bluuebunny/crossref_metadata_2025 huggingface dataset:
Pleomorphic Liposarcoma Arising in a Lipoleiomyosarcoma of the Uterus: Report of a Case With Genetic Profiling by a Next Generation Sequencing Panel
Authors: Schoolmeester J. Kenneth , Stamatakos Michael D. , Moyer Ann M. , Park Kay J. , Fairbairn Melissa , Fader Amanda N.
Published: November 2015

Uterine tumors with adipocytic differentiation are very uncommon. Mature adipocytes are sometimes seen as an element of smooth muscle neoplasms, more often as lipoleiomyoma, but also in the rare lipoleiomyosarcoma. Exceptional cases have been reported of various subtypes of liposarcoma associated with uterine smooth muscle tumors with or without adipocytic differentiation. We present a case of pleomorphic liposarcoma arising in a lipoleiomyosarcoma of the uterus. Genomic profiling was performed using a validated next generation sequencing panel covering 410 common cancer genes. Alterations were identified in TP53, PTEN, RB1, FAT1 and TERT. The patient's presentation and clinical course as well as the tumor's morphologic, immunohistochemical and molecular genetic findings are reviewed.
Nomogram to Predict Risk of Lymph Node Metastases in Patients With Endometrioid Endometrial Cancer
Authors: Pollom Erqi L. , Conklin Christopher M. J. , von Eyben Rie , Folkins Ann K. , Kidd Elizabeth A.
Published: November 2015

Pelvic lymphadenectomy in early-stage endometrial cancer is controversial, but the findings influence prognosis and treatment decisions. Noninvasive tools to identify women at high risk of lymph node metastasis can assist in determining the need for lymph node dissection and adjuvant treatment for patients who do not have a lymph node dissection performed initially. A retrospective review of surgical pathology was conducted for endometrioid endometrial adenocarcinoma at our institution. Univariate and multivariate logistic regression analysis of selected pathologic features were performed. A nomogram to predict for lymph node metastasis was constructed. From August 1996 to October 2013, 296 patients underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy for endometrioid endometrial adenocarcinoma. Median age at surgery was 62.7 yr (range, 24.9–93.6 yr). Median number of lymph nodes removed was 13 (range, 1–72). Of all patients, 38 (12.8%) had lymph node metastases. On univariate analysis, tumor size ≥4 cm, grade, lymphovascular space involvement, cervical stromal involvement, adnexal or serosal or parametrial involvement, positive pelvic washings, and deep (more than one half) myometrial invasion were all significantly associated with lymph node involvement. In a multivariate model, lymphovascular space involvement, deep myometrial invasion, and cervical stromal involvement remained significant predictors of nodal involvement, whereas tumor size of ≥4 cm was borderline significant. A lymph node predictive nomogram was constructed using these factors. Our nomogram can help estimate risk of nodal disease and aid in directing the need for additional surgery or adjuvant therapy in patients without lymph node surgery. Lymphovascular space involvement is the most important predictor for lymph node metastases, regardless of grade, and should be consistently assessed.
Undifferentiated Carcinoma of the Endometrium: An Expanded Immunohistochemical Analysis Including PAX-8 and Basal-Like Carcinoma Surrogate Markers
Authors: Ramalingam Preetha , Masand Ramya P. , Euscher Elizabeth D. , Malpica Anais
Published: November 2015

Undifferentiated carcinoma of the endometrium (UCAe) is an aggressive, underrecognized high-grade carcinoma that can occur either in pure form or in conjunction with low-grade endometrioid adenocarcinoma (i.e. dedifferentiated carcinoma). The typical solid growth pattern of UCAe can create a diagnostic dilemma as it is frequently misinterpreted as the solid component of an endometrial carcinoma or as a sarcoma. In addition, the high nuclear:cytoplasmic ratio, high mitotic index, and geographic necrosis are reminiscent of basal-like carcinoma of breast (BLCB). This study was undertaken to determine the role of a selected group of immunomarkers in the distinction of UCAe from other endometrial carcinomas, and assess the expression of DNA mismatch repair proteins, and surrogate BLCB immunomarkers in this type of tumor. Cases of UCAe were stained with antibodies against keratin cocktail, CK8/18, PAX-8, and estrogen receptor: 35 cases; progesterone receptor and Her-2/neu: 33 cases; CD44, e-cadherin, p16, and p53: 32 cases; and CK5/6, EGFR, and c-Kit: 18 cases. In addition, mismatch repair protein markers MLH1, MSH2, MSH6, and PMS2 were performed in 34 cases. We found that PAX-8 expression was lost in most cases (83%). In addition, estrogen and progesterone receptors were negative in 83% and 82% of cases, respectively. Seventy-seven percent of cases were positive for keratin cocktail and keratin 8/18, whereas only 11% of cases were positive for keratin 5/6. p16 was diffusely positive in 34% of cases, whereas p53 was expressed in >75% of the tumor cells in 31% of cases. MLH1 and PMS2 were concurrently lost in 50% of cases, whereas MSH2 and MSH6 were lost in 1 case (3%). E-cadherin and CD44 were completely lost in 50% of cases, whereas Her-2/neu was negative in all cases. EGFR was negative in 67% of cases, whereas 22% of cases showed diffuse membranous staining for this marker. UCAe is a high-grade carcinoma of Müllerian origin which tends to be negative for PAX-8. The loss of this marker appears to be a more reliable discriminator than the loss of keratin expression in the differential diagnosis with endometrioid carcinoma or serous carcinoma. UCAe tends to be diffusely positive for p53, but patchy positive for p16. Although UCAe appears to share not only some histologic features with BLCB, but also some of its immunohistochemical features (loss of estrogen receptor, progesterone receptor, and Her-2/neu, a tendency to loose e-cadherin and to express CD44), UCAe appears not to be related to BLCB because it usually lacks the expression EGFR, CK5/6, and c-Kit.
From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes
Authors: Brunet Thibaut , Arendt Detlev
Published: November 2015

Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization–contraction–secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an ‘emergency response’ to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory–effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system.
A flexible genetic toolkit for arthropod neurogenesis
Authors: Stollewerk Angelika
Published: November 2015

Arthropods show considerable variations in early neurogenesis. This includes the pattern of specification, division and movement of neural precursors and progenitors. In all metazoans with nervous systems, including arthropods, conserved genes regulate neurogenesis, which raises the question of how the various morphological mechanisms have emerged and how the same genetic toolkit might generate different morphological outcomes. Here I address this question by comparing neurogenesis across arthropods and show how variations in the regulation and function of the neural genes might explain this phenomenon and how they might have facilitated the evolution of the diverse morphological mechanisms of neurogenesis.
The molecular evolution of the vertebrate behavioural repertoire
Authors: Grant Seth G. N.
Published: November 2015

How the sophisticated vertebrate behavioural repertoire evolved remains a major question in biology. The behavioural repertoire encompasses the set of individual behavioural components that an organism uses when adapting and responding to changes in its external world. Although unicellular organisms, invertebrates and vertebrates share simple reflex responses, the fundamental mechanisms that resulted in the complexity and sophistication that is characteristic of vertebrate behaviours have only recently been examined. A series of behavioural genetic experiments in mice and humans support a theory that posited the importance of synapse proteome expansion in generating complexity in the behavioural repertoire. Genome duplication events, approximately 550 Ma, produced expansion in the synapse proteome that resulted in increased complexity in synapse signalling mechanisms that regulate components of the behavioural repertoire. The experiments demonstrate the importance to behaviour of the gene duplication events, the diversification of paralogues and sequence constraint. They also confirm the significance of comparative proteomic and genomic studies that identified the molecular origins of synapses in unicellular eukaryotes and the vertebrate expansion in proteome complexity. These molecular mechanisms have general importance for understanding the repertoire of behaviours in different species and for human behavioural disorders arising from synapse gene mutations.
Evolution of central pattern generators and rhythmic behaviours
Authors: Katz Paul S.
Published: November 2015

Comparisons of rhythmic movements and the central pattern generators (CPGs) that control them uncover principles about the evolution of behaviour and neural circuits. Over the course of evolutionary history, gradual evolution of behaviours and their neural circuitry within any lineage of animals has been a predominant occurrence. Small changes in gene regulation can lead to divergence of circuit organization and corresponding changes in behaviour. However, some behavioural divergence has resulted from large-scale rewiring of the neural network. Divergence of CPG circuits has also occurred without a corresponding change in behaviour. When analogous rhythmic behaviours have evolved independently, it has generally been with different neural mechanisms. Repeated evolution of particular rhythmic behaviours has occurred within some lineages due to parallel evolution or latent CPGs. Particular motor pattern generating mechanisms have also evolved independently in separate lineages. The evolution of CPGs and rhythmic behaviours shows that although most behaviours and neural circuits are highly conserved, the nature of the behaviour does not dictate the neural mechanism and that the presence of homologous neural components does not determine the behaviour. This suggests that although behaviour is generated by neural circuits, natural selection can act separately on these two levels of biological organization.
YGR042W/MTE1 Functions in Double-Strand Break Repair with MPH1
Authors: Yimit Askar , Kim TaeHyung , Anand Ranjith , Meister Sarah , Ou Jiongwen , Haber James , Zhang Zhaolei , Brown Grant W
Published: November 2015

Double-strand DNA breaks occur upon exposure of cells to agents such as ionizing radiation and ultraviolet light or indirectly through replication fork collapse at DNA damage sites. If left unrepaired double-strand breaks can cause genome instability and cell death. In response to DNA damage, proteins involved in double-strand break repair by homologous recombination re-localize into discrete nuclear foci. We identified 29 proteins that co-localize with the recombination repair protein Rad52 in response to DNA damage. Of particular interest, Ygr042w/Mte1, a protein of unknown function, showed robust colocalization with Rad52. Mte1 foci fail to form when the DNA helicase Mph1 is absent. Mte1 and Mph1 form a complex, and are recruited to double-strand breaks in vivo in a mutually dependent manner. Mte1 is important for resolution of Rad52 foci during double-strand break repair, and for suppressing break-induced replication. Together our data indicate that Mte1 functions with Mph1 in double-strand break repair.
G-quadruplex prediction in E.coli genome reveals a conserved putative G-quadruplex-Hairpin-Duplex switch
Authors: Doluca Osman , Kaplan Oktay I , Berber Burak , Hekim Nezih
Published: November 2015

Many studies show that short non-coding sequences are widely conserved among regulatory elements. More and more conserved sequences are being discovered since the development next generation sequencing technology. A common approach to identify conserved sequences with regulatory roles rely on the topological change such as hairpin formation on the DNA or RNA level. However G quadruplexes, a non-canonical nucleic acid topology with little established biological role, is rarely considered for conserved regulatory element discovery. Here we present the use of G-quadruplex prediction algorithm to identify putative G-quadruplex-forming and conserved elements in E.coli genome. Phylogenetic analysis of 52 G-quadruplex forming sequences revealed two conserved G-quadruplex motifs with potential regulatory role.
Crystal structure of (±)-(5SR,6SR)-6-ethenyl-1-[(RS)-1-phenylethoxy]-1-azaspiro[4.5]decan-2-one
Authors: Oishi Takeshi , Yamamoto Shio , Yokoyama Takashi , Kobayashi Akihiro , Sato Takaaki , Chida Noritaka
Published: November 2015

In the title compound, C19H25NO2, the pyrrolidine ring adopts an envelope form, with the spiro C atom as the flap, while the cyclohexane ring shows a chair form. A weak intramolecular C—H...O interaction supports the molecular conformation, generating anS(6) ring motif. In the crystal, pairs of C—H...O interactions connect the molecules into inversion dimers with anR22(16) ring motif. The dimers are linked by a second pair of C—H...O interactions, enclosing anR42(12) ring motif, into a tape structure along thebaxis.
Utilization of processedVigna mungoL. flour in cookies
Authors: Pasha Imran , Hussain Sehrish , Khan Muhammad Issa , Akram Nadia
Published: November 2015

Purpose

– The purpose of this paper is a study designed to utilizeVigna mungoL. (black gram) flour to improve the protein quality of wheat through supplementation. Wheat is utilized as a cereal crop all over the world, but its protein quality is inferior owing to the deficiency of amino acids like lysine.

Design/methodology/approach

– Black gram seeds were roasted and germinated and then incorporated at 10, 15 and 20 per cent level in wheat flour. The composite flour was evaluated for its chemical composition, physiochemical properties and rheological characteristics, and cookies were developed from the composite flour.

Findings

– Chemical composition of composite flour revealed significant results (p< 0.05). The level of crude protein increased from 9.69 to 11.79 per cent, while ash and crude fat content enhanced from 0.33 to 1.80 per cent and 1.13 to 2.40 per cent, respectively. There was a significant effect (p< 0.05) on the sedimentation value by the addition of black gram in wheat flour. Water absorption of composite flour was higher than control (52.21 per cent), as maximum value was observed in flour having 15 per cent germinated black gram flour (69.45 per cent). Dough development time also increased from 2.90 min to 4.80 min. The pasting properties revealed significant results for all the parameters. Cookies were developed from composite flour, and sensory evaluation has shown that addition of pulse flour at 15 per cent yields cookies with better hedonic response.

Originality/value

– The black gram is a locally grown legume crop, but there is a lack of systematic approach for its chemical composition and product development. Scientists are in urge to explore such economical and assessable food ingredients to cope with the nutritional deficiencies prevailing in the developing societies. In this regard, black gram has been recognized as a rich source of nutrients, so it can be exploited to improve wheat protein quality.
Antioxidant properties and consumer acceptability of pearl millet – tiger nut biscuits
Authors: Omoba Olufunmilayo Sade , Dada Oluwadamilola  Olamiiposi , Salawu Sule Ola
Published: November 2015

Purpose

– This paper aims to focus on the antioxidant properties and consumer acceptability of biscuits produced from pearl millet (PM)–tiger nut (TN) composite blends, with the aim of encouraging the use of these under-utilised food crops in producing value-added products with nutraceutical potential.

Design/methodology/approach

– PM grains and TN seeds were processed into flour and blended at ratios: 15:85 (A), 20:80 (B), 25:75 (C), 30:70 (D), 35:65 (E), 40:60 (F), 45:55 (G), of PM to TN using response surface methodology. The antioxidant properties of the biscuits produced from the flour blends were determined using standard methods, and data obtained were subjected to analysis of variance (ANOVA); differences of means were separated using Duncan multiple range test. The biscuits were subjected to sensory evaluation using 50 untrained panellist and results statistically analysed.

Findings

– The total phenolic content (TPC-mg/GAE) of PM–TN flour blends ranged from 2.65-4.95 (A-G), with an average TPC of 3.85. In PM–TN biscuits, total phenolic values ranged from 1.20-3.42 (A-G), with an average of 2.39. The 2,2′-azino-bis(3-ethyl benzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activities (μmolTEAC/g) of PM–TN flour blends ranged from 26.7-36.4 (A-G), and the values for biscuits ranged from 28.5-38.6 (A-G). There was a highly significant correlation, r = 0.811(p
<
0.001) and r = 0.913 (p
<
0.001) between phenolic content and antioxidant activity for flour and biscuit, respectively. The effect of in vitro digestion of biscuits on the antioxidant assays viz-a-viz: TPC and ABTS radical scavenging activities were also investigated. The order of phenolic release was enzymic
>
aqueous
>
ethanolic digest for TPC, while for ABTS, the order of release was enzymic
>
ethanolic
>
aqueous. The highest values for antioxidant properties were found in the simulated in vitro enzyme digested biscuits. Consumer acceptability revealed that the overall acceptability scores of the biscuits were not significantly different except for biscuit sample G.

Originality/value

– The paper has demonstrated the antioxidant potentials and consumer acceptability of PM–TN biscuits. It also shows the effect of in vitro digestion on the antioxidant activities of the biscuit and its potential health benefit, as a source of antioxidant.
Effective treatments for paronychia caused by oncology pharmacotherapy
Authors: Goto Hiroyuki , Yoshikawa Shusuke , Mori Keita , Otsuka Masaki , Omodaka Toshikazu , Yoshimi Kosuke , Yoshida Yuichi , Yamamoto Osamu , Kiyohara Yoshio
Published: November 2015

Cutaneous adverse events are relatively common in patients being treated with molecular‐targeted drugs. Paronychia is one of the cutaneous adverse events that influences the patient's quality of life because of pain, and it often affects anticancer treatments in severe cases. However, there are few effective treatments, especially for severe paronychia. Here, we present our experiences of treatment for paronychia due to oncology pharmacotherapy. Although we treated paronychia with various methods, only corticosteroid ointment and phenol chemical matricectomy significantly improved the paronychia. Dermatologists must perform appropriate and effective treatments for paronychia in order to enable patients to continue anticancer drug treatment without impairing their quality of life.
Clinical pharmacokinetic properties of magnesium sulphate in women with pre‐eclampsia and eclampsia
Authors: Okusanya BO , Oladapo OT , Long Q , Lumbiganon P , Carroli G , Qureshi Z , Duley L , Souza JP , Gülmezoglu AM
Published: November 2015

Background

The pharmacokinetic basis of magnesium sulphate (MgSO4) dosing regimens for eclampsia prophylaxis and treatment is not clearly established.

Objectives

To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre‐eclampsia and/or eclampsia.

Search strategy

MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies.

Selection criteria

All study types investigating pharmacokinetic properties of MgSO4 in women with pre‐eclampsia and/or eclampsia.

Data collection and analysis

Two authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens.

Main results

Twenty‐eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre‐eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65–49.00 l) but the plasma clearance was fairly similar (4.28–5.00 l/hour) across populations.

Conclusion

The profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure–response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens.

Tweetable abstract

Minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.
Multidetector CT diagnosis of non‐traumatic gastroduodenal perforation
Authors: Lee Dabee , Park Mi‐hyun , Shin Byung Seok , Jeon Gyeong Sik
Published: November 2015

Introduction

To identify reliable CT features and assess the diagnostic performance of 64‐multidetector CT (MDCT) in diagnosing non‐traumatic gastroduodenal perforation (GDP).

Methods

We retrospectively reviewed 136 CT scans of patients with surgically proven non‐traumatic gastrointestinal perforation during 7 years. 92 patients had GDP and 44 patients had other sites of perforation. CT features of perforation were evaluated and the sensitivity, specificity and likelihood ratios of each CT feature were estimated.

Results

The cause of GDP was peptic ulcer in 90 patients, gastric cancer in one patient, and foreign body of duodenal diverticulum in one patient. Extraluminal gas (97%) was most common CT feature of GDP, following by fluid or fat strand along gastroduodenum (89%), ascites (89%), wall defect and/or ulcer (84%), and wall thickening (72%). Of CT features, wall defect and/or ulcer showed the best positive likelihood ratios for GDP (36.83). Wall thickening also showed high positive likelihood ratios (10.52). Combined, these CT features showed 95% sensitivity and 93% specificity for localization of perforation site of GDP.

Conclusion

MDCT is useful in diagnosis of presence and site of GDP. Wall defect and/or ulcer and wall thickening have a high positive predictive value for localization of perforation site.
Reducing emergency CT radiation doses with simple techniques: A quality initiative project
Authors: Sulagaesuan Chakkarat , Saksobhavivat Nitima , Asavaphatiboon Sawwanee , Kaewlai Rathachai
Published: November 2015

Introduction

Use of indication‐specific CT protocols and adjustment of scan parameters to decrease radiation exposure may result in significant dose reduction. We implemented these strategies and compare pre‐ and post‐implementation radiation dose in emergency department (ED) patients.

Method

This was a descriptive, retrospective study. Patients older than 15 years who had undergone emergency CT examinations of the head, chest, abdomen, pelvis and abdominopelvic region in periods before and after dose‐reduction implementation were included. The primary outcome was volume CT dose index (CTDIvol) and dose length products (DLP).

Results

There were 786 studies in the pre‐implementation (group 1) and 955 studies in the post‐implementation (group 2) periods. Radiation dose from all CT types significantly reduced in the post‐implementation period. Average CTDIvol for head, chest, abdomen, pelvis and abdominopelvic region (doses during pre‐implementation period in parentheses) were 51.5 (109), 8.1 (30.4), 13.1 (41.8), 11 (38), 11.2 (41.8) mGy, respectively. Average DLP was also significantly lower (pre‐implementation dose in parentheses) in all CT types, which were 943 (2232), 324 (2517), 944 (5605), 280 (4024), 809 (7118) mGy●cm, respectively. Patients' age, gender, body mass index and size were not significantly different between the two groups. Image quality decreased but almost all examinations received an acceptable diagnostic subjective image quality.

Conclusion

Simple methods could help significantly reduce CT radiation exposure in ED patients while maintaining an acceptable level of diagnostic image quality.
Efficacy of diffusion‐weighted MRI in the differentiation of all liver hydatid cyst types
Authors: Koken Deniz , Cagli Bekir , Tuncel Sedat Alpaslan , Sengul Ersin , Yilmaz Erdem , Unlu Mehmet Ercument
Published: November 2015

Introduction

The aim of this study was to evaluate the efficacy of diffusion‐weighted images (DWIs) in the differentiation of hydatid cysts (HCs) of the liver.

Methods

In this prospective study, 54 patients with 92 HC lesions were evaluated. The mean apparent diffusion coefficient (ADC) values of each lesion were calculated using the ADC maps derived from the DWIs at b‐values of 50, 500 and 1000 s/mm2. We compared the mean ADC values of the different HC types, which had already been classified using the sonographic criteria. A receiver operator curve (ROC) analysis was used for determining the diagnostic performance of the ADC values of the HC types.

Results

When the mean ADC values of each type of HC were compared using each of the b‐values, no statistically significant differences were obtained between (cystic echinococcosis) CE1 and CE2 or CE3, CE2 and CE3, CE3 and CE4, or CE4 and CE5. In addition, the mean ADC values of CE1 and CE2 were significantly higher than those of CE4 and CE5. For discrimination between types CE1, CE2 and CE3, and types CE4 and CE5, the sensitivity and specificity values were, respectively, 75.9 and 89.5 for the b50 DWI, 87.0 and 86.8 for the b500 DWI, and 75.9 and 89.5 for the b1000 DWI in the ROC analysis.

Conclusion

Diffusion‐weighted imaging may be useful for providing additional data to determine the type of HC, and for differentiating types CE1, CE2 and CE3 from types CE4 and CE5.
Sex‐related variation in the vulnerability of wandering albatrosses to pelagic longline fleets
Authors: Jiménez S. , Domingo A. , Brazeiro A. , Defeo O. , Wood A. G. , Froy H. , Xavier J. C. , Phillips R. A.
Published: November 2015

The population of wandering albatrosses Diomedea exulans at South Georgia is decreasing because of bycatch in longline fisheries. Until at least the early 1990s, the survival rate of females was lower than males, consistent with the adult female‐biased bycatch reported for fisheries operating around the Brazil‐Falklands Confluence (BFC). Here we use extensive tracking data (1990–2012) from breeding birds at South Georgia to investigate overlap with longline fishing effort reported to the International Commission for the Conservation of Atlantic Tunas (ICCAT). Using data from multiple years, we conclude that breeding females are at higher risk than males from all the main pelagic longline fleets in the south‐west Atlantic. Our overlap index (based on fishing effort and bird distributions) correlated positively with numbers of ringed birds reported dead on longliners, indicating that the metric was a good proxy of bycatch risk. The consistent sex bias in overlap across years, and the likely resulting sex‐biased mortality, could account for lower adult female survival rate at the colony. The risk from fisheries changed seasonally; both sexes overlapped with pelagic longline effort during incubation (January–March), and particularly during post‐brood chick‐rearing (May–December), whereas overlap was negligible during brooding (April). The highest percentage of overlap was with the Taiwanese fleet, then vessels flagged to Brazil, Uruguay, Spain, Japan and Portugal. Females were consistently at greatest risk in the BFC region, whereas males showed lower and more variable levels of overlap with fisheries from 35 to 45°S. Our results have important implications for management of ICCAT longline fisheries and conservation of this highly threatened albatross population.
Glucocorticoid receptor but not mineralocorticoid receptor mediates the activation of ERK pathway and CREB during morphine withdrawal
Authors: Navarro‐Zaragoza Javier , Laorden M. Luisa , Milanés M. Victoria
Published: November 2015

Recent research suggests that glucocorticoids are involved in the development of addiction to drugs of abuse. They share this role with dopamine (DA), and with different signalling pathways and/or transcription factors such as extracellular‐signal regulated kinases (ERK) and cAMP response element binding protein (CREB). However, the relation between them is not completely elucidated. In this report, we further characterize the role of glucocorticoid and mineralocorticoid receptor (GR and MR) signalling in DA turnover at the Nacc, and in opiate withdrawal‐induced tyrosine hydroxylase (TH) expression, ERK and CREB phosphorylation (activation) in the nucleus of tractus solitarius (NTS‐A2). The role of GR and MR signalling was assessed with the selective GR antagonist, mifepristone or the MR antagonist, spironolactone (i.p.). Rats were implanted two morphine (or placebo) pellets. Six days later rats were pretreated with mifepristone, spironolactone or vehicle 30 min before naloxone, and DA turnover, TH expression, ERK and CREB phosphorylation, were measured using HPLC and immunoblotting. Glucocorticoid receptor blockade attenuated ERK and CREB phosphorylation and the TH expression induced by morphine withdrawal. In contrast, no changes were seen after MR blockade. Finally, GR and MR blockade did not alter the morphine withdrawal‐induced increase seen both in DA turnover and DA metabolite production, in the NAcc. These results show that not only ERK and CREB phosphorylation but also TH expression in the NTS is modulated by GR signalling. The present results suggest that GR is a therapeutic target to improve aversive events associated with opiate withdrawal.
Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long‐term cocaine self‐administration
Authors: Gao Ping , Limpens Jules H. W. , Spijker Sabine , Vanderschuren Louk J. M. J. , Voorn Pieter
Published: November 2015

The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs) implicated in transcriptional regulation, synaptic plasticity and intracellular signalling. However, little is known about how IEG expression patterns change during long‐term drug self‐administration. The present study, therefore, compares the effects of 10 and 60‐day self‐administration of cocaine and sucrose on the expression of 17 IEGs in brain regions implicated in addictive behaviour, i.e. dorsal striatum, ventral striatum and medial prefrontal cortex (mPFC). Increased expression after cocaine self‐administration was found for 6 IEGs in dorsal and ventral striatum (c‐fos, Mkp1, Fosb/ΔFosb, Egr2, Egr4, and Arc) and 10 IEGs in mPFC (same 6 IEGs as in striatum, plus Bdnf, Homer1, Sgk1 and Rgs2). Five of these 10 IEGs (Egr2, Fosb/ΔFosb, Bdnf, Homer1 and Jun) and Trkb in mPFC were responsive to long‐term sucrose self‐administration. Importantly, no major differences were found between IEG expression patterns after 10 or 60 days of cocaine self‐administration, except Fosb/ΔFosb in dorsal striatum and Egr2 in mPFC, whereas the amount of cocaine obtained per session was comparable for short‐term and long‐term self‐administration. These steady changes in IEG expression are, therefore, associated with stable self‐administration behaviour rather than the total amount of cocaine consumed. Thus, sustained impulses to IEG regulation during prolonged cocaine self‐administration may evoke neuroplastic changes underlying compulsive drug use.
Outcome of attempted vaginal delivery after a previous vacuum extraction: a population‐based study
Authors: Elvander Charlotte , Cnattingius Sven
Published: November 2015

Introduction

Few studies have investigated long‐term effects of a first vaginal instrumental delivery on subsequent mode of delivery. We investigated risks of repeat vacuum extraction and risk factors associated with a repeat vacuum extraction delivery.

Material and methods

This is a population‐based register study including 391 160 women with two consecutive singleton term (≥37 weeks) live births in cephalic presentation between/within the time period of 1992–2010 in Sweden. Rates and risk ratios of mode of delivery in second pregnancy in relation to primary mode of delivery were calculated using descriptive analyses and generalized linear models. Risk of repeat vacuum extraction was adjusted for maternal age and height, interpregnancy interval, gestational length, birthweight, induction, sex and occiput posterior position.

Results

Compared with women with a primary spontaneous vaginal delivery, women with a primary vacuum extraction had an almost five‐fold risk of vacuum extraction delivery and nearly a three‐fold risk of emergency cesarean section at second delivery. For women with a primary emergency cesarean section, corresponding risks were substantially higher. Risk factors for a repeat vacuum extraction were increasing maternal age and an interpregnancy interval >4 years, decreasing maternal stature, increasing gestation length and birthweight, induction, giving birth to a male infant and occiput posterior position.

Conclusions

Nine of ten women who attempted a vaginal birth after a primary vacuum extraction succeeded in having a spontaneous vaginal delivery at second delivery. Compared with women with a primary spontaneous vaginal delivery, women with a primary vacuum extraction were at increased risk of repeat vacuum extraction and emergency cesarean section in subsequent delivery although their risk was not as high as that of women with a primary emergency cesarean section.
A 4‐gene expression score associated with high levels of Wilms Tumor‐1 (WT1) expression is an adverse prognostic factor in acute myeloid leukaemia
Authors: Niavarani Ahmadreza , Herold Tobias , Reyal Yasmin , Sauerland Maria C. , Buchner Thomas , Hiddemann Wolfgang , Bohlander Stefan K. , Valk Peter J. M. , Bonnet Dominique
Published: November 2015

Wilms Tumor‐1 (WT1) expression level is implicated in the prognosis of acute myeloid leukaemia (AML). We hypothesized that a gene expression profile associated with WT1 expression levels might be a good surrogate marker. We identified high WT1 gene sets by comparing the gene expression profiles in the highest and lowest quartiles of WT1 expression in two large AML studies. Two high WT1 gene sets were found to be highly correlated in terms of the altered genes and expression profiles. We identified a 17‐probe set signature of the high WT1 set as the optimal prognostic predictor in the first AML set, and showed that it was able to predict prognosis in the second AML series after adjustment for European LeukaemiaNet genetic groups. The gene signature also proved to be of prognostic value in a third AML series of 163 samples assessed by RNA sequencing, demonstrating its cross‐platform consistency. This led us to derive a 4‐gene expression score, which faithfully predicted adverse outcome. In conclusion, a short gene signature associated with high WT1 expression levels and the resultant 4‐gene expression score were found to be predictive of adverse prognosis in AML. This study provides new clues to the molecular pathways underlying high WT1 states in leukaemia.
Subclonal heterogeneity in chronic lymphocytic leukaemia: revealing the importance of the lymphoid tumour microenvironment
Authors: Apollonio Benedetta , Ramsay Alan G.
Published: November 2015

The article by Giudice et al, cited in this Editorial Comment, is published in issue 172:3 (http://onlinelibrary.wiley.com/doi/10.1111/bjh.13859/abstract).
Taxation and top incomes in Canada
Authors: Milligan Kevin , Smart Michael
Published: November 2015

We estimate the elasticity of reported income with respect to tax rates for high earners using sub‐national variation across Canadian provinces. We argue this allows for better identification of tax elasticities than the existing literature. We find that elasticities of reported income at the provincial level are large for incomes in the top 1%, but small for lower earners. There are strong indications that the response happens both through earned and capital income. While our estimated elasticities are large, changes in tax rates cannot explain much of the overall long‐run trend of higher income concentration in Canada.
From the bench to clinical practice: understanding the challenges and uncertainties in immunogenicity testing for biopharmaceuticals
Authors: Gunn G R , Sealey D C F , Jamali F , Meibohm B , Ghosh S , Shankar G
Published: November 2015

Unlike conventional chemical drugs where immunogenicity typically does not occur, the development of anti-drug antibodies following treatment with biologics has led to concerns about their impact on clinical safety and efficacy. Hence the elucidation of the immunogenicity of biologics is required for drug approval by health regulatory authorities worldwide. Published ADA ‘incidence’ rates can vary greatly between same-class products and different patient populations. Such differences are due to disparate bioanalytical methods and interpretation approaches, as well as a plethora of product-specific and patient-specific factors that are not fully understood. Therefore, the incidence of ADA and their association with clinical consequences cannot be generalized across products. In this context, the intent of this review article is to discuss the complex nature of ADA and key nuances of the methodologies used for immunogenicity assessments, and to dispel some fallacies and myths.
Efficacy of neuromuscular electrical stimulation in patients with COPD followed in intensive care unit
Authors: Akar Olcay , Günay Ersin , Sarinc Ulasli Sevinc , Ulasli Alper Murat , Kacar Emre , Sariaydin Muzaffer , Solak Özlem , Celik Sefa , Ünlü Mehmet
Published: November 2015

Introduction

Serious problems on muscle strength and functional status can be seen in bedridden‐patients with chronic obstructive pulmonary diseases (COPD) receiving mechanical ventilation. We aimed to investigate the impact of active extremity mobilization and neuromuscular electrical stimulation (NMES) on weaning processes, discharge from hospital and inflammatory mediators in COPD patients receiving mechanical ventilation.

Methods

Thirty conscious COPD patients (F/M:15/15) hospitalized in the intensive care unit (ICU) with diagnosis of respiratory failure were enrolled to this study. Patients were randomized into three groups, including 10 patients for each. Active extremity‐exercise training and NMES were applied to Group‐1, only NMES was applied to Group‐2 and active extremity exercise training was applied to Group‐3. Muscle strengths, mobilization duration and weaning situation were evaluated. Serum cytokine levels were evaluated.

Results

Lower extremity muscle‐strength was significantly improved in Group‐1 (from 3.00 to 5.00, P = 0.014) and 2 (from 4.00 to 5.00, P = 0.046). Upper extremity muscle strength was also significantly improved in all three groups (from 4.00 to 5.00 for all groups, P = 0.038, P = 0.046 and P = 0.034, respectively). Duration of mobilization and discharge from the ICU were similar among groups. There was a significant decrease in serum interleukin (IL)‐6 level in Group‐1 and in serum IL‐8 level in Group‐1 and Group‐2 after rehabilitation.

Conclusion

This study indicates that pulmonary rehabilitation can prevent loss of muscle strength in ICU. Nevertheless, we consider that further studies with larger populations are needed to examine the impact of NMES and/or active and passive muscle training in bedridden ICU patients who are mechanically ventilated.
Comparative review of dipeptidyl peptidase‐4 inhibitors and sulphonylureas
Authors: Deacon C. F. , Lebovitz H. E.
Published: November 2015

Type 2 diabetes (T2DM) is a progressive disease, and pharmacotherapy with a single agent does not generally provide durable glycaemic control over the long term. Sulphonylurea (SU) drugs have a history stretching back over 60 years, and have traditionally been the mainstay choice as second‐line agents to be added to metformin once glycaemic control with metformin monotherapy deteriorates; however, they are associated with undesirable side effects, including increased hypoglycaemia risk and weight gain. Dipeptidyl peptidase (DPP)‐4 inhibitors are, by comparison, more recent, with the first compound being launched in 2006, but the class now globally encompasses at least 11 different compounds. DPP‐4 inhibitors improve glycaemic control with similar efficacy to SUs, but do not usually provoke hypoglycaemia or weight gain, are relatively free from adverse side effects, and have recently been shown not to increase cardiovascular risk in large prospective safety trials. Because of these factors, DPP‐4 inhibitors have become an established therapy for T2DM and are increasingly being positioned earlier in treatment algorithms. The present article reviews these two classes of oral antidiabetic drugs (DPP‐4 inhibitors and SUs), highlighting differences and similarities between members of the same class, as well as discussing the potential advantages and disadvantages of the two drug classes. While both classes have their merits, the choice of which to use depends on the characteristics of each individual patient; however, for the majority of patients, DPP‐4 inhibitors are now the preferred choice.
An Exploratory Evaluation of the Family Meal Intervention for Adolescent Anorexia Nervosa
Authors: Herscovici Cecile Rausch , Kovalskys Irina , Orellana Liliana
Published: November 2015

Although weight restoration is a crucial factor in the recovery of anorexia nervosa (AN), there is scarce evidence regarding which components of treatment promote it. In this paper, the author reports on an effort to utilize research methods in her own practice, with the goal of evaluating if the family meal intervention (FMI) had a positive effect on increasing weight gain or on improving other general outcome measures. Twenty‐three AN adolescents aged 12–20 years were randomly assigned to two forms of outpatient family therapy (with [FTFM] and without [FT]) using the FMI, and treated for a 6‐month duration. Their outcome was compared at the end of treatment (EOT) and at a 6‐month posttreatment follow‐up (FU). The main outcome measure was weight recovery; secondary outcome measures were the Morgan Russell Global Assessment Schedule (MRHAS), amenorrhea, general psychological symptoms, and eating disorder symptoms. The majority of the patients in both groups improved significantly at EOT, and these changes were sustained through FU. Given its primarily clinical nature, findings of this investigation project preclude any conclusion. Although the FMI did not appear to convey specific benefits in causing weight gain, clinical observation suggests the value of a flexible stance in implementation of the FMI for the severely undernourished patient with greater psychopathology.
Early Language Learning for All: Examination of a Prekindergarten French Program in an Inclusion Setting
Authors: Regalla Michele , Peker Hilal
Published: November 2015

This preliminary study examined a prekindergarten multimodal French program conducted for students in an inclusion charter school. Due to the age and varied ability levels of the students, media such as video and songs combined with kinesthetic activities served as the primary instructional approach. Data on children's ability to understand and use simple language were obtained from videorecordings as well as from vocabulary recognition and recall measures. Additional data from teacher questionnaires showed that students of all abilities developed basic communication skills in French and demonstrated enjoyment of the French program.
Variability and evolution of global land surface phenology over the past three decades (1982–2012)
Authors: Garonna Irene , de Jong Rogier , Schaepman Michael E.
Published: November 2015

Monitoring land surface phenology (LSP) is important for understanding both the responses and feedbacks of ecosystems to the climate system, and for representing these accurately in terrestrial biosphere models. Moreover, by shedding light on phenological trends at a variety of scales, LSP provides the potential to fill the gap between traditional phenological (field) observations and the large‐scale view of global models. In this study, we review and evaluate the variability and evolution of satellite‐derived growing season length (GSL) globally and over the past three decades. We used the longest continuous record of Normalized Difference Vegetation Index data available to date at global scale to derive LSP metrics consistently over all vegetated land areas and for the period 1982–2012. We tested GSL, start‐ and end‐of‐season metrics (SOS and EOS, respectively) for linear trends as well as for significant trend shifts over the study period. We evaluated trends using global environmental stratification information in place of commonly used land cover maps to avoid circular findings. Our results confirmed an average lengthening of the growing season globally during 1982–2012 – averaging 0.22–0.34 days yr−1, but with spatially heterogeneous trends. About 13–19% of global land areas displayed significant GSL change, and over 30% of trends occurred in the boreal/alpine biome of the Northern Hemisphere, which showed diverging GSL evolution over the past three decades. Within this biome, the ‘Cold and Mesic’ environmental zone appeared as an LSP change hotspot. We also examined the relative contribution of SOS and EOS to the overall changes, finding that EOS trends were generally stronger and more prevalent than SOS trends. These findings constitute a step towards the identification of large‐scale phenological drivers of vegetated land surfaces, necessary for improving phenological representation in terrestrial biosphere models.