bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin ETA receptor/lipid peroxides/COX‐2/TGF‐β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats
Authors: Helmy Maged W , El‐Gowelli Hanan M , Ali Rabab M , El‐Mas Mahmoud M
Published: May 2015

Background and Purpose

Cyclosporine (CSA) and non‐steroidal anti‐inflammatory drugs (NSAIDs) are co‐prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up‐regulation of endothelin (ET) receptor signalling.

Experimental Approach

The effects of a 10 day treatment with CSA (20 mg·kg−1·day−1), indomethacin (5 mg·kg−1·day−1) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ETA receptor and COX‐2 pathways in the interaction were evaluated.

Key Results

Oral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF‐β1, and reduced immunohistochemical expressions of ETA receptors and COX‐2. CSA, but not indomethacin, increased renal ET‐1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET‐1 and decreased ETA receptor and COX‐2 expressions. Blockade of ETA receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin‐evoked reductions in the expression of ETA receptor and COX‐2 protein.

Conclusions and Implications

The exaggerated oxidative insult and associated dysregulation of the ETA receptor/COX‐2/TGF‐β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ETA receptor antagonism might be exploited therapeutically.
53BP1 suppresses epithelial–mesenchymal transition by downregulating ZEB1 through microRNA‐200b/429 in breast cancer
Authors: Kong Xiangnan , Ding Xia , Li Xiaoyan , Gao Sumei , Yang Qifeng
Published: May 2015

Epithelial–mesenchymal transition (EMT) is an important mechanism of cancer invasion and metastasis. Although p53 binding protein 1 (53BP1) has been implicated in several biological processes, its function in EMT of human cancers has not yet been reported. Here, we show that 53BP1 negatively regulated EMT by modulating ZEB1 through targeting microRNA (miR)‐200b and miR‐429. Furthermore, 53BP1 promoted ZEB1‐mediated upregulation of E‐cadherin and also inhibited the expressions of mesenchymal markers, leading to increased migration and invasion in MDA‐MB‐231 breast cancer cells. Consistently, in MCF‐7 breast cancer cells, low 53BP1 expression reduced E‐cadherin expression, resulting in increased migration and invasion. These effects were reversed by miR‐200b and miR‐429 inhibition or overexpression. Sections of tumor xenograft model showed increased ZEB1 expression and decreased E‐cadherin expression with the downregulation of 53BP1. In 18 clinical tissue samples, expression of 53BP1 was positively correlated with miR‐200b and mir‐429 and negatively correlated with ZEB1. It was also found that 53BP1 was associated with lymph node metastasis. Taken together, these results suggest that 53BP1 functioned as a tumor suppressor gene by its novel negative control of EMT through regulating the expression of miR‐200b/429 and their target gene ZEB1.
Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma
Authors: Nakao Keisuke , Tanaka Shinji , Miura Tomoya , Sato Kota , Matsumura Satoshi , Aihara Arihiro , Mitsunori Yusuke , Ban Daisuke , Ochiai Takanori , Kudo Atsushi , Arii Shigeki , Tanabe Minoru
Published: May 2015

We previously identified Aurora B kinase as the only independent factor predictive of the aggressive recurrence of hepatocellular carcinoma (HCC). In this preclinical study, JNJ‐28841072, a novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor, was evaluated for treatment of HCC. In vitro and in vivo effects of JNJ‐28841072 were analyzed using human HCC cell cultures and xenograft models. An orthotopic liver xenograft model was used for the pharmacobiological effects on Aurora kinase and vascularization in hepatic tumors. JNJ‐28841072 suppressed in vitro phosphorylation of histone H3 with induction of cell polyploidy and death in a dose‐dependent manner (IC50 = 0.8–1.2 μM). In s.c. human HCC xenografts, remarkable inhibition of tumor growth was observed after JNJ‐28841072 treatment (P = 0.0005). In orthotopic liver xenografts, the treatment with JNJ‐28841072 significantly suppressed in vivo phosphorylation of histone H3 (P = 0.0008), vessel formation (P = 0.018), normoxic area (P = 0.0001), and hepatoma growth (P = 0.038). Our preclinical studies indicate that JNJ‐28841072 is a promising novel therapeutic approach for the treatment of HCC. It might be worthy of evaluation in further studies.
Controller Design for Multi‐Skilled Bipedal Characters
Authors: Firmin M. , van de Panne M.
Published: May 2015

Developing motions for simulated humanoids remains a challenging problem. While there exists a multitude of approaches, few of these are reimplemented or reused by others. The predominant focus of papers in the area remains on algorithmic novelty, due to the difficulty and lack of incentive to more fully explore what can be accomplished within the scope of existing methodologies. We develop a language, based on common features found across physics‐based character animation research, that facilitates the controller authoring process. By specifying motion primitives over a number of phases, our language has been used to design over 25 controllers for motions ranging from simple static balanced poses, to highly dynamic stunts. Controller sequencing is supported in two ways. Naive integration of controllers is achieved by using highly stable pose controllers (such as a standing or squatting) as intermediate transitions. More complex controller connections are automatically learned through an optimization process. The robustness of our system is demonstrated via random walkthroughs of our integrated set of controllers.
Review of natural product databases
Authors: Xie Tao , Song Sicheng , Li Sijia , Ouyang Liang , Xia Lin , Huang Jian
Published: May 2015

Objectives

Many natural products have pharmacological or biological activities that can be of therapeutic benefit in treating diseases, and are also an important source of inspiration for development of potential novel drugs. The past few decades have witnessed extensive study of natural products for their promising prospects in application of medicinal chemistry, molecular biology and pharmaceutical sciences.

Materials and methods

Natural product databases have provided systematic collection of information concerning natural products and their derivatives, including structure, source and mechanisms of action, which significantly support modern drug discovery.

Results

Currently, a considerable number of natural product databases, such as TCM Database@Taiwan, TCMID, CEMTDD, SuperToxic and SuperNatural, have been developed, providing data such as integrated medicinal herbs, ingredients, 2D/3D structures of the compounds, related target proteins, relevant diseases, and metabolic toxicity and more.

Conclusions

We focus on an analytical overview of current natural product databases, and further discuss the good, bad or imperfection of current ones, in the hope of better integrating existing relevant outcomes, thus providing new routes for future drug discovery.
Public Interest in Medical Research Participation: Does It Matter if Patients or Community Members Have Helped Design the Study?
Authors: Cobb Enesha M. , Gebremariam Achamyeleh , Singer Dianne , Davis Matthew M.
Published: May 2015

Purpose

We determined national levels of public participation in medical research study design. We compared public interest in medical research participation (MRP) in studies overall, versus studies explicitly designed with public involvement.

Method

Cross‐sectional household survey of US population in June 2013. Descriptive statistics estimated participation in medical research study design. Chi‐square test compared levels of interest in MRP if respondent knew patients or community members helped design the study.

Results

Of 2,048 respondents (participation rate 60%), 5% knew someone who had helped design a medical research study. There was no association between having known someone or personal participation in study design and willingness to engage in MRP. Although the overall proportion of respondents who would consider MRP initially (51%) was similar to the proportion who would consider MRP with community member involvement in study design (49%), the changes in respondents' views across the different scenarios were significantly greater than what would have been expected by chance.

Conclusions

We found similar levels of interest in MRP whether or not the public is involved in medical research study design. This finding may indicate that public involvement in study design, like community‐based participatory research, may not affect overall rates of MRP.
Rethinking the concepts of ‘local or global processors’: evidence from Williams syndrome, Down syndrome, and Autism Spectrum Disorders
Authors: D'Souza Dean , Booth Rhonda , Connolly Monica , Happé Francesca , Karmiloff‐Smith Annette
Published: May 2015

Both Williams syndrome (WS) and Autism Spectrum Disorder (ASD) have been characterized as preferentially processing local information, whereas in Down syndrome (DS) the reported tendency is to process stimuli globally. We designed a cross‐syndrome, cross‐task comparison to reveal similarities and differences in local/global processing in these disorders. Our in‐depth study compared local/global processing across modalities (auditory‐verbal/visuo‐spatial) and levels of processing (high/low) in the three syndromes. Despite claims in the literature, participants with ASD or WS failed to show a consistent local processing bias, while those with DS failed to show a reliable global processing bias. Depending on the nature of the stimuli and the task, both local and global processing biases were evident in all three neurodevelopmental disorders. These findings indicate that individuals with neurodevelopmental disorders cannot simply be characterized as local or global processors.
Antibody biomarkers in CNS demyelinating diseases – a long and winding road
Authors: Berger T. , Reindl M.
Published: May 2015

Over several decades, studies sought potential markers to diagnose and to predict the clinical course of central nervous system (CNS) demyelinating disorders, especially in multiple sclerosis, acute disseminated encephalomyelitis and neuromyelitis optica spectrum disorders. Reliable biomarkers would ensure correct diagnoses, determine future disease evolvements, stratify patients for appropriate treatments and monitor disease activity and treatment effects – in summary, meet the longing for personalized medicine in these diseases. Out of a plethora of potential biomarker candidates antibodies have turned (again) into the scientific focus, due to pivotal immunological and neuropathological findings in the past 20 years. A major breakthrough and stimulus for further research was the identification of anti‐aquaporin‐4 antibodies in neuromyelitis optica. Various other myelin and non‐myelin antigens were investigated in detail for diagnostic and prognostic purposes, such as antibodies to myelin oligodendrocyte glycoprotein or to the potassium channel KIR4.1. Further, the use of biopharmaceutical treatments in multiple sclerosis led to intense research activities to identify anti‐treatment neutralizing antibodies and their clinical consequences. This review briefly summarizes the current knowledge on antibodies in the diagnosis, prognosis, disease and treatment monitoring of CNS demyelinating disorders.
Skin response to a carcinogen involves the xenobiotic receptor pregnane X receptor
Authors: Elentner Andreas , Ortner Daniela , Clausen Björn , Gonzalez Frank J. , Fernández‐Salguero Pedro M. , Schmuth Matthias , Dubrac Sandrine
Published: May 2015

Skin is in daily contact with potentially harmful molecules from the environment such as cigarette smoke, automobile emissions, industrial soot and groundwater. Pregnane X receptor (PXR) is a transcription factor expressed in liver and intestine that is activated by xenobiotic chemicals including drugs and environmental pollutants. Topical application of the tumor initiator 7,12‐dimethylbenz(a)anthracene (DMBA) enhances Pxr, Cyp1a1, Cyp1b1 and Cyp3a11, but not Ahr expression in the skin. Surprisingly, DMBA‐induced Pxr upregulation is largely impaired in Langerin+ cell‐depleted skin, suggesting that DMBA mainly triggers Pxr in Langerin+ cells. Furthermore, PXR deficiency protects from DNA damage in epidermal cells but to a lesser extent than aryl hydrocarbon receptor (AHR) deficiency. Interestingly, skin exposure to low doses of DMBA induces migration of PXR‐deficient but not of wild‐type and AHR‐deficient Langerhans cells (LCs). PXR‐humanized mice show a marked increase in DNA damage to epidermal cells after topical application of DMBA, demonstrating relevance of these findings in human tissue. This is the first report suggesting that carcinogens might trigger PXR in epidermal cells, particularly in LCs, thus leading to DNA damage. Further studies are required to better delineate the role of PXR in cutaneous carcinogenesis.
Global DNA hypomethylation and hypoxia‐induced expression of the ten eleven translocation (TET) family, TET1, in scleroderma fibroblasts
Authors: Hattori Mai , Yokoyama Yoko , Hattori Tomoyasu , Motegi Sei‐ichiro , Amano Hiroo , Hatada Izuho , Ishikawa Osamu
Published: May 2015

The precise mechanisms of tissue fibrosis have not yet been elucidated in systemic sclerosis (SSc). However, studies of the regulation of DNA methylation, the most widely studied epigenetic mechanism, have confirmed the involvement of the TET family proteins, recently identified DNA demethylases, in the pathogenesis of SSc. The mRNA levels of TET family members were compared in normal and SSc fibroblasts. The effects of hypoxia and siRNA specific to HIF‐1α on TET expression were also examined. Global methylation status was analysed by LUMA. The presence of 5‐hydroxymethylcytosine (5hmC) in SSc was examined by immunohistochemistry. The level of TET1 mRNA in SSc fibroblasts was elevated by 1.68 fold compared with that of normal fibroblasts, but the expression levels of TET2 and TET3 were comparable between both cell types. The expression levels of DNMT1 and DNMT3B mRNA have a tendency to elevate in SSc fibroblasts. Among TET family members, the expression of TET1 was exclusively induced by hypoxia via HIF‐1α‐independent pathways in SSc fibroblasts, but not in normal fibroblasts. The methylation level was decreased in SSc fibroblasts relative to normal fibroblasts, and 5hmC was present in dermal fibroblasts of skin sections from patients with SSc. TET1 expression in SSc fibroblasts was abnormally regulated in the hypoxic environment and accompanied by global DNA hypomethylation, suggesting the involvement of aberrant DNA methylation in the pathogenesis of SSc.
Macrozooplankton and the persistence of the deep chlorophyll maximum in a stratified lake
Authors: Pannard Alexandrine , Planas Dolors , Beisner Beatrix E.
Published: May 2015

Deep chlorophyll maxima (DCM) are common in deep, oligotrophic stratified lakes. The DCM refer to the maximal chlorophyll a concentration found at depth, and not at the lake surface. While control of the DCM is thought to be via physicochemical factors in many lakes, a role for zooplankton grazing in epilimnetic waters remains a possibility. The occurrence and dynamics of DCM are poorly documented in smaller lakes, where zooplankton grazing is likely to have a stronger structuring effect. In small, shallow stratified lakes, biological control by grazing may be magnified by the short vertical gradient and overall higher water temperature.

The respective contributions of several physical, chemical and biological parameters to the vertical distribution of phytoplankton biomass in a small stratified lake were examined. Associations between phytoplankton depth distribution and vertical gradients in temperature, light and nutrients and the density of herbivorous zooplankton were established through regressions and generalised linear models.

Colimitation of the DCM by light from above and nutrients from below was detected. A threshold was detected at 3% incident light (100 μmol photon m−2 s−1), below which the DCM disappeared. Epilimnetic biomass was related to nutrient availability, with a threshold concentration at 4 μg P L−1, below which the DCM dominated.

Greater stability of the water mass and more zooplankton were associated with higher phytoplankton biomass in the DCM. Stability is likely to have controlled vertical nutrient fluxes, which were intercepted by the metalimnetic phytoplankton. Zooplankton grazing of epilimnetic biomass could have increased incident light reaching the top of the metalimnion, thereby favouring proliferation of photosynthetic biomass in the DCM.

Wind mixing events, as detected by a reduction in Lake number (LN, a measure of the influence of wind forcing on vertical structure), induced vertical intrusions of metalimnetic water, rich in nutrients and phytoplankton, into the epilimnion. We can infer that dominance of phytoplankton in the epilimnion would have occurred earlier during the summer if grazing by zooplankton had not removed epilimnetic phytoplankton. Our results suggest that, while stable stratification is necessary for initial DCM formation, zooplankton grazing may promote the persistence of a DCM.
Impacts of nitrogen addition on plant biodiversity in mountain grasslands depend on dose, application duration and climate: a systematic review
Authors: Humbert Jean‐Yves , Dwyer John M. , Andrey Aline , Arlettaz Raphaël
Published: May 2015

Although the influence of nitrogen (N) addition on grassland plant communities has been widely studied, it is still unclear whether observed patterns and underlying mechanisms are constant across biomes. In this systematic review, we use meta‐analysis and metaregression to investigate the influence of N addition (here referring mostly to fertilization) upon the biodiversity of temperate mountain grasslands (including montane, subalpine and alpine zones). Forty‐two studies met our criteria of inclusion, resulting in 134 measures of effect size. The main general responses of mountain grasslands to N addition were increases in phytomass and reductions in plant species richness, as observed in lowland grasslands. More specifically, the analysis reveals that negative effects on species richness were exacerbated by dose (ha−1 year−1) and duration of N application (years) in an additive manner. Thus, sustained application of low to moderate levels of N over time had effects similar to short‐term application of high N doses. The climatic context also played an important role: the overall effects of N addition on plant species richness and diversity (Shannon index) were less pronounced in mountain grasslands experiencing cool rather than warm summers. Furthermore, the relative negative effect of N addition on species richness was more pronounced in managed communities and was strongly negatively related to N‐induced increases in phytomass, that is the greater the phytomass response to N addition, the greater the decline in richness. Altogether, this review not only establishes that plant biodiversity of mountain grasslands is negatively affected by N addition, but also demonstrates that several local management and abiotic factors interact with N addition to drive plant community changes. This synthesis yields essential information for a more sustainable management of mountain grasslands, emphasizing the importance of preserving and restoring grasslands with both low agricultural N application and limited exposure to N atmospheric deposition.
Conservation status assessment of Paraphlebia damselflies in Mexico
Authors: Cuevas‐Yáñez Karina , Rivas Miguel , Muñoz Jesús , Córdoba‐Aguilar Alex
Published: May 2015

We assessed the conservation status of the three Mexican Paraphlebia damselflies based on the criterion B of the Red List of the International Union for Conservation of Nature's (IUCN): P. hyalina, P. quinta, and P. zoe. According to this List, P. hyalina has not been evaluated, P. quinta appears as least concern, and P. zoe appears as Vulnerable. Geographical records were taken from literature, enquiries to specialists and field visits. We also projected the future potential geographical range area.

We generated species distribution models (SDM) for P. quinta and P. zoe (as there were not enough records for P. hyalina) as a surrogate of the extension of occurrence (EOO) and also calculated the area of occupancy. Future distributions were projected for years 2020, 2050, and, 2080 based on predicted changes in climatic conditions.

Species distribution models predicted current EOO areas for P. quinta and P. zoe as 18 860 and 16 440 km2, respectively, and around 50% of their distribution coincides with agricultural, pasture or urban sites.

Our SDM results indicate that IUCN‐based conservation status of the three species should be changed as follows: P. quinta and P. zoe moved to endangered category, and P. hyalina to data‐deficient category based on the reduced EOO areas and the historical loss of habitat.

For P. quinta, future climatic projections suggest an initial reduction (2020) followed by an expansion (2050 and 2080) in suitable areas, whereas for P. zoe there will be a decrease in predicted area for the three time periods. Preserving areas that provide shade, high humidity and perching sites seems to be a key for Paraphlebia species survival.
Western solidarity with Pussy Riot and the Twittering of cosmopolitan selves
Authors: Weij Frank , Berkers Pauwke , Engelbert Jiska
Published: May 2015

This article aims to explain the widespread attention to contemporary protesting artists among Western audiences by focusing on the case of Pussy Riot. Social movement scholarship provides a first step into understanding how Pussy Riot legitimately protests Russian politics through its punk performances. It then turns to the concept of cosmopolitanism as a performance in everyday life to explain Pussy Riot's appeal among Western audiences. By collecting and analyzing 9001 tweets through a thematic hashtag analysis and topic modeling, this article analyzes how audiences talk about Pussy Riot and shows how Twitter affords users to perform cosmopolitan selves by sharing their ideas and experiences on Pussy Riot with others. Although we distinguish between four types of cosmopolitan selves, the results clearly show Pussy Riot is mainly reflected upon in a media context: Twitter users predominantly talk about Pussy Riot's media appearances rather than readily engage with its explicit political advocacy.
Two‐sided urethra‐sparing reconstruction combining dorsal preputial skin plus ventral buccal mucosa grafts for tight bulbar strictures
Authors: Palminteri Enzo , Berdondini Elisa , Florio Mirko , Cucchiarale Giuseppina , Milan Gianluca , Valentino Francesco , Sedigh Omid , Di Pierro Giovanni B
Published: May 2015

Objectives

To report our initial experience with urethra‐sparing reconstruction combining dorsal preputial skin and ventral buccal mucosa grafts for tight bulbar urethral strictures.

Methods

Between November 2006 and September 2012, 26 patients with tight bulbar strictures underwent urethroplasty. Using a ventral urethrotomy approach, the two‐sided urethral reconstruction was carried out avoiding the transection of urethra and augmenting the preserved urethral plate by dorsal preputial skin plus ventral buccal mucosa grafts. The primary outcome was the objective urinary result, defined as the absence of stricture recurrence. The outcome was considered a failure when any postoperative instrumentation was required. Postoperative sexual dysfunctions were investigated using a validated questionnaire.

Results

Mean follow up was 30.1 months (range 12–79 months). Mean stricture length was 3.3 cm (range 1.5–6 cm). Mean length for dorsal preputial skin and ventral buccal mucosa grafts was 3.2 cm (range 2–7 cm) and 4.9 cm (range 4–6 cm), respectively. Of 26 cases, 23 (88.5%) were successful and three (11.5%) were failures with stricture recurrence. Failures were treated with perineal urethrostomy in one case, ventral buccal graft urethroplasty in one case and internal urethrotomy in one case. Among 12 sexually active men preoperatively, none reported postoperative penile curvature/shortening, impaired erection or dissatisfaction regarding erection; sexual activity was unaltered pre‐ and post‐surgery.

Conclusions

In tight bulbar urethra strictures, the two‐sided urethroplasty combining dorsal preputial skin and ventral buccal mucosa grafts provides a safe and effective semi‐circumferential reconstruction by augmenting the preserved urethral plate, with no impact on sexual function.
Haemocyanin is essential for embryonic development and survival in the migratory locust
Authors: Chen B. , Ma R. , Ma G. , Guo X. , Tong X. , Tang G. , Kang L.
Published: May 2015

Haemocyanins are commonly known as copper‐containing oxygen carriers within the haemolymph of arthropods, and have been found in many orders of insects. However, it remains unresolved why haemocyanins persist in insects that possess elaborate tracheal systems for oxygen diffusion to cells. Here we identified haemocyanins in the migratory locust Locusta migratoria that consists of two distinct subunits, Hc1 and Hc2. Genomic sequence analysis indicated that Hc1 and Hc2 have four and three gene copies, respectively, which may have evolved via gene duplication followed by divergent evolution of introns. The two subunits exhibit abundant and embryonic‐specific expression at the mRNA and protein level; their expression peaks in the mid‐term embryo and is not detectable in the late nymphal and adult stages. A larger proportion of the haemocyanins is present in the yolk compared with that in the embryo. Immunostaining shows that haemocyanins in the embryo are mainly expressed in the epidermis. Knockdown of Hc1 and Hc2 results in significant embryonic developmental delay and abnormality as well as reduced egg hatchability, ie the proportion of hatched eggs. These results reveal a previously unappreciated and fundamental role for haemocyanins in embryonic development and survival in insects, probably involving the exchange of molecules (eg O2) between the embryo and its environment.
Test ordering in an evidence free zone: Rates and associations of Australian general practice trainees’ vitamin D test ordering
Authors: Tapley Amanda , Magin Parker , Morgan Simon , Henderson Kim , Scott John , Thomson Allison , Spike Neil , McArthur Lawrie , van Driel Mieke , McElduff Patrick , Bonevski Billie
Published: May 2015

Rationale, aims and objectives

Indiscriminate health screening is increasingly seen as being problematic. In particular, vitamin D testing rates are increasing rapidly despite recommendations against population screening. The purpose of this study was to determine the level of vitamin D testing among family practice/general practitioner (GP) trainees and to establish associations of this testing.

Methods

Cross‐sectional analysis of data from the ReCEnT (Registrars Clinical Encounters in Training) cohort study. The setting was GP practices in four Australian states. Data from 60 consecutive consultations per trainee were recorded each 6‐month training term (up to four terms).

Results

Vitamin D tests were ordered in 726 (1.0%) of encounters (n = 69 412). Vitamin D test ordering was significantly associated with patients being older, female and non‐English speaking. Trainees were more likely to test if they worked in a completely bulk‐billing practice (i.e. a practice without any patient payment), if more problems were dealt with, more pathology tests were ordered in the consultation and if a lipid profile was ordered. They were less likely to test if they sought in‐consultation advice or information. The most common reasons for testing were ‘check‐up’ and ‘health maintenance’.

Conclusions

In this first report of associations of vitamin D testing in the GP setting, we found that non‐targeted vitamin D testing (testing inconsistent with current guidelines) is widespread in GP trainees’ practice. Adoption of more rational testing approaches is needed.
The RAGE receptor and its ligands are highly expressed in astrocytes in a grade‐dependant manner in the striatum and subependymal layer in Huntington's disease
Authors: Kim Joanne , Waldvogel Henry J. , Faull Richard L. M. , Curtis Maurice A. , Nicholson Louise F. B.
Published: May 2015

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of theCAGrepeat in the huntingtin gene. One of the brain changes that occurs inHDis the expression of the receptor for advanced glycation end products (RAGE), a receptor protein capable of activating multiple signalling pathways by interacting with a range of ligands leading to either beneficial or harmful effects to the cell. Here, we demonstrate in humanHDbrains a high degree of co‐localization ofRAGEwith its putative ligands S100B and N‐carboxymethyllysine (CML) in the caudate nucleus (CN) and the subependymal layer (SEL). The level of co‐staining for bothRAGE‐S100B andRAGE‐CMLwas the highest in the astrocytes but was low in neurons and microglia. The immunostaining forRAGE, S100B andCMLextended in a medio‐lateral (SEL‐CN) direction with increasing grade, such that any change in the expression and co‐localization pattern between grades was less prominent in the lateralCN. Additionally, signalling molecules that are downstream ofRAGEactivation showed changes in their activation status inHDbrains. A larger number ofRAGE‐positive astrocytic cells hadNF‐kBtranslocated to the nucleus and the level of phospho‐ERK1/2 was also increased inHDbrains. Interestingly, the level ofmDia‐1, that interacts directly with the cytoplasmic domain ofRAGE, decreased inHD. Overall, the results suggest a correlation between the functions ofRAGEand theHDpathology, but the influence ofRAGEon astrocytes and the impact of this onHDprogression requires further study.

image

RAGE (receptor for advanced glycation end products) binds multiple types of ligand to produce either neurotrophic or neurotoxic effects. Immunohistochemical staining of HD human brains showed that both RAGE and its ligands were expressed primarily in astrocytes. The pattern of staining corresponded to the grade and region‐wise pattern of neurodegeneration suggesting a possible role for RAGE in HD pathology.
Aspartate aminotransferase and free thyroid hormones in vaginal washing fluid as markers for preterm pre‐labor rupture of membranes
Authors: Farag Amr H. , Elghetany Sherif S. , Elkashif Mohamed S.
Published: May 2015

Aim

To evaluate the diagnostic value of vaginal fluid aspartate aminotransferase (AST), free triiodothyronine (T3) and free thyroxine (T4) in women with preterm pre‐labor rupture of membranes (PPROM).

Methods

A case–control study was carried out of 100 women: 50 with PPROM (study group) and 50 age‐, gestational age‐ and weight‐matched women with intact membranes (control group). All women underwent sterile speculum vaginal examination. The vaginal posterior fornix was irrigated and the retrieved fluid was sent for AST, free T3 and free T4 assays.

Results

Median vaginal fluid free T3, free T4 and AST were significantly higher in the PPROM group compared with the control group, with vaginal fluid free T4 having the largest area under the curve on receiver operating characteristic curve analysis (P<0.001). Sensitivity, specificity, positive and negative predictive values for free T3 (cut‐off, 1.06 pg/mL) were 88%, 70%, 74.6% and 85.4%, respectively, while those for free T4 (cut‐off 0.063 ng/dL) were 86%, 72%, 75.4% and 83.7%, and those for AST (4.5 IU/L) were 56%, 70%, 65.1% and 61.4%, respectively. Vaginal fluid AST had less diagnostic accuracy when compared with either free T3 or free T4.

Conclusions

Vaginal fluid AST, free T3 and free T4 seem to be useful and simple markers in diagnosis of PPROM.
The Race for Education: Class, White Tone, and Desegregated Schooling in South Africa
Authors: Hunter Mark
Published: May 2015

In the early 1990s, privileged “white” South African public schools began to admit “black” pupils. Drawing on interviews, ethnography, and archival sources related to formerly‐white schools in Durban, this article addresses two main questions: first, why did white parents so enthusiastically vote for schooling desegregation when apartheid was still in place?; and second, why, over time, did intense competition emerge between schools, and become so focused on improving sports results? In addressing these questions this study takes an historical‐geographical approach, paying particular attention to two areas of Durban: the middle‐class central Berea area and the more working‐class areas in Durban's south. This story begins in the 1950s, a period of major schooling expansion and urban segregation, tracing how a hierarchy of white schools developed in relation to the city's uneven geographies of race and class. It is this schooling hierarchy and the way it became contested in the 1990s that is key to understanding the schools' shift from “cooperative desegregation” to “aggressive competition.” More broadly, the article argues that education provides a window into key post‐apartheid tensions – namely between the deracialization of privilege, the continued dividend of whiteness, and efforts to redistribute resources to the poor. Finally, in an age of mass education, it argues that the actions of schools play an important role in shaping raced and classed divisions in society.
Direct costs of first‐generation protease inhibitors for the treatment of genotype 1 chronic hepatitis C viral infection
Authors: Sethi N. , Tapper E. B. , Vong A. , Sethi S. , Rourke M. , Afdhal N. H.
Published: May 2015

To evaluate the cost‐effectiveness of Hepatitis C therapy, robust real‐world data are needed to understand the costs and benefits of treatment alternatives. The objective of this study was to evaluate the true direct cost of treatment in an unselected sequential population of patients treated at a tertiary care centre for hepatitis C virus genotype 1. A total of 200 consecutive patients were treated with interferon, ribavirin and a first‐generation direct‐acting antiviral agent (DAA) between 2011 and 2013. A total of 41% had cirrhosis, 31% were prior relapsers, and 41% were prior partial or null responders. Costs used were wholesale acquisition cost prices for medications, average hospital costs per day for each diagnosis code based on US inpatient hospital charges. All costs were adjusted to 2013 dollars. Sustained virologic response (SVR) was achieved in 97 patients (48.5%). A total of 14% experienced relapse, 19% breakthrough or nonresponse, and 18.5% discontinued secondary to side effects. Twenty per cent of patients had at least one hospitalization attributable to a complication of therapy. Thirty‐seven per cent of patients required erythropoietin‐stimulating agents, 16% received filgastrim, and 15% needed a red blood cell transfusion. The mean overall cost of treatment was $83 851 per patient. The cost per SVR was $172 889; $266 670 for patients with cirrhosis. The costs per SVR after treatment with first‐generation DAAs are dependent on the stage of disease and therapy side effects. These real‐world costs significantly exceed those described in prior cost‐effectiveness assessments and should be used instead for future studies.
Relevance of Candida and other mycoses for morbidity and mortality in severe sepsis and septic shock due to peritonitis
Authors: Lichtenstern Christoph , Herold Christina , Mieth Markus , Brenner Thorsten , Decker Sebastian , Busch Cornelius J. , Hofer Stefan , Zimmermann Stefan , Weigand Markus A. , Bernhard Michael
Published: May 2015

This single‐centre retrospective cohort study evaluated the incidence and outcome of mycoses in critical ill patients (n = 283) with sepsis due to peritonitis. Overall mortality was 41.3%, and the 28‐day mortality was 29.3%. Fungal pathogens were found in 51.9%. The common first location was the respiratory tract (66.6%), followed by the abdominal site (19.7%). Candida colonisation was found in 64.6%, and invasive Candida infection in 34.0%. Identified fungi were Candida spp. in 98.6% and Aspergillus spp. in 6.1%. Patients with fungal pathogens showed a higher rate of postoperative peritonitis, APACHE II and tracheotomy. In comparison to patients without fungal pathogens, these patients showed a longer duration on mechanical ventilation, and a higher overall mortality. Patients with Candida‐positive swabs from abdominal sites had more fascia dehiscence and anastomosis leakage. Seventy‐two patients (48.9%) received antifungal therapy, 26 patients were treated empirically. Antifungal therapy was not associated with a decrease in mortality. Age and renal replacement therapy were associated with mortality. In conclusion, fungi are common pathogens in critically ill patients with peritonitis, and detection of fungi is associated with an increase in overall mortality. Particularly, Candida‐positive abdominal swabs are associated with an increase in morbidity. However, we were not able to demonstrate a survival benefit for antifungal therapy in peritonitis patients.
Diaries and memories following an ICU stay: a 2‐month follow‐up study
Authors: Glimelius Petersson Cecilia , Ringdal Mona , Apelqvist Gustav , Bergbom Ingegerd
Published: May 2015

Background

Many patients lack a clear recollection from their stay in the intensive care unit (ICU). Diaries have been introduced as a tool to complete memories and reduce the risk of posttraumatic stress disorder (PTSD).

Aims

To describe and compare patients' memories and PTSD in relation to having received and read or not received a diary and patients' experiences of having received and read their diary, without having discussed the contents with ICU staff.

Design

Descriptive and comparative.

Methods

Patients received their diaries at ICU discharge. After 2 months patients answered the ICU Memory Tool, a screening instrument for PTSD (PTSS‐14) and a questionnaire including space for own comments about the diaries.

Results

Of 96 patients, 52(54%) received a diary, 44 did not. Patients with diaries had significantly longer stay and more mechanical ventilation. Of these, 40 patients responded to PTSS‐14 and had evaluated and read the diary and 34 patients served as controls. No significant differences were found in presence/absence of memories between these groups. In the diary‐group patients with emotional memories had lower APACHE. Feelings of being anxious or frightened were more common in the diary‐group. At 2 months, 12% scored above cut‐off on the PTSS14 with no difference between groups. The diaries were helpful for understanding the ICU‐stay.

Conclusions

Diaries seem valuable in understanding what happened, as an act of caring and as a tool for discussion with relatives and friends. Patients valued reading their diaries. None expressed the wish to have read the diary together with a member of staff. The diary and non‐diary groups however reported similar memories.

Relevance to clinical practice

Diaries seem to be valuable in understanding what happened, giving a feeling of trust and for talking about their ICU‐stay. As many patients described stressful memories, sessions should be offered with ICU staff.
Interparental disagreement over in‐law choice
Authors: APOSTOLOU MENELAOS
Published: May 2015

Parents are influential over their children's mate choices, which raises the question of whether mothers and fathers agree when it comes to selecting spouses for their daughters and sons. Based on evolutionary reasoning, this article hypothesizes that there is interparental disagreement over in‐law choice. In particular, it is predicted that fathers are more willing than mothers to make in‐law choices so as to benefit themselves at the expense of their children. Evidence from 2 independent studies provided support for this hypothesis. Two interaction effects were also found—namely, mother–father disagreement is higher when the cost of mate selection is higher for their children than when it is lower, and disagreement more often occurs over the mate choices of daughters.
Effect of relationship status on perceptions of physical attractiveness for alternative partners
Authors: PETIT WHITNEY E. , FORD THOMAS E.
Published: May 2015

Coupled people, those in a relationship, devaluate the attractiveness of an alternative partner compared to noncoupled people (D. J. Johnson & C. E. Rusbult, 1989). The present research tested two competing hypotheses about the mechanisms underlying this phenomenon. According to the motivational hypothesis, coupled and noncoupled people initially perceive opposite‐sex others as equally attractive. Coupled people, however, recalibrate their perceptions. In contrast, the perceptual hypothesis proposes that coupled people do not perceive opposite‐sex others as attractive. The present study tested these competing hypotheses by measuring both involuntary and self‐reported perceptions of attractiveness of opposite‐sex models. Supporting the motivational hypothesis, coupled participants (n = 38) and noncoupled participants (n = 34) exhibited the same degree of pupil dilation, however, coupled participants reported lower attractiveness ratings.
Vitamin D insufficiency and deficiency in pediatric renal transplant recipients
Authors: Ebbert Kirsten , Chow Josephine , Krempien Jennifer , Matsuda‐Abedini Mina , Dionne Janis
Published: May 2015

Vitamin D deficiency is prevalent in the pediatric CKD population. Recognizing that renal transplant recipients have CKD, we assessed the prevalence of vitamin D insufficiency and deficiency in pediatric renal transplant recipients, compared to a healthy pediatric population. We prospectively studied 25(OH)D levels in 29 pediatric renal transplant recipients and 45 control patients over one yr. The overall prevalence of vitamin D insufficiency and deficiency was common in both populations, at 76% (95% CI: 61, 87%) in the pediatric renal transplant recipients and 91% (95% CI: 80, 98%) in the control group. In the paired renal transplant samples, the mean 25(OH)D level was 52.3 ± 17.9 nmol/L in the winter and 65.6 ± 18.8 nmol/L in the summer (95% CI diff.: 3.9, 22.7), in keeping with a significant seasonal difference. The mean dietary intake of vitamin D in the renal transplant recipients, assessed by three‐day dietary record, was 5.7 μg/day, with a vitamin D intake below the EAR in the majority. We did not find an association between vitamin D intake and 25(OH)D levels in this study, likely due to the low dietary intake of vitamin D within the transplant population, identifying a potential area for intervention and improvement.
Disruption of the ‘disease triangle’ by chemical and physical environmental change
Authors: Chappelka A. H. , Grulke N. E.
Published: May 2015

The physical and chemical environment of the Earth has changed rapidly over the last 100 years and is predicted to continue to change into the foreseeable future. One of the main concerns with potential alterations in climate is the propensity for increases in the magnitude and frequency of extremes to occur. Even though precipitation is predicted to increase in some locations, in others precipitation is expected to decrease and evapotranspiration increase with air temperature, resulting in exacerbated drought in the future. Chemical [ozone (O3) and other air contaminants] and subsequent physical alterations in the environment will have a profound effect on the ‘disease triangle’ (a favourable environment, a susceptible host and a virulent pathogen) and should be included in any analysis of biological response to climate change. The chemical and physical environment affects plant health and alters plant susceptibility to insect and pathogen attack through increased frequency, duration and severity of drought and reduction in host vigour. The potential effects of climate change and O3 on tree diseases with emphasis on the western United States are discussed. We describe a generalised modelling approach to incorporate the complexities of the ‘disease triangle’ into dynamic vegetation models.
Local influence analysis for Poisson autoregression with an application to stock transaction data
Authors: Zhu Fukang , Liu Shuangzhe , Shi Lei
Published: May 2015

In statistical diagnostics and sensitivity analysis, the local influence method plays an important role and has certain advantages over other methods in several situations. In this paper, we use this method to study time series of count data when employing a Poisson autoregressive model. We consider case‐weights, scale, data, and additive perturbation schemes to obtain their corresponding vectors and matrices of derivatives for the measures of slope and normal curvatures. Based on the curvature diagnostics, we take a stepwise local influence approach to deal with data with possible masking effects. Finally, our established results are illustrated to be effective by analyzing a stock transactions data set.
Glucocorticoid-induced myopathy in the intensive care unit
Authors: Eddelien Heidi Shil , Hoffmeyer Henrik Westy , Lund Eva Løbner , Lauritsen Anne Øberg
Published: May 2015

Glucocorticoids (GC) are used for intensive care unit (ICU) patients on several indications. We present a patient who was admitted to the ICU due to severe respiratory failure caused by bronchospasm requiring mechanical ventilation and treated with methylprednisolone 240 mg/day in addition to antibiotics and bronchiolytics. When the sedation was lifted on day 10, the patient was awake but quadriplegic. Blood samples revealed elevated muscle enzymes, electromyography showed myopathy, and a muscle biopsy was performed. Glucocorticoid-induced myopathy was suspected, GC treatment was tapered, and muscle strength gradually returned. The patient made full recovery from the quadriplegia a few months later.
Biosimilars in rheumatology: what the clinician should know
Authors: Castañeda-Hernández Gilberto , González-Ramírez Rodrigo , Kay Jonathan , Scheinberg Morton A
Published: May 2015

Biosimilars are now a reality in rheumatology. Although analytical and non-clinical procedures to establish similarity have evolved significantly, clinical trials demonstrating equivalent efficacy and safety are absolutely required for all biosimilars. The design of such trials, including equivalence and non-inferiority statistical approaches, are discussed. Clinical evidence on biosimilars that have been approved recently or are presently being developed for use in rheumatology is also reviewed and contrasted with that available for biomimics (or intended copies), which are non-innovator biologics that are marketed in several countries but have not undergone review according to a regulatory pathway for biosimilars.