bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of 3D hybrid profile order technique with 3T magnetic resonance cholangiography: Comparison of image quality and acquisition time
Authors: Yokoyama Koichi , Nakaura Takeshi , Iyama Yuji , Sakamoto Seiji , Takemura Atsushi , Okuaki Tomoyuki , Harada Kazunori , Yamashita Yasuyuki
Published: May 2016

Purpose

To evaluate the image quality and acquisition time of magnetic resonance cholangiopancreatography (MRCP) with and without the 3D hybrid profile order technique.

Materials and Methods

We studied 32 consecutive patients at 3T. They underwent MRCP with and without the 3D hybrid profile order imaging technique during free breathing and MRCP with the 3D hybrid profile order technique during a single breath‐hold. The image acquisition time was 82% shorter with the 3D hybrid profile order technique than without it. The contrast, signal‐to‐noise‐ratio (SNR), and contrast‐noise‐ratio (CNR) between the common bile duct (CBD) and periductal tissues on 3D‐MRCP were evaluated quantitatively.

Results

The contrast, SNR, and CNR of the CBD under free breathing was significantly higher with the 3D hybrid profile order technique than without it (P < 0.01). The contrast, SNR, and CNR of the CBD under a single breath‐hold was significantly higher with the 3D hybrid profile order technique than without it (P < 0.01). There were no significant differences in the contrast, SNR, and CNR of the CBD between the 3D hybrid profile order with a single breath‐hold and with free breathing (P = 0.12, 0.28, 0.28, respectively).

Conclusion

Using 3T MRI for MRCP with the 3D hybrid profile order sequence yielded significantly improved contrast and CNR with a shorter image acquisition time without sacrificing image quality when compared to imaging without the 3D hybrid profile order sequence. J. Magn. Reson. Imaging 2016;44:1346–1353.
Comparison of two models of post‐traumatic osteoarthritis; temporal degradation of articular cartilage and menisci
Authors: Fischenich Kristine M. , Button Keith D. , DeCamp Charlie , Haut Roger C. , Donahue Tammy L. Haut
Published: May 2016

The objective of this study was to compare longitudinal results from two models of combined anterior cruciate ligament (ACL) and meniscal injury. A modified ACL transection (mACLT) model and a traumatic impact (ACLF) model were used to create an ACL rupture and acute meniscal damage in a Flemish Giant animal model. The animals were euthanized at time points of 4, 8, or 12 weeks. The menisci were assessed for equilibrium and instantaneous compressive modulus, as well as glycosaminoglycan (GAG) coverage. The articular cartilage was mechanically assessed for thickness, matrix modulus, fiber modulus, and permeability. Articular cartilage GAG coverage, fissuring, tidemark integrity, and subchondral bone thickness were measured. Both models resulted in damage indicative of osteoarthritis, including decreased meniscal mechanics and GAG coverage, increased permeability and fissuring of articular cartilage, and decreased GAG coverage. The mACLT model had an early and lasting effect on the menisci mechanics and GAG coverage, while cartilage damage was not significantly affected until 12 weeks. The ACLF model resulted in an earlier change of articular cartilage GAG coverage and fissuring in both the 8 and 12 week groups. The menisci were only significantly affected at the 12 week time point in the ACLF model. We concluded the progression of post traumatic osteoarthritis was dependent on injury modality: a point to be considered in future investigations. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:486–495, 2017.
Isolation and purification of two antioxidant isomers of resveratrol dimer from the wine grape by counter‐current chromatography
Authors: Kong Qingjun , Ren Xueyan , Hu Ruilin , Yin Xuefeng , Jiang Guoshan , Pan Yuanjiang
Published: May 2016

Resveratrol dimers belong to a group of compounds called stilbenes, which along with proanthocyanidins, anthocyanins, catechins, and flavonols are natural phenolic compounds found in grapes and red wine. Stilbenes have a variety of structural isomers, all of which exhibit various biological properties. Counter‐current chromatography with a two‐phase solvent system composed of n‐hexane/ethyl acetate/methanol/water (2:5:4:5, v/v/v/v) was applied to isolate and purify stilbene from the stems of wine grape. Two isomers of resveratrol dimers trans‐ε‐viniferin and trans‐δ‐viniferin were obtained from the crude sample in a one‐step separation, with purities of 93.2 and 97.5%, respectively, as determined by high‐performance liquid chromatography. The structures of these two compounds were identified by 1H and 13C NMR spectroscopy. In addition, their antioxidant activities were assessed by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) assay. The antioxidant activities of trans‐δ‐viniferin were higher than that of trans‐ε‐viniferin in this model. This work demonstrated that counter‐current chromatography is a powerful and effective method for the isolation and purification of polyphenols from wine grape. Additionally, the DPPH radical assay showed that the isolated component trans‐δ‐viniferin exhibited stronger antioxidant activities than trans‐ε‐viniferin and a little bit weaker than vitamin E at the same concentration.
Therapeutic drug monitoring of cefepime with micellar electrokinetic capillary chromatography: Assay improvement, quality assurance, and impact on patient drug levels
Authors: Theurillat Regula , Joneli Jeannine , Wanzenried Ursula , Schiess Jeannette , Hurni Monika , Weber Thomas , Sendi Parham , Thormann Wolfgang
Published: May 2016

The improvement and performance of a micellar electrokinetic capillary chromatography assay for cefepime in human serum and plasma with a 50 μm id fused‐silica capillary elongated from 40 to 60 cm is reported. Sample preparation with dodecylsulfate protein precipitation at pH 4.5, the pH 9.1 separation medium, and the applied voltage were as reported previously [16]. The change resulted in a significant lower current, higher resolution, and increased detection time intervals. The performance of the assay with multilevel internal calibration was assessed with calibration and control samples. Quality assurance data of a 2‐year period assessed under the new conditions demonstrated the robustness of the assay. In serum samples of patients who received both cefepime and sulfamethoxazole, cefepime could not be detected due to the inseparability of the two compounds. The presence of an interference can be recognized by an increased peak width (width > 0.2 min), the appearance of a shoulder or an unresolved double peak. The patient data gathered during a 3‐year period reveal that introduction of therapeutic drug monitoring led to a 50% reduction of the median drug level. The data suggest that therapeutic drug monitoring can help to minimize the risk of major adverse reactions and to increase drug safety on an individual basis.
Chemoautotrophy and anoxygenic photosynthesis within the water column of a large meromictic tropical lake (Lake Kivu, East Africa)
Authors: Morana Cédric , Roland Fleur A. E. , Crowe Sean A. , Llirós Marc , Borges Alberto V. , Darchambeau François , Bouillon Steven
Published: May 2016

We quantified chemoautotrophic and anoxygenic photosynthetic microbial production in the water column of Lake Kivu, a permanently stratified tropical lake situated amidst volcanic activity, and aimed to identify the microorganisms involved in these processes through the analysis of their phospholipid fatty acid (PLFA) content and stable isotope (13C) labelling of PLFA in a set of incubation experiments. Data demonstrate the existence of a biogeochemically active chemoautotrophic bacterial community in the redoxcline of Lake Kivu (50–70 m). PLFA data indicate that the bacterial communities are structured vertically in the water column, with a large dissimilarity between the oxic and anoxic waters. Maximum volumetric dark CO2 fixation rates measured in Lake Kivu were in the same range as values reported from H2S‐rich marine redoxclines, such as the Black and Baltic Seas, and the Cariaco Basin. Similarly, maximal chemoautotrophic activities in Lake Kivu were observed in sulfidic waters, just below the oxycline. Anoxygenic photosynthetic production was never observed in the main basin of Lake Kivu. However, anoxygenic phototrophs largely dominated CO2 fixation in the illuminated redoxcline of Kabuno Bay, a shallower ferruginous sub‐basin. Overall, this study supports the idea that chemoautotrophs and/or anoxygenic photoautotrophs might play an important role in the flow of carbon and energy in permanently stratified tropical ecosystems. In Lake Kivu, these processes significantly contribute to organic matter biosynthesis and exert an indirect control on oxygenic photoautotrophs by shortcircuiting the vertical transport of nutrients to the illuminated and oxygenated surface waters.
Organic honey supplementation reverses pesticide‐induced genotoxicity by modulating DNA damage response
Authors: Alleva Renata , Manzella Nicola , Gaetani Simona , Ciarapica Veronica , Bracci Massimo , Caboni Maria Fiorenza , Pasini Federica , Monaco Federica , Amati Monica , Borghi Battista , Tomasetti Marco
Published: May 2016

Scope

Glyphosate (GLY) and organophosphorus insecticides such as chlorpyrifos (CPF) may cause DNA damage and cancer in exposed individuals through mitochondrial dysfunction. Polyphenols ubiquitously present in fruits and vegetables, have been viewed as antioxidant molecules, but also influence mitochondrial homeostasis. Here, honey containing polyphenol compounds was evaluated for its potential protective effect on pesticide‐induced genotoxicity.

Methods and results

Honey extracts from four floral organic sources were evaluated for their polyphenol content, antioxidant activity, and potential protective effects on pesticide‐related mitochondrial destabilization, reactive oxygen and nitrogen species formation, and DNA damage response in human bronchial epithelial and neuronal cells. The protective effect of honey was, then evaluated in a residential population chronically exposed to pesticides. The four honey types showed a different polyphenol profile associated with a different antioxidant power. The pesticide‐induced mitochondrial dysfunction parallels ROS formation from mitochondria (mtROS) and consequent DNA damage. Honey extracts efficiently inhibited pesticide‐induced mtROS formation, and reduced DNA damage by upregulation of DNA repair through NFR2. Honey supplementation enhanced DNA repair activity in a residential population chronically exposed to pesticides, which resulted in a marked reduction of pesticide‐induced DNA lesions.

Conclusion

These results provide new insight regarding the effect of honey containing polyphenols on pesticide‐induced DNA damage response.
Transcriptome analysis of bovine oocytes from distinct follicle sizes: Insights from correlation network analysis
Authors: Labrecque Rémi , Fournier Eric , Sirard Marc‐André
Published: May 2016

Follicle size is recognized as a predictor of the potential for the enclosed oocyte to yield an embryo following in vitro maturation and in vitro fertilization. Oocytes from larger follicles are more likely to reach the blastocyst stage than those from smaller follicles. A growing oocyte accumulates all the transcripts needed to ensure development until the maternal embryonic transition, and this accumulation must be completed before the period of transcriptional arrest. Accordingly, the transcriptomes of bovine germinal‐vesicle‐stage oocytes collected from follicles of increasing sizes (<3, 3–5, >5–8, and >8 mm) were evaluated, using the EmbryoGENE bovine transcriptomic platform (custom Agilent 4 × 44 K), to better understand transcriptional modulation in the oocyte as the follicle becomes larger. Microarray analyses revealed very few differences between oocytes from small follicles (<3 vs. 3–5 mm), whereas an important number of differences were detected at the mRNA level between oocytes from larger follicles. Weighted gene correlation network analysis allowed for the identification of several hub genes involved in crucial functions such as transcriptional regulation (TAF2), chromatin remodeling (PPP1CB), energy production (SLC25A31), as well as transport of key molecules within the cell (NAGPA, CYHR1, and SLC3A12). The results presented here thus reinforce the hypothesis that developmental competence acquisition cannot be seen as a simple one‐step process, especially in regards to the modulation of mRNA. Mol. Reprod. Dev. 83: 558–569, 2016. © 2016 Wiley Periodicals, Inc.
Future research in weight bias: What next?
Authors: Alberga Angela S. , Russell‐Mayhew Shelly , von Ranson Kristin M. , McLaren Lindsay , Ramos Salas Ximena , Sharma Arya M.
Published: May 2016

The 2015 Canadian Weight Bias Summit disseminated the newest research advances and brought together 40 experts, stakeholders, and policy makers in various disciplines in health, education, and public policy to identify future research directions in weight bias. In this paper we aim to share the results of the Summit as well as encourage international and interdisciplinary research collaborations in weight bias reduction. Consensus emerged on six research areas that warrant further investigation in weight bias: costs, causes, measurement, qualitative research and lived experience, interventions, and learning from other models of discrimination. These discussions highlighted three key lessons that were informed by the Summit, namely: language matters, the voices of people living with obesity should be incorporated, and interdisciplinary stakeholders should be included.
Resting and exercise energy metabolism in weight‐reduced adults with severe obesity
Authors: Hames Kazanna C. , Coen Paul M. , King Wendy C. , Anthony Steven J. , Stefanovic‐Racic Maja , Toledo Frederico G.S. , Lowery Jolene B. , Helbling Nicole L. , Dubé John J. , DeLany James P. , Jakicic John M. , Goodpaster Bret H.
Published: May 2016

Objective

To determine effects of physical activity (PA) with diet‐induced weight loss on energy metabolism in adults with severe obesity.

Methods

Adults with severe obesity (n = 11) were studied across 6 months of intervention, then compared with controls with less severe obesity (n = 7) or normal weight (n = 9). Indirect calorimetry measured energy metabolism during exercise and rest. Markers of muscle oxidation were determined by immunohistochemistry. Data were presented as medians.

Results

The intervention induced 7% weight loss (P = 0.001) and increased vigorous PA by 24 min/wk (P = 0.02). During exercise, energy expenditure decreased, efficiency increased (P ≤ 0.03), and fatty acid oxidation (FAO) did not change. Succinate dehydrogenase increased (P = 0.001), but fiber type remained the same. Post‐intervention subjects’ resting metabolism remained similar to controls. Efficiency was lower in post‐intervention subjects compared with normal‐weight controls exercising at 25 W (P ≤ 0.002) and compared with all controls exercising at 60% VO2peak (P ≤ 0.019). Resting and exercise FAO of post‐intervention subjects remained similar to adults with less severe obesity. Succinate dehydrogenase and fiber type were similar across all body weight statuses.

Conclusions

While metabolic adaptations to PA during weight loss occur in adults with severe obesity, FAO does not change. Resulting FAO during rest and exercise remains similar to adults with less severe obesity.
Cerebrospinal fluid levels of insulin, leptin, and agouti‐related protein in relation to BMI in pregnant women
Authors: Gustavsson Carolina , Andersson Hall Ulrika , Pelanis Aurimantas , Karlsson Ove I. , Andersson Louise , Svedin Pernilla , Mallard Carina , Myntti Alexandra , Andreasson Ulf , Zetterberg Henrik , Blennow Kaj , Holmäng Agneta
Published: May 2016

Objective

During pregnancy, metabolic interactions must be adapted, though neuroendocrine mechanisms for increased food intake are poorly understood. The objective of this study was to characterize differences in insulin, leptin, and agouti‐related protein (AgRP) levels in serum and cerebrospinal fluid (CSF) in pregnant women with normal weight (NW) and pregnant women with overweight (OW) or obesity (OB). Placenta as a source for increased peripheral AgRP levels during pregnancy was also investigated.

Methods

Women were recruited at admission for elective cesarean section. Insulin, AgRP, and leptin were measured in serum and CSF from 30 NW, 25 OW, and 21 OB at term. Serum during pregnancy and placenta at term were collected for further AgRP analysis.

Results

Immunohistology showed placental production of AgRP and serum AgRP levels increased throughout pregnancy. CSF AgRP, leptin, and insulin levels were higher in OW and OB than NW. Serum leptin and insulin levels were higher and AgRP lower in OB than NW.

Conclusions

High serum AgRP levels might protect from the suppressive effects of leptin during pregnancy. Pregnant women with OB and OW might further be protected from the suppressive effect of leptin by high CSF AgRP levels. Evidence was found, for the first time, of human placental AgRP production mirrored by levels in the circulation.
Biocompatible reinforcement of poly(Lactic acid) with graphene nanoplatelets
Authors: Gonçalves Carolina , Pinto Artur , Machado Ana Vera , Moreira Joaquim , Gonçalves Inês C. , Magalhães Fernão
Published: May 2016

A recently made available form of graphene nanoplatelets (GNP‐C) is investigated for the first time as reinforcement filler for PLA. GNP‐C, with thickness of about 2 nm and length 1–2 μm, was incorporated at different loadings (0.1–0.5 wt%) in poly(lactic acid) (PLA) by melt blending. The effect of varying mixing time and mixing intensity was studied and the best conditions were identified, corresponding to mixing for 20 min at 50 rpm and 180°C. Thermal analysis (differential scanning calorimetry and thermogravimetric analysis) indicated no relevant differences between pristine PLA and the composites. However, the rate of thermal degradation increased with loading, due to the dominant effect of heat transfer enhancement over mass transfer hindrance. Raman spectroscopy allowed confirming that increasing graphene loading or decreasing mixing time translates into higher nanoplatelet agglomeration, in agreement with the observed mechanical performance and scanning electron microscopy imaging of the composites. The composites exhibited maximum mechanical performance at a loading of 0.25 wt%: 20% increase in tensile strength, 12% increase in Young's modulus, and 16% increase in toughness. The incorporation of 0.25 wt% GNP‐C did not affect human fibroblasts (HFF‐1) metabolic activity or morphology. POLYM. COMPOS., 39:E308–E320, 2018. © 2016 Society of Plastics Engineers
Effects of malting conditions on enzyme activities, chemical, and bioactive compounds of sorghum starchy products as raw material for brewery
Authors: Garzón Antonela Guadalupe , Torres Roberto Luis , Drago Silvina Rosa
Published: May 2016

Two cultivars of sorghum (red, RS and white, WS) were germinated at 25 or 30°C for 1, 2, or 3 days and were evaluated regarding enzyme activities (diastatic power: DP, β‐amylase), chemical compounds (total starch, damaged starch, glucose, free amino acid), and bioactive compounds (free phenolic compounds: FPC and γ‐aminobutyric acid:GABA). For WS and RS (on third germination day at 30°C), DP was 11.3 ± 1.4 and 10.8 ± 1.3 °DP, β‐amylase activity: 33.0 ± 0.9 and 71.1 ± 0.7 UBetamyl/g d.b., respectively, while at 25°C, DP was 6.1 ± 0.7 and 18.0 ± 1.1 °DP, β‐amylase activity: 9.3 ± 0.5 and 57.8 ± 0.3 UBetamyl/g d.b., respectively. Starch degradation, free amino acids, and free glucose content increased during germination, and depended on cultivar, germination time and temperature. The hydrolysis of the protein matrix influenced the release of starch granules, which were more accessible to amylolytic action. FPC and GABA levels were higher after grain germination and depended on sorghum cultivar and germination temperature. Germination at 30°C for 3 days represented the most suitable conditions for obtaining good bio‐functional sorghum malt.
Effect of processing procedure on the formation of resistant starch in tamales
Authors: de Dios Figueroa‐Cárdenas Juan , Véles‐Medina José Juan , Esquivel‐Martínez Anaid Michelle , Mariscal‐Moreno Rosa María , Santiago‐Ramos David , Hernández‐Estrada Zorba Josué
Published: May 2016

Tamales were produced using a traditional nixtamalization process. The nixtamal was milled into masa, mixed with shortening, and boiled to prepare tamales. Enzymatic methods and DSC enthalpies were used to investigate resistant starch (RS) and starch–lipid complexes (resistant starch 5; RS5). The addition of shortening to masa showed an endotherm of lipid melting with To(m), Tp(m), and Tf(m) of approximately 40, 44, and 50°C, respectively. Processing masa by boiling at >90°C for 2 h to make tamales showed three endotherms: one related to amylopectin retrogradation (RS3), one to starch gelatinization (G), and one to Type I complex (RS5). The retrograded amylopectin presented temperatures of 49, 55, and 60°C for To(RS3), Tp(RS3), and Tf(RS3), respectively. The X‐ray diffraction pattern showed that during processing starch Type A complexed with lipids to form a Type V (RS5) amylose–lipid starch complex. The RS5 in tamales estimated by DSC affected blood glucose levels from in vivo tests.
Ways toWINat Vocabulary Learning
Authors: Goodwin Amanda P. , Cho Sun‐Joo , Nichols Sally
Published: May 2016

This teaching tip identifies ways to ‘WIN’ at vocabulary learning. Specifically, the approach conveys three morphological strategies in the mnemonic ‘WIN’. These three strategies remind students to find smaller units of meaning within bigger words, look for those units in other words that they know, and notice the context. Each strategy is described with an example. Also, ways to integrate ‘WIN’ within comprehension instruction and adapt instruction based on word difficulty are included. Overall, this teaching tip provides a framework for educators to use when designing and implementing effective word instruction.
Northern bobwhite autumn and winter food habits in restored pine–bluestem habitats
Authors: Masters Ronald E. , Montague Warren G. , Cram Douglas S.
Published: May 2016

We determined autumn and winter food habits of hunter‐harvested northern bobwhites (Colinus virginianus; n = 388) over 11 years (1998–2009) in a matrix of restored shortleaf pine–bluestem (Pinus echinata–Andropogon–Schizachyrium), and unthinned and unburned stands on the Ouachita National Forest, Arkansas, USA. Restoration treatments involved thinning of midstory hardwoods and midstory and co‐dominant shortleaf pine in a process called wildlife stand improvement (WSI). The WSI was followed by February or March prescribed burns at 3‐year intervals. Species richness of individual bobwhite crops ranged from 0 to 16 and differed among years but not months. Shortleaf pine seed, post oak (Quercus stellata) acorns, and various legume seed (Lespedeza spp., Desmodium spp.) occurred most often of 94 food categories/items (≥110 species) found in quail crops. Shortleaf pine seed had among the highest gross energy (4.58 ± 0.2 kcal/g), fat (21.8 ± 0.6%), and crude protein (31.2 ± 0.5%) of food items analyzed. Green vegetation occurred in 43.3% of all crops, the greatest of any food category, and also was high in crude protein (28.7%), but the lowest in gross energy (3.43 kcal/g). Invertebrates occurred in 35.6% of crops, but were high‐ranked items in autumn and winter diets, particularly Orthopterans (12.4%), which were greatest in crude protein (64.3%). Average dry mass of crop contents was 1.38 g ± 0.16 g. Dry mass of woody plant seeds comprised most of the diet, averaging 0.86 g ± 0.17 g/crop. Bobwhites used a wide variety of plant and invertebrate food items that require or are benefited by open canopy conditions and frequent disturbance such as prescribed fire. © 2016 The Wildlife Society.
Diabetes during pregnancy enhanced neuronal death in the hippocampus of rat offspring
Authors: Lotfi Nassim , Hami Javad , Hosseini Mehran , Haghir Delaram , Haghir Hossein
Published: May 2016

Background

Diabetes in pregnancy has a detrimental effect on central nervous system (CNS) development and is associated with an increased risk of short‐ and long‐term neurocognitive impairment in the offspring. This study aimed to investigate the effect of maternal diabetes and also insulin treatment on the numerical density of apoptotic cells in rat neonate's hippocampi during the first two postnatal weeks.

Methods

Wistar female rats were maintained diabetic from a week before gestation through parturition and their male pup's brains were collected at postnatal days (P); P0, P7 and P14, equivalent to the third trimester in human. Numerical density of total neurons and percentage of apoptotic (TUNEL‐positive) cells in different subfields of hippocampus (CA1, CA2, CA3, and DG) was calculated by stereological methods.

Results

Immediately after birth, we found a significantly decline in the total neuronal density only in hippocampal CA3 area in neonates born to diabetic animals (p < 0.0001). Moreover, the number of neurons was significantly decreased in all hippocampal sub‐regions of diabetic group pups when compared to control and insulin treated diabetic pups at both P7 and P14 (p < 0.0001 each). Nevertheless, in diabetic group, the percentage of apoptotic cells in different subfields of hippocampus were higher in all studied time‐points compared to control or insulin treated diabetic groups (p < 0.0001 each). There were no significant differences either in the total number or apoptotic cells in the different hippocampal sub‐fields between the insulin‐treated diabetic group and controls (p > 0.05).

Conclusion

Our data indicate that diabetes in pregnancy induce the neuronal cell apoptosis in offspring hippocampus. Furthermore, the maternal glycaemia control by insulin treatment in the most cases normalized these effects.
Pyoderma gangrenosum with splenic involvement
Authors: AlDossary Shaikha Jameel , AlFawaz Tariq S. , AlMutairi Awatif K.
Published: May 2016

Pyoderma gangrenosum (PG) is a non-infectious disease characterized by necrotizing, ulcerative, and painful skin. The incidence of PG is approximately 3—10 cases per million people per year. Pyoderma gangrenosum is rarely observed in children, which accounts for less than 4%, but it primarily affects adults between the ages of 25 and 54 years old without gender preference. Here, we present a case report of a 16-month-old toddler diagnosed with pyoderma gangrenous with splenic involvement. The young age of the patient and extracutaneous manifestation are of high interest.
Catheter ablation of anteroseptal accessory pathways from the aortic cusps: A case series and a review of the literature
Authors: Letsas Konstantinos P. , Efremidis Michael , Vlachos Konstantinos , Georgopoulos Stamatis , Karamichalakis Nikolaos , Saplaouras Athanasios , Xydonas Sotirios , Valkanas Kosmas , Sideris Antonios
Published: May 2016

Data regarding catheter ablation of anteroseptal accessory pathways through the aortic cusps are limited. We describe two cases of true para‐Hisian accessory pathways successfully ablated from the aortic cusps (right coronary cusp and non‐coronary cusp, respectively) along with a review of the current literature. Due to the close proximity to the atrioventricular node and the high risk of complication, mapping of the aortic cusps should always be considered in the case of anteroseptal accessory pathways. Anteroseptal accessory pathways can be safely and effectively ablated from the aortic cusps with good long‐term outcomes.
Atriofascicular pathway detection with novel ablation catheter
Authors: Shakkottai Padmanabhan , Baranchuk Adrian , Hobson Neil , Caldwell Jane
Published: May 2016

Atriofascicular pathways are a rare cause of antidromic atrioventricular reciprocating tachycardia. The IntellaTip MiFi ablation catheter (Boston Scientific, MA, USA) is a novel ablation catheter that allows enhanced signal clarity with highly localized electrograms. This is the first report of this catheter being successfully used to map and ablate the atriofascicular pathway potentials.
Red cell distribution width is associated with albuminuria in adults with familial Mediterranean fever
Authors: Uslu Ali Ugur , Yonem Ozlem , Aydin Bahattin , Uncu Tunahan , Seven Dogan , Balta Sevket , Cicekli Emre
Published: May 2016

Systematic inflammation, enhanced oxidative stress, and endothelial dysfunction are important for evolution and progression of renal damage, and they cause an increase in red cell distribution width (RDW). Familial Mediterranean fever (FMF) patients who are in the attack‐free period and its relation with albuminuria and performance on assessment of microalbuminuria. One hundred and seventy‐seven patients who had been diagnosed in accordance with Tel‐hoshmer criteria and were in the attack‐free period, and 143 age‐ and sex‐matched healthy individuals were enrolled in our study. RDW values of FMF patients were higher compared with those of the controls (13.85 ± 1.07 and 13.15 ± 0.91, respectively; p < 0.0001). RDW values of FMF patients with microalbuminuria were higher compared with those of FMF patients with normoalbuminuria and the control group (p = 0.002 and p < 0.0001, respectively). RDW values of FMF patients with normoalbuminuria were higher compared with those of the control group (p < 0.0001). We have showed RDW levels are positively correlated with albuminuria (r = 0.185, p = 0.014). When assessing microalbuminuria with RDW in the patients, a cutoff value of 13.85 with sensitivity of 60%, specificity of 62%, and p = 0.002 (area under curve: 0.651, 95% confidence interval 0.563–0.738), was observed according to receiver‐operating characteristic curve analysis. Among the various variables associated with albuminuria in multivariate logistic regression analyses, RDW remained an independent predictor of albuminuria (95% confidence interval 0.479–0.942, p = 0.021). RDW may be associated with albuminuria in FMF patients and it can be a predictor of microalbuminuria.
Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance
Authors: Paoletti Costanza , Larios Jose M. , Muñiz Maria C. , Aung Kimberly , Cannell Emily M. , Darga Elizabeth P. , Kidwell Kelley M. , Thomas Dafydd G. , Tokudome Nahomi , Brown Martha E. , Connelly Mark C. , Chianese David A. , Schott Anne F. , Henry N. Lynn , Rae James M. , Hayes Daniel F.
Published: May 2016

Fulvestrant is a dose dependent selective estrogen receptor (ER) down‐regulator (SERD) used in ER‐positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance.

Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch® system. Clinical data are limited to a subset of patients with ER‐positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N = 7) or aromatase inhibitors (AIs) (N = 10). CTCs were enumerated and phenotyped for ER and B‐cell lymphoma (BCL2) using the CellSearch® CXC kit.

In preclinical modeling, tamoxifen and AIs resulted in stabilized ER expression, whereas fulvestrant eliminated it. Five of seven patients progressing on fulvestrant had ≥5CTC/7.5 ml WB. Two of these five, treated with 500 mg/month fulvestrant, had no detectable CTC‐expression of ER and BCL2 (an ER regulated gene). Three patients had heterogeneous CTC‐ER and BCL2 expression indicating incomplete degradation of the ER target by fulvestrant. Two of these patients received 250 mg/month whereas the third patient received 500 mg/month fulvestrant. Her cancer harbored a mutation (Y537S) in the estrogen receptor alpha gene (ESR1). All seven ER positive patients progressing on AIs had heterogeneous CTC‐ER expression.

These results suggest heterogeneous mechanisms of resistance to fulvestrant, including insufficient dosage, ESR1 mutation, or conversion to dependence on non‐ER pathways. CTC enumeration, phenotyping, and genotyping might identify patients who would benefit from fulvestrant dose escalation versus switching to alternative therapies.
Avalanche Survival After Rescue With the RECCO Rescue System: A Case Report
Authors: Grasegger Katharina , Strapazzon Giacomo , Procter Emily , Brugger Hermann , Soteras Inigo
Published: May 2016

We report a case of survival of a completely buried avalanche victim after being located with the radar-based RECCO Rescue System. In the winter of 2015, 2 off-piste skiers were completely buried in an avalanche near the secured ski area in Baqueira Beret, Spain. The first victim was located with the RECCO Rescue System in less than 35 minutes and was alive and conscious at extrication. This system emits radio waves and requires a specific reflector. It is a portable device that is used by more than 600 rescue organizations worldwide, especially in secured ski areas. The device should be brought to the avalanche site together with electronic avalanche transceivers, a probing team, and avalanche dogs. In the hands of experienced professionals, the device may allow rapid location of victims not carrying an electronic avalanche transceiver. Although it is not the first successful extrication of a victim with the RECCO Rescue System, it is the first case published in the medical literature and is intended to encourage data collection and to increase our understanding of the effectiveness of this device in avalanche rescue.
The Changing Nature of Relationships at Work—A Symposium
Authors: Freedland Mark
Published: May 2016

This short note introduces a mini-symposium on the changing nature of relationships at work. The mini-symposium essentially consists of two papers by two distinguished judges who are specialists in labour law—Mr Justice Langstaff from the UK and Justice Walton from Australia. In a revised version of my chairman’s introduction to the original lectures given at University College London in April 2015, I present these two judicial authors, I reflect briefly on the topic of their papers and I welcome the comparative and empirically topical discussion which their two lectures instituted and which the two ensuing articles now continue in written and published form.
An unexpected drop in the magnetic field of the X-ray pulsar V0332+53 after the bright outburst occurred in 2015
Authors: Cusumano G. , La Parola V. , D'Aì A. , Segreto A. , Tagliaferri G. , Barthelmy S. D. , Gehrels N.
Published: May 2016

How the accreted mass settling on the surface of a neutron star affects the topology of the magnetic field and how the secular evolution of the binary system depends on the magnetic field change is still an open issue. We report evidence for a clear drop in the observed magnetic field in the accreting pulsar V0332+53 after undergoing a bright 3-month long X-ray outburst. We determine the field from the position of the fundamental cyclotron line in its X-ray spectrum and relate it to the luminosity. For equal levels of luminosity, in the declining phase we measure a systematically lower value of the cyclotron line energy with respect to the rising phase. This results in a drop of ∼1.7 × 1011 G of the observed field between the onset and the end of the outburst. The settling of the accreted plasma on to the polar cap seems to induce a distortion of the magnetic field lines weakening their intensity along the accretion columns. Therefore, the dissipation rate of the magnetic field could be much faster than previously estimated, unless the field is able to restore its original configuration on a time-scale comparable with the outbursts recurrence time.
Academic Performance in Children of Mothers With Schizophrenia and Other Severe Mental Illness, and Risk for Subsequent Development of Psychosis: A Population-Based Study
Authors: Lin Ashleigh , Di Prinzio Patsy , Young Deidra , Jacoby Peter , Whitehouse Andrew , Waters Flavie , Jablensky Assen , Morgan Vera A.
Published: May 2016

Objective

We examined the academic performance at age 12 years of children of mothers diagnosed with schizophrenia or other severe mental illness using a large whole-population birth cohort born in Western Australia. We investigated the association between academic performance and the subsequent development of psychotic illness.

Method

The sample comprised 3169 children of mothers with severe mental illness (schizophrenia, bipolar disorder, unipolar major depression, delusional disorder or other psychoses; ICD-9 codes 295–298), and 88 353 children of comparison mothers without known psychiatric morbidity. Academic performance of children was indexed on a mandatory state-wide test of reading, spelling, writing and numeracy.

Results

A larger proportion of children (43.1%) of mothers with severe mental illness performed below the acceptable standard than the reference group (30.3%; children of mothers with no known severe mental illness). After adjusting for covariates, children of mothers with any severe mental illness were more likely than the reference group to perform below-benchmark on all domains except reading. For all children, poor spelling was associated with the later development of psychosis, but particularly for those at familial risk for severe mental illness (hazard ratio [HR] = 1.81; 95% CI for HR = 1.21, 2.72).

Conclusions

Children of mothers with a severe mental illness are at increased risk for sub-standard academic achievement at age 12 years, placing these children at disadvantage for the transition to secondary school. For children with familial risk for severe mental illness, very poor spelling skills at age 12 years may be an indicator of risk for later psychotic disorder.
A plastic vegetative growth threshold governs reproductive capacity inAspergillus nidulans
Authors: Noble Luke M. , Holland Linda M. , McLachlan Alisha J. , Andrianopoulos Alex
Published: May 2016

Threshold-limited ontogenic phases separating somatic growth from reproduction are a common feature of cellular life. Long recognized for flowering plants and animals, this life-history component may also be prevalent among multicellular fungi. We establish the environmental and genetic basis of developmental competence, the capacity to respond to induction of asexual development, in the model filamentous saprotrophAspergillus nidulans. Density and pH are critical parameters for competence timing, and we identify five genes with heterochronic effects through genetic screens and candidate mutagenesis, including the conserved GTPase RasB and ambient pH sensor PalH. Inheritance of competence timing is quantitative, semi-dominant, transgressive, and extremely variable among progeny. Transcriptional profiling over competence acquisition demonstrates substantial activity in metabolic and signaling networks, highly concordant across species, and a wave of gene expression around centromeres indicative of chromatin remodeling. Competence, likely determined by species-specific endogenous hormones and metabolic capacity, governs much of biology associated with the mature fungal form – asexual and sexual reproduction, secondary metabolism, and, in some species, pathogenesis – and provides a new model for nutrient-limited life-history phases and their elaboration from unicellular origins.
On the validity and errors of the pseudo-first-order kinetics in ligand–receptor binding
Authors: Stroberg Wylie , Schnell Santiago
Published: May 2016

The simple bimolecular ligand–receptor binding interaction is often linearized by assuming pseudo-first-order kinetics when one species is present in excess. Here, a phase-plane analysis allows the derivation of a new condition for the validity of pseudo-first-order kinetics that is independent of the initial receptor concentration. The validity of the derived condition is analyzed from two viewpoints. In the first, time courses of the exact and approximate solutions to the ligand–receptor rate equations are compared when all rate constants are known. The second viewpoint assess the validity through the error induced when the approximate equation is used to estimate kinetic constants from data. Although these two interpretations of validity are often assumed to coincide, we show that they are distinct, and that large errors are possible in estimated kinetic constants, even when the linearized and exact rate equations provide nearly identical solutions.
Genomics of primary chemoresistance and remission induction failure in pediatric and adult acute myeloid leukemia
Authors: Brown Fiona C. , Cifani Paolo , Drill Esther , He Jie , Still Eric , Zhong Shan , Balasubramanian Sohail , Pavlick Dean , Yilmazel Bahar , Knapp Kristina M. , Alonzo Todd A. , Meshinchi Soheil , Stone Richard M. , Kornblau Steven M. , Marcucci Guido , Gamis Alan S. , Byrd John C. , Gonen Mithat , Levine Ross L. , Kentsis Alex
Published: May 2016

Despite intense efforts, the cure rates of children and adults with AML remain unsatisfactory in large part due to resistance to chemotherapy. Whilst cytogenetic risk stratification proved valuable in identifying causes of therapy failure and disease relapse, cytogenetically normal AML remains the most prevalent disease type, with significant heterogeneity of clinical outcomes, including primary chemoresistance. Using targeted sequencing of 670 genes recurrently mutated in hematologic malignancies, we investigated the genetic basis of primary chemotherapy resistance and remission induction failure of 107 primary cases obtained at diagnosis from children and adults with cytogenetically normal AML. Comparative analysis revealed mutations ofSETBP1, ASXL1andRELNto be significantly enriched at diagnosis in primary induction failure as compared to remission cases. In addition, this analysis revealed novel genomic alterations not previously described in AML, as well as distinct genes that are significantly overexpressed in therapy resistant AML. However, identified gene mutations were sufficient to explain only a minority of cases of primary induction failure. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in pediatric and adult acute myeloid leukemias.

Key Points

Targeted gene sequencing of 670 genes in adult and pediatric AML

Profiling of 107 primary AML samples identifies new genomic alterations for primary chemoresistance
Large-scale analysis of post-translational modifications in E. coli under glucose-limiting conditions
Authors: Brown Colin W , Sridhara Viswanadham , Boutz Daniel R , Person Maria D , Marcotte Edward M , Barrick Jeffrey E , Wilke Claus O
Published: May 2016

Background

Post-translational modification (PTM) of proteins is central to many cellular processes across all domains of life, but despite decades of study and a wealth of genomic and proteomic data the biological function of many PTMs remains unknown. This is especially true for prokaryotic PTM systems, many of which have only recently been recognized and studied in depth. It is increasingly apparent that a deep sampling of abundance across a wide range of environmental stresses, growth conditions, and PTM types, rather than simply cataloging targets for a handful of modifications, is critical to understanding the complex pathways that govern PTM deposition and downstream effects.

Results

We utilized a deeply-sampled dataset of MS/MS proteomic analysis covering 9 timepoints spanning theEscherichia coligrowth cycle and an unbiased PTM search strategy to construct a temporal map of abundance for all PTMs within a 400 Da window of mass shifts. Using this map, we are able to identify novel targets and temporal patterns for N-terminal Nα acetylation, C-terminal glutamylation, and asparagine deamidation. Furthermore, we identify a possible relationship between N-terminal Na acetylation and regulation of protein degradation in stationary phase, pointing to a previously unrecognized biological function for this poorly-understood PTM.

Conclusions

Unbiased detection of PTM in MS/MS proteomics data facilitates the discovery of novel modification types and previously unobserved dynamic changes in modification across growth timepoints.
Genetic prediction of the effectiveness of biologics for psoriasis treatment
Authors: Nishikawa Rika , Nagai Hiroshi , Bito Toshinori , Ikeda Tetsuya , Horikawa Tatsuya , Adachi Atsuko , Matsubara Tsukasa , Nishigori Chikako
Published: May 2016

Anti‐tumor necrosis factor (TNF)‐α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome‐wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti‐TNF‐α therapy using Human Omni Express‐8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti‐TNF‐α agents (strongest effect, P < 7.11E‐06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti‐TNF‐α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF‐α production, was previously reported to be associated with treatment responses to TNF‐α inhibitors.
Three hundred and eight nanometer excimer light therapy for alopecia universalis that is resistant to other treatments: A clinical study of 11 patients
Authors: Arakawa Yukiyasu , Nomiyama Tomoko , Katoh Norito
Published: May 2016

Three hundred and eight nanometer excimer light therapy has recently been reported to be effective against patchy alopecia areata (AA) in several clinical studies. However, these studies only included a few patients with severe forms of AA, and all of them exhibited poor outcomes. We further investigated the use of excimer light as a therapeutic option for cases of alopecia universalis (AU) that are resistant to other treatments. Eleven treatment‐resistant AU patients were treated with a 308‐nm excimer light at 2‐week intervals for more than 16 sessions. Four patients achieved good responses and two patients exhibited poor responses. Three patients had Japanese skin type 1 and all of them achieved good responses. The radiation dose was increased until the patients exhibited marked erythema. The patients with Japanese skin type 3 who achieved good responses exhibited strong pigmentation at the irradiated sites. In conclusion, 308‐nm excimer light therapy has significant effects on some AU patients who are resistant to other treatments and may be an alternative therapeutic option for AU. During the treatment of AU, high doses of radiation should be administrated until a strong inflammatory skin reaction is seen.