bluuebunny/crossref_metadata_2025 huggingface dataset:
Photodynamic therapy vs. imiquimod 5% cream as skin cancer preventive strategies in patients with field changes: a randomized intraindividual comparison study
Authors: Sotiriou E. , Apalla Z. , Vrani F. , Lallas A. , Chovarda E. , Ioannides D.
Published: April 2014

Background

Actinic damage is responsible for the development of multiple, recurrent non‐melanoma skin cancers (NMSCs), including actinic keratoses (AKs). Photodynamic therapy (PDT) and imiquimod cream (IMIQ) 5% are recommended as field‐directed treatment options.

Objectives

To compare efficacy and safety of methyl aminolevulinate (MAL)‐PDT vs. IMIQ 5% in the prevention of new NMSCs development patients with field changes.

Methods

Patients with field cancerization of the face or scalp were randomized to receive MAL‐PDT on one side, and IMIQ 5% on the mirror field. The primary endpoint was the number of new lesions on the treated fields during a 12‐month follow‐up period. Secondary assessments included adverse events and patient preference.

Results

Forty‐four patients completed the study. MAL‐PDT and IMIQ did not differ concerning the primary endpoint, as there was no statistically significant difference in terms of development of new NMSCs at any point of follow‐up. Both treatment regimens were safe and well tolerated. Patients' preference based on the procedure, response rates and future choice favoured MAL‐PDT.

Conclusions

MAL‐PDT and IMIQ 5% are safe and well‐tolerated treatments that equally prevent development of new AKs in patients suffering from field changes. MAL‐PDT treatment appears to be superior in terms of patients' preference.
Natural resilience in Arctic charrSalvelinus alpinus: life history, spatial and dietary alterations along gradients of interspecific interactions
Authors: Hammar J.
Published: April 2014

The Arctic charrSalvelinus alpinusspecies complex has been shown to be exceptionally vulnerable to rapid abiotic and biotic changes.Salvelinus alpinus, however, inhabit environmental extremes ranging from lakes and rivers in the High Arctic to deep multi‐fish species lakes far outside the polar region. Long‐term responses to post‐glacial environmental variations and successively increased interspecific interactions reveal an essential degree of natural ecological resilience and phenotypic flexibility. Case studies in Scandinavia and Newfoundland illustrate the alternate trophic roles ofS. alpinus, and its flexible niche use and life‐history changes in order to regain or maintain body size in gradients of lakes with increasing fish species diversity. While allopatric in northern low‐productive upland lakes, landlocked populations are commonly structured by cannibalism. In sympatry with other fish species,S. alpinusmostly serve as prey, with their decreasing growth and body size reflecting the successive diet shift from littoral macro‐benthos to zooplankton and profundal microbenthos as interspecific competition for food and habitat intensifies. Interactions with natural and introduced superior zooplankton feeders and ultimate predators finally become detrimental. Consequently, the niche ofS. alpinusis increasingly compressed in lakes along latitudinal and altitudinal gradients, although certain natural key conditions offerS. alpinustemporary asylum in the inescapable process towards local and regional extinction. The water temperature drop during winter allowsS. alpinusto temporarily resume the richer littoral dietary and spatial niche use in low diversity lakes. In southern lowland and coastal lakes with more complex fish communities, access to key prey species such as profundal macro‐crustaceans and smeltOsmerusspp. allowS. alpinusto regain its original niche space and characteristics as a large piscivore. In conclusion,S. alpinusalong its evolutionary landscape demonstrates associated alterations of life‐history characteristics, such as body size and longevity, and thus reproductive traits demonstrating similarities between northern cannibals and southern piscivores. Although including a high degree of natural resilience, obviously differing amongS. alpinuspopulations along its range, differences seen in extreme marginal populations may have been adaptive and the product of an evolutionary response with optimized growth resulting from natural selection due to ultimate intra or inter‐specific competition and predation.
Intermittent Auscultation of the Fetal Heart Rate During Labor: An Opportunity for Shared Decision Making
Authors: Hersh Sally , Megregian Michele , Emeis Cathy
Published: April 2014

Electronic fetal heart rate monitoring is the most common form of intrapartal fetal assessment in the United States. Intermittent auscultation of the fetal heart rate is an acceptable option for low‐risk laboring women, yet it is underutilized in the hospital setting. Several expert organizations have proposed the use of intermittent auscultation as a means of promoting physiologic childbirth. Within a shared decision‐making model, the low‐risk pregnant woman should be presented with current evidence about options for fetal heart rate assessment during labor.
Additional surgical risk factors and patient characteristics for mesh erosion after abdominal sacrocolpopexy
Authors: Akyol Alpaslan , Akca Aysu , Ulker Volkan , Gedikbasi Ali , Kublay Arzu , Han Agahan , Ark Hasan Cemal , Numanoglu Ceyhun
Published: April 2014

Aim

The aim of this study is to determine the risk factors of mesh exposures following abdominal sacral colpopexy (ASC) in which polypropylene mesh is used.

Methods

This is a retrospective cohort study of patients who underwent ASC and were subsequently followed for development of mesh exposure for vaginal/vault prolapse between 2002 and 2012. Demographics and risk factors of the patients who did develop mesh exposure after ASC and the ones who did not were compared.

Results

In 42 months of survey, 19 of the 292 patients who underwent ASC developed mesh exposure. It was found that rates of patients with stage 3–4 prolapse were significantly greater in the mesh exposure group than in the control group (P = 0.04). Rates of mesh exposure were lower in patients with previous hysterectomy (P = 0.03). Also, it was found that concomitant hysterectomy or three or more additional procedures increased the risk of mesh exposure (P = 0.03 and P = 0.02).

Conclusion

In abdominal sacrocolpopexy operations in which polypropylene meshes are used, stage 3 or 4 prolapse, concomitant hysterectomy and three or more additional procedures increase the risk of mesh exposure development.
Establishing measurements of subcutaneous and visceral fat area ratio in the early second trimester by magnetic resonance imaging in obese pregnant women
Authors: Takahashi Kayo , Ohkuchi Akihide , Furukawa Rieko , Matsubara Shigeki , Suzuki Mitsuaki
Published: April 2014

Aim

Our aim was to establish measurements of subcutaneous fat area ratio (SFAR) and visceral fat area ratio (VFAR) in the early second trimester using magnetic resonance imaging (MRI) in an obese pregnant cohort.

Methods

Obesity was defined as pre‐pregnancy body mass index of 25.0 or more. One hundred and twelve obese pregnant women with a singleton pregnancy gave written informed consent between April 2007 and April 2010. For determining the most suitable MRI slice level, four women lacking MRI slices at the level of L2–3 or L3–4, and two women upon whom MRI was performed at 14 and 19 weeks were excluded, and the remaining 106 women were analyzed. We developed a novel method for calculating SFAR and VFAR at 15–18 weeks using a T1‐weighted spin echo sequence with fluid‐attenuated inversion recovery for MRI where fat shows high signal intensity.

Results

MRI slices just above the uterine fundus at 15–18 weeks of gestation never included either the fundus or liver, but the other three slices always included either the liver or the uterus. In addition, the mean value of VFAR just above the uterine fundus was significantly larger than those at L2–3, L3–4 and navel position (47.3 ± 1.1% vs 37.3 ± 1.0%, 45.1 ± 1.2%, 45.6 ± 1.2%, respectively [P < 0.001]).

Conclusion

The most suitable MRI slice level for calculating SFAR and VFAR may be just above the uterine fundus in pregnant women at 15–18 weeks of gestation. The evaluation of clinical significance of visceral adiposity for gestational diabetes mellitus is warranted.
Regulation of decidualization and angiogenesis in the human endometrium: Mini review
Authors: Okada Hidetaka , Tsuzuki Tomoko , Shindoh Hisayuu , Nishigaki Akemi , Yasuda Katsuhiko , Kanzaki Hideharu
Published: April 2014

Aim

The human endometrium is a dynamic tissue that undergoes regular cycles of menstruation, menstrual repair, proliferation and secretory differentiation in response to hypoxia and the female sex hormones.

Methods

We identified new target genes that are regulated by progesterone during the decidualization of human endometrial stromal cells (ESC), including interleukin‐15 (IL‐15), fibulin‐1 (FBLN‐1), and heart and neural crest derivatives expressed transcript 2 (HAND2).

Results

IL‐15 is deeply involved in the hormonal control of the human endometrium by progesterone and may be important in embryo implantation. FBLN‐1 has been shown to be an important extracellular matrix that mediates progesterone action in human ESC differentiation toward implantation. Moreover, progestin‐induced HAND2 is a transcription factor that contributes to the increased levels of FBLN‐1 in human ESC. Several mediators, including vascular endothelial growth factor (VEGF), angiopoietin (ANGPT) and stromal cell‐derived factor 1 (SDF‐1), regulate human endometrial angiogenesis. Hypoxia increased the expression of VEGF and decreased the expression of SDF‐1 in ESCs. Furthermore, hypoxia reduced ANGPT1 levels in ESC; however, ANGPT2 levels were unaffected. Estradiol simultaneously induced the expressions of VEGF and SDF‐1, suppressing ANGPT1 production. Therefore, hypoxia and estradiol caused an increase in the ANGPT2/ANGPT1 ratio.

Conclusion

Hypoxia and female sex hormones are involved in the regulation of angiogenic factors in an independent manner in human ESC. Analysis of the process of decidualization and angiogenesis in the human endometrium would provide useful information for the fields of reproductive biology, regenerative medicine and tissue engineering.
Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients
Authors: Raouf H. E. , Yassin A. S. , Megahed S. A. , Ashour M. S. , Mansour T. M.
Published: April 2014

Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real‐time PCR. HCV was detected by real‐time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non‐HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV‐positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV‐positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV‐positive paediatric cancer patients especially in endemic areas as Egypt.
Two‐stage model in perceptual learning: toward a unified theory
Authors: Shibata Kazuhisa , Sagi Dov , Watanabe Takeo
Published: April 2014

Training or exposure to a visual feature leads to a long‐term improvement in performance on visual tasks that employ this feature. Such performance improvements and the processes that govern them are called visual perceptual learning (VPL). As an ever greater volume of research accumulates in the field, we have reached a point where a unifying model of VPL should be sought. A new wave of research findings has exposed diverging results along three major directions in VPL: specificity versus generalization of VPL, lower versus higher brain locus of VPL, and task‐relevant versus task‐irrelevant VPL. In this review, we propose a new theoretical model that suggests the involvement of two different stages in VPL: a low‐level, stimulus‐driven stage, and a higher‐level stage dominated by task demands. If experimentally verified, this model would not only constructively unify the current divergent results in the VPL field, but would also lead to a significantly better understanding of visual plasticity, which may, in turn, lead to interventions to ameliorate diseases affecting vision and other pathological or age‐related visual and nonvisual declines.
New canine models of copper toxicosis: diagnosis, treatment, and genetics
Authors: Fieten Hille , Penning Louis C. , Leegwater Peter A.J. , Rothuizen Jan
Published: April 2014

The One Health principle recognizes that human health, animal health, and environmental health are inextricably linked. An excellent example is the study of naturally occurring copper toxicosis in dogs to help understand human disorders of copper metabolism. Besides the Bedlington terrier, where copper toxicosis is caused by a mutation in the COMMD1 gene, more complex hereditary forms of copper‐associated hepatitis were recognized recently in other dog breeds. The Labrador retriever is one such breed, where an interplay between genetic susceptibility and exposure to copper lead to clinical copper toxicosis. Purebred dog populations are ideal for gene mapping studies, and because genes involved in copper metabolism are highly conserved across species, newly identified gene mutations in the dog may help unravel the genetic complexity of different human forms of copper toxicosis. Furthermore, increasing knowledge with respect to diagnosis and treatment strategies will benefit both species.
Transcriptional profiling of human gingival fibroblasts in response to multi‐species in vitro subgingival biofilms
Authors: Belibasakis G.N. , Bao K. , Bostanci N.
Published: April 2014

Periodontitis is an infectious inflammatory disease that destroys the tooth‐supporting tissues. It is initiated by complex subgingival biofilms, triggering an inflammatory response by the juxtaposed gingival tissue. The range of transcriptional events initiated in the gingiva following biofilm challenge is not fully elucidated. By employing gene microarray technology, this study aimed to characterize the overall transcriptional changes (more than two‐fold regulation) of cultured human gingival fibroblasts in response to a 10‐species in vitro subgingival biofilm model (BF), over a challenge period of 6 h. The relative involvement of the three ‘red complex’ species in these transcriptional events was evaluated by omitting these species from the biofilm composition (BF‐RC). When compared with the unchallenged control, challenge with BF and BF‐RC differentially regulated 386 and 428 genes, respectively, with an overlap of 52–75%. Interestingly, the expression of only three genes was significantly different between the BF and BF‐RC challenged groups. There was also a strong overlap of the affected signalling pathways and gene ontology processes. These signalling pathways involved primarily the immune response, and included toll‐like receptors, interleukin‐1, interleukin‐17 and heat‐shock proteins 60 and 70. In conclusion, subgingival biofilms elicited a large number of transcriptional changes in gingival fibroblasts, while the presence of the ‘red complex’ in the biofilm did not yield any substantial differences. These findings show a uniform ‘non‐specific’ transcriptional response of host cells to subgingival biofilms, and denote that redundancies may exist in the virulence properties of individual bacterial species within a polymicrobial biofilm community.
Evaluation of a semi‐controlled test as a selection tool for frost tolerance in durum wheat (Triticum durum)
Authors: Sieber Alisa‐Naomi , Würschum Tobias , Longin Carl Friedrich Horst
Published: April 2014

Most durum wheat (Triticum durum) varieties possess only low winter hardiness due to their frost susceptibility. In North America and Central Europe, durum wheat is therefore typically sown in spring to circumvent the local winter conditions. However, the yield potential of durum in these regions could be much better exploited if durum varieties with increased frost tolerance were available, which could be sown in autumn. A factor limiting breeding for increased frost tolerance is the variation in the occurrence of frost stress across years. The ‘Weihenstephaner Auswinterungsanlage’ is a semi‐controlled test that exposes the plants to all weather conditions. Snow coverage of the plants, serving as frost protection, is prevented by the movable glass lid of the semi‐controlled test. In this study, different scorings for frost tolerance based on this semi‐controlled test were evaluated and compared with frost tolerance data in the field. Our results illustrate the potential of the ‘Weihenstephaner Auswinterungsanlage’ as an indirect selection tool for frost tolerance in durum breeding programmes, especially when regular frost tolerance data from the field are not available.
A Dynamic Disaggregation Approach to Approximate Linear Programs for Network Revenue Management
Authors: Vossen Thomas W. M. , Zhang Dan
Published: April 2014

The linear programming approach to approximate dynamic programming has received considerable attention in the recent network revenue management (RM) literature. A major challenge of the approach lies in solving the resulting approximate linear programs (ALPs), which often have a huge number of constraints and/or variables. Starting from a recently developed compact affine ALP for network RM, we develop a novel dynamic disaggregation algorithm to solve the problem, which combines column and constraint generation and exploits the structure of the underlying problem. We show that the formulation can be further tightened by considering structural properties satisfied by an optimal solution. We prove that the sum of dynamic bid‐prices across resources is concave over time. We also give a counterexample to demonstrate that the dynamic bid‐prices of individual resources are not concave in general. Numerical experiments demonstrate that dynamic disaggregation is often orders of magnitude faster than existing algorithms in the literature for problem instances with and without choice. In addition, adding the concavity constraints can further speed up the algorithm, often by an order of magnitude, for problem instances with choice.
A Sense of Powerlessness Fosters System Justification: Implications for the Legitimation of Authority, Hierarchy, and Government
Authors: van der Toorn Jojanneke , Feinberg Matthew , Jost John T. , Kay Aaron C. , Tyler Tom R. , Willer Robb , Wilmuth Caroline
Published: April 2014

In an attempt to explain the stability of hierarchy, we focus on the perspective of the powerless and how a subjective sense of dependence leads them to imbue the system and its authorities with legitimacy. In Study 1, we found in a nationally representative sample of U.S. employees that financial dependence on one's job was positively associated with the perceived legitimacy of one's supervisor. In Study 2, we observed that a general sense of powerlessness was positively correlated with the perceived legitimacy of the economic system. In Studies 3 and 4, priming experimental participants with feelings of powerlessness increased their justification of the social system, even when they were presented with system‐challenging explanations for race, class, and gender disparities. In Study 5, we demonstrated that the experience of powerlessness increased legitimation of governmental authorities (relative to baseline conditions). The processes we identify are likely to perpetuate inequality insofar as the powerless justify rather than strive to change the hierarchical structures that disadvantage them.
The Endometrium of Cycling Cows Contains Populations of Putative Mesenchymal Progenitor Cells
Authors: Cabezas J , Lara E , Pacha P , Rojas D , Veraguas D , Saravia F , Rodríguez‐Alvarez L , Castro FO
Published: April 2014

Contents

Endometrial stem cells have been identified in humans, mice and pigs. This study was designed to determine whether the uterine endometrium of cycling cows contains such cells, to identify markers of stemness and ultimately to isolate putative stem/progenitor cell and evaluate their capability to differentiate into mesodermal derivatives. Uteri from healthy cows in the early (days 1–5) and late luteal phases (days 13–18) of the oestrous cycle were collected. Total RNA and proteins were isolated and searched for gene markers of embryonic (OCT4, NANOG, SOX2) and mesenchymal (CD44, STAT3, CD‐117) stem cells and for protein markers (Oct4, Sox2, Cd44) in Western blots or immunostaining of paraffin‐embedded tissue. Primary cell cultures were isolated; characterized in terms of morphology, colony formation and gene/protein expression; and induced osteogenic and chondrogenic differentiation. We identified expression of embryonic (OCT4 and SOX2, but not NANOG) and mesenchymal (STAT3, CD44 and c‐KIT) gene markers in the endometrium of cycling cows and the encoded proteins (Oct4, Sox2 and Cd44) in both stages of the oestrous cycle. Derived cell lines displayed essentially the same gene expression pattern; however, at the protein level, Oct4 was not detected. No clear influence of the stage of the oestrous cycle was found. Cell lines from late luteal phase displayed osteogenic and chondrogenic differentiation potential upon chemical stimulation. In this research, we demonstrated the presence of mesenchymal progenitor cell populations of apparently mesenchymal origin in the endometrium of cycling cows, in both the early and late phases of the oestrous cycle. The cells isolated from the late luteal phase were more acquiescent to differentiate into mesodermal derivatives than cells in the early luteal phase. Our findings might have implications for the understanding of uterine stem cell biology in cows and other farm animal species.
Semiparametric Time Series Models with Log‐concave Innovations: Maximum Likelihood Estimation and its Consistency
Authors: Chen Yining
Published: April 2014

We study semiparametric time series models with innovations following a log‐concave distribution. We propose a general maximum likelihood framework that allows us to estimate simultaneously the parameters of the model and the density of the innovations. This framework can be easily adapted to many well‐known models, including autoregressive moving average (ARMA), generalized autoregressive conditionally heteroscedastic (GARCH), and ARMA‐GARCH models. Furthermore, we show that the estimator under our new framework is consistent in both ARMA and ARMA‐GARCH settings. We demonstrate its finite sample performance via a thorough simulation study and apply it to model the daily log‐return of the FTSE 100 index.
Technologies for increasing carbon storage in soil to mitigate climate change
Authors: Whitmore A. P. , Kirk G. J. D. , Rawlins B. G.
Published: April 2014

Means to enhance storage of carbon in soil or avoid its loss from soil are discussed and examined from the viewpoint of policy. In particular, technologies that have until now received little attention are assessed. The main means by which soil carbon might be increased are first listed. These are the following: (i) increasing the rate of input of organic matter; (ii) decreasing the rate of its decomposition by biological or chemical means; (iii) increasing the rate of its stabilization by physico‐chemical protection within aggregates and organo‐mineral complexes; and (iv) increasing the depth or more correctly the total soil volume sequestering carbon at maximum rate. Immediate gains in carbon storage might be made by switching to more perennial crops, especially grasses that, as a result of breeding, are able to put more carbon into soil. In the longer term, targets for research such as understanding the role of enzymes in carbon turnover and the exploitation of the capacity in subsoils are suggested. Increased fixation of CO2 as inorganic carbonate in soils by application of silicate wastes may have some role.
Association of IGF1R polymorphisms with the development of HBV‐related hepatocellular carcinoma
Authors: Xie H.‐Y. , Xing C.‐Y. , Wei B.‐J. , Xu X. , Wu J. , Chen L.‐M. , Cao G.‐Q. , Chen H. , Chen K.‐J. , Yin S.‐Y. , Wu L.‐M. , Zhou L. , Zheng S.‐S.
Published: April 2014

Although the involvement of insulin‐like signaling in cancer has been well documented in various types of cancers, the association between the genetic variants in the insulin‐like signaling and the development of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) remains unclear. In this study, a total of 498 individuals including 173 HBV related cirrhosis patients, 171 HBV‐related HCC patients, and 154 healthy controls were enrolled. Sixteen single nucleotide polymorphisms (SNPs) in IGF1, IGF2, IGF1R and IGF2R have been genotyped by employing SNaPshot assays. We found A/A genotype at rs3743251 of IGF1R was negatively associated with HBV related HCC [odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.20–0.72, P = 0.037]; A/G genotype decreased the risk of portal vein thrombosis (OR = 0.38, 95%CI = 0.18–0.82, P = 0.01). These results indicate that rs3743251 polymorphism in IGF1R is associated with the susceptibility of HBV‐related HCC.
Somatic mutation in acute myelogenous leukemia cells imitate novel germline HLA‐A allele: a case report
Authors: Mrazek F. , Onderkova J. , Szotkowski T. , Königova N. , Ambruzova Z. , Raida L.
Published: April 2014

A somatic mutation of the human leukocyte antigen (HLA)‐A gene revealed in tumour cells of acute myelogenous leukemia (AML) is described. A patient with AML and her siblings were routinely typed for HLA in order to find a suitable donor for haematopoietic stem cell transplantation. Sequencing‐based typing of the initial patient's sample characterized by high proportion of blasts revealed unknown G/A exchange at position 781 of the HLA‐A gene (exon 4) associated with HLA‐A*02:01 allele. Importantly, this G781A variant was completely absent in the patient's remission sample obtained after the clearance of blasts. Our results are a reminder that HLA mutations in tumour cells may interfere with routine HLA typing and should always be considered, namely, in patients with haematological malignancies.
The CTLA4 +49 A/G (rs231775) polymorphism influences susceptibility to SLE in South Indian Tamils
Authors: Devaraju P. , Gulati R. , Singh B. K. , Mithun C. B. , Negi V. S.
Published: April 2014

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with complex etiology. Loss of immune tolerance and synthesis of autoantibodies against nuclear antigens contributes to the disease. Genetic aberrations disrupting the functions of immune regulatory receptors may facilitate the development of autoimmune diseases. Cytotoxic T‐lymphocyte antigen 4 (CTLA4) is an inhibitory receptor for T cells and this study was carried out to analyze the influence of CTLA4 +49A/G (rs231775) polymorphism on susceptibility to SLE in ethnic Tamils. Three hundred SLE patients and 460 age and sex similar, ethnicity‐matched controls were screened for the +49 A/G polymorphism by real time polymerase chain reaction (PCR). The wild allele (A) frequency in controls and cases was 63% and 47%, respectively. The presence of heterozygous (AG) and homozygous mutant (GG) genotype was associated with a significant risk to develop SLE (P = 0.0001, OR‐2.29, 95% confidence interval (CI), 1.6–3.3) and (P = 0.0001, OR‐4.3, 95% CI, 2.8–6.99). The frequency of mutant allele (G) in patients was also significantly associated with SLE (P = 0.0001, OR‐1.9, 95% CI, 1.5–2.4). However, this polymorphism did not influence the clinical or serological phenotypes in our study. Therefore the CTLA4 +49 A/G polymorphism is a potential genetic risk factor for lupus susceptibility in South Indian Tamils, but does not appear to influence either the clinical or serological phenotype.
Pregnancy and spinal cord injury
Authors: Dawood Rehana , Altanis Efstathios , Ribes‐Pastor Pura , Ashworth Felicity
Published: April 2014

Key content

Pregnancy exacerbates most problems associated with spinal cord injury (SCI).

Diagnosis of labour in women with spinal cord injury above T10 of the spinal cord can be challenging.

Women with SCI should aim for a vaginal delivery.

Autonomic dysreflexia is life threatening and requires immediate treatment.

Early epidural analgesia in labour will reduce the incidence of autonomic dysreflexia.

Learning objectives

Antenatal management of women with SCI.

Care of a woman in labour.

Diagnosis and treatment of autonomic dysreflexia.

Ethical issues

Women with chronic SCI are knowledgeable about the management of their disability, at times more than the attending medical personnel. Not listening to them may undermine the confidence they have in their care.

Women with SCI are concerned that a spinal or epidural analgesia may cause further injury to their spinal cord.
Idiopathic intracranial hypertension in pregnancy
Authors: Thirumalaikumar Lakshmi , Ramalingam Kalaivani , Heafield Tom
Published: April 2014

Key content

Idiopathic intracranial hypertension is a rare condition that usually affects overweight women.

It is a diagnosis of exclusion in a pregnant woman presenting with headache.

It is important to understand the medical and surgical treatment options in pregnancy.

The mode of delivery is usually decided by obstetric factors.

The risk of visual impairment is the same in pregnant and non‐pregnant women with idiopathic intracranial hypertension.

Learning objectives

To identify how idiopathic intracranial hypertension presents in pregnancy.

To know how to monitor and manage women with this condition during pregnancy.

To understand the intrapartum, postpartum and long‐term implications of this condition.

Ethical issues

What is the extent of investigation before reaching the diagnosis of idiopathic intracranial hypertension?

Do we need a high index of suspicion in all pregnant women presenting with headache?

What is the preferred mode of delivery in idiopathic intracranial hypertension – do they all need a caesarean section?
The art of reviewing a paper
Authors: Joy Jolly , McClure Neil
Published: April 2014

Key content

As with all skills, the art of reviewing a scientific paper can be acquired, refined and perfected.

It is not only a compliment to be invited to review an article but the knowledge acquired in the process, along with the continuing professional development credits gained, makes it a valuable opportunity for the reviewer, quite apart from it being a service to the journal and the scientific community.

This article describes the basic principles and responsibilities of reviewing a medical paper.

A considered peer review gives constructive feedback to the authors, enhances the credibility and value of the journal and is a service to medical science.

Learning objectives

To understand the basic principles of reviewing a paper.

To be aware of the responsibilities of a reviewer.

To know how to write feedback for authors and the editor.

Ethical issues

Plagiarism can be committed by the reviewer or author.

Does the allegiance of the reviewer lie with the journal or the author?
Inequality, Saving and Global Imbalances: A New Theory with Evidence from OECD and Asian Countries
Authors: Gu Xinhua , Dong Baomin , Huang Bihong
Published: April 2014

Global imbalances are attributable to savings deficiency in some economies and savings glut in others. The recent global crisis has triggered widespread social conflict over income inequality. The inequality‐saving link has again become a pressing issue needing serious attention. We present a new theory to explain why the link between inequality and saving is negative in OECD countries but positive in emerging Asia. We also offer an econometric analysis of differences in inequality‐saving links between those economies. We find that aggressive financial services lead to a negative link by creating income illusion for overconsumption, but imperfect financial markets contribute to a positive link by interacting with industrial policies as part of growth strategies while ignoring liquidity constraints on consumption.
Maternal alcohol consumption in pregnancy enhances arterial stiffness and alters vasodilator function that varies between vascular beds in fetal sheep
Authors: Parkington Helena C. , Kenna Kelly R. , Sozo Foula , Coleman Harold A. , Bocking Alan , Brien James F. , Harding Richard , Walker David W. , Morley Ruth , Tare Marianne
Published: April 2014

Key points

To date, the effects of maternal alcohol consumption in pregnancy have focused on neurodevelopmental outcomes, with the impact on the arterial system poorly understood.

In this study we investigated the effects of moderate maternal alcohol consumption (∼3 standard drinks per day) in late pregnancy on the ability of arteries in the fetus to relax, and hence deliver blood, and on arterial stiffness in five important organs.

Maternal alcohol consumption in late pregnancy resulted in a marked increase in stiffness in arteries of the heart, kidney, gut, leg muscle and brain in the fetus, and this could slow contraction and relaxation and overall blood delivery.

Coronary artery endothelial vasodilator function was severely blunted as a result of alcohol exposure, while in contrast endothelium‐dependent relaxation in renal and mesenteric arteries was enhanced.

Together, the results of this study provide a warning for pregnant women and their carers that maternal consumption of ∼3 standard drinks per day, levels that do not evoke physical abnormalities or growth restriction, can dramatically alter arterial function in the fetus.

While the impact of alcohol consumption by pregnant women on fetal neurodevelopment has received much attention, the effects on the cardiovascular system are not well understood. We hypothesised that repeated exposure to alcohol (ethanol) in utero would alter fetal arterial reactivity and wall stiffness, key mechanisms leading to cardiovascular disease in adulthood. Ethanol (0.75 g (kg body weight)–1) was infused intravenously into ewes over 1 h daily for 39 days in late pregnancy (days 95–133 of pregnancy, term ∼147 days). Maternal and fetal plasma ethanol concentrations at the end of the hour were ∼115 mg dl−1, and then declined to apparent zero over 8 h. At necropsy (day 134), fetal body weight and fetal brain–body weight ratio were not affected by alcohol infusion. Small arteries (250–300 μm outside diameter) from coronary, renal, mesenteric, femoral (psoas) and cerebral beds were isolated. Endothelium‐dependent vasodilatation sensitivity was reduced 10‐fold in coronary resistance arteries, associated with a reduction in endothelial nitric oxide synthase mRNA (P = 0.008). Conversely, vasodilatation sensitivity was enhanced 10‐fold in mesenteric and renal resistance arteries. Arterial stiffness was markedly increased (P = 0.0001) in all five vascular beds associated with an increase in elastic modulus and, in cerebral vessels, with an increase in collagen Iα mRNA. Thus, we show for the first time that fetal arteries undergo marked and regionally variable adaptations as a consequence of repeated alcohol exposure. These alcohol‐induced vascular effects occurred in the apparent absence of fetal physical abnormalities or fetal growth restriction.
The role of hydrogen sulphide in the control of breathing in hypoxic zebrafish (Danio rerio)
Authors: Porteus Cosima S. , Abdallah Sara J. , Pollack Jacob , Kumai Yusuke , Kwong Raymond W. M. , Yew Hong M. , Milsom William K. , Perry Steve F.
Published: April 2014

Key points

Hydrogen sulphide (H2S), a gaseous neurotransmitter, is involved in oxygen sensing in glomus cells, which are oxygen‐sensing cells found in the mammalian carotid body.

Neuroepithelial cells (NECs) are oxygen‐sensing cells of fish and are thought to be phylogenetic precursors of mammalian glomus cells; however, the oxygen‐sensing mechanisms of these cells remain largely unknown.

Both adult and larval zebrafish responded to exogenous H2S by increasing ventilation in a dose‐dependent manner; H2S increased intracellular [Ca2+] in NECs.

Inhibiting endogenous H2S production decreased or abolished the ventilatory response to hypoxia in both adult and larval zebrafish.

The results demonstrate an important role for H2S in oxygen sensing in zebrafish.

The current study investigated the role of hydrogen sulphide (H2S) in oxygen sensing, intracellular signalling and promotion of ventilatory responses to hypoxia in adult and larval zebrafish (Danio rerio). Both larval and adult zebrafish exhibited a dose‐dependent increase in ventilation to sodium sulphide (Na2S), an H2S donor. In vertebrates, cystathionine β‐synthase (CBS) and cystathionine γ‐lyase (CSE) are enzymes that catalyse the endogenous production of H2S. In adult zebrafish, inhibition of both CBS and CSE with aminooxyacetate (AOA) and propargyl glycine (PPG) blunted or abolished the hypoxic hyperventilation, and the addition of Na2S to the water partially rescued the effects of inhibiting endogenous H2S production. In zebrafish larvae (4 days post‐fertilization), gene knockdown of either CBS or CSE using morpholinos attenuated the hypoxic ventilatory response. Furthermore, the intracellular calcium concentration of isolated neuroepithelial cells (NECs), which are putative oxygen chemoreceptors, increased significantly when these cells were exposed to 50 μm Na2S, supporting a role for H2S in Ca2+‐evoked neurotransmitter release in these cells. Finally, immunohistochemical labelling showed that NECs dissociated from adult gill contained CBS and CSE, whereas cutaneous NECs in larval zebrafish expressed only CSE. Taken together, these data show that H2S can be produced in the putative oxygen‐sensing cells of zebrafish, the NECs, in which it appears to play a pivotal role in promoting the hypoxic ventilatory response.
Autonomic neural control of heart rate during dynamic exercise: revisited
Authors: White Daniel W. , Raven Peter B.
Published: April 2014

The accepted model of autonomic control of heart rate (HR) during dynamic exercise indicates that the initial increase is entirely attributable to the withdrawal of parasympathetic nervous system (PSNS) activity and that subsequent increases in HR are entirely attributable to increases in cardiac sympathetic activity. In the present review, we sought to re‐evaluate the model of autonomic neural control of HR in humans during progressive increases in dynamic exercise workload. We analysed data from both new and previously published studies involving baroreflex stimulation and pharmacological blockade of the autonomic nervous system. Results indicate that the PSNS remains functionally active throughout exercise and that increases in HR from rest to maximal exercise result from an increasing workload‐related transition from a 4 : 1 vagal–sympathetic balance to a 4 : 1 sympatho–vagal balance. Furthermore, the beat‐to‐beat autonomic reflex control of HR was found to be dependent on the ability of the PSNS to modulate the HR as it was progressively restrained by increasing workload‐related sympathetic nerve activity. In conclusion: (i) increases in exercise workload‐related HR are not caused by a total withdrawal of the PSNS followed by an increase in sympathetic tone; (ii) reciprocal antagonism is key to the transition from vagal to sympathetic dominance, and (iii) resetting of the arterial baroreflex causes immediate exercise‐onset reflexive increases in HR, which are parasympathetically mediated, followed by slower increases in sympathetic tone as workloads are increased.
Wave reflections in the pulmonary arteries analysed with the reservoir–wave model
Authors: Bouwmeester J. Christopher , Belenkie Israel , Shrive Nigel G. , Tyberg John V.
Published: April 2014

Key points

In the pulmonary artery, we use the reservoir–wave model to separate the effects of a charging and discharging, elastic arterial reservoir from the effects of waves created by the contracting and relaxing heart.

Wave intensity analysis quantifies the effects of waves that cause changes in pressure and flow and precisely identifies when waves created by the heart and reflections of these waves start and end.

We show that negative wave reflections arise from the junction of lobar arteries stemming from the left and right pulmonary arteries.

When blood volume is increased and pulmonary arteries become distended, the strength of negative wave reflections increases when 100% O2 is used for ventilation.

Negative reflections suck blood downstream and, as they arrive when the heart is developing maximal pressure, negative reflections help to lower the back pressure the heart must pump against and, thus, they tend to increase the forward flow of blood.

Conventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir–wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end‐expiratory pressure were observed. The reservoir–wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in ‘excess’ quantities, which were treated as wave‐related. Wave intensity analysis quantified the contributions of waves originating upstream (forward‐going waves) and downstream (backward‐going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end‐expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow.
A novel short‐term plasticity of intrinsic excitability in the hippocampal CA1 pyramidal cells
Authors: Sánchez‐Aguilera A. , Sánchez‐Alonso J. L. , Vicente‐Torres M. A. , Colino A.
Published: April 2014

Key points

Changes in neuronal activity often trigger compensatory mechanisms that stabilize neuron output.

We have identified a novel form of short‐term plasticity of membrane excitability, which develops early after the eye‐opening period in rats.

Holding the membrane potential of CA1 neurons at subthreshold depolarization from 15 s to several minutes induces a reduction of the excitability.

This plasticity requires an influx of T‐type Ca2+ current that modulates the A‐type K+ current.

These results help us understand that the resting potential history could modify cell intrinsic excitability.

Changes in neuronal activity often trigger compensatory mechanisms aimed at regulating network activity homeostatically. Here we have identified and characterized a novel form of compensatory short‐term plasticity of membrane excitability, which develops early after the eye‐opening period in rats (P16–19 days) but not before that developmental stage (P9–12 days old). Holding the membrane potential of CA1 neurons right below the firing threshold from 15 s to several minutes induced a potentiation of the repolarizing phase of the action potentials that contributed to a decrease in the firing rate of CA1 pyramidal neurons in vitro. Furthermore, the mechanism for inducing this plasticity required the action of intracellular Ca2+ entering through T‐type Ca2+ channels. This increase in Ca2+ subsequently activated the Ca2+ sensor K+ channel interacting protein 3, which led to the increase of an A‐type K+ current. These results suggest that Ca2+ modulation of somatic A‐current represents a new form of homeostatic regulation that provides CA1 pyramidal neurons with the ability to preserve their firing abilities in response to membrane potential variations on a scale from tens of seconds to several minutes.
Understanding Urban Development Through a Sport Events Portfolio: A Case Study of London, Ontario
Authors: Clark Richelle , Misener Laura
Published: April 2014

This study investigates the underdeveloped area of event portfolios in an attempt to fill a gap in the existing literature. This research article examines strategic positioning of events and the critical role they play in local development. To understand this, a case study design was performed in a medium-sized city in Canada. The purpose of the study was to determine how the city has used sport events for broader local development and enhancement of the civic brand. Interviews with local city actors and document analyses were used to further understand the strategies within the community. The results show that although a city may possess the necessary portfolio components as per Ziakas & Costa (2011), it is essential that there is a strategy that bridges the pieces of the portfolio for sustainable development. Consequently, we found that sequencing, or the strategic timing of events and political grounds, played a crucial role in this process.