bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol induces apoptosis associated with mitochondrial dysfunction in bladder carcinoma cells
Authors: Lin Xi , Wu Gang , Huo Wen‐Qian , Zhang Yao , Jin Feng‐Shuo
Published: May 2012

Objective:  Resveratrol shows chemopreventive activity in a variety of human cancers by targeting mitochondria and triggering apoptosis. The purpose of this study was to investigate the antitumor action of resveratrol in bladder cancer and its underlying mechanism.

Methods:  Using two different bladder cell lines, BTT739 and T24, the cytotoxicity of resveratrol were determined by MTT assay. The apoptosis induced by resveratrol was assayed by transferase dUTP nick end labeling staining. To show whether the mitochondrial dysfunction involved in the effects of resveratrol, mitochondrial function was detected by mitochondrial membrane potential, reactive oxygen species production and adenosine 5′‐triphosphate content. In addition, the markers of apoptosis in the intrinsic mitochondrial‐dependent pathway were analyzed by the release of cytochrome c and the activities of caspase‐9 and caspase‐3.

Results:  Resveratrol effectively decreased cell viability and induced apoptosis in a concentration‐ and time‐dependent manner. In addition, resveratrol significantly disrupted the mitochondrial membrane potential in both intact cells and isolated mitochondria. Resveratrol also increased reactive oxygen species production and reduced adenosine 5′‐triphosphate concentrations. Western blot analysis showed that resveratrol provoked the release of cytochrome c from mitochondria to the cytosol. Furthermore, resveratrol significantly promoted the activation of caspase‐9 and caspase‐3.

Conclusions:

These findings suggest that resveratrol efficiently triggers apoptosis in bladder cancer cells through the intrinsic mitochondrial‐dependent pathway, which is associated with mitochondrial dysfunction. Resveratrol might have great pharmacological promise in the treatment of bladder cancer.
Shaping brain connections through spontaneous neural activity
Authors: Yamamoto Nobuhiko , López‐Bendito Guillermina
Published: May 2012

An overwhelming number of observations demonstrate that neural activity and genetic programs interact to specify the composition and organization of neural circuits during all stages of development. Spontaneous neuronal activities have been documented in several developing neural regions in both invertebrates and vertebrates, and their roles are mostly conserved among species. Among these roles, Ca2+ spikes and levels of electrical activity have been shown to regulate neurite growth, axon extension and axon branching. Here, we review selected findings concerning the role of spontaneous activity on circuit development.
Termination and initial branch formation of SNAP‐25‐deficient thalamocortical fibres in heterochronic organotypic co‐cultures
Authors: Blakey Daniel , Wilson Michael C. , Molnár Zoltán
Published: May 2012

We are interested in the role of neural activity mediated through regulated vesicular release in the stopping and early branching of the thalamic projections in the cortex. Axon outgrowth, arrival at the cortical subplate, side‐branch formation during the waiting period and cortical plate innervation of embryonic thalamocortical projections occurs without major abnormalities in the absence of regulated release in Snap25 −/− null mutant mice [Washbourne et al. (2002) Nat. Neurosci. 5:19–26; Molnár et al. (2002) J. Neurosci. 22:10313–10323]. The fact that Snap25 −/− null mutant mice die at birth limited our previous experiments to the prenatal period. We therefore investigated the behaviour of thalamic projections in co‐culture paradigms by using heterochronic thalamic [embryonic day (E)16–E18] and cortical [postnatal day (P)0–P3] explants, in which the stopping and branching behaviour has been previously documented. Our current co‐culture experiments established that thalamic projections from E16–E18 Snap25+/+ or Snap25 −/− explants behaved in an identical fashion in P0–P3 Snap25 +/+ cortical explants after 7 days in vitro. Thalamic projections from Snap25 −/− explants developed similar patterns of fibre ingrowth to the cortex, and stopped and formed branches at a similar depth in the Snap25+/+ cortical slice as in control cultures. These results imply that thalamic projections can reach their ultimate target cells in layer 4, stop, and start to develop branches in the absence of regulated vesicular transmitter release from their own terminals.
Knowledge and barriers associated with assessment and treatment for hepatitis C virus infection among people who inject drugs
Authors: TRELOAR CARLA , HULL PETER , DORE GREGORY J. , GREBELY JASON
Published: May 2012

Introduction and Aims. Uptake of treatment for hepatitis C virus (HCV) infection among people who inject drugs is low. Further understanding is required of the relationship between HCV knowledge and treatment willingness, assessment and treatment in this population.

Design and Methods. A cross‐sectional self‐administered survey was conducted with clients of four opioid substitution therapy (OST) clinics and the Medically Supervised Injecting Centre in Sydney, Australia.

Results. Of 132 participants, 85 (64%) self‐reported having HCV infection. HCV knowledge was mixed (mean 6.5, range 0–12) and was relatively lower on items measuring knowledge of factors impacting HCV‐related disease progression. The likelihood of being in a higher knowledge category was associated with being female [adjusted odds ratio (AOR) = 3.78, 95% confidence interval (CI) (1.79, 7.98)], higher formal education [AOR = 3.28, 95% CI (1.57, 6.88)], being on a current OST program [AOR = 2.61, 95% CI (1.10, 6.19)] and being older [AOR = 1.04, 95% CI (1.01, 1.09)]. Participants receiving OST were more likely to report higher willingness to have HCV treatment [OR = 4.45, 95% CI (2.23, 8.17)]. Having been assessed for HCV treatment was associated with younger age [AOR = 0.93; CI 95% (0.88, 1.00)] and higher formal education [AOR = 7.81; 95% CI (1.62, 37.71)].

Discussion and Conclusions. Overall, knowledge scores were mid‐range. Knowledge of modifiable factors influencing HCV‐related liver disease progression was particularly low indicating the need for ongoing education. Education should also be targeted at older people and those not on OST, and be inclusive of those with lower literacy levels.[Treloar C, Hull P, Dore GJ, Grebely J. Knowledge and barriers associated with assessment and treatment for hepatitis C virus infection among people who inject drugs. Drug Alcohol Rev 2012]
The Rise of the For‐Profit Sector in US Higher Education and the Brazilian Effect*
Authors: Douglass John Aubrey
Published: May 2012

What accounts for the rapid growth in the For‐Profit (FP) higher education sector in the US? How will its growth influence educational opportunity and degree attainment rates in a country that first pioneered a mass higher education built largely on expanding public colleges and universities? The current US experience is a version of what I call the ‘Brazilian Effect’: when public higher education cannot keep pace with growing public demand for access and programmes, governments often allow FP's to rush in and help fill the gap, becoming a much larger and sometimes dominant provider. This is the pattern in many developing economies such as Brazil, Korea, Poland and other parts of the world. Despite new federal regulations intended to better regulate For‐Profits, my prediction is that they will continue to grow over the long‐term in the US not so much because they meet societal demands for diverse forms of higher education, but because of the inability of the public sector to return to the levels of public subsidies they had in the past. The result now, and in the future, is a kind of policy default: the future tertiary market will not be the result of a well thought out policy at the national or state levels, but a quasi‐free market consequence that will foster lower quality providers and fail to meet national goals for increasing the educational attainment level of Americans. This article discusses how higher education policymaking is about broad issues of socioeconomic mobility and economic competitiveness, but it is also about money, big business, and political influence.
FAST FOOD PRICES AND ADULT BODY WEIGHT OUTCOMES: EVIDENCE BASED ON LONGITUDINAL QUANTILE REGRESSION MODELS
Authors: HAN EUNA , POWELL LISA M.
Published: May 2012

With a parallel increase in the consumption of food away from home, particularly fast food, and the obesity prevalence in the United States, evidence on the potential effectiveness of fiscal pricing policies to curb obesity is needed. We estimate changes in the dispersion of the entire conditional distribution of body mass index (BMI) associated with changes in fast food prices for adults using the National Longitudinal Survey of Youth 1979 in cross‐sectional and longitudinal quantile regression models. We find that the ordinary least squares estimate for men underestimates the negative relationship of fast food prices with BMI at the 50th and upper quantiles in cross‐sectional models although the statistical significance disappears in the longitudinal individual fixed effects quantile regression. Among subpopulations, we find that a 10% increase in the price of fast food is associated with 0.9% and 0.7% lower BMI for low‐income women and women with any children, respectively, at the 90th quantile in a longitudinal individual fixed effects model. Our results imply that fiscal pricing policies such as fast food taxes might have a greater impact on the weight outcomes of low‐income women or women with children in the upper tail of the conditional BMI distribution (JEL I00, I19).
Needs of South African adolescents orphaned by AIDS: evidence from photography and photo‐elicitation
Authors: Thupayagale‐Tshweneagae G. , Mokomane Z.
Published: May 2012

THUPAYAGALE‐TSHWENEAGAE G. & MOKOMANE Z. (2013) Needs of South African adolescents orphaned by AIDS: evidence from photography and photo‐elicitation. International Nursing Review60, 88–95

Background:  Available evidence shows that over half of all orphans under the age of 18 years are adolescents aged between 12 and 17 years. Despite this, the needs of adolescents orphaned by AIDS are seldom recognized or adequately addressed in policy and programmes. Instead, the focus tends to be on the needs of orphans and vulnerable children. However, there are several factors that render adolescent‐specific programmes important.

Purpose:  Using data from an urban area in South Africa, this paper illuminates the needs of adolescents orphaned by AIDS.

Method:  A phenomenological study using photography and photo‐elicitation was used with 15 adolescents aged between 14 and 18 years orphaned by AIDS.

Results:  The study participants captured different objects that were grouped under six broad themes: symbols of death, nature, people, past life, children and hope. The photographic component of the study was followed by photo‐elicitation. From the meanings the adolescents made of their images, the needs of adolescents orphaned by AIDS were discerned as love, care and acceptance, safety, and security and support.

Conclusion:  Overall, the results showed that adolescents orphaned by AIDS want to feel secure, safe, wanted by caregivers and to feel that caregivers support them in their grieving journey.
Nurse scholars' knowledge and use of electronic theses and dissertations
Authors: Goodfellow L.M. , Macduff C. , Leslie G. , Copeland S. , Nolfi D. , Blackwood D.
Published: May 2012

Goodfellow L.M., Macduff C., Leslie G., Copeland S., Nolfi D. & Blackwood D. (2012) Nurse scholars' knowledge and use of electronic theses and dissertations. International Nursing Review

Background:  Electronic theses and dissertations (ETDs) are a valuable resource for nurse scholars worldwide. ETDs and digital libraries offer the potential to radically change the nature and scope of the way in which doctoral research results are presented, disseminated and used. An exploratory study was undertaken to better understand ETD usage and to address areas where there is a need and an opportunity for educational enhancement.

Aims:  The primary objective was to gain an initial understanding of the knowledge and use of ETDs and digital libraries by faculty, graduate students and alumni of graduate programs at schools of nursing.

Design:  A descriptive online survey design was used.

Methods:  Purposeful sampling of specific schools of nursing was used to identify institutional participants in Australia, New Zealand, the UK and the US. A total of 209 participants completed the online questionnaire.

Results:  Only 44% of participants reported knowing how to access ETDs in their institutions' digital libraries and only 18% reported knowing how to do so through a national or international digital library. Only 27% had cited an ETD in a publication. The underuse of ETDs was found to be attributable to specific issues rather than general reluctance to use online resources.

Conclusions:  This is the first international study that has explored awareness and use of ETDs, and ETD digital libraries, with a focus on nursing and has set the stage for future research and development in this field. Results show that most nursing scholars do not use ETDs to their fullest potential.
Terra Economica: Waste and the Production of Enclosed Nature
Authors: Goldstein Jesse
Published: May 2012

Abstract:  This essay provides an analysis of the “dirty” history and geography of enclosure, as both an instance of primitive accumulation and a production of nature. Specifically, I reconsider the English enclosures as a struggle over the land‐use designation of “waste”. Whereas both open fields and common waste lands were an essential and valuable part of the common right economy, advocates of enclosure came to see these same lands as wasted commons; lands that were potentially, but not yet, improved. This dialectic of waste and potential permeates the fabric of the nature produced through enclosure, which I name terra economica. Typically, this terrain has been understood as a passive repository of free resources, extending across absolute space. While such accounts consider the making of nature into a universal means of production, it is equally important to consider the ways in which nature is produced as a universal condition of production.
Moral Harm and Moral Responsibility: A Defence of Ascriptivism*
Authors: DENARO PIETRO
Published: May 2012

This paper investigates the relations between the concepts of moral harm and moral responsibility, arguing for a circularity between the two. On this basis the conceptual soundness of descriptivism, on which consequentialist and non‐consequentialist arguments are often grounded, is questioned. In the last section a certain version of ascriptivism is defended: The circularity is relevant in order to understand how a restricted version of ascriptivism may in fact be well founded.
The Domestic Politics of Institutional Design: Producer Preferences over Trade Agreement Rules
Authors: Kucik Jeffrey
Published: May 2012

What explains variation in the design of international institutions? Recent literature shows that providing members with opportunities to shirk their contractual obligations actually promotes agreement formation and durability. Yet, in spite of these benefits, institutions continue to exhibit wide variation in the “flexibility” of their rules. I show that, in the context of preferential trade agreements (PTAs), the benefits of permitting escape are enjoyed unevenly across the market. In particular, import‐competing industries gain from the protection that escape clauses provide while their export‐dependent counterparts bear the costs. This asymmetry creates domestic political competition over agreement design between the two traded sectors of the market. I explore this competition using new data on the design of 330 PTA agreements since 1960.
Bayes Factor Based on the Trend Test Incorporating Hardy–Weinberg Disequilibrium: More Power to Detect Genetic Association
Authors: Xu Jinfeng , Yuan Ao , Zheng Gang
Published: May 2012

In the analysis of case‐control genetic association, the trend test and Pearson’s test are the two most commonly used tests. In genome‐wide association studies (GWAS), Bayes factor (BF) is a useful tool to support significant P‐values, and a better measure than P‐value when results are compared across studies with different sample sizes. When reporting the P‐value of the trend test, we propose a BF directly based on the trend test. To improve the power to detect association under recessive or dominant genetic models, we propose a BF based on the trend test and incorporating Hardy–Weinberg disequilibrium in cases. When the true model is unknown, or both the trend test and Pearson’s test or other robust tests are applied in genome‐wide scans, we propose a joint BF, combining the previous two BFs. All three BFs studied in this paper have closed forms and are easy to compute without integrations, so they can be reported along with P‐values, especially in GWAS. We discuss how to use each of them and how to specify priors. Simulation studies and applications to three GWAS are provided to illustrate their usefulness to detect nonadditive gene susceptibility in practice.
Temporal sequence in the formation of midline dermis and dorsal vertebral elements in avian embryos
Authors: Pu Qin , Christ Bodo , Huang Ruijin
Published: May 2012

Somites compartmentalize into a dorsal epithelial dermomyotome and a ventral mesenchymal sclerotome. While sclerotomes give rise to vertebrae and intervertebral discs, dermomyotomes contribute to skeletal muscle and epaxial dermis. Bone morphogenetic protein (BMP)‐signals from the lateral mesoderm induce the lateral portion of the dermomyotome to form chondrogenic precursor cells, forming the cartilage of the scapula blade. The fact that BMPs are expressed in the roof plate of the neural tube where they induce cartilage formation led to the question why cells migrating from the medial part of the dermomyotome do not undergo chondrogenic differentiation and do not contribute to the dorsal part of the vertebrae. In the present study, we traced dermomyotomal derivatives by using the quail–chick marker technique. Our study reveals a temporal sequence in the formation of the vertebral cartilage and the midline dermis. The dorsal mesenchyme overlying the roof plate of the neural tube is formed prior to the de‐epithelialization of the dermomyotome. Dermomyotomal cells start to migrate medially into the sub‐ectodermal space to form the midline dermis after chondrogenesis of the dorsal mesenchyme has occurred. This time delay between chondrogenesis of the dorsal vertebra and dermal formation allows an undisturbed development of these two tissue components within a narrow region of the embryo.
Repression of transcription of presenilin‐1 inhibits γ‐secretase independent ER Ca2+ leak that is impaired by FAD mutations
Authors: Das Hriday K. , Tchedre Kissaou , Mueller Brett
Published: May 2012

J. Neurochem. (2012) 122, 487–500.

Genetic deletion or mutations of presenilin genes (PS1/PS2) cause familial Alzheimer’s disease and calcium (Ca2+) signaling abnormalities. PS1/PS2 act as endoplasmic reticulum (ER) Ca2+ leak channels that facilitate passive Ca2+ leak across ER membrane. Studies with PS1/PS2 double knockout (PS1/PS2‐DKO) mouse embryonic fibroblasts showed that PS1/PS2 were responsible for 80% of passive Ca2+ leak from the lumen of endoplasmic reticulum to cytosol. Transient transfection of the wild type PS1 expression construct increased cytoplasmic Ca2+ as a result of Ca2+ leak across ER membrane whereas the FADPS1 (PS1‐M146V) mutation construct alone or in combination with the wild type PS1 expression construct abrogated Ca2+ leak in SK‐N‐SH cells. Inhibition of basal c‐jun‐NH2‐terminal kinase (JNK) activity by JNK inhibitor SP600125 repressed PS1 transcription and PS1 protein expression by augmenting p53 protein level in SK‐N‐SH cells (Lee and Das 2008). In this report we also showed that repression of PS1 transcription by JNK inhibitor SP600125 inhibited passive Ca2+ leak across ER membrane which could be rescued by expressing PS1 wild type and not by expressing FADPS1 (PS1‐M146V) under a SP600125 non‐responsive promoter. Treatment of SK‐N‐SH cells with SP600125 also triggered InsP3R‐mediated Ca2+ release from the ER by addition of 500 nM bradykinin, an agonist of InsP3 receptor (InsP3R1) without changing the expression of InsP3R1. This data confirms that SP600125 increases the Ca2+ store in the ER by inhibiting PS1‐mediated Ca2+ leak across ER membrane. p53, ZNF237 and Chromodomain helicase DNA‐binding protein 3 which are repressors of PS1 transcription, also reduced Ca2+ leak across ER membrane in SK‐N‐SH cells but γ‐secretase inhibitor or dominant negative γ‐secretase–specific PS1 mutant (PS1‐D257A) had no significant effect. Therefore, p53, ZNF237, and Chromodomain helicase DNA‐binding protein 3 inhibit the function ER Ca2+ leak channels to regulate both ER and cytoplasmic Ca2+ levels and may potentially control Ca2+‐signaling function of PS1.
Thermally‐induced structural and chemical alteration of organic‐walled microfossils: an experimental approach to understanding fossil preservation in metasediments
Authors: Schiffbauer J. D. , Wallace A. F. , Hunter J. L. , Kowalewski M. , Bodnar R. J. , Xiao S.
Published: May 2012

The identification and confirmation of bona fide Archean–Paleoproterozoic microfossils can prove to be a challenging task, further compounded by diagenetic and metamorphic histories. While structures of likely biological origin are not uncommon in Precambrian rocks, the search for early fossil life has been disproportionately focused on lesser thermally altered rocks, typically greenschist or lower‐grade metamorphism. Recently, however, an increasing number of inferred micro‐ and macrofossils have been reported from higher‐grade metasediments, prompting us to experimentally test and quantify the preservability of organic‐walled microfossils over varying durations of controlled heating and under two differing redox conditions. Because of their relatively low‐intensity natural thermal alteration, acritarchs from the Mesoproterozoic Ruyang Group were chosen as subjects for experimental heating at approximately 500°C, with durations ranging from 1 to 250 days and in both oxic (normal present day conditions) and anoxic conditions. Upon extraction, the opacity, reflectivity, color, microchemistry, and microstructures of the heated acritarchs were characterized using optic microscopy, scanning electron microscopy, Raman spectroscopy, and X‐ray photoelectron spectroscopy. The results differ for acritarchs prepared under oxic vs. anoxic conditions, with the anoxic replicates surviving experimental heating longer and retaining biological morphologies better, despite an increasing degree of carbonization with continuous heating. Conversely, the oxic replicates show aggressive degradation. In conjunction with fossils from high‐grade metasediments, our data illustrate the preservational potential of organic‐walled microfossils subjected to metamorphism in reducing conditions, offer insights into the search for microfossils in metasediments, and help to elucidate the influence of time on the carbonization/graphitization processes during thermal alteration.
Geography, libertarian paternalism and neuro‐politics in the UK
Authors: Whitehead Mark , Jones Rhys , Pykett Jessica , Welsh Marcus
Published: May 2012

This Commentary explores what the implications of the emergence of a putative ‘nudgeocracy’, and associated forms of neurologically‐infused policy development, mean for human geographical research. Drawing on a 3‐year research project into the rise of libertarian paternalism within the British polity, and our involvement in the recent House of Lords Behaviour Change Inquiry (House of Lords 2011 Behaviour change report[HL paper 179] Stationary Office, London), we argue that geographical research can make important contributions to the wider political and philosophical debates surrounding soft paternalist society.
Pseudohalide anions reveal a novel extracellular site for potentiators to increase CFTR function
Authors: Li Man‐Song , Cowley Elizabeth A , Linsdell Paul
Published: May 2012

BACKGROUND AND PURPOSE There is great interest in the development of potentiator drugs to increase the activity of the cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis. We tested the ability of several anions to potentiate CFTR activity by a novel mechanism.

EXPERIMENTAL APPROACH Patch clamp recordings were used to investigate the ability of extracellular pseudohalide anions (Co(CN)63−, Co(NO2)63−, Fe(CN)63−, IrCl63−, Fe(CN)64−) to increase the macroscopic conductance of mutant CFTR in intact cells via interactions with cytoplasmic blocking anions. Mutagenesis of CFTR was used to identify a possible molecular mechanism of action. Transepithelial short‐circuit current recordings from human airway epithelial cells were used to determine effects on net anion secretion.

KEY RESULTS Extracellular pseudohalide anions were able to increase CFTR conductance in intact cells, as well as increase anion secretion in airway epithelial cells. This effect appears to reflect the interaction of these substances with a site on the extracellular face of the CFTR protein.

CONCLUSIONS AND IMPLICATIONS Our results identify pseudohalide anions as increasing CFTR function by a previously undescribed molecular mechanism that involves an interaction with an extracellular site on the CFTR protein. Future drugs could utilize this mechanism to increase CFTR activity in cystic fibrosis, possibly in conjunction with known intracellularly‐active potentiators.
Targeting cannabinoid receptor CB2 in cardiovascular disorders: promises and controversies
Authors: Steffens Sabine , Pacher Pál
Published: May 2012

Cardiovascular disease is the leading cause of death and disability worldwide, which can be largely attributed to atherosclerosis, a chronic inflammation of the arteries characterized by lesions containing immune and smooth muscle cells, lipids and extracellular matrix. In recent years, the lipid endocannabinoid system has emerged as a new therapeutic target in variety of disorders associated with inflammation and tissue injury, including those of the cardiovascular system. The discovery that Δ‐9‐tetrahydrocannabinol (Δ9‐THC), the main active constituent of marijuana, inhibited atherosclerotic plaque progression via a cannabinoid 2 (CB2) receptor‐dependent anti‐inflammatory mechanism, and that certain natural and synthetic cannabinoid ligands could modulate the myocardial or cerebral ischaemia–reperfusion‐induced tissue damage, have stimulated impetus for a growing number of studies investigating the implication of CB2 receptors in atherosclerosis, restenosis, stroke, myocardial infarction and heart failure. The aim of this review is to update on recent findings and controversies on the role of CB2 receptors in cardiovascular disease. Particular emphasis will be placed on novel insights in the potential cellular targets of CB2 stimulation in cardiovascular system (e.g. endothelial and vascular smooth muscle cells, cardiomyocytes, infiltrating and/or resident monocytes/macrophages and leukocytes, etc.), their interplay and intracellular signalling mechanisms identified, as well as on experimental and clinical studies.
Feline exocrine pancreatic carcinoma: a retrospective study of 34 cases
Authors: Linderman M. J. , Brodsky E. M. , de Lorimier L.‐P. , Clifford C. A. , Post G. S.
Published: May 2012

Thirty‐four cases were reviewed in this retrospective study for information on clinical presentation, prognostic indicators, survival time and response to various therapies. The most common presenting clinical signs were weight loss, decreased appetite, vomiting, palpable abdominal mass and diarrhoea. Metastatic disease was confirmed in 11 cats. The overall median survival was 97 days. The median survival times for patients who received chemotherapy or had their masses surgically removed was 165 days. Those patients who had an abdominal effusion present at the time of diagnosis survived a median of 30 days. Cats that received non‐steroidal anti‐inflammatory drug therapy had a median survival of 26 days. This study confirms that exocrine pancreatic carcinoma in cats is an aggressive tumour with a high metastatic rate and poor prognosis, although three patients survived over 1 year. Fifteen percent of the patients were diabetic, which raises the question as to what the link between diabetes and pancreatic cancer in people and cats may be.
Report of the Editor‐in‐Chief
Authors: Harvey David
Published: May 2012

Submissions to the Journal continue to show an increasingly international pattern, with the submission rate apparently stabilising after a recent rapid increase. Our response times still mostly meet our target of four months, with some regrettable lapses. The JAE’s citation impact factor has slipped again in 2010, though indications from data on 2011 citations strongly suggest a significant improvement in the 2011 impact factor (due to be published in June 2012). Wiley‐Blackwell continue to provide a strong publishing platform with our full archive generating rapidly increasing numbers of downloads.
Intensity of Care and better Outcomes among Hemodialysis Patients: A Role for the Medical Director
Authors: Lacson Eduardo , Maddux Franklin W.
Published: May 2012

The Medical Director is responsible for all levels of quality patient care in the facility as mandated by the 2008 revision of the Medicare Conditions for Coverage of dialysis facilities. He/she is the leader and primary individual tasked with ensuring that facility processes are in place to meet or exceed key quality goals or adopt new ones and prioritize them appropriately—all to drive improved facility performance, particularly the ultimate outcomes of morbidity and mortality rates. Management of vascular access, dialysis dose, mineral metabolism, acid‐base balance, sodium and fluid management, anemia, among other aspects of care, have representative intermediate clinical outcomes that are often called “surrogate” or “process” measures—because they may reflect the quality of care delivery while impacting “primary” outcomes such as death and hospitalization. The proportion of dialysis patients within a dialysis facility meeting a selected group among these goals has become the standard “care process” metric since the 1990s. Evidence supports its use, in that graded improvements in the facility patients’ primary outcomes have been documented as more patients in a facility achieved a greater number of these “process” goals. A caveat: these process measures do not represent overall quality by themselves because nonclinical processes also influence primary outcomes. Nevertheless, process improvement in meeting facility goals should be led by the Medical Director, particularly those with the strongest links to primary outcomes such as reduction of hemodialysis catheter exposure, forming the cornerstone of quality improvement efforts. Specific recommendations on how to effectively lead a care team to achieve these goals are discussed.
Microphthalmia with Linear Skin Defects Syndrome
Authors: García‐Rabasco Ana , De‐Unamuno Blanca , Martínez Francisco , Febrer‐Bosch Isabel , Alegre‐de‐Miquel Víctor
Published: May 2012

Abstract:  Microphthalmia with linear skin defects (MLS) or microcornea, dermal aplasia and sclerocornea (MIDAS) syndrome is a rare X‐linked‐dominant disorder. We present a patient with agenesis of corpus callosum, ocular abnormalities, and multiple skin defects. The cytogenetic studies of the MLS critical region (Xp22.2) were normal, but a skewed X‐chromosome inactivation pattern (85:15) was observed.
Serum Interleukin‐9 Levels Are Associated With Clinical Severity in Children With Atopic Dermatitis
Authors: Ciprandi Giorgio , De Amici Mara , Giunta Vania , Marseglia Alessia , Marseglia Gianluigi
Published: May 2012

Abstract:  Atopic dermatitis (AD) is an inflammatory disorder of the skin characterized by impaired immune response. Th9 cells are a sub‐population of T cells that release interleukin (IL)‐9. No study has investigated the role of IL‐9 in AD. This study compared 64 children with AD with 45 healthy children. Serum IL‐9 levels were measured and clinical symptoms were assessed. Children with AD had higher serum IL‐9 levels than controls (p = 0.01). Clinical severity was significantly related to IL‐9 level, indicating that IL‐9 might exert a pathogenic role in symptom occurrence in individuals with AD. Children with AD may have higher serum IL‐9 levels than healthy children, and IL‐9 levels are significantly related to symptom severity.
Onychomycosis in the Denver Pediatrics Population, A Retrospective Study
Authors: Young Lindsay S. , Arbuckle Harvey A. , Morelli Joseph G.
Published: May 2012

Abstract:  Onychomycosis (OM) is a common nail disorder in adults but has been rare in children. Recent international studies have demonstrated a rise in the prevalence of OM in children and adolescents, with Trichophyton rubrum being the most common pathogen. This 5‐year retrospective chart review of children (aged <18) found that 66 of 141 patients (46.8%) presenting to Children’s Hospital Colorado or Denver Health Medical Center Dermatology clinics with nail complaints had OM, with the highest prevalence in those aged 6 to 10 and a slight male predominance. Toenails were more commonly affected, and Trichophyton rubrum was the most common pathogen.
Satoyoshi Syndrome: A Cause of Alopecia Universalis in Association with Neurologic and Bony Abnormalities
Authors: Merino de Paz Nayra , Rodriguez‐Martin Marina , Contreras Ferrer Patricia , Eliche Maria Pestana , Noda Cabrera Antonio
Published: May 2012

Abstract:  Satoyoshi syndrome is a rare multisystemic disorder characterized by alopecia, diarrhea, muscle spasms, osseous abnormalities, and endocrinopathies. We report a case of Satoyoshi syndrome misdiagnosed as vitamin D‐dependent rickets for several years.
The extracellular space and epileptic activity in the adult brain: Explaining the antiepileptic effects of furosemide and bumetanide
Authors: Hochman Daryl W.
Published: May 2012

Treatments that modulate the size of the extracellular space (ECS) also block epileptiform activity in adult brain tissue. This includes the loop diuretics furosemide and bumetanide, and alterations of the osmolarity of the ECS. These treatments block epileptiform activity in a variety of laboratory adult seizure models regardless of the underlying synaptic and physiologic mechanisms generating the seizure activity. Optical imaging studies on adult hippocampal slices show that the blockade of epileptiform activity by these treatments is concomitant with their blockade of activity‐driven changes of the ECS. Here we develop and analyze the hypothesis that activity‐driven changes in the size of the ECS are necessary for the maintenance of hypersynchronous epileptiform activity. In support of this hypothesis is an accumulation of data from a number of studies suggesting that furosemide and bumetanide mediate antiepileptic effects through their blockade of cell swelling, dependent on their antagonism of the glial Na+‐K‐2Cl cotransporter (NKCC1).
In vitro mechanical strain trauma alters neuronal calcium responses: Implications for posttraumatic epilepsy
Authors: Gurkoff Gene G. , Shahlaie Kiarash , Lyeth Bruce G.
Published: May 2012

Traumatic brain injury (TBI) is known to initiate a series of chemical cascades resulting in neuronal dysfunction and death. Epidemiology studies have found that a prior incidence of TBI is the most important cause of remote symptomatic epilepsy in young adults and children. TBI‐induced changes in neuronal sensitivity to stimulation may contribute to acute seizures and the eventual generation of epilepsy. This study examined TBI‐induced changes in neuronal sensitivity to stimulation by measuring intracellular calcium ([Ca++]i) responses in neurons during glutamate application in vitro. Initial experiments examined neuronal and glial cell death and determined that a 31% mechanical strain trauma to mixed neuronal‐astrocyte rat cortical cultures produced a trend, but no significant cell death at 48 h after injury. Subsequent experiments utilized this magnitude of trauma to examine the sensitivity of cortical neurons to changes in [Ca++]i in response to 100‐μm glutamate at five time points postinjury (1, 6, 24, 48, and 72 h). Traumatically strain‐injured neurons responded with a dynamic change in the accumulation of [Ca++]i, with a significant increase at 48 h and a significant decrease at 72 h as compared to uninjured cultures. These data highlight that TBI leads to abnormal responsiveness to stimulation, an indicator of neuronal dysfunction in surviving cells. Such changes in sensitivity to stimulation may also be associated with changes in excitability in the first hours to days after TBI, and may play a role in early posttraumatic seizures observed in patients with TBI. In addition, this study provides an in vitro paradigm for testing the function of surviving cells following treatment interventions targeted at reducing cell death and dysfunction.
New insights into the role of hilar ectopic granule cells in the dentate gyrus based on quantitative anatomic analysis and three‐dimensional reconstruction
Authors: Scharfman Helen E. , Pierce Joseph P.
Published: May 2012

The dentate gyrus is one of two main areas of the mammalian brain where neurons are born throughout adulthood, a phenomenon called postnatal neurogenesis. Most of the neurons that are generated are granule cells (GCs), the major principal cell type in the dentate gyrus. Some adult‐born granule cells develop in ectopic locations, such as the dentate hilus. The generation of hilar ectopic granule cells (HEGCs) is greatly increased in several animal models of epilepsy and has also been demonstrated in surgical specimens from patients with intractable temporal lobe epilepsy (TLE). Herein we review the results of our quantitative neuroanatomic analysis of HEGCs that were filled with Neurobiotin following electrophysiologic characterization in hippocampal slices. The data suggest that two types of HEGCs exist, based on a proximal or distal location of the cell body relative to the granule cell layer, and based on the location of most of the dendrites, in the molecular layer or hilus. Three‐dimensional reconstruction revealed that the dendrites of distal HEGCs can extend along the transverse and longitudinal axis of the hippocampus. Analysis of axons demonstrated that HEGCs have projections that contribute to the normal mossy fiber innervation of CA3 as well as the abnormal sprouted fibers in the inner molecular layer of epileptic rodents (mossy fiber sprouting). These data support the idea that HEGCs could function as a “hub” cell in the dentate gyrus and play a critical role in network excitability.
Abnormal dendrite and spine morphology in primary visual cortex in the CGG knock‐in mouse model of the fragile X premutation
Authors: Berman Robert F. , Murray Karl D. , Arque Gloria , Hunsaker Michael R. , Wenzel H. Jürgen
Published: May 2012

The fragile X mental retardation 1 gene (Fmr1) is polymorphic for CGG trinucleotide repeat number in the 5′‐untranslated region, with repeat lengths <45 associated with typical development and repeat lengths >200 resulting in hypermethylation and transcriptional silencing of the gene and mental retardation in the fragile X Syndrome (FXS). Individuals with CGG repeat expansions between 55 and 200 are carriers of the fragile X premutation (PM). PM carriers show a phenotype that can include anxiety, depression, social phobia, and memory deficits. They are also at risk for developing fragile X–associated tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by tremor, ataxia, cognitive impairment, and neuropathologic features including intranuclear inclusions in neurons and astrocytes, loss of Purkinje cells, and white matter disease. However, very little is known about dendritic morphology in PM or in FXTAS. Therefore, we carried out a Golgi study of dendritic complexity and dendritic spine morphology in layer II/III pyramidal neurons in primary visual cortex in a knock‐in (KI) mouse model of the PM. These CGG KI mice carry an expanded CGG trinucleotide repeat on Fmr1, and model many features of the PM and FXTAS. Compared to wild‐type (WT) mice, CGG KI mice showed fewer dendritic branches proximal to the soma, reduced total dendritic length, and a higher frequency of longer dendritic spines. The distribution of morphologic spine types (e.g., stubby, mushroom, filopodial) did not differ between WT and KI mice. These findings demonstrate that synaptic circuitry is abnormal in visual cortex of mice used to model the PM, and suggest that such changes may underlie neurologic features found in individuals carrying the PM as well as in individuals with FXTAS.
Pharmacokinetics and drug interactions of eslicarbazepine acetate
Authors: Bialer Meir , Soares‐da‐Silva Patricio
Published: May 2012

Eslicarbazepine acetate (ESL) is a novel once‐daily antiepileptic drug (AED) approved in Europe since 2009 that was found to be efficacious and well tolerated in a phase III clinical program in adult patients with partial onset seizures previously not controlled with treatment with one to three AEDs, including carbamazepine (CBZ). ESL shares with CBZ and oxcarbazepine (OXC) the dibenzazepine nucleus bearing the 5‐carboxamide substitute, but is structurally different at the 10,11 position. This molecular variation results in differences in metabolism, preventing the formation of toxic epoxide metabolites such as carbamazepine‐10,11‐epoxide. Unlike OXC, which is metabolized to both eslicarbazepine and (R)‐licarbazepine, ESL is extensively converted to eslicarbazepine. The systemic exposure to eslicarbazepine after ESL oral administration is approximately 94% of the parent dose, with minimal exposure to (R)‐licarbazepine and OXC. After ESL oral administration, the effective half‐life (t1/2,eff) of eslicarbazepine was 20–24 h, which is approximately two times longer than its terminal half‐life (t1/2). At clinically relevant doses (400–1,600 mg/day) ESL has linear pharmacokinetics (PK) with no effects of gender or moderate liver impairment. However, because eslicarbazepine is eliminated primarily (66%) by renal excretion, dose adjustment is recommended for patients with renal impairment. Eslicarbazepine clearance is induced by phenobarbital, phenytoin, and CBZ and it dose‐dependently decreases plasma exposure of oral contraceptive and simvastatin.
Gendered Paths to Legal Citizenship: The Case of Latin-American Immigrants in Phoenix, Arizona
Authors: Salcido Olivia , Menjívar Cecilia
Published: May 2012

In this paper we seek to contribute to a greater understanding of legal citizenship by exploring the gendered experiences of Latin-American-origin immigrants in the greater Phoenix metropolitan area as they go through the legalization process. To explore this gendered angle we rely on in-depth interviews conducted from 1998 through 2008 with women and men from Guatemala, El Salvador, Honduras, and Mexico. The data reveal that although immigration policies and procedures are presumably gender neutral, they are in fact inflected with gendered meanings and enacted in gendered social structures. Gender ideologies permeate the processes to differentially affect the legalization, permanent legal residence, and citizenship processes of immigrant women and men. This article points to key gender inequalities in immigration law.
Specters of Indigeneity in British-Indian Migration, 1914
Authors: Mawani Renisa
Published: May 2012

Colonial legal histories of indigeneity and British-Indian migration have not often been placed in conversation with one another. This article pursues such a project by tracing indigeneity as a spectral presence that emerged with uneven regularity in juridico-political conflicts over British-Indian migration. Specifically, I focus on the 1914 journey of the Komagata Maru, a Japanese steamship carrying 376 Punjabi migrants that sailed from Hong Kong to Shanghai, Moji to Yokohama, and across the Pacific, eventually arriving in Vancouver, Canada. Crisscrossing continents and approaching law in its broadest sense, I explore three struggles over the ship and its passengers: a satirical cartoon published in the Hindi Punch (Bombay), a legal test case heard by the British Columbia Court of Appeal (Vancouver), and a public debate on the racial meanings of Imperial subjecthood that ensued among Indian middle-class supporters of the ship and unfolded in English newspapers in various Indian cities. In each moment of struggle, I examine the changing conceptions of indigeneity that were strategically appropriated, never by indigenous peoples themselves or on their own terms, but by the Dominion of Canada and by British Indians, each deploying indigeneity to its own advantage and to achieve particular effects. Ultimately, this article considers the political and legal work that the spectral figure of indigeneity performed, the conceptions of time that underwrote its recurrence, and the temporalities that it sustained and called into question.
The International Transmission of Bank Liquidity Shocks: Evidence from an Emerging Market
Authors: SCHNABL PHILIPP
Published: May 2012

I exploit the 1998 Russian default as a negative liquidity shock to international banks and analyze its transmission to Peru. I find that after the shock international banks reduce bank‐to‐bank lending to Peruvian banks and Peruvian banks reduce lending to Peruvian firms. The effect is strongest for domestically owned banks that borrow internationally, intermediate for foreign‐owned banks, and weakest for locally funded banks. I control for credit demand by examining firms that borrow from several banks. These results suggest that international banks transmit liquidity shocks across countries and that negative liquidity shocks reduce bank lending in affected countries.
Decoding Inside Information
Authors: COHEN LAUREN , MALLOY CHRISTOPHER , POMORSKI LUKASZ
Published: May 2012

Exploiting the fact that insiders trade for a variety of reasons, we show that there is predictable, identifiable “routine” insider trading that is not informative about firms’ futures. A portfolio strategy that focuses solely on the remaining “opportunistic” traders yields value‐weighted abnormal returns of 82 basis points per month, while abnormal returns associated with routine traders are essentially zero. The most informed opportunistic traders are local, nonexecutive insiders from geographically concentrated, poorly governed firms. Opportunistic traders are significantly more likely to have SEC enforcement action taken against them, and reduce trading following waves of SEC insider trading enforcement.
The Rate of Proprietorship Among Metropolitan Areas: The Impact of the Local Economic Environment and Capital Resources
Authors: Coomes Paul A. , Fernandez Jose , Gohmann Stephan F.
Published: May 2012

Legal rules and the economic environment play an important role in the decision to become an entrepreneur. Many studies examine the effect of such institutions at the national or state level. The metropolitan area may be a more appropriate geography to examine, since entrepreneurs often serve a more localized market and there is wide variation in both the environment for and incidence of proprietorship among metropolitan areas. We find that proprietorship increases with home equity, intangible wealth, unemployment, relative earnings of proprietors, and population. It decreases with higher state income tax rates and minimum wages.