bluuebunny/crossref_metadata_2025 huggingface dataset:
Negotiating Conflict between Personal Desires and Others' Expectations in Lives of Gujarati Women
Authors: Raval Vaishali V.
Published: November 2009

AbstractA substantial body of literature in psychological anthropology has challenged the stereotypical depiction of South Asian women as passive subordinates in patriarchal families, and has provided accounts of these women as actors in their social world. Focusing specifically on situations of interpersonal conflict in this article, I analyze the narratives of Gujarati women from two cohorts, daughters‐in‐law in Gujarat, India and mothers‐in‐law in Gujarati immigrant families in Canada, to argue that these women actively engage in negotiating the conflict between their wishes and others' expectations. The mode of agency that they exercise is less egocentric and more relational—the decision making and negotiations occur within the parameters of their familial roles, rather than rebellion against family structures, and their actions are driven by motivations involving the welfare of their children and grandchildren, rather than “individualistic” desires. These narratives, along with ethnographic works exploring South Asian personhood, call for the need to broaden the conceptualization of agency, and challenge the appropriateness of traditional individualistic feminism in understanding the lives of women globally. [India, women, personhood, agency, interpersonal conflict]
“It's Just You and Satan, Hanging Out at a Pre‐School:” Notions of Evil and the Rehabilitation of Sexual Offenders
Authors: Waldram James B.
Published: November 2009

Notions of “evil” are a feature of everyday discourse in civil society. Sexual offenders, individuals often labeled as “evil,” are well aware of public images of themselves and their crimes. This article examines public discourses of “evil” as they pertain to sexual offenders, and the views of sexual offenders themselves on what this means to them. The ethnographic research was undertaken in a prison unit designed for the treatment of sexual offenders. As a result, the issue of rehabilitation figured centrally in their conceptualizations of evil. While admitting to being bad, and perhaps even having committed evil acts, they generally reject the label of “evil” as understood in essentialist terms. The fundamental issue of concern for my analysis here is how secular views on the nature of evil speak to the issue of rehabilitation, an inherently human, “natural” capability. To be essentially “evil,” in their view, is to be almost nonhuman—a view shared by much of the public as well—and, therefore, beyond rehabilitation.
Three‐Dimensional Digital Subtraction Angiography in Evaluation of Vertebro‐Basilar Artery Dissections: Comparison with 2D DSA
Authors: Sorimachi Takatoshi , Suzuki Kenji , Sasaki Osamu , Koike Tetsuo , Fujii Yukihiko
Published: November 2009

BACKGROUND AND PURPOSE

The purpose of this study was to clarify characteristic findings on three‐dimensional (3D) digital subtraction angiography (DSA), and to investigate diagnostic usefulness of 3D DSA in vertebro‐basilar dissections (VBD).

METHODS

In 25 consecutive patients with VBD, two‐dimensional (2D) DSA, and 3D DSA findings were evaluated by a scoring system. The effects of 3D DSA results on diagnosis were scored in comparison with 2D DSA results.

RESULTS

A proximal stenosis, a distal stenosis, a bleb, and a relationship between the posterior inferior cerebellar artery and the dissection were significantly better visualized in 3D DSA than those in 2D DSA (P < .05). A characteristic finding of VBD on 3D DSA was a combination of an aneurysmal bulging and its proximal and distal stenoses, which was observed in 92% of the 25 patients.

CONCLUSIONS

Three‐dimensional DSA was more useful for diagnosis in patients with VBD in comparison with 2D DSA.
Intimate Partner Violence: Development of a Brief Risk Assessment for the Emergency Department
Authors: Snider Carolyn , Webster Daniel , O’Sullivan Chris S. , Campbell Jacquelyn
Published: November 2009

Objectives:  Women assaulted by intimate partners are frequently patients in emergency departments (EDs). Many victims and health care providers fail to take into account the potential risks of repeat partner violence. The objective of this study was to use data from a larger study of domestic violence risk assessment methods to develop a brief assessment for acute care settings to identify victims at highest risk for suffering severe injury or potentially lethal assault by an intimate partner or former partner.

Methods:  Victims of intimate partner violence (IPV) were interviewed twice between 2002 and 2004. The baseline interview included the 20 items of Campbell’s Danger Assessment (DA; predictor). The follow‐up interview, conducted 9 months later on average, assessed abuse inflicted since the baseline interview (outcome). Multiple logistic regression was used to identify questions on the DA most predictive of severe abuse and potentially lethal assaults. Female IPV victims were recruited from New York City family courts, Los Angeles County Sheriff’s Department 9‐1‐1 calls, New York City and Los Angeles shelters, and New York City hospitals; 666 women responded to the DA at baseline, and 60% participated in follow‐up interviews.

Results:  Severe injuries or potentially lethal assaults were experience by 14.9% of retained study participants between the baseline and follow‐up interviews. The best brief prediction instrument has five questions. A positive answer to any three questions has a sensitivity of 83% (95% confidence interval = 70.6% to 91.4%).

Conclusions:  This instrument can help predict which victims may be at increased risk for severe injury or potentially lethal assault and can aid clinicians in differentiating which patients require comprehensive safety interventions.
Emergency Medicine Resident Attitudes and Perceptions of HIV Testing Before and After a Focused Training Program and Testing Implementation
Authors: Hsieh Yu‐Hsiang , Jung Julianna J. , Shahan Judy B. , Moring‐Parris Daniel , Kelen Gabor D. , Rothman Richard E.
Published: November 2009

Objectives:  The objectives were to determine attitudes and perceptions (A&P) of emergency medicine (EM) residents toward emergency department (ED) routine provider‐driven rapid HIV testing services and the impact of both a focused training program (FTP) and implementation of HIV testing on A&P.

Methods:  A three‐phase, consecutive, anonymous, identity‐unlinked survey was conducted pre‐FTP, post‐FTP, and 6 months postimplementation. The survey was designed to assess residents’ A&P using a five‐point Likert scale. A preimplementation FTP provided both the rationale for the HIV testing program and the planned operational details of the intervention. The HIV testing program used only indigenous ED staff to deliver HIV testing as part of standard‐of‐care in an academic ED. The impact of the FTP and implementation on A&P were analyzed by multivariate regression analysis using generalized estimating equations to control for repeated measurements in the same individuals. A “favorable” A&P was operationally defined as a mean score of >3.5, “neutral” as mean score of 2.5 to 3.5, and “unfavorable” as mean score of <2.5.

Results:  Thirty of 36 residents (83.3%) participated in all three phases. Areas of favorable A&P found in phase I and sustained through phases II and III included “ED serving as a testing venue” (score range = 3.7–4.1) and “emergency medicine physicians offering the test” (score range = 3.9–4.1). Areas of unfavorable and neutral A&P identified in phase I were all operational barriers and included required paperwork (score = 3.2), inadequate staff support (score = 2.2), counseling and referral requirements (score range = 2.2–3.1), and time requirements (score = 2.9). Following the FTP, significant increases in favorable A&P were observed with regard to impact of the intervention on modification of patient risk behaviors, decrease in rates of HIV transmission, availability of support staff, and self‐confidence in counseling and referral (p < 0.05). At 6 months postimplementation, all A&P except for time requirements and lack of support staff scored favorably or neutral. During the study period, 388 patients were consented for and received HIV testing; six (1.5%) were newly confirmed HIV positive.

Conclusions:  Emergency medicine residents conceptually supported HIV testing services. Most A&P were favorably influenced by both the FTP and the implementation. All areas of negative A&P involved operational requirements, which may have influenced the low overall uptake of HIV testing during the study period.
Emergency Medicine Public Health Research Funded by Federal Agencies: Progress and Priorities
Authors: D’Onofrio Gail , Goldstein Amy B. , Denisco Richard A. , Hingson Ralph , Heffelfinger James D. , Post Lori A.
Published: November 2009

The emergency department (ED) visit provides an opportunity to impact the health of the public throughout the entire spectrum of care, from prevention to treatment. As the federal government has a vested interest in funding research and providing programmatic opportunities that promote the health of the public, emergency medicine (EM) is prime to develop a research agenda to advance the field. EM researchers need to be aware of federal funding opportunities, which entails an understanding of the organizational structure of the federal agencies that fund medical research, and the rules and regulations governing applications for grants. Additionally, there are numerous funding streams outside of the National Institutes of Health (NIH; the primary federal health research agency). EM researchers should seek funding from agencies according to each agency’s mission and aims. Finally, while funds from the Department of Health and Human Services (HHS) are an important source of support for EM research, we need to look beyond traditional sources and appeal to other agencies with a vested interest in promoting public health in EDs. EM requires a broad skill set from a multitude of medical disciplines, and conducting research in the field will require looking for funding opportunities in a variety of traditional and not so traditional places within and without the federal government. The following is the discussion of a moderated session at the 2009 Academic Emergency Medicine consensus conference that included panel discussants from the National Institutes of Mental Health, Drug Abuse, and Alcoholism and Alcohol Abuse and the Centers for Disease Control and Prevention (CDC). Further information is also provided to discuss those agencies and centers not represented.
Erectile Dysfunction and Correlated Factors in Brazilian Men Aged 18–40 years
Authors: Martins Fernando Gonini , Abdo Carmita Helena Najjar
Published: November 2009

Introduction

Few population-based studies in erectile dysfunction (ED) included subjects less than 40 years old and analyzed the several factors and consequences potentially associated with this condition.

Aim

Evaluation of the prevalence of erectile dysfunction (ED) and associated factors in a sample of Brazilian men aged 18 to 40 years old.

Methods

Cross-sectional study in which subjects were contacted in public places of 18 major Brazilian cities and interviewed using an anonymous questionnaire. Survey data were submitted to chi-squared, student’s t-test and logistic regression analyses.

Main Outcome Measures

The data were collected by means of a self-administered questionnaire with 87 questions about sociodemographic variables, general health, habits and lifestyle-related factors, sexual behavior and sexual difficulties, including ED which was assessed by a single question.

Results

Prevalence of ED in 1,947 men was 35.0% (73.7% mild, 26.3% moderate/complete). Greater frequency of ED was seen in subjects that never had information about sex, experienced difficulties in the beginning of sexual life and have never masturbated. ED was associated to lower level of education, but not to race, sexual orientation, employment or marital status. Also, no association was found between ED and smoking, alcoholism, obesity, sedentary life, diabetes, hypertension, cardiovascular disease, hyperlipidemia, depression or anxiety. ED caused negative impact in men’s self-esteem, interpersonal relationships, work and leisure activities, and in sexual life satisfaction. Less than 10% of men with ED had received medical treatment for this problem.

Conclusions

Prevalence of ED in this young population was high, mostly of mild severity. Low education and psychosocial problems were associated to ED and, due probably to the sample subjects’ young age, no association was found with organic problems. Measures in the fields of education and psychosocial difficulties prevention would have a positive impact in the control of erectile dysfunction in the young population.
More than Sexual Function: Predictors of Sexual Satisfaction in a Sample of Women Age 40–70
Authors: Dundon Carolyn Marie , Rellini Alessandra H.
Published: November 2009

Introduction

The literature provides a complex picture of sexual satisfaction and its predictors. To date, studies have provided a list of predictors of sexual satisfaction, including relational and psychological factors, but very little information is available on the direct effects of these predictors in midlife women, independently from the effects of sexual function on sexual satisfaction.

Aim

The main aim of this article is to provide empirical evidence on factors that predict sexual satisfaction in middle-aged women above and beyond the explanation provided by sexual function.

Main Outcome Measures

The three items on sexual satisfaction from the Female Sexual Functioning Index were used to assess different aspects of sexual satisfaction.

Methods

A sample of 86 women age 40–70 years recruited from a clinic completed a battery of questionnaires on sexual satisfaction and potential predictors, including, psychological well-being, body attitudes, menopausal symptoms, and relationship adjustment.

Results

Relationship adjustment, psychological well-being, and menopausal symptoms predicted sexual satisfaction above and beyond sexual functioning. Body attitudes did not predict sexual satisfaction in midlife women.

Conclusions

Data supported the hypothesis that sexual satisfaction is only partially explained by sexual function. Other factors involved in women’s lives, such as psychological well-being, relationship adjustment, and, to a lesser extent, menopausal symptoms, affect sexual satisfaction independently from sexual function.
Acute Vardenafil Administration Improves Bladder Oxygenation in Spontaneously Hypertensive Rats
Authors: Morelli Annamaria , Filippi Sandra , Comeglio Paolo , Sarchielli Erica , Chavalmane Aravinda K. , Vignozzi Linda , Fibbi Benedetta , Silvestrini Enrico , Sandner Peter , Gacci Mauro , Carini Marco , Vannelli Gabriella B. , Maggi Mario
Published: November 2009

Introduction

In human bladder, phosphodiesterase type 5 (PDE5) is present not only in the muscular wall but also in the vascular beds, suggesting a role for PDE5 inhibitors in favoring bladder blood flow and tissue oxygenation.

Aim

To investigate whether acute administration of vardenafil could affect bladder oxygenation in spontaneously hypertensive rats (SHR), an animal model of naturally occurring overactive bladder.

Main Outcome Measures

The effect of vardenafil on hypoxia-induced alterations was studied in vivo in SHR by acute dosing (10 mg/kg, 90 minutes before sacrifice) and in vitro in human bladder smooth muscle cells (hBCs).

Methods

Bladder oxygenation was detected using the hypoxyprobe immunostaining. The expression of some hypoxia markers (vascular endothelial growth factor [VEGF] and endothelin-1 type B [ETB] receptor) was also evaluated by immunohistochemistry and Western blot. Gene expression in hBC was quantified by real-time reverse transcription-polymerase chain reaction.

Results

Rat bladder PDE5 immunopositivity was detected in the muscular wall and in the endothelial and smooth muscle cells of blood vessels. In SHR bladder, a significant increase of hypoxic cells, VEGF, and ETB expression was observed when compared with their normotensive counterpart Wistar Kyoto rats (WKY). Vardenafil treatment dramatically decreased hypoxyprobe staining, as well as VEGF and ETB expression in SHR bladder up to WKY level. Accordingly, in SHR bladder, vardenafil administration significantly blunted relaxation induced by the selective ETB agonist IRL-1620. In hBCs, experimental hypoxia significantly induced gene expression of hypoxia markers (carbonic anhydrase IX and VEGF), which was not changed by simultaneous treatment with vardenafil. Conversely, the hypoxia-related induction of smooth muscle-specific genes (αSMA, SM22α, and desmin) was significantly reduced by vardenafil.

Conclusions

SHR showed bladder hypoxia which was significantly reduced by acute vardenafil treatment. Thus, besides relaxing muscular wall, PDE5 inhibition may positively affect urinary vesicle blood perfusion.
Brief Review on Methods of Estimation of the Location of a Fresh Water–Salt Water Interface with Hydraulic Heads or Pressures in Coastal Zones
Authors: Xun Zhou , Ying Wang
Published: November 2009

Methods of estimation of the location of a sharp fresh water–salt water interface with hydraulic heads or pressures are relatively simple and are widely used. Progress has been made in the recent decade toward the mathematical relations describing the position of the sharp interface using hydraulic heads or pressures in coastal zones. This paper reviews several methods for estimation of the location of fresh water–salt water interface in coastal aquifers, including the classical Ghyben–Herzberg relation. The location of the fresh water–salt water interface in a coastal homogeneous, isotropic unconfined aquifer can be estimated based on piezometric heads at two points in the same vertical line tapping, respectively, the salt water zone (including the interface) and the fresh water zone (from the water table to the interface) when the groundwater flow system is in a steady state and satisfies the Dupuit assumption. If pressures are measured at two points in the fresh water and salt water zones in the same vertical line in the coastal aquifer under the same assumption, then the position of the interface can still be estimated with the pressure data. If the Dupuit assumption is not met in coastal aquifers and the vertical fresh water head gradients can be approximated with a straight line, the position of the interface can roughly be estimated by using the water level data in a partially penetrating well during drilling of the well.
New developments in incretin‐based therapies: The current state of the field
Authors: Robertson Carolyn
Published: November 2009

Purpose: To update readers on developments in incretin therapies since the previous JAANP supplement in 2007; specifically, to describe clinical data for currently available incretin‐based therapies as well as those under consideration by regulatory agencies.

Data source: Medline search for peer‐reviewed publications.

Conclusions: Incretin‐based therapies have pharmacologic properties that avoid some key limitations of previous treatments, such as hypoglycemia and weight gain. Certain agents also lower blood pressure and have the potential to reduce cardiovascular risk. The insulin‐secreting action of incretin‐based therapies only occurs under hyperglycemic conditions, thus minimizing the risk of hypoglycemia, unless combined with a sulfonylurea. The DPP‐4 inhibitors are orally administered and demonstrate modest A1c reductions (0.6%–0.8%); the best results occur when combined with metformin. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists liraglutide and exenatide have shown greater A1c reductions (typically ≥ 1.1% and as high as 1.7%), and these agents have beneficial ancillary effects, including weight and systolic blood pressure reduction. Both DPP‐4 inhibitors and GLP‐1 receptor agonists have shown the ability to improve pancreatic beta‐cell function in early studies.

Implications for practice: Data are provided on the efficacy and tolerability of approved incretin therapies, and on treatments currently in regulatory review, in order to inform readers and guide their practice.
Biomarkers in Huntington's and Parkinson's Disease
Authors: O’Keeffe Gráinne C. , Michell Andrew W. , Barker Roger A.
Published: November 2009

Parkinson's (PD) and Huntington's disease (HD) are chronic neurodegenerative conditions of the brain with a variety of clinical presentations including a disorder of movement and a range of nonmotor deficits. HD is genetic in origin and the causative gene and protein known, namely mutant Huntingtin, which leads to widespread early neuronal dysfunction and death throughout the brain. In contrast, the etiology of sporadic PD is unknown, and the pathology targets the nigrostriatal dopaminergic neurons with the formation of α‐synuclein positive Lewy bodies. In both diseases, the ability to accurately diagnose the disease in the early stages and monitor progression over time remains a major challenge given the majority of the pathology is sited deep within the CNS. This challenge has gained extra significance as the development of disease‐modifying drugs starts to emerge into the clinic. To this end, there is a need to find biomarkers that will help in the accurate diagnosis of the disease and/or prediction of its clinical onset as well as biomarkers that are able to faithfully track disease progression independent of any symptomatic effects of any therapies. In addition, these same markers may also help stratify each of these heterogeneous disorders into specific subtypes that share particular clinical and pathological characteristics.
The Uses of Biomarkers in Drug Development
Authors: Hurko Orest
Published: November 2009

Although the value of “surrogate biomarkers” (strictly speaking, those biomarkers that can serve as surrogate primary endpoints in registration trials) is significant, such biomarkers are few. However, “nonsurrogate biomarkers” are increasingly being used to reduce the risks of drug development. Any given biomarker is usually useful for only one of four types of risk reduction: that associated with (1) an inappropriate dosing regimen; (2) enrollment of nonresponsive subjects into clinical trials; (3) an inability to detect an efficacy signal quickly and reliably in chronic disorders; or (4) delayed recognition of potential side effects and/or toxicity. A biomarker suitable for one purpose is usually not suitable for the other three. Although these considerations apply to all drug development, both the need and availability of appropriate biomarkers in each category vary between therapeutic areas. The focus is on diseases of the brain.
Glucocorticoids
Authors: Wolkowitz Owen M. , Burke Heather , Epel Elissa S. , Reus Victor I.
Published: November 2009

Elevated circulating levels of glucocorticoids are associated with psychiatric symptoms across several different conditions. It remains unknown if this hormonal abnormality is a cause or an effect of the psychiatric conditions. For example, the hypercortisolemia observed in a subset of patients with depression may have a direct impact on the symptoms of depression, but it is also possible that the hypercortisolemia merely reflects the stress associated with depression. Further, rather than causing depression, hypercortisolemia could represent a homeostatic attempt to overcome glucocorticoid resistance. Each of these possibilities will be considered, and correlational and causal evidence will be reviewed. This article will focus on the relationships between glucocorticoids and psychiatric symptoms in Cushing's syndrome, major depression, and steroid psychosis/steroid dementia, as well as the effects of exogenously administered glucocorticoids in normal volunteers. Similarities and differences in the relationship of glucocorticoid hormones to psychiatric symptoms in these conditions will be reviewed. Possible mediators of glucocorticoid effects on the brain and behavior, as well as possible “pro‐aging” effects of glucocorticoids in certain cells of the body, will be reviewed. The article concludes with a conceptual model of glucocorticoid actions in the brain that may lead to novel therapeutic opportunities.
Effects of Glucocorticoids on Mood, Memory, and the Hippocampus
Authors: Brown E. Sherwood
Published: November 2009

Corticosteroids, such as prednisone and dexamethasone, are commonly prescribed medications that suppress the immune system and decrease inflammation. Common side effects of long‐term treatment with corticosteroids include weight gain, osteoporosis, and diabetes mellitus. This paper reviews the literature on psychiatric and cognitive changes during corticosteroid therapy and potential treatment options. Hypomania and mania are the most common mood changes during acute corticosteroid therapy, although depression has also been reported. However, depression is reported to be more common than mania during long‐term treatment with corticosteroids. A decline in declarative and working memory is also reported during corticosteroid therapy. Corticosteroids are associated with changes in the temporal lobe, detected by structural, functional, and spectroscopic imaging. The mood and cognitive symptoms are dose dependent and frequently occur during the first few weeks of therapy. Other risk factors are not well characterized. Controlled trials suggest that lithium and phenytoin can prevent mood symptoms associated with corticosteroids. Lamotrigine and memantine also have been shown to reverse, at least partially, the declarative memory effects of corticosteroids. Uncontrolled trials suggest that antipsychotics, anti‐seizure medications, and perhaps some antidepressants can also be useful for normalizing mood changes associated with corticosteroids. Thus, both the symptoms and treatment response are similar to those of bipolar disorder. Moreover, corticosteroid‐induced mood and cognitive alterations have been shown to be reversible with dose reduction or discontinuation of treatment.
Sex Hormones and Mood in the Perimenopause
Authors: Schmidt Peter J. , Rubinow David R.
Published: November 2009

The focus of this chapter is the relationship between the onset of depression in women and the reproductive events of the menopause transition. Epidemiologic studies have documented that the majority of women do not become depressed during the menopause transition. However, recent longitudinal studies suggest that in some women, the reproductive events related to the menopause transition could play a role in the onset of depression. No abnormality of ovarian hormones has been identified that distinguishes women with depression from those who remain asymptomatic during the menopause transition. Nonetheless, several findings suggest a role of ovarian hormones in the onset of these depressions. First, episodes of depression cluster during the stage of the menopause transition that is accompanied by estradiol withdrawal. Second, randomized controlled trials have documented the short‐term (3–6 weeks) antidepressant efficacy of estradiol in depressed perimenopausal women. Third, experimentally induced estradiol withdrawal triggers mood symptoms in some women. Thus, although depression is not a uniform accompaniment of the menopause transition, in some women, age‐related changes in ovarian estrogen production may alter central nervous system function and predispose them to develop depression.
Cytokines and Glucocorticoid Receptor Signaling
Authors: Pace Thaddeus W. W. , Miller Andrew H.
Published: November 2009

Data suggest that the activation of immune responses and the release of inflammatory cytokines may play a role in the pathophysiology of major depression. One mechanism by which cytokines may contribute to depression is through their effects on the glucocorticoid receptor (GR). Altered GR function in depression has been demonstrated by neuroendocrine challenge tests that reliably reveal reduced GR sensitivity as manifested by nonsuppression of cortisol following dexamethasone administration in vivo and lack of immune suppression following administration of glucocorticoids in vitro. Relevant to the GR, cytokines have been shown to decrease GR expression, block translocation of the GR from cytoplasm to nucleus, and disrupt GR‐DNA binding through nuclear protein‐protein interactions. In addition, cytokines have been shown to increase the expression of the relatively inert GR beta isoform. Specific cytokine signaling molecules that have been shown to be involved in the disruption of GR activity include p38 mitogen‐activated protein kinase, which is associated with reduced GR translocation, and signal transducer and activator of transcription (STAT)5, which binds to GR in the nucleus. Nuclear factor‐κB (NF‐κB) also has been shown to lead to GR suppression through mutually inhibitory GR‐NF‐κB nuclear interactions. Interestingly, several antidepressants have been shown to enhance GR function, as has activation of protein kinase A (PKA). Antidepressants and PKA activation have also been found to inhibit inflammatory cytokines and their signaling pathways, suggesting that drugs that target both inflammatory responses and the GR may have special efficacy in the treatment of depression.
Clinical Features Associated with Glucocorticoid Receptor Polymorphisms
Authors: Manenschijn Laura , van den Akker Erica L. T. , Lamberts Steven W. J. , van Rossum Elisabeth F. C.
Published: November 2009

The glucocorticoid receptor (GR) is crucial for the effects of glucocorticoids (GCs). Several polymorphisms of the GR are associated with altered sensitivity to GCs. For the ER22/23EK polymorphism, a relative GC resistance has been demonstrated. In vivo, this was suggested by a smaller response to a dexamethasone suppression test (DST), whereas in vitro experiments showed a diminished transactivational activity. The associated features of ER22/23EK carriers consist of favorable metabolic and body compositional conditions. In elderly subjects this polymorphism was associated with longevity and decreased risk of dementia. Interestingly, recent studies also showed an increased risk of major depression. In contrast, the N363S polymorphism was reported to be associated with an enhanced sensitivity to GCs, as was demonstrated by a DST. This polymorphism has also been associated with increased body mass index (BMI) and LDL‐cholesterol levels, as well as increased risk of cardiovascular disease. However, additional studies yielded conflicting results, showing no associations with being overweight. The BclI polymorphism is also associated with increased GC sensitivity. In addition, associations with increased abdominal fat mass, Crohn's disease and, remarkably, major depression have been reported. Another GR polymorphism, located in exon 9β, is associated with increased expression and stabilization of the dominant negative splice variant GR‐β. Carriers of this polymorphism displayed a relative GC resistance in vitro as evidenced by diminished transrepressional activity, which is important for the immune system and inflammation. Associations have been found with increased inflammatory parameters, cardiovascular disease, and rheumatoid arthritis. In this article, studies concerning these clinically relevant GR variants are discussed.
Identifying Early Markers of Alzheimer's Disease using Quantitative Multiplex Proteomic Immunoassay Panels
Authors: Soares Holly D. , Chen Yu , Sabbagh Marwin , Rohrer Alex , Schrijvers Elisabeth , Breteler Monique
Published: November 2009

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with incidence expected to increase four‐fold over the next decade. Extensive research efforts are focused upon identifying new treatments, and early diagnosis is considered key to successful intervention. Although imaging and cerebrospinal fluid biomarkers have shown promise in identifying patients in very early stages of the disease, more noninvasive cost‐effective tools have remained elusive. Recent studies have reported that an 18‐analyte multiplexed plasma panel can differentiate AD from controls suggesting plasma‐based screening tools for early AD diagnosis exists. The current study tested the reproducibility of a subset of the original 18‐analyte panel using a bead‐based multiplex technology. Preliminary results suggest diagnostic accuracy using the subset was 61%. Multivariate analysis of an 89‐analyte multivariate panel yielded a diagnostic accuracy of 70% suggesting a plasma‐based AD signature that may be a useful screening tool.
CREATIVE IRON MANAGEMENT—A PRACTICAL GUIDE
Authors: Jenkins Karen
Published: November 2009

The use of intravenous (IV) iron is now part of the every day management of anaemia in people with Chronic Kidney Disease (CKD). The increase in the number of referrals to renal services since the introduction of estimated glomerular filtration rate (eGFR) reporting in 2006 in England means that people with CKD are being identified earlier and consequently, complications such as anaemia are being highlighted sooner. The prevalence of anaemia of CKD has been estimated in a population study of stage 3–5 CKD as 4.5% (John et al. 2004). People with stage 3 CKD and diabetes have a 22% incidence of anaemia that is much greater than the incidence of 7.9% in those without diabetes (El Achkar et al. 2005). The increase in numbers requiring anaemia management is having an impact on resources and service provision, in particular the treatment of iron deficiency with IV iron. A need to be creative and investigate alternative ways of using resources and providing services in different settings was identified by the multiprofessional members of the Anaemia Nurse Specialist Association (ANSA) and the CKD forum (a project group of the British Renal Society). The outcome has been the production of a practical guide for healthcare professionals to assist with the development of IV iron services in a nonacute hospital setting. The guide was launched at the annual ANSA conference (April 2009) and British Renal Society conference (June 2009).
IRON THERAPY IN CHRONIC KIDNEY DISEASE: CURRENT CONTROVERSIES
Authors: Kovesdy Csaba P , Kalantar‐Zadeh Kamyar
Published: November 2009

Anaemia in chronic kidney disease (CKD) is a complex disease that requires an integrated approach to incorporate both diagnostic and therapeutic interventions and to address the different facets of its aetiology and pathophysiology. The advent of erythropoiesis stimulating agents (ESA) has revolutionised the therapy of anaemia of CKD, and has resulted in a significant decline in the need for blood transfusions in CKD patients. The routine application of ESA has also led to the need for concomitant iron supplementation. ESA and iron therapy now form the cornerstone of anaemia management in CKD. Intravenous iron administration is effective with acceptable safety, and may improve ESA responsiveness. However, less is known about the long‐term safety of iron supplementation in CKD patients. Whereas maintenance (weekly to monthly) intravenous iron has been routinely used in maintenance dialysis patients, iron replacement in patients with non‐dialysis‐dependent CKD is less well studied, in spite of the much larger number of patients affected. This review discusses iron supplementation in CKD with an emphasis toward controversial issues that continue to pose dilemmas in clinical practice. Concerns related to both the optimal amount of iron supplementation and to the safety of various agents available in clinical practice are presented.
EVOLUTION OF IV IRON COMPOUNDS OVER THE LAST CENTURY
Authors: Macdougall Iain C
Published: November 2009

Administration of intravenous (IV) iron has become pivotal in the management of anaemia in patients with chronic kidney disease (CKD). Since parenteral iron was first introduced for human use in the 1930s, things have come a long way. Seventy years ago, iron was toxic, administered as an iron oxyhydroxide complex. This problem was circumvented with the introduction of compounds containing iron in a core surrounded by a carbohydrate shell. The carbohydrate shell consists of molecules such as dextran, sucrose, dextrin or gluconate. The first dextran‐containing IV iron preparations carried a small risk of anaphylaxis, but the more recently introduced low molecular weight iron dextran preparation has significantly less risk of this. Iron reactions occur with all IV iron preparations, but are generally not thought to be immune based. Recently, newer IV iron preparations have appeared in the market, including Ferumoxytol (Feraheme®) and ferric carboxymaltose (Ferinject®). These latest IV iron preparations do not contain a requirement for a test dose, and a much higher dose of iron can be delivered as a single administration. Thus, giving supplemental iron to man has come a long way since 1930s; we are now in an era when we are able to administer higher doses of iron with acceptable safety and without significant adverse effects. However, the long‐term safety of the newer IV iron preparations is not yet established.
AN EVIDENCE‐BASED APPROACH TO ANAEMIA MANAGEMENT IN PREDIALYSIS CHRONIC KIDNEY DISEASE
Authors: Pugh‐Clarke Karen , Cooper Liz , Turner June , Fermin Jenny
Published: November 2009

The use of Evidence‐based practice (EBP) is a decision‐making process, which integrates the best available research, clinician expertise, and client characteristics, integrating quality patient care in terms of clinical outcomes and cost‐effectiveness. This paper describes the application of EBP to an outpatient intravenous (IV) iron clinic for patients with predialysis chronic kidney disease (CKD).

There has been an increasing focus on managing anaemia in patients with predialysis CKD. Along with the use of erythropoiesis stimulating agents, there has been an emerging interest in the use of IV iron preparations to treat anaemia in this patient population. Using EBP, we introduced a single dose preparation Ferinject® to replace our original IV iron protocol using Venofer®. As a test dose of Ferinject® is not required, it is extremely appropriate for use in busy nurse‐led IV iron clinics.

Based upon the evidence generated from our initial trial of using Ferinject®, and our clinical experience of using this preparation, we have now converted our IV iron protocol to Ferinject®. Although the evaluation of Ferinject® in our predialysis population is ongoing, we are continuing to observe the benefits of using this preparation, both in terms of patient outcome and cost‐effectiveness. We consider that the use of Ferinject® has reduced waiting time and waiting list pressure, and also reduced material and hospital transport costs, which are significant due to the large geographical area covered by our CKD service.
Ploidy level analysis of apomictic Hieracium (Asteraceae) reveal unexpected patterns and variation
Authors: Tyler Torbjörn , Jönsson Jane
Published: November 2009

The DNA ploidy level of 673 accessions belonging to 238 species of Hieracium have been analyzed by flow cytometry. 222 of the species were of Scandinavian origin as members of the exclusively apomictic H. sectt. Bifida, Hieracium, Oreadea, Tridentata and Vulgata. For the overwhelming majority of the species, the ploidy level (or chromosme number) has never been investigated before. Approximately 50% of the Scandinavian species, previously believed to be exclusively triploid, were found to be tetraploid. In addition, two pentaploid samples, viz. H. intermarginatum Johanss. & Sam. from Sweden and H. cf. plumbeum Blytt & Fr. from Germany, were found. Although two or more accessions from geographically remote sites were analyzed for approximately 50% of the Scandinavian species, only 2 (<2%) taxonomically undisputed species were found to consist of plants with more than one ploidy level. An intriguing pattern was revealed among Scandinavian members of H. sectt. Bifida and Vulgata when ploidy level and morphometric variation was compared, viz. the most typical or extreme representatives of these sections were found to be exclusively triploid whereas tetraploids dominate among species with intermediate morphology and among species morphologically intermediate between these sections and H. sect. Hieracium. This pattern may indicate that the tetraploids, which tend to have mainly northern distributions, have originated as the result of rare sexual hybridizations between triploid members of different sections, plausibly during or after the northward migration of the parental linages after the last glaciation. The results are believed to be highly relevant for understanding the processes of evolution and speciation within the predominantly apomictic genus Hieracium, but it is emphazised that additional data from e.g. molecular markers and pollen viability analysis are needed before any trustworthy conclusions can be made as far as evolutionary processes are concerned.
Detection of antinuclear antibodies by the Inno‐Lia ANA update test in canine systemic rheumatic disease
Authors: Hansson‐Hamlin Helene , Rönnelid Johan
Published: November 2009

Background: Certain systemic autoimmune diseases in dogs are characterized by high titers of circulating antinuclear antibodies (ANA), which can be demonstrated by indirect immunofluorescence (IIF). In an earlier study of IIF‐ANA–positive dogs, the Ouchterlony double immunodiffusion (DID) test was used to identify specific autoantibodies. The DID test has largely been replaced with line blot tests in human diagnostic settings.

Objective: The objective of this study was to investigate whether the line blot assay Inno‐Lia ANA update test is a useful tool in demonstrating ANA specificities in canine patients with previously diagnosed IIF‐ANA–positive rheumatic disorders.

Methods: Serum samples from 3 clinically healthy control dogs and 20 canine patients with clinical signs of systemic rheumatic disease and documented positive results for IIF‐ANA and DID tests were included in the study. The Inno‐Lia ANA update assay was performed with an anti‐canine detection antibody.

Results: Six serum samples that had DID positivity with anti‐spliceosomal small nuclear ribonucleoproteins (snRNP) reactivity showed reactivity to multiple snRNP proteins in the Inno‐Lia test. Samples from 2 dogs that had other types of DID positivity also had clear SmB reactivity and 1 had weak reactivity to RNP‐70K. The other serum samples, including controls, were negative.

Conclusions: Using the Inno‐Lia ANA update test, multiple snRNP specificities were demonstrated in some canine patients with autoimmune rheumatic disorders. Other canine autoantibodies may exist that are not detected by this test. Further studies are necessary to characterize the target antigen(s) of these remaining autoantibodies in canine sera.
Metabolism of haem in Caco‐2 cells
Authors: Uc Aliye , McDonagh Antony F. , Stokes John B.
Published: October 2009

The haem oxygenase‐1–biliverdin reductase system degrades haem and generates biliverdin and bilirubin, both of which possess antioxidant and anti‐inflammatory properties. Biliverdin and bilirubin are protective in intestinal injury models, but little is known about their generation and fate in the intestine. In the present work, an in vitro intestinal epithelial cell model, Caco‐2 cells, were exposed to haem from either the apical or the basolateral side, and bile pigment generation and transport were measured spectrophotometrically and with high‐pressure liquid chromatography. The Caco‐2 cells generated bilirubin and bilirubin glucuronides upon exposure to haem. Bilirubin appeared predominantly in the apical medium regardless of the side to which haem was applied. In contrast to an earlier report, significant bidirectional haem transport was not observed. We conclude that Caco‐2 cells metabolize haem and export its metabolic product, bilirubin, principally to the lumen, where it may exert antioxidant and anti‐inflammatory functions.
Cell‐to‐cell communication in intact taste buds through ATP signalling from pannexin 1 gap junction hemichannels
Authors: Dando Robin , Roper Stephen D.
Published: November 2009

Isolated taste cells, taste buds and strips of lingual tissue from taste papillae secrete ATP upon taste stimulation. Taste bud receptor (Type II) cells have been identified as the source of ATP secretion. Based on studies on isolated taste buds and single taste cells, we have postulated that ATP secreted from receptor cells via pannexin 1 hemichannels acts within the taste bud to excite neighbouring presynaptic (Type III) cells. This hypothesis, however, remains to be tested in intact tissues. In this report we used confocal Ca2+ imaging and lingual slices containing intact taste buds to test the hypothesis of purinergic signalling between taste cells in a more integral preparation. Incubating lingual slices with apyrase reversibly blocked cell‐to‐cell communication between receptor cells and presynaptic cells, consistent with ATP being the transmitter. Inhibiting pannexin 1 gap junction hemichannels with CO2‐saturated buffer or probenecid significantly reduced cell–cell signalling between receptor cells and presynaptic cells. In contrast, anandamide, a blocker of connexin gap junction channels, had no effect of cell‐to‐cell communication in taste buds. These findings are consistent with the model for peripheral signal processing via ATP and pannexin 1 hemichannels in mammalian taste buds.
Functional and structural identification of amino acid residues of the P2X2 receptor channel critical for the voltage‐ and [ATP]‐dependent gating
Authors: Keceli Batu , Kubo Yoshihiro
Published: November 2009

The extracellular ATP‐gated cation channel P2X2 is known to show voltage‐dependent gating in spite of the absence of a canonical voltage sensor domain. We previously observed that the hyperpolarization‐evoked activation of P2X2 at the steady state in the presence of ATP varied depending on [ATP]. With increasing [ATP], the conductance–voltage (G–V) relationship shifted to more depolarized potentials and the activation kinetics were accelerated. Using a three‐state model consisting of an ATP binding step and a rate limiting gating step, we successfully reproduced the voltage‐dependent gating including its [ATP] dependence. In this study, in order to identify the structural basis of voltage and ATP dependence, we analysed various mutants in the Xenopus oocyte expression system under two‐electrode voltage clamp. In the ATP binding region mutant K308R, the G–V relationship was shifted towards more hyperpolarized potentials, there was no clear [ATP] dependence, and activation was faster than in wild‐type (WT). These results could be simulated by assuming an increase in the off rate of the gating step, in addition to changes in the ATP binding step. With F44C mutation in the 1st transmembrane (TM) region (TM1) or T339S in TM2, activation in low [ATP] was slow and the channel was constitutively active at all membrane potentials in high [ATP]. These results could be simulated by reducing the off rate of the gating step. Phenotypes of the double mutants, K308R/F44C and K308R/T339S, were similar to WT, suggesting that TM and ATP binding region mutants offset the effect of each other. Analysis of the effects on WT of two other agonists, ADP and AP4A, revealed that the electrostatic charge is not the sole critical factor. Taking these results together with the recently reported crystal structure, it was suggested that upon binding of ATP, the occupied binding site indirectly interacts with the extracellular end of the TM regions to trigger conformational changes for gating in a voltage‐dependent manner.