned issues with the current radioxenon detection systems, a prototype detector utilizing two coplanar CZT detectors was built and tested at Oregon State University. The detection system measures xenon radioisotopes through beta-gamma coincidence technique by detecting coincidence events between the two detectors. In this paper, we introduce the detector design and report our measurement results with radioactive lab sources and 135Xe produced in the OSU TRIGA reactor. Minimum Detectable Concentration (MDC) for 135Xe was calculated to be 1.47 ± 0.05 mBq/m3.
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Characteristics of radio-cesium transport and discharge between different basins near to the Fukushima Dai-ichi Nuclear Power Plant after heavy rainfall events
Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Kazuyuki Sakuma, Akihiro Kitamura, Alex Malins, Hiroshi Kurikami, Masahiko Machida, Koji Mori, Kazuhiro Tada, Takamaru Kobayashi, Yasuhiro Tawara, Hiroyuki Tosaka
This paper describes watershed modeling of catchments surrounding the Fukushima Dai-ichi Nuclear Power Plant to understand radio-cesium redistribution by water flows and sediment transport. We extended our previously developed three-dimensional hydrogeological model of the catchments to calculate the migration of radio-cesium in both sediment-sorbed and dissolved forms. The simulations cover the entirety of 2013, including nine heavy rainfall events, as well as Typhoon Roke in September 2011. Typhoons Man-yi and Wipha were the strongest typhoons in 2013 and had the largest bearing on radio-cesium redistribution. The simulated 137Cs discharge quantities over the nine events in 2013 are in good agreement with field monitoring observations. Deposition mainly occurs on flood plains and points where the river beds broaden in the lower basins, and within dam reservoirs along the rivers. Differences in 137Cs discharge ratios between the five basins are explained by differences in the initial fallout distribution within the basins, the presence of dam reservoirs, and the input supply to watercourses. It is possible to use these simulation results to evaluate future radioactive material distributions in order to support remediation planning.
http://ift.tt/2jJTsIL
Oxidative stress and NO generation in the rat pancreatitis induced by pancreatic duct ligation
Source:Acta Histochemica
Author(s): Igor Buchwalow, Jürgen Schnekenburger, Dmitri Atiakshin, Vera Samoilova, Eduard Wolf, Werner Boecker, Katharina Tiemann
The interaction between nitric oxide (NO) and superoxides is critical in the development of an acute pancreatitis. Previously, we reported that the expression of superoxides and of the NO-generating enzyme (NO synthase, NOS) was up-regulated in the human pancreatitis, especially within the exocrine compartment indicating an exceptional susceptibility of the exocrine parenchyma to oxidative stress. The aim of the present study was to compare the regulation of NO signalling pathways in the human pancreatitis and in an animal model of an acute pancreatitis induced by pancreatic duct ligation (PDL) in rats. In the PDL-induced rat pancreatitis, we revealed a similar pattern of oxidative stress and NOS up-regulation in acinar and in ductal compartments, like in the human pancreatitis. This demonstrates that the PDL-induced rat pancreatitis is a proper model for further studies of acute pancreatitis development in humans.
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Ribosome biogenesis and cancer
Source:Acta Histochemica
Author(s): Massimo Derenzini, Lorenzo Montanaro, Davide Trerè
There is growing evidence indicating that the human pathological conditions characterized by an up-regulated ribosome biogenesis are at an increased risk of cancer onset. At the basis of this relationship is the close interconnection between the ribosome biogenesis and cell proliferation. Cell proliferation-stimulating factors also stimulate ribosome production, while the ribosome biogenesis rate controls the cell cycle progression. The major tumour suppressor, the p53 protein, plays an important balancing role between the ribosome biogenesis rate and the cell progression through the cell cycle phases. The perturbation of ribosome biogenesis stabilizes and activates p53, with a consequent cell cycle arrest and/or apoptotic cell death, whereas an up-regulated ribosome production down-regulates p53 expression and activity, thus facilitating neoplastic transformation.In the present review we describe the interconnection between ribosome biogenesis and cell proliferation, while highlighting the mechanisms by which quantitative changes in ribosome biogenesis may induce cancer.
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Starch-derived absorbable polysaccharide hemostat enhances bone healing via BMP-2 protein
Publication date: Available online 3 February 2017
Source:Acta Histochemica
Author(s): Wen Niu, Yanxia Wang, Yi Liu, Bo Zhang, Manling Liu, Ying Luo, Pengtao Zhao, Yao Zhang, Hanrong Wu, Lei Ma, Zhichao Li
Surgical hemostasis is critical in reducing the likelihood of excessive bleeding and blood transfusion. In treating some cases, commonly used hemostatic agent showed limited efficacy and prolonged degradation and clearance, causing an inhibition of bone healing. Starch absorbable polysaccharide (SAPH) is a novel hemostatic agent made from a plant starch, which can be completely absorbed and achieve better hemostatic effects than many commonly used hemostatic agents. However, whether SAPH can induce a promotion of bone healing remains unknown. In this study, we used a model of rabbit parietal bone defect and a mouse osteoblast cell line MC3T3-E1 to evaluate the effects of SAPH on bone healing. We found that SAPH significantly decreased bone healing scores, reduced defective area of parietal bone, and increased the areas of bone trabeculae and cavitas medullaris. In addition, SAPH enhanced MC3T3-E1 osteoblasts proliferation, up-regulated the expressions of alkaline phosphatase (ALP) and osteocalcin and increased the level of bone morphogenetic protein 2 (BMP-2) in MC3T3-E1 osteoblasts. These SAPH-induced benefits in MC3T3-E1 osteoblasts were significantly abolished by the application of BMP-2-siRNA. These findings suggested that SAPH enhances bone healing, promotes the proliferation, differentiation and maturation of osteoblast by up-regulating BMP-2 expression in osteoblastic cells.
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The effect of different cleaning methods on the surface and temperature of failed titanium implants: an in vitro study
Abstract
The aims of this in vitro study are to compare the efficacy of different cleaning methods in removing debris of failed implants and to detect thermal changes of the implants treated by various scaling instruments. Twenty-seven failed implants and two unused implants as control were included to this study—group 1: plastic curette (P), group 2: titanium curette (T), group 3: carbon curette (C), group 4: titanium brush (TB), group 5: Er:YAG laser (laser 1 (L1) 100 mJ/pulse at 10 Hz), group 6: Er:YAG laser (laser 2 (L2) 150 mJ/pulse at 10 Hz), group 7: Er:YAG laser (laser 3 (L3) 200 mJ/pulse at 10 Hz), group 8: ultrasonic scaler appropriate for titanium (US), group 9: air abrasive method (AA) + citric acid, and group 10: implantoplasty (I). The changes on the treated/untreated titanium surfaces and remnant debris were observed by scanning electron microscopy (SEM). Temperature of the implants before and after treatment was detected using a thermocouple. The use of air abrasive and citric acid combination and Er:YAG laser groups was found as the best methods for the decontamination of titanium surfaces of failed implant. When the hand instruments were compared, titanium curette was found better than both the plastic and the carbon curettes which leave plastics and carbon remnants on the titanium surface. The temperature was higher after hand instrumentation when compared to other experimental groups (p < 0.05). Within the limitations of the present in vitro model, it can be concluded that the best method for decontamination of the implant surface is the use of air abrasives and Er:YAG laser.
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Marginal and internal fit of posterior three-unit fixed zirconia dental prostheses fabricated with two different CAD/CAM systems and materials
Abstract
Objectives
The purpose of this in vitro study was to compare the precision of fit of frameworks milled from semi-sintered regular zirconia and high-translucent (HT) zirconia blanks, fabricated with two different CAD/CAM systems.
Material and methods
Three-unit, posterior fixed dental prostheses (FDP) frameworks were fabricated for standardized dies (n = 11) with two different laboratory computer-aided design (CAD)/computer-aided manufacturing (CAM) systems (Cercon/Ceramill). The replica technique was used to evaluate the marginal and internal fit under an optical microscope. Evaluation of the data was performed according to prior studies at a level of significance of 5%.
Results
The systems showed a statistically significant influence on the internal fit of the frameworks (p ≤ 0.001) and on the marginal fit (p < 0.001). The type of material showed no influence on the marginal fit for the Cercon system (p = 0.636) and on the marginal fit (p = 0.064) and the internal fit (p = 0.316) for the Ceramill system, while regular zirconia from Cercon showed higher internal values than HT zirconia (p = 0.016).
Conclusions and clinical relevance
Both investigated systems showed clinically acceptable values within the limitations of this in vitro study. However, one showed less internal accuracy when regular zirconia was used.
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Events
Source:Materials Today
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Molecular Diagnostic Techniques for Onychomycosis: Validity and Potential Application
Abstract
Background
Diagnosis of onychomycosis requires positive findings by direct microscopy and fungal culture. Fungal culture is slow and difficult, with low yields. We compared two dermatophyte identification methods, one using a real-time polymerase chain reaction (PCR) method, and the other using fungal culture to validate the molecular method.
Methods
Nail specimens were collected from 149 patients with distal and lateral subungual onychomycosis who were positive for fungal elements by direct microscopy using potassium hydroxide. Each specimen was subjected to the modified real-time PCR assay of Miyajima et al. and fungal culture.
Results
Of 149 specimens, 142 (95.3%) were positive for Trichophyton rubrum or Trichophyton mentagrophytes including Trichophyton interdigitale by PCR, while only 104 (69.8%) were positive by fungal culture performed simultaneously. No specimen was negative by PCR, but positive by culture. All specimens positive for T. rubrum or T. mentagrophytes by culture were also positive by PCR, showing complete concordance for Trichophyton species. The culture of 17 specimens yielded fungi other than T. rubrum or T. mentagrophytes, whereas PCR identified T. rubrum in 11 of these specimens. Among 28 culture-negative specimens, 23 showed T. rubrum and four showed T. mentagrophytes by PCR. PCR allowed more rapid identification of causative fungi (≤2 days vs. ≤28 days).
Conclusion
Real-time PCR achieved a higher dermatophyte identification rate and showed complete concordance with conventional culture for two Trichophyton species. Specimens never yielded both T. mentagrophytes and T. rubrum simultaneously, suggesting that mixed infection is uncommon.
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Colonic transcriptional response to 1α,25(OH)2 vitamin D3 in African- and European-Americans
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Dereck Alleyne, David Witonsky, Brandon Mapes, Shigeki Nakagome, Meredith Sommars, Ellie Hong, Katy A. Muckala, Anna Di Rienzo, Sonia S. Kupfer
Colorectal cancer (CRC) is a significant health burden especially among African Americans (AA). Epidemiological studies have correlated low serum vitamin D with CRC risk, and, while hypovitaminosis D is more common and more severe in AA, the mechanisms by which vitamin D modulates CRC risk and how these differ by race are not well understood. Active vitamin D (1α,25(OH)2D3) has chemoprotective effects primarily through transcriptional regulation of target genes in the colon. We hypothesized that transcriptional response to 1α,25(OH)2D3 differs between AA and European Americans (EA) irrespective of serum vitamin D and that regulatory variants could impact transcriptional response. We treated ex vivo colon cultures from 34 healthy subjects (16 AA and 18 EA) with 0.1μM 1α,25(OH)2D3 or vehicle control for 6hours and performed genome-wide transcriptional profiling. We found 8 genes with significant differences in transcriptional response to 1α,25(OH)2D3 between AA and EA with definitive replication of inter-ethnic differences for uridine phosphorylase 1 (UPP1) and zinc finger-SWIM containing 4 (ZSWIM4). We performed expression quantitative trait loci (eQTL) mapping and identified response cis-eQTLs for ZSWIM4 as well as for histone deacetylase 3 (HDAC3), the latter of which showed a trend toward significant inter-ethnic differences in transcriptional response. Allele frequency differences of eQTLs for ZSWIM4 and HDAC3 accounted for observed transcriptional differences between populations. Taken together, our results demonstrate that transcriptional response to 1α,25(OH)2D3 differs between AA and EA independent of serum 25(OH)D levels. We provide evidence in support of a genetic regulatory mechanism underlying transcriptional differences between populations for ZSWIM4 and HDAC3. Further work is needed to elucidate how response eQTLs modify vitamin D response and whether genotype and/or transcriptional response correlate with chemopreventive effects. Relevant biomarkers, such as tissue-specific 1α,25(OH)2D3 transcriptional response, could identify individuals likely to benefit from vitamin D for CRC prevention as well as elucidate basic mechanisms underlying CRC disparities.
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1,25(OH)2D3 and calcipotriol, its hypocalcemic analog, exert a long-lasting anti-inflammatory and anti-proliferative effect in synoviocytes cultured from patients with rheumatoid arthritis and osteoarthritis
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Johanna A. Huhtakangas, Johanna Veijola, Sanna Turunen, Anna Karjalainen, Maarit Valkealahti, Tomi Nousiainen, Susanna Yli-Luukko, Olli Vuolteenaho, Petri Lehenkari
ObjectivesWe investigated the effects of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3), i.e. biologically active vitamin D and calcipotriol, a vitamin D analogue, on growth and secretion of inflammatory mediators in synovial stromal cells (SSC) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA).MethodsSynovial stromal cells (SSC) isolated during knee prosthesis surgery from four patients with RA and four with OA were exposed to 1,25(OH)2D3 or calcipotriol with or without stimulation of cells with IL-1β or TNF-α. The proliferation of cells was studied by MTT assay. Levels of cytokines were analyzed by a magnetic bead–based multiplex assay (a panel of 27 important cytokines and IL-6 alone) and RT-PCR was used to validate the concentrations of the key cytokines secreted by SSC. The vitamin D receptor (VDR) was visualized by immunofluorescence in SSC and by immunohistochemistry in the synovial tissues of three RA and three OA patients.ResultsWe detected intense staining for VDR in the synovial lining and vascular endothelium in tissue sections from all our RA and OA patients. Both 1,25(OH)2D3 and calcipotriol inhibited SSC proliferation for a prolonged time (up to 23 days with calcipotriol), but dexamethasone tended to increase SSC proliferation in a 4-day culture. 1,25(OH)2D3, calcipotriol and dexamethasone reduced the secretion of most inflammatory factors. Calcipotriol and dexamethasone additively reduced the secretions of IL-6, IFN-γ, basic FGF and VEGF in TNF-α stimulated SSC. The level of IL-6 was still diminished at 10 days after exposure, emphasizing the long-term impact of calcipotriol on SSC.ConclusionsExposure for 24-48-hours to 1,25(OH)2D3 or calcipotriol causes a long-lasting inhibition of cell proliferation and cytokine production in SSC in vitro.
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DIABETES ALTERS MYELIN LIPID PROFILE IN RAT CEREBRAL CORTEX: PROTECTIVE EFFECTS OF DIHYDROPROGESTERONE
Publication date: Available online 3 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Gaia Cermenati, Silvia Giatti, Matteo Audano, Marzia Pesaresi, Roberto Spezzano, Donatella Caruso, Nico Mitro, Roberto Cosimo Melcangi
Due to the emerging association of diabetes with several psychiatric and neurodegenerative events, the evaluation of the effects of this pathology on the brain function has now a high priority in biomedical research. In particular, the effects of diabetes on myelin compartment have been poorly taken into consideration. To this purpose, we performed a deep lipidomic analysis of cortical myelin in the streptozotocin-induced diabetic rat model. In male rats three months of diabetes induced an extensive alterations in levels of phosphatidylcholines and phosphatidylethanolamines (the main species present in myelin membranes), plasmalogens as well as phosphatidylinositols and phosphatidylserines. In addition, the levels of cholesterol and myelin basic protein were also decreased. Because these lipids exert important functional and structural roles in the myelin compartment, our data indicate that cerebral cortex myelin is severely compromised in diabetic status. Treatment for one-month with a metabolite of progesterone, dihydroprogesterone, restored the lipid and protein myelin profiles to the levels observed in non-diabetic animals. These data suggest the potential of therapeutic efficacy of DHP to restore myelin in the diabetic brain.
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Histone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cells
Abstract
Purpose
Histone deacetylase inhibitors (HDACi) are anti-neoplastic agents that are known to affect the growth of different cancer types, but their underlying mechanisms are still incompletely understood. Here, we compared the effects of two HDACi, i.e., Trichostatin A (TSA) and Valproic Acid (VPA), on the induction of cell death and autophagy in pancreatic cancer-derived cells that exhibit a high metastatic capacity and carry KRAS/p53 double mutations.
Methods
Cell viability and proliferation tests were carried out using Trypan blue dye exclusion, MTT and BrdU assays. FACS analyses were carried out to assess cell cycle progression, apoptosis, reactive oxygen species (ROS) production and mitochondrial depolarization, while Western blot and immunoprecipitation analyses were employed to detect proteins involved in apoptosis and autophagy.
Results
We found that both VPA and TSA can induce apoptosis in Panc1 and PaCa44 pancreatic cancer-derived cells by triggering mitochondrial membrane depolarization, Cytochrome c release and Caspase 3 activation, although VPA was more effective than TSA, especially in Panc1 cells. As underlying molecular events, we found that ERK1/2 was de-phosphorylated and that the c-Myc and mutant p53 protein levels were reduced after VPA and, to a lesser extent, after TSA treatment. Up-regulation of p21 and Puma was also observed, concomitantly with mutant p53 degradation. In addition, we found that in both cell lines VPA increased the pro-apoptotic Bim level, reduced the anti-apoptotic Mcl-1 level and increased ROS production and autophagy, while TSA was able to induce these effects only in PaCA44 cells.
Conclusions
From our results we conclude that both VPA and TSA can induce pancreatic cancer cell apoptosis and autophagy. VPA appears have a stronger and broader cytotoxic effect than TSA and, thus, may represent a better choice for anti-pancreatic cancer therapy.
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Preclinical evaluation of taxane-binding peptide-modified polymeric micelles loaded with docetaxel in an orthotopic breast cancer mouse model
Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Jennifer Logie, Ahil N. Ganesh, Ahmed M. Aman, Rima S. Al-awar, Molly S. Shoichet
We developed a novel taxane-binding peptide (TBP) modified, biodegradable polymeric micelle that overcomes limitations of drug loading and poor serum stability typically seen with particle delivery, leading to enhanced pharmacokinetics and tumor distribution of docetaxel (DTX). The use of the taxane-binding peptide to increase docetaxel loading is particularly compelling as it takes advantage of a known intracellular binding mechanism in a new way. Docetaxel is a potent chemotherapeutic with a therapeutic index often limited by the toxicity of the excipients that are necessary to enhance its solubility for intravenous delivery. Our polymeric micelle has terminal furan groups that enable facile antibody Fab conjugation by Diels-Alder chemistry for targeted delivery. Compared to the conventional ethanolic polysorbate 80 formulation (Free DTX), our nanoparticle (NP DTX) formulation exhibited a two-fold increase in exposure and tumor accumulation. Notably, the reduced toxicity of the NP DTX formulation increased the therapeutic index and allowed for higher dosing regimens, with a maximum tolerated dose (MTD) 1.6-fold higher than that of the Free DTX formulation, which is significant and similar to enhancements observed in clinical products for docetaxel and other drugs. These improved properties led to enhanced mouse survival in an orthotopic model of breast cancer; however, the targeted formulation of Fab-NP DTX did not further improve efficacy. Together, these results clearly demonstrate the benefits of the TBP-modified polymeric micelles as promising carriers for docetaxel.
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Corrigendum to “Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs” [Biomaterials 76C (2015) 399–407]
Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Li Fan, Yongsheng Zhang, Fuli Wang, Qian Yang, Jiali Tan, Renata Grifantini, Hong Wu, Chaojun Song, Boquan Jin
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Metformin prevents metabolic side effects during systemic glucocorticoid treatment
Objectives
Patients receiving glucocorticoid treatment are prone to develop metabolic complications. In preclinical studies, metformin prevented the development of the metabolic syndrome during glucocorticoid excess. We herein investigated the metabolic effect of metformin during glucocorticoid treatment in non-diabetic patients.
MethodsIn a double-blind, placebo-controlled trial, patients starting glucocorticoid treatment (prednisone, prednisolone or methylprednisolone) for four weeks were randomised to concomitantly receive metformin (850 mg once daily for one week followed by 850 mg twice daily for three weeks) or placebo. All patients underwent a standardised oral glucose tolerance test at baseline and after four weeks. The primary endpoint was change in the 2-h area under the curve (AUC) of glucose during the oral glucose tolerance test between baseline and four weeks.
Results29 of 34 randomised non-diabetic patients completed the trial (17 metformin and 12 placebo). In patients allocated to placebo, median glucose 2-h AUC increased from baseline to four weeks (836 (IQR 770–966) to 1202 (1009–1271) mmol/L per min; P = 0.01). In contrast, glucose levels remained similar to baseline in the metformin group (936 (869–1003) to 912 (825–1011) mmol/L per min; P = 0.83). This change within four weeks was different between both groups (P = 0.005). Glucocorticoid equivalent doses were similar in both groups (placebo: 980.0 (560.0–3259.8) mg/28 days; metformin: 683.0 (437.5–1970.5) mg/28 days; P = 0.26).
ConclusionsIn this first randomised controlled trial of metformin targeting metabolic complications in patients needing glucocorticoid therapy, we observed a beneficial effect of metformin on glycaemic control. Metformin thus seems to be a promising drug for preventing metabolic side effects during systemic glucocorticoid treatment.
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The neuroendocrine sequelae of paediatric craniopharyngioma: a 40-year meta-data analysis of 185 cases from three UK centres
Objectives
The management of paediatric craniopharyngiomas was traditionally complete resection (CR), with better reported tumour control compared to that by partial resection (PR) or limited surgery (LS). The subsequent shift towards hypothalamic sparing, conservative surgery with adjuvant radiotherapy (RT) to any residual tumour aimed at reducing neuroendocrine morbidity, has not been systematically studied. Hence, we reviewed the sequelae of differing management strategies in paediatric craniopharyngioma across three UK tertiary centres over four decades.
MethodsMeta-data was retrospectively reviewed over two periods before (1973–2000 (Group A: n = 100)) and after (1998–2011 (Group B: n = 85)) the introduction of the conservative strategy at each centre.
ResultsPatients had CR (A: 34% and B: 19%), PR (A: 48% and B: 46%) or LS (A: 16% and B: 34%), with trends reflecting the change in surgical approach over time. Overall recurrence rates between the two periods did not change (A: 38% vs B: 32%). More patients received RT in B than A, but recurrence rates were similar: for A, 28% patients received RT with 9 recurrences (32%); for B, 62% received RT with 14 recurrences (26%). However, rates of diabetes insipidus (P = 0.04), gonadotrophin deficiency (P < 0.001) and panhypopituitarism (P = 0.001) were lower in B than those in A. In contrast, post-operative obesity (BMI SDS >+2.0) (P = 0.4) and hypothalamic (P = 0.1) and visual (P = 0.3) morbidity rates were unchanged.
ConclusionThe shift towards more conservative surgery has reduced the prevalence of hormone deficiencies, including diabetes insipidus, which can be life threatening. However, it has not been associated with reduced hypothalamic and visual morbidities, which remain a significant challenge. More effective targeted therapies are necessary to improve outcomes.
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Inaugural Go Red for Women Issue.
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Improving the Cardiovascular Health of Women in the Nation: Moving Beyond the Bikini Boundaries.
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Breast Arterial Calcification: Expanding the Reach of Cardiovascular Prevention.
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Improving Cardiovascular Health in Diverse Populations: A Conversation With Anushka Patel, MBBS, SM, PhD.
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Sex Differences in Faculty Rank Among Academic Cardiologists in the United States.
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Anti-Mullerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women: Results From the Doetinchem Cohort Study.
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Women Are Less Likely Than Men to Be Full Professors in Cardiology: Why Does This Happen and How Can We Fix It?.
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Sex Differences in 1-Year All-Cause Rehospitalization in Patients After Acute Myocardial Infarction: A Prospective Observational Study.
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Race and Sex Differences in Post-Myocardial Infarction Angina Frequency and Risk of 1-Year Unplanned Rehospitalization.
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Sex-Based Differences in Cardiometabolic Biomarkers.
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Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease.
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Preterm Delivery and Maternal Cardiovascular Disease in Young and Middle-Aged Adult Women.
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Harnessing the Power of Pregnancy and Pregnancy-Related Events to Predict Cardiovascular Disease in Women.
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Atrial Fibrillation and Ventricular Arrhythmias: Sex Differences in Electrophysiology, Epidemiology, Clinical Presentation, and Clinical Outcomes.
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Go Red for Women Strategically Focused Research Network Centers.
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Women May Benefit From Cardiac Rehabilitation Programs Tailored to Their Specific Needs.
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Flexibility and Mentoring Key to Boosting the Ranks of Women in Cardiology.
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Outcomes Associated With Paroxysmal Supraventricular Tachycardia During Pregnancy.
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Burden of Arrhythmia in Pregnancy.
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Number of Pregnancies and Atrial Fibrillation Risk: The Women's Health Study.
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Risks for Staphylococcus aureus Colonization in Psoriasis Patients: A Systematic Review and Meta-Analysis
Abstract
Evidence on whether psoriasis patients have a higher risk for staphylococcal colonization than healthy controls remained controversial. To synthesize the current literature, we performed a systematic review on prevalence and relative risk (RR) of S. aureus colonization in psoriasis patients. We modified the QUADAS-2 instrument to assess the reporting quality of individual studies and applied random-effects models in meta-analysis. Overall, we identified 21 eligible studies, of which 15 enrolled one or more comparison groups. The pooled prevalence of staphylococcal colonization in psoriasis patients was 35.3% (95% confidence interval [CI]: 25.0%, 45.6%) on lesional skin and 39.2% (95%CI: 33.7%, 44.8%) in the nares. Psoriasis patients were 4.5-times more likely to be colonized by S. aureus than healthy controls were on the skin (RR: 5.54; 95% CI: 3.21,9.57) and in the nares (RR: 1.60; 95%CI: 1.11, 2.32). Cutaneous and nasal colonization by methicillin-resistant strains (MRSA) also appeared higher in psoriasis patients (pooled prevalence: 8.6%) than in healthy subjects (2.6%) yet the difference was not statistically significant (P: 0.740). In contrast, despite of a similar risk for nasal staphylococcal colonization (RR: 0.67, 95%CI: 0.38, 1.18), psoriasis patients were less likely to carry S. aureus on lesional skin than atopic patients (RR: 0.64; 95%CI: 0.40, 1.02). In summarizing the current literature, we found that psoriasis patients were at an increased risk for staphylococcal colonization as compared to healthy individuals. Prospective studies on how bacterial loads correlate with disease activity can guide the clinical management of bacterial colonization while preventing the emergence of drug-resistant strains.
This article is protected by copyright. All rights reserved.
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States of water in proton exchange membranes: Part A - Influence of chemical structure and composition
Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Abhishek Roy, Michael A. Hickner, Hae-Seung Lee, Tom Glass, Mou Paul, Anand Badami, Judy S. Riffle, James E. McGrath
Disulfonated poly(arylene ether) and polyimide copolymers can phase separate to form nanoscale hydrophilic and hydrophobic domain morphology. Water in these domains has been assigned to three different states, tightly bound, loosely bound and free water. The states of water were characterized using DSC, NMR relaxation and TGA. The chemical structures of the proton exchange membranes were varied in chemical composition, microstructure (random and block) and also regarding functional sulfonic acid groups fixed to the polymer backbones. A strong dependence of the types of water on the ion content and morphology was observed. For the random copolymers, the formation of free water in the system occurs after reaching a certain ion content. For the multi-blocks, in addition to the ion content, free water also develops with increasing block lengths. The formation of continuous morphology in the copolymers was correlated to the onset of free water. Influences of the states of water on PEM transport properties will be reported separately.
Graphical abstract
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Efficient hydrosilylation reaction in polymer blending: An original approach to structure PA12/PDMS blends at multiscales
Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): J.P. Li, P. Cassagnau, F. Da Cruz-Boisson, F. Mélis, P. Alcouffe, V. Bounor-Legaré
An in situ amide hydrosilylation reaction was developed to prepare polyamide 12 (PA12)/polysiloxane copolymers by reactive blending. This reaction is focused on the addition of hydrogenosilane groups (SiH) from polysiloxane to the carbonyl group from the PA12 amide function. To evidence this carbonyl hydrosilylation onto an amide based polymer, an approach on model compounds (use of N-methylpropionamide) was carried out. The mechanism and kinetics were investigated with multinuclear NMR (1H, 13C and 29Si). During kinetics studies, the concentration of N-silylated copolymers can reach 70 mol% after 2 h reaction at 100 °C.Amide hydrosilylation reaction was extended to the reactive blending of polyamide 12 with PDMS-SiH under molten processing conditions. Formation of a structured blend was investigated by rheology and electronic microscopy at different scales. The impact of both shearing and reaction on the final morphology was deeply studied and the interfacial enhancement by compatibilization was confirmed. As a result, the dispersion of PDMS domains decreased from 3 to 4 μm to around 0.8 μm in diameter forming submicronic morphology. Furthermore, it was possible to control the dispersion of PDMS at different scales by modifying the physico-chemical parameters (molar mass and functionality) of both components.
Graphical abstract
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Phosphonate TSA-built macromatric polymer catalysts as chymotrypsin mimics for the amidolysis of amino acid p-nitroanilides: Effect of the nature and extent of crosslinker on amidase activities
Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Divya Mathew, Benny Thomas, K.S. Devaky
Transition state analogue-built-polymer catalysts containing l-histidine, l-aspartic acid and l-serine moieties were synthesized using a racemic transition state analogue 'phenyl-1-(N-benzyloxycarbonylamino)-2-(phenyl)ethyl phosphonate' for the amidolysis of p-nitroanilide of N-(benzyloxycarbonyl)-phenylalanine, Z-L-Phe-PNA. The transition state analogue imprinted and non-imprinted polymer catalysts were prepared with hydrophilic flexible dimethacrylate crosslinkers having varying alkyl chain length-ethyleneglycol dimethacrylate, 1,4-butanediol dimethacrylate and 1,6-hexanediol dimethacrylate. The substrate affinity of the polymer catalysts were evaluated in the framework of Michaelis-Menten kinetics. Among the polymer catalysts with methacrylic crosslinks, higher extreme crosslink density (90%) is found to be essential to preserve the exact geometry of the print molecule, while the increase in alkyl chain length of the crosslinker make the cavity deformed leading to poor shape-selective binding of the substrate. The maximal value of catalytic efficiency was observed with 90% ethylene glycol dimethacrylate crosslinked polymer catalyst. A comparison was also made with polymer catalysts containing hydrophobic divinylbenzene crosslinks. Among divinylbenzene crosslinked polymers, catalyst with 75% crosslinking exhibited better catalytic efficiency. The catalytic activity of the transition state analogue imprinted polymer is observed to be enantioselective, shape-selective and substrate-specific. TSA inhibition studies reveal that the phosphonate TSA is a very competitive inhibitor for Z-L-Phe-PNA.
Graphical abstract
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The importance of environmental factors and matrices in the adsorption, desorption, and toxicity of butyltins: a review
Abstract
Butyltins (BTs) are considered as a group of the most important organometallic compounds in industry and agriculture. Due to their widespread use, large amounts of BTs including tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) have entered into the environment, and subsequently causing detrimental effects on humans and aquatic organisms. This work provides a critical review of recent studies on the adsorption, desorption, bioaccumulation, and toxicity of BTs that can notably influence the distribution of BTs in the environment. Influence of environmental factors (e.g., pH and salinity) and adsorbents in the matrices (e.g., minerals, organic carbons, and quartz) on the adsorption, desorption, and toxicity of BTs is particularly addressed.
http://ift.tt/2l2rojK
Effectiveness of SO 2 emission control policy on power plants in the Yangtze River Delta, China—post-assessment of the 11th Five-Year Plan
Abstract
Facing the air pollution problems in China, emission control strategies have been implemented within the framework of national Five-Year Plan (FYP). According to the lack of post-assessment studies in the literature, this study assessed the effectiveness of the SO2 emission control policies on power plants after the 11th FYP (2006–2010) by modeling emission control scenarios. The idealized emission control policy (the PS90 scenario with assumption of 90% SO2 emission reduction from power plants) could reduce the SO2 and SO42− concentrations by about 51 and 14%, respectively, over the Yangtze River Delta region. While the actual emission control condition (the P2010 scenario based on the actual emissions from power plants in 2010) demonstrated that the actual reduction benefits were 30% of SO2 and 9% of SO42−. On the city scale, the P2010 scenario imposed positive benefits on Shanghai, Nanjing, Nantong, and Hangzhou with SO2 reductions of about 55, 12, 30, and 21%, respectively, while an 11% increase of SO2 concentration was found in Ningbo. The number of days exceeding China's National Ambient Air Quality Standard of Class I daily SO2 concentration was estimated to be 75, 52, 7, 77, and 40 days for Shanghai, Nanjing, Nantong, Ningbo, and Hangzhou under the real SO2 control condition (P2010). The numbers could be decreased by 16, 11, 2, 21, and 11% if the control effect reaches the level of the PS90 scenario. This study serves as a scientific basis to design capable enforcement of emission control strategies in China in the future national plans.
http://ift.tt/2jHF4AM
Arsenic uptake, accumulation and toxicity in rice plants: Possible remedies for its detoxification: A review
Abstract
Arsenic (As) is a toxic metalloid. Serious concerns have been raised in literature owing to its potential toxicity towards living beings. The metalloid causes various water- and food-borne diseases. Among food crops, rice contains the highest concentrations of As. Consuming As-contaminated rice results in serious health issues. Arsenic concentration in rice is governed by various factors in the rhizosphere such as availability and concentration of various mineral nutrients (iron, phosphate, sulfur and silicon) in soil solution, soil oxidation/reduction status, inter-conversion between organic and inorganic As compounds. Agronomic and civil engineering methods can be adopted to decrease As accumulation in rice. Agronomic methods such as improving soil porosity/aeration by irrigation management or creating the conditions favorable for As-precipitate formation, and decreasing As uptake and translocation by adding a inorganic nutrients that compete with As are easy and cost effective techniques at field scale. This review focuses on the factors regulating and competing As in soil-plant system and As accumulation in rice grains. Therefore, it is suggested that judicious use of water, management of soil, antagonistic effects of various inorganic plant-nutrients to As should be considered in rice cultivated areas to mitigate the building up of As in human food chain and with minimum negative impact to the environment.
http://ift.tt/2l4y7pq
Zn- vs Bi-based oxides for o -toluidine photocatalytic treatment under solar light
Abstract
The photodegradation of the highly toxic o-toluidine pollutant was deeply investigated both under UV and solar irradiations by using three different semiconductors: pure ZnO, Bi-impregnated ZnO, and Bi2O3 nanopowders (synthesized by precipitating method). All the samples were deeply characterized on structural, morphological, surface, and optical points of view. The disappearance and the relative mineralization of o-toluidine molecules were followed by linear sweep voltammetry (LSV) and total organic carbon (TOC) determinations, respectively. Hence, correlations between their physico-chemical properties and the photocatalytic performances, passing from UV to solar light, were drawn and a hypothesis on the photodegradation mechanism has been proposed, on the basis of the HPLC/MS results. Bare Bi2O3 samples, due to the exploitation of both their visible light absorption and the negligible intermediates formation, resulted to be higher performing under solar irradiation than either pure or Bi-doped ZnO nanopowders.
http://ift.tt/2l7bkZZ
Modeling of air pollutant concentrations in an industrial region of Turkey
Abstract
The hourly SO2 and PM10 concentrations in ambient air of the Kutahya city located at the western part of Turkey have exceeded the air quality limits in winter months since several years. The region has major industrial plants including lignite-fired power plants and open-cast mining activities, residential areas, and traffic sources. To obtain and quantify the sector-wise anthropogenic emissions and spatial distribution of the major pollutants including SO2, NOx , PM10, and CO, a comprehensive emission inventory with 1-km spatial resolution was prepared for the year of 2014, and the AERMOD dispersion model was used to predict ambient air concentrations in a domain of 140 km by 110 km. Validation of the model results was also done referring to in situ routine measurements at two monitoring stations located in the study area. Total emissions of SO2, PM10, NOx , and CO in the study area were calculated as 64,399, 9770, 24,627, and 29,198 tons/year, respectively. The results showed that industrial plants were the largest sources of SO2, NOx , and PM10 emissions, while residential heating and road traffic were the most contributing sectors for CO emissions. Three major power plants in the region with total annual lignite consumption of 10 million tons per year were main sources of high SO2 concentrations, while high PM10 concentrations mainly originated from two major open-cast lignite mines. Major contributors of high NOx and CO concentrations were traffic including highways and urban streets, and residential heating with high lignite consumption in urban areas. Results of the dispersion model run with the emission inventory resulted in partially high index of agreement (0.75) with SO2 measured in the urban station within the modeled area.
http://ift.tt/2k9jlAi
Removal of β-lactam antibiotics from pharmaceutical wastewaters using photo-Fenton process at near-neutral pH
Abstract
In this work, the photo-Fenton process at near-neutral pH was applied for the removal of the β-lactam antibiotic oxacillin (OXA) in water using artificial and sunlight. Initially, the main variables of the process (Fe(II), H2O2, and light power) were optimized by a statistical factorial design (23 with center points). The experimental design indicated that 90 μmol L−1 of Fe(II), 10 mmol L−1 of H2O2, and 30 W of power light were the favorable conditions for degradation of OXA at 203 μmol L−1. In the photo-Fenton system, the H2O2 alone, UV-light/H2O2, and Fe(II)/H2O2 subsystems presented a significant participation on antibiotic removal. Moreover, based on the primary organic transformation products, a mechanism of OXA degradation was proposed. Under the favorable operational conditions, both the pollutant and the antimicrobial activity were eliminated after 50 min of process application. Although at 480 min of treatment, only 5% of mineralization was achieved, the level of biodegradability of the solutions increased from 0.08 to 0.98. Interestingly, the presence of pharmaceutical additives (glucose, isopropanol, and oxalic acid) had a moderate interference on the efficiency of the pollutant removal. Additionally, the treatment at pilot scale of the β-lactam antibiotic in a pharmaceutical complex matrix using solar radiation allowed the complete removal of the pollutant and its associated antimicrobial activity in a very short time period (5 min). These results evidenced the applicability of the photo-Fenton process to treat wastewaters from pharmaceutical industry loaded with β-lactam antibiotics at near neutral pH values efficiently.
http://ift.tt/2jHyERX
Isotherm, kinetic, and thermodynamic study of ciprofloxacin sorption on sediments
Abstract
In this study, equilibrium isotherms, kinetics and thermodynamics of ciprofloxacin on seven sediments in a batch sorption process were examined. The effects of contact time, initial ciprofloxacin concentration, temperature and ionic strength on the sorption process were studied. The K d parameter from linear sorption model was determined by linear regression analysis, while the Freundlich and Dubinin–Radushkevich (D–R) sorption models were applied to describe the equilibrium isotherms by linear and nonlinear methods. The estimated K d values varied from 171 to 37,347 mL/g. The obtained values of E (free energy estimated from D-R isotherm model) were between 3.51 and 8.64 kJ/mol, which indicated a physical nature of ciprofloxacin sorption on studied sediments. According to obtained n values as measure of intensity of sorption estimate from Freundlich isotherm model (from 0.69 to 1.442), ciprofloxacin sorption on sediments can be categorized from poor to moderately difficult sorption characteristics. Kinetics data were best fitted by the pseudo-second-order model (R 2 > 0.999). Thermodynamic parameters including the Gibbs free energy (ΔG°), enthalpy (ΔH°) and entropy (ΔS°) were calculated to estimate the nature of ciprofloxacin sorption. Results suggested that sorption on sediments was a spontaneous exothermic process.
http://ift.tt/2jHLEai
Influence of nonylphenol and octylphenol exposure on 5-HT, 5-HT transporter, and 5-HT 2A receptor
Abstract
Nonylphenol (NP) and octylphenol (OP) are priority environmental contaminants that have a potential role as endocrine disruptors. They can be biomagnified in the food chain and pose an estrogenic health risk to human health. A 28-day oral toxicity study was performed to observe the impact of single and combined exposure to NP and OP on 5-HT transporter (SERT) as well as 5-HT2A receptor. Results showed that the 5-HT levels in rat plasma increased with exposure to middle-dose and high-dose NP, to high-dose OP, and to low, middle, and high doses of combined NP and OP (P < 0.05), while the 5-HT levels in rat platelets increased when exposed to NP/OP or combined NP and OP of middle or high dose (P < 0.05). The expression levels of SERT in rat platelets decreased when exposed to high-dose NP/OP or high dose of combined NP and OP (P < 0.05). Meanwhile, the expression levels of 5-HT2A in rat platelets decreased when exposed to high-dose NP/OP as well as combined NP and OP (P < 0.05). These findings suggested that exposure to NP and OP could influence the metabolic network of 5-hydroxytryptamine via transportation and receptor binding pathways.
http://ift.tt/2l56BsK
Spatiotemporal evaluation of the groundwater quality in Gharbiya Governorate, Egypt
Abstract
Groundwater quality indicators were monitored over 6 years (2007–2012) from 55 drinking water supply wells in Gharbiya Governorate (Egypt). The prime objective was to characterize, for the first time, the governorate-wide significant and sustained trends in the concentrations of the groundwater pollutants. Quality indicators included turbidity, pH, total dissolved solid (TDS), electric conductivity (EC), Cl−, SO42−, Na+, total alkalinity, hardness (total, Mg, and Ca), Fe2+, Mn2+, Cu2+, Zn2+, F−, NH4+, NO2−, NO3−, PO43−, dissolved oxygen (DO), and SiO2 contents. Detection and estimation of trends and magnitude were carried out applying the non-parametric Mann–Kendall and Thiel–Sen trend statistical tests, respectively. Factor analysis was applied to identify significant sources of quality variation and their loads. Violation of groundwater quality standards clarified emergence of Mn2+ (46%), Fe2+ (35%), and NH4+ (33%). Out of the 55 wells, notable upward trends (deterioration) were significant (>95% level) for TDS (89%), NO3− (85), PO43− (75%), NH4+ (65%), total alkalinity (62%), Fe2+ (58%), NO2− (47%), Mg hardness (36%), turbidity (25%), and Mn2+ (24%). Ranges of attenuation rates (mg/l/year) varied for TDS (24.3, −0.7), Mg hardness (3.8, −0.85), total alkalinity (1.4, −1.2), NO3− (0.52, −0.066), PO43− (0.069, −0.064), NH4+ (0.038, −0.019), Mn2+ (0.015, −0.044), Fe2+ (0.006, −0.014), and NO2− (0.006, −0.00003). Highest rates marked Tanta (total alkalinity and Fe2+), Al-Mehala Al-Kubra (TDS, Mg hardness, and NO3−), Kafr Al-Zayat (NH4+), Zifta (Mn2+), Bassyun (NO2−), and Qutur (PO43−). Precision of the trend estimate varied in goodness of fit, for TDS (86%), Mg hardness (76%), total alkalinity (73%), PO43− (67.4%), NH4+ (66.8%), Mn2+ (55%), and Fe2+ (49.6%), arranged in decreasing order. Two main varimax-rotated factors counted for more than 55% of the quality variance and, in particular, significant loads of salinity (TDS, EC, Cl−, Na+, and SO42−), followed by the alkalinity, hardness, redox potentials (Mn2+ and Fe2+), and NH4+, in decreasing order were identified. The spatial-temporal variation in pollutants originated from organic matter degradation, either naturally from the aquifer peaty sediments or anthropogenic due to improper well head protection in the urban centers or from the agricultural drains in low relief areas. Considering the latest contents of indicators and their rate of increase, the time that the permissible limits would be reached can be accurately estimated and alleviative actions could be effectively set.
http://ift.tt/2l57jpS
Measuring Interobserver Disagreement in Rating Diagnostic Characteristics of Pulmonary Nodule Using the Lung Imaging Database Consortium and Image Database Resource Initiative
Publication date: Available online 3 February 2017
Source:Academic Radiology
Author(s): Hongli Lin, Changxing Huang, Weisheng Wang, Jiawei Luo, Xuedong Yang, Yuling Liu
Rationale and ObjectivesThe purpose of this study was to measure and analyze interobserver disagreement in rating diagnostic characteristics of pulmonary nodules on computed tomography scans using the Lung Imaging Database Consortium and Image Database Resource Initiative (LIDC/IDRI) database, and then to provide investigators with understanding the variability in rating diagnostic characteristics among radiologists.Materials and MethodsA histogram-based accumulated nodule-level approach is proposed to measure interobserver disagreement in rating diagnostic characteristics of pulmonary nodules among radiologists. The mean rating differences of radiologists on nodule level are calculated; next, a histogram of the accumulated nodule-level disagreements is constructed; and finally, mean, variance, skewness, and kurtosis statistics based on the histogram are extracted to analyze and summary interobserver disagreement in terms of the assessment of diagnostic characteristics of radiologists. Using the developed computer scheme, the disagreement of radiologists in rating all of 1880 distinct nodules from 1018 computed tomography scans are analyzed using original ratings as well as combined ratings according to the LIDC/IDRI instruction.ResultsThe interobserver disagreement in rating diagnostic characteristics according to the defined categories of the LIDC/IDRI is substantial. The mean values of disagreement range from 0.0052 to 0.2341. The highest disagreement lies in rating subtlety characteristics, whereas internal structure receives the lowest disagreement of 0.0052. The calcification, texture, spiculation, lobulation, malignancy, sphericity, and margin receive disagreements of 0.0393, 0.1351, 0.1616, 0.1943, 0.2144, 0.2174, and 0.2228, respectively.ConclusionsDisagreements exist across radiologists in rating diagnostic characteristics of pulmonary nodules, and the disagreement levels vary from each other. Agreement among radiologists is improved by combining ratings according to the LIDC/IDRI instruction. For investigators, understanding and appreciating the disagreement level of each diagnostic characteristic is required when using them in related researches.
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The American College of Radiology Incidental Findings Committee Recommendations for Management of Incidental Lymph Nodes
Publication date: Available online 3 February 2017
Source:Academic Radiology
Author(s): Paul Smereka, Ankur M. Doshi, Justin M. Ream, Andrew B. Rosenkrantz
Rationale and ObjectivesTo assess the American College of Radiology Incidental Findings Committee's (ACR-IFC) recommendations for defining and following up abnormal incidental abdominopelvic lymph nodes.Materials and MethodsA total of 59 lymph nodes satisfying ACR-IFC criteria as incidental (no malignancy or lymphoproliferative disorder) and with sufficient follow-up to classify as benign (biopsy, decreased size, ≥12-month stability) or malignant (biopsy, detection of primary malignancy combined with either fluorodeoxyglucose hyperactivity or increase in size of the node) were included. Two radiologists independently assessed nodes for suspicious features by ACR-IFC criteria (round with indistinct hilum, hypervascularity, necrosis, cluster ≥3 nodes, cluster ≥2 nodes in ≥2 stations, size ≥1 cm in retroperitoneum). Outcomes were assessed with attention to ACR-IFC's recommendation for initial 3-month follow-up.ResultsA total of 8.5% of nodes were malignant; 91.5% were benign. Two of six malignant nodes were stable at 3 to <6-month follow-up before diagnosis; diagnosis of four of five malignant nodes was facilitated by later development of non-nodal sites of tumor. A total of 13, 5, 8, and 9 nodes were deemed benign given a decrease at <3 months, 3–5 months, 6–11 months, or ≥12 months of follow-up. No ACR-IFC feature differentiated benign and malignant nodes (P = 0.164–1.0). A cluster ≥3 nodes was present in 88.1%–93.2% of nodes. A total of 96.6%–98.3% had ≥1 suspicious feature for both readers. Necrosis and hypervascularity were not identified in any node.ConclusionsACR-IFC imaging features overwhelmingly classified incidental nodes as abnormal, although did not differentiate benign and malignant nodes. Nodes stable at the ACR-IFC's advised initial 3-month follow-up were occasionally proven malignant or decreased on further imaging. Refinement of imaging criteria to define nodes of particularly high risk, integrated with other clinical criteria, may help optimize the follow-up of incidental abdominopelvic lymph nodes.
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Influence of Cardiovascular Risk Factors on the Prevalence of Coronary Atherosclerosis in Patients with Angiographically Normal Coronary Arteries
Publication date: Available online 3 February 2017
Source:Academic Radiology
Author(s): Daniel O. Bittner, Lutz Klinghammer, Mohamed Marwan, Jasmin Schmid, Christian Layritz, Udo Hoffmann, Stephan Achenbach, Tobias Pflederer
Rationale and ObjectivesCardiovascular (CV) disease is predominately influenced by CV risk factors and coronary computed tomography angiography (CTA) is capable of detecting early-stage coronary artery disease. We sought to determine the influence of CV risk factors on the prevalence of nonobstructive atherosclerosis in patients with normal-appearing coronary arteries in invasive coronary angiography (ICA).Materials and MethodsIn this retrospective analysis, we included 60 consecutive symptomatic patients, having undergone ICA and coronary CTA. Coronary dual source CTA was performed using electrocardiogram-triggered retrospective gated image acquisition at 40%–70% of RR interval (tube voltage 100–120 kV, tube current time product 320–440 mAs, 60 mL contrast, and flow rate 6 mL/s).ResultsOut of 60 patients (32 men, mean age 61 ± 11 years) with a normal coronary artery appearance in ICA, 45 (75%) patients showed atherosclerotic plaque in CTA. Plaque was present in 14 of 60 (23%) left main, 41 of 60 (68%) left anterior descending, 21 of 60 (35%) circumflex coronary arteries, and 24 of 60 (40%) right coronary arteries. More than 15% of all coronary artery segments showed detectable plaques. Interobserver agreement ranged from good to very good on a per-patient, per-vessel, and per-segment level. Patients with presence of plaque were significantly older (P = 0.005) and showed higher incidence of arterial hypertension (P = 0.019) as compared to individuals without coronary plaque in dual source computed tomography.ConclusionsThe prevalence of coronary atherosclerosis by CTA is substantial in symptomatic patients with normal invasive coronary angiogram. Hypertension and older age significantly influence the prevalence of atherosclerotic plaque and highlight the importance of risk-modifying therapy.
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Extraskeletal osteosarcoma: A European Musculoskeletal Oncology Society study on 266 patients
Publication date: March 2017
Source:European Journal of Cancer, Volume 74
Author(s): A. Longhi, S.S. Bielack, R. Grimer, J. Whelan, R. Windhager, A. Leithner, A. Gronchi, D. Biau, P. Jutte, A.H. Krieg, F.M. Klenke, G. Grignani, D.M. Donati, R. Capanna, J. Casanova, C. Gerrand, G. Bisogno, S. Hecker-Nolting, M. De Lisa, L. D'Ambrosio, M. Willegger, G. Scoccianti, S. Ferrari
PurposePrognosis of extraskeletal osteosarcoma (ESOS) is reported to be poorer than that of skeletal osteosarcoma. This multicenter retrospective study aimed to evaluate factors influencing ESOS prognosis.Patients and methodsMembers of the European Musculoskeletal Oncology Society (EMSOS) submitted institutional data on patients with ESOS.ResultsData from 274 patients treated from 1981 to 2014 were collected from 16 EMSOS centres; 266 patients were eligible. Fifty (18.7%) had metastases at diagnosis. Of 216 patients with localised disease, 211 (98%) underwent surgery (R0 = 70.6%, R1 = 27%). Five-year overall survival (OS) for all 266 patients was 47% (95% CI 40–54%). Five-year OS for metastatic patients was 27% (95% CI 13–41%). In the analysis restricted to the 211 localised patients who achieved complete remission after surgery 5-year OS was 51.4% (95% CI 44–59%) and 5-year disease-free survival (DFS) was 43% (95% CI 35–51%). One hundred twenty-one patients (57.3%) received adjuvant or neoadjuvant chemotherapy and 80 patients (37.9%) received radiotherapy. A favourable trend was seen for osteosarcoma-type chemotherapy versus soft tissue sarcoma-type (doxorubicin ± ifosfamide) regimens. For the 211 patients in complete remission after surgery, patient age, tumour size, margins and chemotherapy were positive prognostic factors for DFS and OS by univariate analysis.At multivariate analysis, patient age (≤40 years versus >40 years) (P = 0.05), tumour size (P = 0.0001) and receipt of chemotherapy (P = 0.006) were statistically significant prognostic factors for survival.ConclusionPatient age and tumour size are factors influencing ESOS prognosis. Higher survival was observed in patients who received perioperative chemotherapy with a trend in favour of multiagent osteosarcoma-type regimen which included doxorubicin, ifosfamide and cisplatin.
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Survival impact of waiting time for radical radiotherapy in nasopharyngeal carcinoma: A large institution-based cohort study from an endemic area
Publication date: March 2017
Source:European Journal of Cancer, Volume 73
Author(s): Hu Liang, Yan-Qun Xiang, Xing Lv, Chang-Qing Xie, Su-Mei Cao, Lin Wang, Chao-Nan Qian, Jing Yang, Yan-Fang Ye, Feng Gan, Liang-Ru Ke, Ya-Hui Yu, Guo-Ying Liu, Wen-Ze Qiu, Xin-Jun Huang, Can-Hong Wen, Na You, Xue-Qin Wang, Xiang Guo, Wei-Xiong Xia
BackgroundWhether the waiting time for radical radiotherapy (WRT) detrimentally impacts nasopharyngeal carcinoma (NPC) prognosis is unclear. We estimated the influence of WRT on overall survival (OS) and disease-specific survival (DSS) of NPC.Patients and methodsPatients were identified from prospectively maintained database. WRT was calculated from histological diagnosis to initiation of radiotherapy (RT). Survival analysis was estimated using Weibull parametric model and propensity score analysis (PSA). Recursive partitioning analysis (RPA) identified optimal WRT threshold via conditional inference trees to estimate the greatest survival differences based on randomly selected training and validation sets, and this process was repeated 1000 times to ensure threshold robustness. Sensitivity analysis estimated effects of potential unmeasured confounders.ResultsA total of 9896 patients were included. In multivariate analysis, WRT of 31–60°d, of 61–90°d and of greater than 90°d independently increased mortality risk compared to less than 30°d. Upon RPA, ranges of 30–35°d with the peak of 30°d were confirmed with 89% of simulations validating optimal thresholds. In threshold-based groups, adjusted hazard ratios (HRs) for WRT of greater than 30°d by both Weibull model and PSA were significantly higher than for WRT of less than 30°d [OS: HR = 1.13, 95% confidence interval (CI) 1.04–1.23, P = 0.003; DSS: HR = 1.15, 95% CI 1.05–1.26, P = 0.002]. Sensitivity analysis revealed robustness of results.ConclusionsWRT independently affects survival. Increasing WRT beyond 30°d was most consistently detrimental to survival. WRT of NPC should be as short as reasonably achievable (ASARA).
http://ift.tt/2kyDwbJ
Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group
Source:European Journal of Cancer, Volume 73
Author(s): Geert O. Janssens, Lorenza Gandola, Stephanie Bolle, Henry Mandeville, Monica Ramos-Albiac, Karen van Beek, Helen Benghiat, Bianca Hoeben, Andres Morales La Madrid, Rolf-Dieter Kortmann, Darren Hargrave, Johan Menten, Emilia Pecori, Veronica Biassoni, Andre O. von Bueren, Dannis G. van Vuurden, Maura Massimino, Dominik Sturm, Max Peters, Christof M. Kramm
BackgroundOverall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression.MethodsAt first progression, 31 children with DIPG, aged 2–16 years, underwent re-irradiation (dose 19.8–30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis.ResultsMedian OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3–6 months: 4.0 versus 2.7; P < .01; 6–12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4–5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27–.54; P < .01) and re-irradiation (corrected hazard ratio = .18–.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5).ConclusionsThe majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.
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The mitogen-activated protein kinase pathway in melanoma part I – Activation and primary resistance mechanisms to BRAF inhibition
Publication date: Available online 3 February 2017
Source:European Journal of Cancer
Author(s): Teresa Amaral, Tobias Sinnberg, Friedegund Meier, Clemens Krepler, Mitchell Levesque, Heike Niessner, Claus Garbe
Mitogen-activated protein kinase (MAPK) pathway has an important role in normal cells and can be activated under physiological conditions. MAPK pathway activation is a fundamental step in several intracellular processes requiring a sequential phosphorylation of the different pathway components. In normal cells, when MAPK pathway activation occurs, it leads to cell growth and differentiation. In order to prevent persistent MAPK pathway activation, physiological upstream negative feedback also takes place. In cells harbouring BRAFV600 mutations, the process leading to MAPK pathway activation is different, and the negative physiological feedback does not exist thus leading to permanent MAPK pathway activation, which ultimately can lead to uncontrolled proliferation.Targeted therapy with rapidly accelerated fibrosarcoma – B (BRAF) and/or mitogen-activated extracellular signal-regulated kinase kinase (MEK) inhibitors is indicated in patients with metastatic melanoma harboring BRAFV600 mutations. However, several different resistance mechanisms to this therapy were identified. In this review, we focus on primary or intrinsic resistance mechanisms to BRAF and MEK inhibition. In this setting, although a BRAF mutation is identified, there is no response to treatment with either BRAF or MEK inhibitor.
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MAPK pathway in melanoma part II—secondary and adaptive resistance mechanisms to BRAF inhibition
Publication date: Available online 3 February 2017
Source:European Journal of Cancer
Author(s): Teresa Amaral, Tobias Sinnberg, Friedegund Meier, Clemens Krepler, Mitchell Levesque, Heike Niessner, Claus Garbe
BRAF mutation can be identified in about 45% of the patients with metastatic melanoma. In these patients, BRAF and MEK inhibitors are able to induce rapid responses and to prolong survival. However, a significant percentage of patients will develop resistance to targeted therapy and will have progressive disease.MAPK pathway is the most important pathway involved in BRAF/MEK inhibition resistance, particularly MAPK pathway reactivation.Resistance mechanisms can be classified as 1) primary or intrinsic characterised by no response to therapy, 2) secondary or acquired with MAPK pathway reactivation after a time of tumour regression and 3) as adaptive with initial response and early resistance.BRAF inhibition also alters the immune response. Several publications have described immune effects of BRAF inhibition in melanoma tumours, showing that combining targeted and immunotherapy can improve response, despite a possible cross-resistance.Here, we continue the review on resistance mechanisms to BRAF/MEK inhibition and focus on the secondary and adaptive mechanisms.
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Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization
Publication date: Available online 2 February 2017
Source:Vaccine
Author(s): Jacqueline A. Baker, Emma L. Lewis, Leah M. Byland, Maryam Bonakdar, Tara M. Randis, Adam J. Ratner
Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants, and colonization of the maternal genital tract is the primary risk factor for newborn infection. Despite the importance of mucosal colonization in GBS pathogenesis, relevant host and bacterial factors are incompletely understood. We investigated the role of humoral immunity in clearance of vaginal colonization in vivo. B-cell-deficient mice or those lacking neonatal Fc-receptor, a mediator of IgG transport to the vaginal mucosa, exhibit prolonged GBS vaginal colonization compared to wild type animals. Intranasal but not intramuscular immunization induced systemic and mucosal immune responses and decreased GBS colonization duration without altering initial colonization density. Vaccine-induced clearance of GBS was serotype-specific, suggesting a role for anti-capsule antibodies in protection. Our results support a role for humoral immunity in GBS eradication from the female genital tract and suggest that mucosal vaccination may prime colonization clearance.
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Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation – A systematic review of randomized trials, observational studies and case reports
Publication date: Available online 3 February 2017
Source:Vaccine
Author(s): Evelina Croce, Christoph Hatz, Emile F. Jonker, L.G. Visser, Veronika K. Jaeger, Silja Bühler
BackgroundLive vaccines are generally contraindicated on immunosuppressive therapy due to safety concerns. However, data are limited to corroborate this practice.ObjectivesTo estimate the safety of live vaccinations in patients with immune-mediated inflammatory diseases (IMID) or solid organ transplantation (SOT) on immunosuppressive treatment and in patients after bone-marrow transplantation (BMT).Data SourcesA search was conducted in electronic databases (Cochrane, Pubmed, Embase) and additional literature was identified by targeted searches.Eligibility criteriaRandomized trials, observational studies and case reports.PopulationPatients with IMID or SOT on immunosuppressive treatment and BMT patients <2years after transplantation.Intervention/vaccinations looked atLive vaccinations: mumps, measles, rubella (MMR), yellow fever (YF), varicella vaccine (VV), herpes zoster (HZ), oral typhoid, oral polio, rotavirus, Bacillus Calmette–Guérin (BCG), smallpox.Data extractionOne author performed the data extraction using predefined data fields. It was cross-checked by two other authors.Results7305 articles were identified and 64 articles were included: 40 on IMID, 16 on SOT and 8 on BMT patients. In most studies, the administration of live vaccines was safe. However, some serious vaccine-related adverse events occurred. 32 participants developed an infection with the vaccine strain; in most cases the infection was mild. However, in two patients fatal infections were reported: a patient with RA/SLE overlap who started MTX/dexamethasone treatment four days after the YFV developed a yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and died. The particular vaccine lot was found to be associated with a more than 20 times risk of YEL-AVD. One infant whose mother was under infliximab treatment during pregnancy received the BCG vaccine at the age of three months and developed disseminated BCG infection and died. An immunogenicity assessment was performed in 43 studies. In most cases the patients developed satisfactory seroprotection rates. In the IMID group, YFV and VV demonstrated high seroconversion rates. MTX and tumor necrosis factor inhibitory therapy appeared to reduce immune responses to VV and HZ vaccine, but not to MMR and YF-revaccination. Seroconversion in SOT and BMT patients showed mostly higher rates for rubella than for measles, mumps and varicella.LimitationsRisk of bias was high in the majority of studies since 39 of them were observational and 17 were case series/case reports. Only eight studies were randomized trials. BMT patient numbers included in this review were low.ConclusionsAlthough live vaccinations were safe and sufficiently immunogenic in most studies, some serious reactions and vaccine-related infections were reported in immunosuppressed IMID and SOT patients. Apart from mild vaccine-related infections MMR and VV vaccines were safe when administered less than two years after BMT.Implications of key findingsUntil further data are available, live vaccinations under most immunosuppressive treatments should only be administered after a careful risk benefit assessment of medications and dosages.FundingNone.
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Efficacy of clade 2.3.2 H5 commercial vaccines in protecting chickens from clade 2.3.4.4 H5N8 highly pathogenic avian influenza infection
Source:Vaccine
Author(s): Seong-su Yuk, T.O. Erdene-Ochir, Jung-Hoon Kwon, Jin-Yong Noh, Woo-tack Hong, Jei-Hyun Jeong, Sol Jeong, Gyeong-Bin Gwon, Jong-il Shin, Jung-Hyang Sur, Chang-Seon Song
Emerging clade 2.3.4.4 of the highly pathogenic avian influenza (HPAI) virus strain H5N8, which had been detected sporadically in domestic poultry in China, started to affect wild birds and poultry in South Korea in 2014. The virus was spread to Germany, Italy, the Netherlands, United Kingdom, and even United States by migratory birds. Here, we tested currently used commercial clade 2.3.2 H5 vaccines to evaluate mortality, clinical signs, virus shedding, and histological damage after experimental infection of chickens with the clade 2.3.4.4 HPAI H5N8 virus. Although the vaccination protected chickens from death, it failed to prevent chickens from shedding the virus and from tissue damage according to histological examination. These results suggest that the use of appropriate vaccines that match the currently epidemic HPAI virus is recommended, and continuous HPAI surveillance and testing of currently used commercial vaccines should be performed.
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Microarray profile of the humoral immune response to influenza vaccination in breast cancer patients treated with chemotherapy
Publication date: Available online 3 February 2017
Source:Vaccine
Author(s): M.L. Wumkes, A.M.T. van der Velden, E. de Bruin, A. Meerveld-Eggink, M.P.G. Koopmans, G.F. Rimmelzwaan, G.T. Rijkers, D.H. Biesma
BackgroundPatients treated with chemotherapy have an impaired response to influenza virus vaccination compared to healthy controls. Little is known about the broadness of the antibody response in these patients.MethodsBreast cancer patients on FEC (5-fluorouracil, epirubicin and cyclophosphamide) chemotherapy regimens were vaccinated with influenza virus vaccine. Sera were obtained before and three weeks after vaccination. In addition to the determination of virus-specific antibody titres by hemagglutination inhibition assay, the broadness of the response was assessed by the use of a protein microarray and baseline titres were compared with an age-matched reference group.ResultsWe included 38 breast cancer patients and found a wide variety in serum antibody response after vaccination. Patients with a history of influenza vaccination had higher pre-vaccination titres, which were comparable to the reference group.Increasing number of cycles of chemotherapy did not have a negative effect on influenza array antibody levels, nor on the HI antibody response.ConclusionsOverall there was a broad serum antibody response to the influenza virus vaccine in patients treated with chemotherapy for breast cancer.
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Manipulation of neuraminidase packaging signals and hemagglutinin residues improves the growth of A/Anhui/1/2013 (H7N9) influenza vaccine virus yield in eggs
Source:Vaccine
Author(s): Subrata Barman, Petr S. Krylov, Jasmine C. Turner, John Franks, Robert G. Webster, Matloob Husain, Richard J. Webby
In 2013, a novel avian-origin H7N9 influenza A virus causing severe lower respiratory tract disease in humans emerged in China, with continued sporadic cases. An effective vaccine is needed for this virus in case it acquires transmissibility among humans; however, PR8-based A/Anhui/1/2013 (Anhui/1, H7N9), a WHO-recommended H7N9 candidate vaccine virus (CVV) for vaccine production, does not replicate well in chicken eggs, posing an obstacle to egg-based vaccine production. To address this issue, we explored the possibility that PR8's hemagglutinin (HA) and neuraminidase (NA) packaging signals mediate improvement of Anhui/1 CVV yield in eggs. We constructed chimeric HA and NA genes having the coding region of Anhui/1 HA and NA flanked by the 5′ and 3′ packaging signals of PR8's HA and NA, respectively. The growth of CVVs containing the chimeric HA was not affected, but that of those containing the chimeric NA gene grew in embryonated chicken eggs with a more than 2-fold higher titer than that of WT CVV. Upon 6 passages in eggs further yield increase was achieved although this was not associated with any changes in the chimeric NA gene. The HA of the passaged CVV, did, however, exhibit egg-adaptive mutations and one of them (HA-G218E) improved CVV growth in eggs without significantly changing antigenicity. The HA-G218E substitution and a chimeric NA, thus, combine to provide an Anhui/1 CVV with properties more favorable for vaccine manufacture.
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Development of a single-dose recombinant CAMP factor entrapping poly(lactide-co-glycolide) microspheres-based vaccine against Streptococcus agalactiae
Source:Vaccine
Author(s): Gang Liu, Jinhua Yin, Herman W. Barkema, Liben Chen, Muhammad Shahid, Otto Szenci, Jeroen De Buck, John P. Kastelic, Bo Han
Streptococcus agalactiae is an important contagious bovine mastitis pathogen. Although it is well controlled and even eradicated in most Northern European and North American dairy herds, the prevalence of this pathogen remains very high in China. However, research on development of a vaccine against S. agalactiae mastitis is scarce. The aims of the present study were to: (1) develop a single-dose vaccine against S. agalactiae based on poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) encapsulated CAMP factor, a conserved virulent protein encoded by S. agalactiae's cfb gene; and (2) evaluate its immunogenicity and protective efficacy in a mouse model. The cfb gene was cloned and expressed in a recombinant Escherichia coli strain Trans1-T1. The CAMP factor was tested to determine a safe dose range and then encapsulated in MS of PLGA (50:50) to assess its release pattern in vitro and immune reaction in vivo. Furthermore, a mouse model and a histopathological assay were developed to evaluate bacterial burden and vaccine efficacy. In the low dosage range (<100μg), CAMP factor had no obvious toxicity in mice. The release pattern in vitro was characterized by an initial burst release (44%), followed by a sustained and slower release over 7wk. In mice immunized with either pure CAMP factor protein or PLGA-CAMP, increased antibody titers were detected in the first 2wk, whereas only PLGA-CAMP immunization induced a sustained increase of antibody titers. In mice vaccinated with PLGA-CAMP, mortality and bacteria counts were lower (compared to a control group) after S. agalactiae challenge. Additionally, no pathological lesions were detected in the vaccinated group. Therefore, PLGA-CAMP conferred protective efficacy against S. agalactiae in our mouse model, indicating its potential as a vaccine against S. agalactiae mastitis. Furthermore, the slow-release kinetics of PLGA MS warranted optimism for development of a single-dose vaccine.
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Doses per vaccine vial container: An understated and underestimated driver of performance that needs more evidence
Publication date: Available online 3 February 2017
Source:Vaccine
Author(s): Alexis Heaton, Kirstin Krudwig, Tina Lorenson, Craig Burgess, Andrew Cunningham, Robert Steinglass
The widespread use of multidose vaccine containers in low and middle income countries' immunization programs is assumed to have multiple benefits and efficiencies for health systems, yet the broader impacts on immunization coverage, costs, and safety are not well understood. To document what is known on this topic, how it has been studied, and confirm the gaps in evidence that allow us to assess the complex system interactions, the authors undertook a review of published literature that explored the relationship between doses per container and immunization systems. The relationships examined in this study are organized within a systems framework consisting of operational costs, timely coverage, safety, product costs/wastage, and policy/correct use, with the idea that a change in dose per container affects all of them, and the optimal solution will depend on what is prioritized and used to measure performance.Studies on this topic are limited and largely rely on modeling to assess the relationship between doses per container and other aspects of immunization systems. Very few studies attempt to look at how a change in doses per container affects vaccination coverage rates and other systems components simultaneously. This article summarizes the published knowledge on this topic to date and suggests areas of current and future research to ultimately improve decision making around vaccine doses per container and increase understanding of how this decision relates to other program goals.
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Metabolites as biomarkers of adverse reactions following vaccination: A pilot study using nuclear magnetic resonance metabolomics
Publication date: Available online 3 February 2017
Source:Vaccine
Author(s): Bruce M. McClenathan, Delisha A. Stewart, Christina E. Spooner, Wimal W. Pathmasiri, Jason P. Burgess, Susan L. McRitchie, Y. Sammy Choi, Susan C.J. Sumner
An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers.
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Impact of vaccination on influenza mortality in children <5years old in Mexico
Source:Vaccine
Author(s): Evelyn L. Sánchez-Ramos, Joel Monárrez-Espino, Daniel E. Noyola
BackgroundInfluenza is a leading cause of respiratory tract infections among children. In Mexico, influenza vaccination was included in the National Immunization Program since 2004. However, the population health effects of the vaccine on children have not been fully described. Thus, we estimated the impact of influenza immunization in terms of mortality associated with this virus among children younger than 5years of age in Mexico.MethodsMortality rates and years of life lost associated with influenza were estimated using national mortality register data for the period 1998–2012. Age-stratified and cause-specific mortality rates were estimated for all-cause, respiratory and cardiovascular events. Influenza-associated mortality was compared between the period prior to introduction of the influenza vaccine as part of the National Immunization Program (1998–2004) and the period thereafter (2004–2012).ResultsDuring the 1998–2012 winter seasons, the average number of all-cause, respiratory and cardiovascular deaths attributable to influenza were 1186, 794 and 21, respectively. Influenza-associated mortality was higher prior to the vaccination period than after influenza was included in the immunization program for all-cause (mean 1660 vs. 780) and respiratory (mean 1063 vs. 563) mortality, but no reduction was seen for cardiovascular mortality. The proportion of all-cause and respiratory deaths attributable to influenza was significantly lower in the post-vaccine period compared with the pre-vaccine period (P<0.001), but no reduction was seen in the proportion of cardiovascular deaths. There was an average annual reduction of 66,558years of life lost in the post-vaccine compared with the pre-vaccine period.ConclusionThe introduction of influenza vaccination within the Mexican Immunization Program was associated with a reduction in mortality rates attributable to this virus among children younger than 5years of age.
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Early sexual debut warrants HPV vaccination at an earlier age
Source:Vaccine
Author(s): Abbey B. Berenson, Sharon Croisant
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Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2–49years
Publication date: Available online 2 February 2017
Source:Vaccine
Author(s): Roger Baxter, Abigail Eaton, John Hansen, Laurie Aukes, Herve Caspard, Christopher S. Ambrose
BackgroundQuadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013–2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2–49years.MethodsThis was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients.ResultsA total of 62,040 eligible Q/LAIV recipients were identified during the 2013–2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2–4, 5–8, 9–17, and 18–49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV.ConclusionIn this large population study of individuals aged 2–49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years.Trial registration: ClinicalTrials.gov NCT01985997
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Dermoscopy of Biett's sign and differential diagnosis with annular maculo-papular rashes with scaling
Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):270-273
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The effect of statins on severity of psoriasis: A systematic review
Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):154-161
Background: Psoriasis is becoming increasingly recognized as a chronic systemic inflammatory disease. Statins are generally well-tolerated drugs with pleiotropic effects including decreasing inflammation and may have the potential to reduce psoriasis severity. Aims: To examine whether oral statins reduce the severity of psoriatic skin disease. Methods: We searched MEDLINE, EMBASE and adapted for Google Scholar, Cochrane Central Register for Controlled Trials and Clinical trials.gov to January 6, 2016. We primarily examined randomized controlled trials that assessed the change in PASI score over a follow-up period of at least 8 weeks, for participants with an established diagnosis of psoriasis taking an oral statin versus placebo or other active treatment. Beyond this, we also examined other interventional studies that investigated the effect of statins on psoriasis severity using other designs. We extracted efficacy and adverse event data. The two study authors examined issues of study quality and study inclusion independently. Results: Three studies were identified which measured the change in psoriasis severity using PASI, comparing statin with placebo or standard therapy alone in a prospective, randomized study design; these showed conflicting results. However, among the excluded studies, majority of which used a single arm, non-placebo controlled study design, most showed an improvement in PASI scores after statin use. Limitations: Included studies were of limited sample size and quality. They were not amenable to pooled analysis. Conclusions: This review highlights the paucity of high quality, randomized, double-blinded, placebo-controlled trials investigating the effects of statins on psoriasis severity using clinically objective measures. There is insufficient evidence that the use of oral statins as an adjunctive therapy can reduce the severity of psoriasis.
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In vitro antifungal susceptibility of Malassezia isolates from pityriasis versicolor lesions
Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):249-251
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Utility of high-frequency ultrasonography in the diagnosis of benign and malignant skin tumors
Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):162-182
Various benign and malignant tumors may arise from the skin. These may be of epidermal, dermal, subcutaneous or appendageal origin. Skin biopsy is the gold standard for diagnosis of skin tumors. There is paucity of published data on the role of imaging modalities in diagnosis of skin tumors. High-frequency ultrasonography (7–50 MHz) is a potential non-invasive, objective modality which can be utilized in the diagnosis and localization of skin tumors. It provides valuable information about the tumor characteristics such as size, shape, depth, consistency and vascularity before invasive skin biopsy or surgery is planned. Sentinel lymph nodes in malignant melanoma can be well visualized and studied by this technique. It is also a good modality to detect local recurrence of tumors during post-operative follow up, especially those with a high likelihood of local recurrence or lesions excised with inadequate margins. High-frequency ultrasonography is additive to clinical diagnosis and can be considered a useful non-invasive method to plan the management of various skin tumors and is of prognostic value in some cases.
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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