Androgen Receptors in a Cichlid Fish, Astatotilapia Burtoni: Structure, Localization, and Expression Levels

The Journal of Comparative Neurology. Sep, 2007  |  Pubmed ID: 17614300

Androgens are an important output of the hypothalamic-pituitary-gonadal (HPG) axis that controls reproduction in all vertebrates. In male teleosts two androgens, testosterone and 11-ketotestosterone, control sexual differentiation and development in juveniles and reproductive behavior in adults. Androgenic signals provide feedback at many levels of the HPG axis, including the hypothalamic neurons that synthesize and release gonadotropin-releasing hormone 1 (GnRH1), but the precise cellular site of androgen action in the brain is not known. Here we describe two androgen receptor subtypes, ARalpha and ARbeta, in the cichlid Astatotilapia burtoni and show that these subtypes are differentially located throughout the adult brain in nuclei known to function in the control of reproduction. ARalpha was expressed in the ventral part of the ventral telencephalon, the preoptic area (POA) of the hypothalamus and the ventral hypothalamus, whereas ARbeta was more widely expressed in the dorsal and ventral telencephalon, the POA, and the ventral and dorsal hypothalamus. We provide the first evidence in any vertebrate that the GnRH1-releasing neurons, which serve as the central control point of the HPG axis, express both subtypes of AR. Using quantitative real-time PCR, we show that A. burtoni AR subtypes have different expression levels in adult tissue, with ARalpha showing significantly higher expression than ARbeta in the pituitary, and ARbeta expressed at a higher level than ARalpha in the anterior and middle brain. These data provide important insight into the role of androgens in regulating the vertebrate reproductive axis.

The Safety and Efficacy of Dressings with Silver - Addressing Clinical Concerns

International Wound Journal. Jun, 2007  |  Pubmed ID: 17651232

With the increasing use of silver as a topical application in wound care, concerns focussing on its role are bound to arise. These concerns, which centre on issues such as resistance and toxicity, clinical efficacy and cost-effectiveness, need to be addressed and openly discussed so that they are viewed from a rational perspective. While clinical efficacy and safety, along with cost-benefit, are of obvious interest, the origin of some of these concerns is a matter of debate. The silver-containing dressing segment of the medical device market is of huge commercial importance, and, consequently, marketing and promotional issues occasionally obscure the evidence that clinicians need to have in order that they may provide appropriate treatment for their patients. The impact of silver application on the wound bioburden needs to be examined carefully to heighten our awareness of any deleterious effects on the healing process, without inducing any unfounded anxieties.

An Economic Model of Adverse Events and Costs for Oral Anticoagulants Used for Atrial Fibrillation

Current Medical Research and Opinion. Sep, 2007  |  Pubmed ID: 17651537

To construct a semi-Markov model to compare health outcomes and medical costs associated with warfarin and a second anticoagulant over 1- and 5-year periods.

Healthcare Costs of Acute and Chronic Pain Associated with a Diagnosis of Herpes Zoster

Journal of the American Geriatrics Society. Aug, 2007  |  Pubmed ID: 17661954

To determine the healthcare costs of acute and chronic pain associated with herpes zoster.

Additional Uses for the Classic Matrix Band

Operative Dentistry. Jul-Aug, 2007  |  Pubmed ID: 17695616

Left Ventricular Torsional Mechanics After Left Ventricular Reconstruction Surgery for Ischemic Cardiomyopathy

The Journal of Thoracic and Cardiovascular Surgery. Oct, 2007  |  Pubmed ID: 17903502

Surgical left ventricular reconstruction improves symptoms and potentially prognosis in patients with ischemic cardiomyopathy; however, the effects of reconstruction on myocardial mechanics are not well defined. Therefore, we have computed left ventricular rotation and torsion in patients undergoing left ventricular reconstruction to determine its effects on these quantitative measures of myocardial mechanics.

The Effects of Race/ethnicity and Sex on the Risk of Venous Thromboembolism

Current Opinion in Pulmonary Medicine. Sep, 2007  |  Pubmed ID: 17940480

Recently, studies on large diverse populations have described important ethnic/racial differences in venous thromboembolism incidence, and sex has been reported as an important predictor of recurrence. We review the influence of race/ethnicity and sex on venous thromboembolism, concentrating on articles from 2005 to 2007.

Comment: Oral Oxymorphone for Pain Management

The Annals of Pharmacotherapy. Dec, 2007  |  Pubmed ID: 17971405

How Global is the Global Biodiversity Information Facility?

PloS One. 2007  |  Pubmed ID: 17987112

There is a concerted global effort to digitize biodiversity occurrence data from herbarium and museum collections that together offer an unparalleled archive of life on Earth over the past few centuries. The Global Biodiversity Information Facility provides the largest single gateway to these data. Since 2004 it has provided a single point of access to specimen data from databases of biological surveys and collections. Biologists now have rapid access to more than 120 million observations, for use in many biological analyses. We investigate the quality and coverage of data digitally available, from the perspective of a biologist seeking distribution data for spatial analysis on a global scale. We present an example of automatic verification of geographic data using distributions from the International Legume Database and Information Service to test empirically, issues of geographic coverage and accuracy. There are over 1/2 million records covering 31% of all Legume species, and 84% of these records pass geographic validation. These data are not yet a global biodiversity resource for all species, or all countries. A user will encounter many biases and gaps in these data which should be understood before data are used or analyzed. The data are notably deficient in many of the world's biodiversity hotspots. The deficiencies in data coverage can be resolved by an increased application of resources to digitize and publish data throughout these most diverse regions. But in the push to provide ever more data online, we should not forget that consistent data quality is of paramount importance if the data are to be useful in capturing a meaningful picture of life on Earth.

Targeting Patients for Anticoagulant Prophylaxis Trials in Patients with Cancer: Who is at Highest Risk?

Thrombosis Research. 2007  |  Pubmed ID: 18023711

It is not clear which cancer patients are at highest risk for developing venous thromboembolism (VTE).

Complex Regulation of Cyp26a1 Creates a Robust Retinoic Acid Gradient in the Zebrafish Embryo

PLoS Biology. Nov, 2007  |  Pubmed ID: 18031199

Positional identities along the anterior-posterior axis of the vertebrate nervous system are assigned during gastrulation by multiple posteriorizing signals, including retinoic acid (RA), fibroblast growth factors (Fgfs), and Wnts. Experimental evidence has suggested that RA, which is produced in paraxial mesoderm posterior to the hindbrain by aldehyde dehydrogenase 1a2 (aldh1a2/raldh2), forms a posterior-to-anterior gradient across the hindbrain field, and provides the positional information that specifies the locations and fates of rhombomeres. Recently, alternative models have been proposed in which RA plays only a permissive role, signaling wherever it is not degraded. Here we use a combination of experimental and modeling tools to address the role of RA in providing long-range positional cues in the zebrafish hindbrain. Using cell transplantation and implantation of RA-coated beads into RA-deficient zebrafish embryos, we demonstrate that RA can directly convey graded positional information over long distances. We also show that expression of Cyp26a1, the major RA-degrading enzyme during gastrulation, is under complex feedback and feedforward control by RA and Fgf signaling. The predicted consequence of such control is that RA gradients will be both robust to fluctuations in RA synthesis and adaptive to changes in embryo length during gastrulation. Such control also provides an explanation for the fact that loss of an endogenous RA gradient can be compensated for by RA that is provided in a spatially uniform manner.

Connecting Multiple Open Wounds to a Single Negative-pressure Dressing

American Journal of Orthopedics (Belle Mead, N.J.). Nov, 2007  |  Pubmed ID: 18075612

We present a new technique for connecting open wounds to a negative-pressure device. In this technique, a flexible, small-diameter intravenous tube is used to bridge the gap between open wounds on the same extremity. After these connections are made, the first layer of plastic is placed, and only 1 fenestrated connection is made to the device. This technique allows use of multiple sponges with only 1 fenestrated cap and 1 connection to the device. The smaller intravenous tube must not be placed directly on skin, as it may cause a pressure ulcer underneath.

Treating Curable Sexually Transmitted Infections to Prevent HIV in Africa: Still an Effective Control Strategy?

Journal of Acquired Immune Deficiency Syndromes (1999). Mar, 2008  |  Pubmed ID: 18176323

Evidence regarding the effectiveness of sexually transmitted infection (STI) treatment for HIV prevention in Africa is equivocal, leading some policy makers to question whether it should continue to be promoted for HIV control. We explore whether treating curable STIs remains a cost-effective HIV control strategy in Africa.

Global Monitoring of Autumn Gene Expression Within and Among Phenotypically Divergent Populations of Sitka Spruce (Picea Sitchensis)

The New Phytologist. 2008  |  Pubmed ID: 18194148

Cold acclimation in conifers is a complex process, the timing and extent of which reflects local adaptation and varies widely along latitudinal gradients for many temperate and boreal tree species. Despite their ecological and economic importance, little is known about the global changes in gene expression that accompany autumn cold acclimation in conifers. Using three populations of Sitka spruce (Picea sitchensis) spanning the species range, and a Picea cDNA microarray with 21,840 unique elements, within- and among-population gene expression was monitored during the autumn. Microarray data were validated for selected genes using real-time PCR. Similar numbers of genes were significantly twofold upregulated (1257) and downregulated (967) between late summer and early winter. Among those upregulated were dehydrins, pathogenesis-related/antifreeze genes, carbohydrate and lipid metabolism genes, and genes involved in signal transduction and transcriptional regulation. Among-population microarray hybridizations at early and late autumn time points revealed substantial variation in the autumn transcriptome, some of which may reflect local adaptation. These results demonstrate the complexity of cold acclimation in conifers, highlight similarities and differences to cold tolerance in annual plants, and provide a solid foundation for functional and genetic studies of this important adaptive process.

Afferent Arteriolar Dilation to 11, 12-EET Analogs Involves PP2A Activity and Ca2+-activated K+ Channels

Microcirculation (New York, N.Y. : 1994). Feb, 2008  |  Pubmed ID: 18260004

The epoxygenase metabolite, 11, 12-epoxyeicosatrienoic acid (11, 12-EET), has renal vascular actions. 11, 12-EET analogs have been developed to determine the structure activity relationship for 11, 12-EET and as a tool to investigate signaling mechanisms responsible for afferent arteriolar dilation. We hypothesized that 11, 12-EET mediated afferent arteriolar dilation involves increased phosphoprotein phosphatase 2A (PP2A) and large-conductance calcium activated K+ (KCa) channels. We evaluated the chemically and/or metabolically table 11, 12-EET analogs: 11, 12-EET-N-methylsulfonimide (11, 12-EET-SI), 11-nonyloxy-undec-8(Z)-enoic acid (11, 12-ether-EET-8-ZE), and 11, 12-trans-oxidoeicosa-8(Z)-eonoic acid (11, 12-tetra-EET-8-ZE). Afferent arteriolar responses were assessed. Activation of KCa channels by 11, 12-EET analogs were established by single cell channel recordings in renal myocytes. Assessment of renal vascular responses revealed that 11, 12-EET analogs increased afferent arteriolar diameter. Vasodilator responses to 11, 12-EET analogs were abolished by K+ channel or PP2A inhibition. 11, 12-EET analogs activated renal myocyte large-conductance KCa channels. 11, 12-EET analogs increased cAMP by 2-fold and PP2A activity increased 3-8 fold in renal myocytes. PP2A inhibition did not significantly affect the 11, 12-EET analog mediated increase in cAMP and PP2A increased renal myocyte KCa channel activity to a much greater extent than PKA. These data support the concept that 11, 12-EET utilizes PP2A dependent pathways to activate large-conductance KCa channels and dilate the afferent arteriole.

Melanoma Biology and the Promise of Zebrafish

Zebrafish. Dec, 2008  |  Pubmed ID: 19133823

Advantageous organismal and technical attributes of the zebrafish are being increasingly applied to study cancer biology. Along with other tumor models, zebrafish that develop melanomas have been generated. In both genetics and phenotype, zebrafish melanomas are strikingly similar to their human counterparts. For this reason, studies in the zebrafish are poised to make significant contributions to melanoma biology. In this review, we summarize important features of human melanoma and discuss how the zebrafish can be used to address many questions that remain unanswered about this devastating disease.

The Effect of a Depth Gradient on the Mating Behavior, Oviposition Site Preference, and Embryo Production in the Zebrafish, Danio Rerio

Zebrafish. Dec, 2008  |  Pubmed ID: 19133832

Captive zebrafish (Danio rerio) exhibit a limited repertoire of mating behaviors, likely due to the somewhat unnatural environment of aquaria. Observations in their natural habitat led us to believe that a depth gradient within the mating setup would positively affect fish mating. By tilting the tank to produce a depth gradient, we observed novel behaviors along with a preference for oviposition in the shallow area. Although we did not see an increase in the likelihood of a pair of fish to mate, we did see an increase in the embryo output in both adults and juveniles. In the adults, tilting led to a significant increase in embryo production (436 +/- 35 tilted vs. 362 +/- 34 untilted; p < 0.05). A similar effect was seen in juvenile fish as they progressed through sexual maturity. These results suggest that tilting of mating cages in the laboratory setting will lead to demonstrable improvements in embryo production for zebrafish researchers, and highlights the possibility of other manipulations to increase fecundity.

Influence of Coronary Artery Stenosis Severity and Coronary Collateralization on Extent of Chronic Myocardial Scar: Insights from Quantitative Coronary Angiography and Delayed-enhancement MRI

The Open Cardiovascular Medicine Journal. 2008  |  Pubmed ID: 19337359

In patients with chronic ischemic heart disease, the relationship between coronary artery lesion severity and myocardial scarring is unknown.The purpose of this study was to examine the relationship between proximal coronary artery stenosis severity, the amount of coronary collateralization, and myocardial scar extent in the distal distribution of the affected coronary artery based on both quantitative coronary angiography (QCA) and delayed-enhancement magnetic resonance imaging (DE-MRI).

Interpreting the Clinical Importance of Treatment Outcomes in Chronic Pain Clinical Trials: IMMPACT Recommendations

The Journal of Pain : Official Journal of the American Pain Society. Feb, 2008  |  Pubmed ID: 18055266

A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. PERSPECTIVE: Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments.

GPR87 is an Overexpressed G-protein Coupled Receptor in Squamous Cell Carcinoma of the Lung

Disease Markers. 2008  |  Pubmed ID: 18057535

Lung cancer is the leading cause of cancer death worldwide. The overall 5-year survival after therapy is about 16% and there is a clear need for better treatment options, such as therapies targeting specific molecular structures. G-protein coupled receptors (GPCRs), as the largest family of cell surface receptors, represent an important group of potential targets for diagnostics and therapy. We therefore used laser capture microdissection and GPCR-focused Affymetrix microarrays to examine the expression of 929 GPCR transcripts in tissue samples of 10 patients with squamous cell carcinoma and 7 with adenocarcinoma in order to identify novel targets in non-small cell lung carcinoma (NSCLC). The relative gene expression levels were calculated in tumour samples compared to samples of the neighbouring alveolar tissue in every patient. Based on this unique study design, we identified 5 significantly overexpressed GPCRs in squamous cell carcinoma, in the following decreasing order of expression: GPR87 > CMKOR1 > FZD10 > LGR4 > P2RY11. All are non-olfactory and GRAFS (glutamate, rhodopsin, adhesion, frizzled/taste2, secretin family) classified. GPR87, LGR4 and CMKOR1 are orphan receptors. GPR87 stands out as a candidate for further target validation due to its marked overexpression and correlation on a mutation-based level to squamous cell carcinoma.

Melanocytes in Development, Regeneration, and Cancer

Cell Stem Cell. Sep, 2008  |  Pubmed ID: 18786412

The genes required for stem cell specification and lineage restriction during embryogenesis also play fundamental roles in adult tissue regeneration and cancer. This "development-regeneration-cancer" axis is exemplified by the vertebrate pigmentation system. Melanocytes exhibit almost unlimited self-renewal capacity during regenerative processes such as mammalian hair recoloration and zebrafish fin regeneration. Melanoma utilizes many regulatory signals and pathways required during ontogeny and regeneration. A discussion of these interconnections highlights how studies of stem cell function in embryonic and regenerative contexts can yield insights into melanoma biology.

How Degrading: Cyp26s in Hindbrain Development

Developmental Dynamics : an Official Publication of the American Association of Anatomists. Oct, 2008  |  Pubmed ID: 18816852

The vitamin A derivative retinoic acid performs many functions in vertebrate development and is thought to act as a diffusible morphogen that patterns the anterior-posterior axis of the hindbrain. Recent work in several systems has led to insights into how the spatial distribution of retinoic acid is regulated. These have shown local control of synthesis and degradation, and computational models suggest that degradation by the Cyp26 enzymes plays a critical role in the formation of a morphogen gradient as well as its ability to compensate for fluctuations in RA levels.

Risk of Fatal Pulmonary Embolism Was 0.49 Per 100 Person-years After Discontinuing Anticoagulant Therapy for Venous Thromboembolism

Evidence-based Medicine. Oct, 2008  |  Pubmed ID: 18836122

Control of Sexually Transmitted Infections for HIV Prevention

Lancet. Oct, 2008  |  Pubmed ID: 18929894

Generation and Characterization of Gasoline Engine Exhaust Inhalation Exposure Atmospheres

Inhalation Toxicology. Oct, 2008  |  Pubmed ID: 18951232

Exposure atmospheres for a rodent inhalation toxicology study were generated from the exhaust of a 4.3-L gasoline engine coupled to a dynamometer and operated on an adapted California Unified Driving Cycle. Exposure levels were maintained at three different dilution rates. One chamber at the lowest dilution had particles removed by filtration. Each exposure atmosphere was characterized for particle mass, particle number, particle size distribution, and detailed chemical speciation. The majority of the mass in the exposure atmospheres was gaseous carbon monoxide, nitrogen oxides, and volatile organics, with small amounts of particle-bound carbon/ions and metals. The atmospheres varied according to the cycle, with the largest spikes in volatile organic and inorganic species shown during the "cold start" portion of the cycle. Ammonia present from the exhaust and rodents interacted with the gasoline exhaust to form secondary inorganic particles, and an increase in exhaust resulted in higher proportions of secondary inorganics as a portion of the total particle mass. Particle size had a median of 10-20 nm by number and approximately 150 nm by mass. Volatile organics matched the composition of the fuel, with large proportions of aliphatic and aromatic hydrocarbons coupled to low amounts of oxygenated organics. A new measurement technique revealed organics reacting with nitrogen oxides have likely resulted in measurement bias in previous studies of combustion emissions. Identified and measured particle organic species accounted for about 10% of total organic particle mass and were mostly aliphatic acids and polycyclic aromatic hydrocarbons.

Activated Partial Thromboplastin Time and Risk of Future Venous Thromboembolism

The American Journal of Medicine. Mar, 2008  |  Pubmed ID: 18328308

Lower activated partial thromboplastin times are associated with higher levels of some coagulation factors and may represent a procoagulant tendency.

Multidetector Computed Tomographic Angiography in Planning of Reoperative Cardiothoracic Surgery

The Annals of Thoracic Surgery. Apr, 2008  |  Pubmed ID: 18355503

Redo cardiothoracic surgery is associated with increased morbidity and mortality compared with primary operations. Multidetector computed tomographic angiography (MDCTA) delineates the course of previous coronary artery bypass grafts (CABG) and proximity of mediastinal structures to the chest wall. We sought to determine if high-risk preoperative MDCTA findings were associated with greater use of preventive surgical strategies during redo cardiac surgery in patients with prior CABG.

Cruciate-retaining Total Knee Arthroplasty in Patients with at Least Fifteen Degrees of Coronal Plane Deformity

The Journal of Arthroplasty. Apr, 2008  |  Pubmed ID: 18358374

There has been debate regarding the superiority of posterior stabilized (PS) or cruciate-retaining knee designs in total knee arthroplasty (TKA). The proponents of PS TKA argue that a relative contraindication to the use of cruciate-retaining total knee arthroplasty is that of significant coronal plane deformity. The purpose of this study is to compare our minimum 10-year results of posterior cruciate ligament-retaining TKAs in patients with preoperative coronal plane deformity of at least 15 degrees (> or =10 degrees of varus or > or =20 degrees of valgus) to historical results of PS TKA designs in similar patients. We found, at a minimum 10-year follow-up, very good results with a 93% (95% confidence interval, 87%-98%) revision-free survivorship at 10 years and no revisions for instability or loosening.

Health Care Expenditure Burden of Persisting Herpes Zoster Pain

Pain Medicine (Malden, Mass.). Apr, 2008  |  Pubmed ID: 18366512

Pain can persist long after the resolution of herpes zoster, but little is known regarding its health care costs. The objective of this study was to determine the health care expenditures associated with persisting pain following herpes zoster by comparing expenditures for patients with postherpetic neuralgia or subacute herpetic neuralgia with a control group without these conditions.

Transparent Adult Zebrafish As a Tool for in Vivo Transplantation Analysis

Cell Stem Cell. Feb, 2008  |  Pubmed ID: 18371439

The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish. To address this, we have created a transparent adult zebrafish in which we transplanted either hematopoietic stem/progenitor cells or tumor cells. In a hematopoiesis radiation recovery assay, transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr-5 weeks posttransplant. Using FACS analysis, both transparent and wild-type fish had equal engraftment, but this could only be visualized in the transparent recipient. In a tumor engraftment model, transplantation of RAS-melanoma cells allowed for visualization of tumor engraftment, proliferation, and distant metastases in as little as 5 days, which is not seen in wild-type recipients until 3 to 4 weeks. This transparent adult zebrafish serves as the ideal combination of both sensitivity and resolution for in vivo stem cell analyses.

Tissue Viability in Tomorrow's NHS

Journal of Wound Care. Mar, 2008  |  Pubmed ID: 18376649

This article is based on the inaugural lecture of the UK's first and only Professor of Tissue Viability, Richard White, given at the University of Worcester in January. In it he asks how our discipline can best adapt to meet existing and future needs.

Cancer Risk in a Cohort of Patients with Systemic Lupus Erythematosus (SLE) in California

Cancer Causes & Control : CCC. Oct, 2008  |  Pubmed ID: 18386139

We conducted a retrospective cohort study to examine cancer risk in a large cohort of systemic lupus erythematosus (SLE) patients in California.

Death Due to Recurrent Thromboembolism Among Younger Healthier Individuals Hospitalized for Idiopathic Pulmonary Embolism

Thrombosis and Haemostasis. Apr, 2008  |  Pubmed ID: 18392326

The incidence of death due to recurrent pulmonary embolism (PE) after a first-time idiopathic PE is not well defined. We conducted a retrospective study of patients age 18 to 56 years who had idiopathic PE between 1994-2001. The incidence and cause of death within five years was determined using linked discharge records and a master death registry. A total of 3,456 patients had a first-time idiopathic PE. The rate of recurrent VTE 0-6 months after the index event was 13.1%/year, and 2.9%/year 6-60 months after the event. During the mean follow-up of 3.2 years 118 (3.4%, 95% confidence interval [CI] = 2.8-4.1%) patients died. Fifty-two (44%) deaths occurred <29 days after the index PE (case-fatality rate = 1.5%, 95%CI = 1.1-2.0%). Among the 66 cases (1.9%) that died after 28 days, 18 (0.52%) were due to recurrent PE or its sequelae: eight had recurrent PE alone, five had recurrent PE and a serious co-morbid illness, and five had thromboembolic pulmonary hypertension with or without acute PE. The person-time rate of death (deaths per 100 patient-years) attributed to any recurrent thromboembolism 6-60 months after the event was 0.16% (95%CI = 0.1-0.26%). Ten of the 18 (56%) late thromboembolic deaths reflected a first-time recurrent PE. The 28-day case-fatality rate for recurrent VTE was 2.8% (95%CI = 1.5-4.9%). In this cohort of younger patients with idiopathic PE, the rate of death due to recurrent VTE, particularly to first-time recurrent PE, was low. Among the patients who died of thromboembolism >28 days after the index PE, 28% had developed pulmonary hypertension.

Cryoablative Therapy in Breast Cancer: No

Journal of Surgical Oncology. May, 2008  |  Pubmed ID: 18425784

Monoterpene-induced Molecular Responses in Arabidopsis Thaliana

Phytochemistry. Jun, 2008  |  Pubmed ID: 18468649

Terpenoid volatiles mediate various forms of chemical communications of plants with other organisms. In this paper we demonstrate that exposure of intact Arabidopsis thaliana plants to monoterpene volatiles results in substantial changes of the plant transcriptome and induction of methyl jasmonate (MeJA) accumulation. We used a heterologous pinII::GUS reporter system to test monoterpenes for their potential to induce a response in A. thaliana. Plants showed increased pinII-promoter activity upon exposure to different monoterpene volatiles, similar to the response induced by MeJA, mechanical wounding, or insect feeding. Microarray gene expression profiling indicated induced changes in the abundance of several hundred transcripts in wild-type plants upon either exposure to myrcene volatiles or exposure to a blend of ocimene volatiles consisting of (E)-beta-ocimene, (Z)-beta-ocimene, and allo-ocimene. Many of the monoterpene-induced transcripts are annotated as either transcription factors or as stress or defense genes including several steps in the octadecanoid pathway. Metabolite analysis showed that exposure of Arabidopsis for 2h to myrcene or ocimene induced increased tissue levels of MeJA. Octadecanoid biosynthesis (aoc) and signaling (coi1) mutants showed some reduced ocimene-induction of gene expression.

Pain Assessment and Management in Patients with Chronic Wounds

Nursing Standard (Royal College of Nursing (Great Britain) : 1987). Apr 16-22, 2008  |  Pubmed ID: 18481605

Pain is a frequent symptom in patients with chronic wounds. It contributes to significant levels of suffering and distress, as well as reduced quality of life. This article considers interventions and procedures for managing pain in patients with chronic wounds.

Life Events As Predictors of Mania and Depression in Bipolar I Disorder

Journal of Abnormal Psychology. May, 2008  |  Pubmed ID: 18489203

To date, few prospective studies of life events and bipolar disorder are available, and even fewer have separately examined the role of life events in depression and mania. The goal of this study was to prospectively examine the role of negative and goal-attainment life events as predictors of the course of bipolar disorder. One hundred twenty-five individuals with bipolar I disorder were interviewed monthly for an average of 27 months. Negative and goal-attainment life events were assessed with the Life Events and Difficulties Schedule. Changes in symptoms were evaluated using the Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Scale. The clearest results were obtained for goal-attainment life events, which predicted increases in manic symptoms over time. Negative life events predicted increases in depressive symptoms within regression models but were not predictive within multilevel modeling of changes in depressive symptoms. Given different patterns for goal attainment and negative life events, it appears important to consider specific forms of life events in models of bipolar disorder.

Understanding the Impact of Male Circumcision Interventions on the Spread of HIV in Southern Africa

PloS One. 2008  |  Pubmed ID: 18493593

Three randomised controlled trials have clearly shown that circumcision of adult men reduces the chance that they acquire HIV infection. However, the potential impact of circumcision programmes--either alone or in combination with other established approaches--is not known and no further field trials are planned. We have used a mathematical model, parameterised using existing trial findings, to understand and predict the impact of circumcision programmes at the population level.

N-of-1 Trials of Expensive Biological Therapies: a Third Way?

Archives of Internal Medicine. May, 2008  |  Pubmed ID: 18504330

In developing policies for use of expensive agents, such as those used for the treatment of rheumatoid arthritis, managed care organizations have invoked "stepped care," in which physicians and patients must first try more established and less costly agents. N-of-1 clinical trials are multiple crossover trials in a single patient. In this cost-minimization analysis, we show that offering patients with rheumatoid arthritis the opportunity to participate in an n-of-1 trial comparing methotrexate with etanercept could save costs relative to open access while preserving clinical freedom relative to mandatory stepped care. In the primary model, the n-of-1 trial option was 15% more expensive than stepped care but 47% cheaper than open access to etanercept. More research is needed on the acceptability, safety, and generalizability of this promising approach.

Don't Give Me Evidence, Give Me Reality!

British Journal of Nursing (Mark Allen Publishing). Mar 27-Apr 9, 2008  |  Pubmed ID: 18521992

Core Outcome Domains and Measures for Pediatric Acute and Chronic/recurrent Pain Clinical Trials: PedIMMPACT Recommendations

The Journal of Pain : Official Journal of the American Pain Society. Sep, 2008  |  Pubmed ID: 18562251

Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 26 professionals from academia, governmental agencies, and the pharmaceutical industry participated in a 2-stage Delphi poll and a consensus meeting that identified core outcome domains and measures that should be considered in clinical trials of treatments for acute and chronic pain in children and adolescents. Consensus was refined by consultation with the international pediatric pain community through announcement of our recommendations on the Pediatric Pain List and inviting and incorporating comments from external sources. There was consensus that investigators conducting pediatric acute pain clinical trials should consider assessing outcomes in pain intensity; global judgment of satisfaction with treatment; symptoms and adverse events; physical recovery; emotional response; and economic factors. There was also agreement that investigators conducting pediatric clinical trials in chronic and recurrent pain should consider assessing outcomes in pain intensity; physical functioning; emotional functioning; role functioning; symptoms and adverse events; global judgment of satisfaction with treatment; sleep; and economic factors. Specific measures or measurement strategies were recommended for different age groups for each domain. PERSPECTIVE: Based on systematic review and consensus of experts, core domains and measures for clinical trials to treat pain in children and adolescents were defined. This will assist in comparison and pooling of data and promote evidence-based treatment, encourage complete reporting of outcomes, simplify the review of proposals and manuscripts, and facilitate clinicians making informed decisions regarding treatment.

The Dimensions of Pain Quality: Factor Analysis of the Pain Quality Assessment Scale

The Clinical Journal of Pain. Jul-Aug, 2008  |  Pubmed ID: 18574365

To provide a better empirical understanding of the dimensionality of neuropathic and non-neuropathic pain quality.

Structured Reporting: Coronary CT Angiography: a White Paper from the American College of Radiology and the North American Society for Cardiovascular Imaging

Journal of the American College of Radiology : JACR. Jul, 2008  |  Pubmed ID: 18585655

With the growing use of electronic medical records, the trend of diagnostic imaging reporting is toward a more structured format. Advantages include improved quality and consistency of the reporting and ease of data mining. The essential elements of a structured report are provided and illustrated for coronary artery computed tomographic angiograms.

Systematic Review of Orogenital HIV-1 Transmission Probabilities

International Journal of Epidemiology. Dec, 2008  |  Pubmed ID: 18664564

The objective was to assess the risk of HIV transmission from orogenital intercourse (OI).

Recurrent Venous Thromboembolism After Pregnancy-associated Versus Unprovoked Thromboembolism

Thrombosis and Haemostasis. Aug, 2008  |  Pubmed ID: 18690344

It is not known whether women who develop venous thromboembolism (VTE) during pregnancy have a higher or lower incidence of recurrent VTE than women with unprovoked VTE. The aim of the study was to compare the risk of recurrent VTE among women with pregnancy-associated VTE to women with unprovoked VTE. Hospital discharge data identified women age 18-46 years old with pregnancy-associated or unprovoked index VTE between 1994 and 2005. Risk of recurrent VTE was compared between six and 60 months after the index event using both age-matched comparison of disease-free survival and proportional hazard modelling, adjusting for age and other risk factors. The Kaplan-Meier incidence of recurrent VTE in 1085 women with pregnancy-associated VTE was 5.8% versus 10.4% in 7625 women with unprovoked VTE (p = 0.02). Twelve of 34 (35%) recurrent events in the pregnancy-associated group occurred during a subsequent pregnancy compared with 29 of 331 (8.7%) events in the unprovoked group (p < 0.001). In the risk-adjusted multivariate model, women with pregnancy-associated VTE had a significantly lower risk of recurrent VTE (HR = 0.6, 95%CI = 0.4-0.9). Overall, the incidence of recurrent VTE during subsequent pregnancies was higher in the pregnancy group, 21 of 465 (4.5%), than in the unprovoked group, 37 of 1353 (2.7%, RR = 1.7, CI: 1.0-2.8). Compared to women with unprovoked VTE, women with pregnancy-associated VTE had a significantly lower long-term risk of recurrent VTE but a higher risk of recurrent VTE during a subsequent pregnancy. These findings should be considered when decisions are made about VTE prophylaxis in women with a history of pregnancy-associated VTE.

Analyzing Multiple Endpoints in Clinical Trials of Pain Treatments: IMMPACT Recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials

Pain. Oct, 2008  |  Pubmed ID: 18706763

The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity. To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.

Shostakovich Versus the Central Committee: the Power of Music

Clinical Medicine (London, England). Aug, 2008  |  Pubmed ID: 18724608

The centenary of Shostakovich's birth, celebrated in 2006, generated considerable interest in his life and music. During the Cold War his music was rarely played in the West, and it was not until after his death in 1975 that it re-emerged. The publication of his memoirs in the UK, in 1979, gave new insights into his life in Soviet Russia. Music, like art and literature, has the power to shock and can reflect anger and frustration at contemporary social issues. Much debate has focused on whether Shostakovich was a victim or mouthpiece of Communism. In order to fully appreciate his music, it is essential to understand his personal and professional life under Josef Stalin--in particular his public humiliation by the Central Committee, and by professional musicians who were Communist Party members.

Identifying Unprovoked Thromboembolism Patients at Low Risk for Recurrence Who Can Discontinue Anticoagulant Therapy

CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne. Aug, 2008  |  Pubmed ID: 18725614

Whether to continue oral anticoagulant therapy beyond 6 months after an "unprovoked" venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants.

Male Circumcision for HIV Prevention in Sub-Saharan Africa: Who, What and When?

AIDS (London, England). Sep, 2008  |  Pubmed ID: 18753931

Male circumcision (circumcision) reduces HIV incidence in men by 50-60%. The United Nations Joint Programme on HIV/AIDS (UNAIDS) recommends the provision of safe circumcision services in countries with high HIV and low circumcision prevalence, prioritizing 12-30 years old HIV-uninfected men. We explore how the population-level impact of circumcision varies by target age group, coverage, time-to-scale-up, level of risk compensation and circumcision of HIV infected men.

Role of Phosphodiesterases in Modulation of BKCa Channels in Hypertensive Pulmonary Arterial Smooth Muscle

Therapeutic Advances in Respiratory Disease. Jun, 2008  |  Pubmed ID: 19124364

BKCa channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BK(Ca) channels, but little is known about PKC-mediated modulation of BKCa channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BKCa channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BKCa channels in FHR PASMC, which was blocked by PKC activation, and reversed by the phosphodiesterase (PDE) inhibitors IBMX, milrinone, and zaprinast. PDE inhibition also blocked the vasoconstrictor response to PKC activation in FHR pulmonary arteries. These results indicate that PKC inhibits cAMP-induced activation of BKCa channels and causes pulmonary vasoconstriction in hypertensive pulmonary arterial smooth muscle via PDE, which further suggests PDE inhibitors for treatment of pulmonary hypertension.

Seasonal Dynamics of Soil Micronutrients in Compost-amended Bermudagrass Turf

Bioresource Technology. May, 2008  |  Pubmed ID: 17570655

Compost application to turfgrasses can increase plant-available nutrient concentrations in soil and improve growth, but may alter micronutrient dynamics and increase leaching and runoff losses. The objectives of this study were to investigate the influence of compost on the seasonal dynamics of plant-available Mn, Fe, Cu, and Zn in soil after a single application to bermudagrass [Cynodon dactylon (L.) Pers.] turf. Extractable Mn increased from 270 to 670 mg kg(-1) and Cu from 0.36 to 9.89 mg kg(-1) from 0 to 29 months. In contrast, extractable Fe and Zn decreased by 52% and 57% during the same time period. Seasonal trends in extractable Mn and Cu were closely related to dissolved organic C (DOC), and appeared influenced by bermudagrass growth and dormancy patterns and subsequent impacts on DOC. Losses of Mn and Cu from the soil surface occurred after high levels of precipitation during winter dormancy but not during the growing season, while Fe and Zn exhibited an opposite pattern. Thus, seasonal variation of soil micronutrients was likely related to seasonal patterns of bermudagrass growth and dormancy and their effects on DOC, and precipitation events which probably leached DOC and complexed nutrients from surface soil. Composts only influenced the magnitude of changes in micronutrient concentrations, as similar seasonal trends occurred for both compost-amended and unamended soils.

Mepitel: a Non-adherent Wound Dressing with Safetac Technology

British Journal of Nursing (Mark Allen Publishing). Jan 8-21, 2009  |  Pubmed ID: 19127235

Wound pain and tissue trauma are two main considerations of wound management, and appropriate dressing selection plays an important role in both. Traditional dressings may adhere to wounds resulting in significant pain and trauma to new tissue upon removal. The development of primary wound contact materials has provided a unique approach to solving this problem. This article aims to aid clinicians in identifying wound types on which Mepitel, a primary wound contact dressing with Safetac soft silicone adhesive technology, can be used by summarizing the published clinical literature relating to its use.

Amygdaloid Neurosurgery for Aggressive Behaviour, Sydney, 1967-1977: Chronological Narrative

Australasian Psychiatry : Bulletin of Royal Australian and New Zealand College of Psychiatrists. 2009  |  Pubmed ID: 20455804

OBJECTIVE: The aim of this paper is to record an historical narrative of amygdaloid neurosurgery at Callan Park Mental Hospital, Sydney in the period 1967-1977. In this paper, this is denoted the Amygdaloid Neurosurgery Project (ANP). The goal of the project was to ameliorate aggressive or self-harming behaviour by selective ablative surgery on the amygdaloid nucleus. CONCLUSIONS: In 1964, Professor Leslie Gordon Kiloh became acting director of the newly built neurosurgical research facility at Callan Park Mental Hospital. In 1966, he advised bilateral amygdaloidotomy for the treatment of a 16-year-old aggressive and self-harming male patient. Following major improvement in that patient's condition, a further 19 patients were treated by amygdaloid surgery. In 1974, Kiloh's team reported that 39% of the first 18 patients treated had persisting improvement but one patient sustained persisting hemiplegia. The program was suspended in 1977 by the New South Wales (NSW) Government, following allegations by a senior nurse that patients at the neurosurgical unit had been mistreated. A Ministerial Committee of Inquiry proposed that stringent legislative controls should be applied to psychosurgery. The Committee expressed reservations about amygdaloid psychosurgery in particular. Psychosurgery referrals declined after that date. Since 2007, under the revised NSW Mental Health Act, all forms of neurosurgery for psychiatric disorder are prohibited.

Amygdaloid Neurosurgery for Aggressive Behaviour, Sydney, 1967-1977: Societal, Scientific, Ethical and Other Factors

Australasian Psychiatry : Bulletin of Royal Australian and New Zealand College of Psychiatrists. 2009  |  Pubmed ID: 20455805

OBJECTIVES: In 1967, despite escalating international hostility towards psychosurgery, a program of amygdaloid neurosurgery for the reduction of aggressive and self-harming behaviour commenced in Sydney. In this paper, the second of two articles on the Amygdaloid Neurosurgery Project (ANP), we analyse the relative contributions of seven nominated societal, ethical and other factors to the genesis and demise of the ANP, and consider implications of the history of the ANP for the future of neurosurgery for psychiatric disorders (NPD) in New South Wales (NSW) and elsewhere. CONCLUSIONS: Leadership and the availability of resources were crucial factors in the genesis of the project. Its scientific foundations were doubtful in 1967, and remain so in 2009. Ethical issues became the focus of hostile media and Government attention in 1977 and precipitated the project's demise. Lessons derived from an historical analysis of the ANP should assist the medical profession develop appropriate approaches to recent advances in NPD, including deep brain stimulation, new ablative procedures and stem cell implantation.

Topical Silver-impregnated Dressings and the Importance of the Dressing Technology

International Wound Journal. Oct, 2009  |  Pubmed ID: 19912397

A wide variety of silver-impregnated wound dressings has become available in recent years. This has given the practitioner choice but little evidence by which an appropriate dressing may be selected. In many instances, the ancillary function(s) of the dressing will become differentiating factors that influence choice. For example, the dressing capacity to manage exudate, maintain an optimum moist environment, reduce or avoid maceration, maintain an intimate contact with the wound bed, promote autolytic debridement, sequester bacteria and bind matrix metallo proteases (MMPs) are some of those functions that are of clinical significance and may dictate choice. In this article we present the evidence for these functions, thereby enabling practitioners to evaluate comparative dressing attributes, and so make an informed choice of which silver dressing best suits the needs of the wound under differing circumstances.

Oncogenic NRAS Cooperates with P53 Loss to Generate Melanoma in Zebrafish

Zebrafish. Dec, 2009  |  Pubmed ID: 19954345

NRAS mutations are a common oncogenic event in skin cancer, occurring frequently in congenital nevi and malignant melanoma. To study the role of NRAS in zebrafish, a transgenic approach was applied to generate fish that express human oncogenic NRAS(Q61K) under the control of the melanocyte-restricted mitfa promoter. By screening the progeny of the injected animals, two strains stably expressing the NRAS transgene were identified: Tg(mitfa:EGFP:NRAS(Q61K))(1) and Tg(mitfa:EGFP:NRAS(Q61K))(2). Stable expression of this transgene results in hyperpigmented fish displaying a complete ablation of the normal pigment pattern. Although oncogenic NRAS expression alone was found to be insufficient to promote tumor formation, loss of functional p53 was found to collaborate with NRAS expression in the genesis of melanoma. The tumors derived from these animals are variably pigmented and closely resemble human melanoma. Underscoring the pathological similarities between these tumors and human disease and suggesting that common pathways are similar in these models and human disease, gene set enrichment analysis performed on microarray data found that the upregulated genes from zebrafish melanomas are highly enriched in human tumor samples. This work characterizes two zebrafish melanoma models that will be useful tools for the study of melanoma pathogenesis.

Strong Association Between In-Migration and HIV Prevalence in Urban Sub-Saharan Africa

Sexually Transmitted Diseases. Dec, 2009  |  Pubmed ID: 19959971

BACKGROUND:: Enormous variation exists in HIV prevalence between countries in sub-Saharan Africa. The contribution of migration to the spread of HIV has long been recognized, but its effect at the population level has never been assessed. In this ecological analysis, we explore how much variation in HIV prevalence in urban sub-Saharan Africa is explained by in-migration. METHODS:: We performed a linear regression to analyze the association between the proportion of recent in-migrants and HIV prevalence for men and women in urban areas, using 60 data points from 28 sub-Saharan African countries between 1987 and 2005. RESULTS:: We found a strong association between recent in-migration and HIV prevalence for women (Pearson R = 57%, P < 0.001) and men (R = 24%, P = 0.016), taking the earliest data point for each country. For women, the association was also strong within east/southern Africa (R = 50%, P = 0.003). For both genders, the association was strongest between 1985 and 1994, slightly weaker between 1995 and 1999, and nonexistent as from 2000. The overall association for both men and women was not confounded by the developmental indicators GNI per capita, income inequalities, or adult literacy. CONCLUSIONS:: Migration explains much of the variation in HIV spread in urban areas of sub-Saharan Africa, especially before the year 2000, after which HIV prevalences started to level off in many countries. Our findings suggest that migration is an important factor in the spread of HIV, especially in rapidly increasing epidemics. This may be of relevance to the current HIV epidemics in China and India.

The Darzi Report: Implications for Tissue Viability Nurses

British Journal of Nursing (Mark Allen Publishing). Oct 8-21, 2009  |  Pubmed ID: 19966725

'Transforming community services' (Darzi, 2009) is the second healthcare report to be authored by Lord Ara Darzi, which was published in July 2009. As the title suggests, it targets community services and includes specific, and sometimes disingenuous, implications for tissue viability in the community setting.

Health Care Disparities and Diabetes Care: Practical Considerations for Primary Care Providers

Clinical Diabetes : a Publication of the American Diabetes Association. Jun, 2009  |  Pubmed ID: 21289869

Disparities in diabetes care are prevalent in the United States. This article provides an overview of these disparities and discusses both potential causes and efforts to address them to date. The authors focus the discussion on aspects relevant to the patient-provider dyad and provide practical considerations for the primary care provider's role in helping to diminish and eliminate disparities in diabetes care.

Acetabular Loosening Using an Extended Offset Polyethylene Liner

Clinical Orthopaedics and Related Research. Jan, 2009  |  Pubmed ID: 18781370

The use of extended offset femoral components and acetabular liners helps restore preoperative offset during hip arthroplasty. We report a relatively high acetabular component aseptic loosening rate with the use of offset polyethylene liners. We reviewed 1919 primary and 346 revision total hip arthroplasties (THAs). A 7-mm offset acetabular liner was used in 120 of the primary and 100 of the revision THAs. The aseptic loosening rate in the primary THA group was 0.12% in the standard offset and 4.2% in the extended offset groups at a minimum of 2 years (mean, 3.6 years; range, 2-9 years) followup. The aseptic loosening rate in the revision group was 1.7% in the standard and 7% in the extended offset groups at a mean of 4 years (range, 2-9 years) followup. Although extended offset acetabular liners help restore hip offset, torsional force applied to the implant-bone interface may have a detrimental effect on fixation. We found a relatively high failure rate in our primary and revision acetabular components used with an offset liner. Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Medical Malpractice and the Sports Medicine Clinician

Clinical Orthopaedics and Related Research. Feb, 2009  |  Pubmed ID: 18989733

More individuals are participating in athletics today than ever before. Physicians treating athletes confront unique diagnostic and treatment challenges and an increased risk of legal liability. The key areas regarding liability are preparticipation examinations, determination of eligibility, evaluation of significant on-field injuries, and information disclosure. The issues surrounding preparticipation physicals and determination of eligibility are closely linked. Physicians must be prepared to seek guidance from specialists, particularly when there are cardiac, spinal, or neurologic issues. Appropriate on-field evaluation of potential concussions, spinal injuries, and heat stroke are key areas of concern for the physician. Privacy issues have become more complex in the age of federal regulation. Physicians and all athletic staff should be aware of privacy laws and ensure proper consent documentation is obtained from all athletes or their parents. All athletic programs should develop a plan that details roles and procedures to be followed in a medical emergency. Sports caregivers must take affirmative steps that better protect their patients from harm and physicians from legal liability.

Will GnRH Antagonists Improve Prostate Cancer Treatment?

Trends in Endocrinology and Metabolism: TEM. Jan, 2009  |  Pubmed ID: 19008119

Androgen ablation forms a basis for treating prostate cancer and is achieved either by surgical castration, or pharmacologically using oestrogens, anti-androgens and/or gonadotropin-releasing hormone (GnRH) analogues. GnRH antagonists (or blockers) offer a new means of treatment by directly blocking GnRH receptors. Advantages of GnRH antagonists include lack of the initial stimulation of gonadotropin and testosterone production, lack of gonadotropin microsurges and sustained follicle-stimulating hormone suppression; disadvantages include increased histamine release. This review discusses advantages and disadvantages of the GnRH antagonists currently in development, in light of receptor physiology and pre-clinical and clinical data. Comparative clinical trials will ultimately establish their efficacy in comparison to other pharmacotherapies. Therefore, continuing development and refinement is needed to improve prostate cancer treatment.

ACC/AHA/ACR/ASE/ASNC/HRS/NASCI/RSNA/SAIP/SCAI/ SCCT/SCMR/SIR 2008 Key Data Elements and Definitions for Cardiac Imaging: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Cardiac Imaging)

Circulation. Jan, 2009  |  Pubmed ID: 19064685

Population-level Effect of Potential HSV2 Prophylactic Vaccines on HIV Incidence in Sub-Saharan Africa

Vaccine. Feb, 2009  |  Pubmed ID: 19071187

Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30-40% after 20 years (range 4-66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine.

Venous Thromboembolism in Patients with Acute Leukemia: Incidence, Risk Factors, and Effect on Survival

Blood. Apr, 2009  |  Pubmed ID: 19088376

A population-based cohort was used to determine the incidence and risk factors associated with development of venous thromboembolism (VTE) among Californians diagnosed with acute leukemia between 1993 to 1999. Principal outcomes were deep vein thrombosis in both the lower and upper extremities, pulmonary embolism, and mortality. Among 5394 cases with acute myelogenous leukemia (AML), the 2-year cumulative incidence of VTE was 281 (5.2%). Sixty-four percent of the VTE events occurred within 3 months of AML diagnosis. In AML patients, female sex, older age, number of chronic comorbidities, and presence of a catheter were significant predictors of development of VTE within 1 year. A diagnosis of VTE was not associated with reduced survival in AML patients. Among 2482 cases with acute lymphoblastic leukemia (ALL), the 2-year incidence of VTE in ALL was 4.5%. Risk factors for VTE were presence of a central venous catheter, older age, and number of chronic comorbidities. In the patients with ALL, development of VTE was associated with a 40% increase in the risk of dying within 1 year. The incidence of VTE in acute leukemia is appreciable, and is comparable with the incidence in many solid tumors.

ACC/AHA/ACR/ASE/ASNC/HRS/NASCI/RSNA/SAIP/SCAI/SCCT/SCMR/SIR 2008 Key Data Elements and Definitions for Cardiac Imaging A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Cardiac Imaging)

Journal of the American College of Cardiology. Jan, 2009  |  Pubmed ID: 19118731

Use of Wound Dressings with Soft Silicone Adhesive Technology

Paediatric Nursing. Apr, 2009  |  Pubmed ID: 19397129

To evaluate how pain, during and in-between dressing changes, is affected by the introduction of Mepilex Border Lite, a wound dressing manufactured by Mölnlycke Health Care using Safetac soft silicone adhesive technology, to the treatment of different types of paediatric wounds/skin injuries.

Diabetes Numeracy: an Overlooked Factor in Understanding Racial Disparities in Glycemic Control

Diabetes Care. Sep, 2009  |  Pubmed ID: 19401443

Understanding the reasons and eliminating the pervasive health disparities in diabetes is a major research, clinical, and health policy goal. We examined whether health literacy, general numeracy, and diabetes-related numeracy explain the association between African American race and poor glycemic control (A1C) in patients with diabetes.

Testing for Thrombophilia: Pitfalls, Limitations, and Marginal Impact on Treatment Duration Recommendations

The Mount Sinai Journal of Medicine, New York. Jun, 2009  |  Pubmed ID: 19421974

High-throughput Sequencing of the Zebrafish Antibody Repertoire

Science (New York, N.Y.). May, 2009  |  Pubmed ID: 19423829

Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism's antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.

Long-term Incidence of Death Due to Thromboembolic Disease Among Patients with Unprovoked Pulmonary Embolism

Current Opinion in Pulmonary Medicine. Sep, 2009  |  Pubmed ID: 19458530

To summarize recent studies that have quantified the incidence of death due to late thromboembolic disease among patients initially diagnosed with acute unprovoked pulmonary embolism. These findings will aid clinicians who must weigh the risk versus the benefits of long-term anticoagulant therapy.

Effect of Intraoperative Radiocolloid Injection on Sentinel Lymph Node Biopsy in Patients with Breast Cancer

Annals of Surgical Oncology. Aug, 2009  |  Pubmed ID: 19484310

Preoperative injection of radiocolloid before a sentinel lymph node (SLN) biopsy is painful for patients with breast cancer. Injection after anesthesia eliminates this discomfort but allows less time for radiocolloid migration. Our goal was to validate the efficacy of intraoperative injection.

Canine Laryngeal Surgery: Time to Rethink?

Veterinary Surgery : VS. Jun, 2009  |  Pubmed ID: 19538661

Trichobezoar Obstruction After Stapled Jejunal Anastomosis in a Dog

Veterinary Surgery : VS. Apr, 2009  |  Pubmed ID: 19573108

To describe an unusual long-term complication of circular end-to-end anastomosis (CEEA) stapling in a dog.

Polyethylene Exchange in a Second-generation Cementless Acetabular Component

The Journal of Arthroplasty. Sep, 2009  |  Pubmed ID: 19577889

Some have suggested that isolated polyethylene exchange in a well-fixed Harris-Galante II acetabular component (Zimmer, Warsaw, Ind) necessitates cementing the liner or complete revision because the locking mechanism is suboptimal. We reviewed 29 hip revisions during which the polyethylene was exchanged using the native locking mechanism. Mean follow-up was 5.1 years (2-13 years). Of the 29 patients, one had a disengagement of the revision polyethylene at 2.5 years. At the time of this patient's original revision, one of the tines was fractured, but a direct exchange was performed. There were 4 other revisions (one for loosening and 3 for instability). There were no other complications attributable to the direct polyethylene exchange and no further reoperations. This series suggests that polyethylene exchange with the Harris-Galante II prosthesis can be performed safely using the native locking mechanism in the absence of fractured tines.

Mutation of Protein Kinase C Phosphorylation Site S1076 on Alpha-subunits Affects BK(Ca) Channel Activity in HEK-293 Cells

American Journal of Physiology. Lung Cellular and Molecular Physiology. Oct, 2009  |  Pubmed ID: 19592459

Large conductance, calcium- and voltage-activated potassium (BK(Ca)) channels are important modulators of pulmonary vascular smooth muscle membrane potential, and phosphorylation of BK(Ca) channels by protein kinases regulates pulmonary arterial smooth muscle function. However, little is known about the effect of phosphorylating specific channel subunits on BK(Ca) channel activity. The present study was done to determine the effect of mutating protein kinase C (PKC) phosphorylation site serine 1076 (S1076) on transfected human BK(Ca) channel alpha-subunits in human embryonic kidney (HEK-293) cells, a heterologous expression system devoid of endogenous BK(Ca) channels. Results showed that mutating S1076 altered the effect of PKC activation on BK(Ca) channels in HEK-293 cells. Specifically, the phospho-deficient mutation BK(Ca)-alpha(S1076A)/beta(1) attenuated the excitatory effect of the PKC activator phorbol myristate acetate (PMA) on BK(Ca) channels, whereas the phospho-mimetic mutation BK(Ca)-alpha(S1076E)/beta(1) increased the excitatory effect of PMA on BK(Ca) channels. In addition, the phospho-null mutation S1076A blocked the activating effect of cGMP-dependent protein kinase G (PKG) on BK(Ca) channels. Collectively, these results suggest that specific putative PKC phosphorylation site(s) on human BK(Ca) channel alpha-subunits influences BK(Ca) channel activity, which may subsequently alter pulmonary vascular smooth muscle function and tone.

A Radiologic "alcohol Breathalyzer" Test

Neurology. Jan, 2009  |  Pubmed ID: 19139373

Prognostic Utility of 64-slice Computed Tomography in Patients with Suspected but No Documented Coronary Artery Disease

European Heart Journal. Feb, 2009  |  Pubmed ID: 19153177

Although multislice computed tomography (MSCT) detects obstructive coronary artery disease (CAD) with high diagnostic accuracy, there is a paucity of long-term prognostic data. We sought to assess the incremental prognostic value of 64-slice CT in patients with suspected but no documented CAD.

Heterosexual Risk of HIV-1 Infection Per Sexual Act: Systematic Review and Meta-analysis of Observational Studies

The Lancet Infectious Diseases. Feb, 2009  |  Pubmed ID: 19179227

We did a systematic review and meta-analysis of observational studies of the risk of HIV-1 transmission per heterosexual contact. 43 publications comprising 25 different study populations were identified. Pooled female-to-male (0.04% per act [95% CI 0.01-0.14]) and male-to-female (0.08% per act [95% CI 0.06-0.11]) transmission estimates in high-income countries indicated a low risk of infection in the absence of antiretrovirals. Low-income country female-to-male (0.38% per act [95% CI 0.13-1.10]) and male-to-female (0.30% per act [95% CI 0.14-0.63]) estimates in the absence of commercial sex exposure (CSE) were higher. In meta-regression analysis, the infectivity across estimates in the absence of CSE was significantly associated with sex, setting, the interaction between setting and sex, and antenatal HIV prevalence. The pooled receptive anal intercourse estimate was much higher (1.7% per act [95% CI 0.3-8.9]). Estimates for the early and late phases of HIV infection were 9.2 (95% CI 4.5-18.8) and 7.3 (95% CI 4.5-11.9) times larger, respectively, than for the asymptomatic phase. After adjusting for CSE, presence or history of genital ulcers in either couple member increased per-act infectivity 5.3 (95% CI 1.4-19.5) times versus no sexually transmitted infection. Study estimates among non-circumcised men were at least twice those among circumcised men. Low-income country estimates were more heterogeneous than high-income country estimates, which indicates poorer study quality, greater heterogeneity of risk factors, or under-reporting of high-risk behaviour. Efforts are needed to better understand these differences and to quantify infectivity in low-income countries.

Risk of Cancer Among Rheumatoid Arthritis Patients in California

Cancer Causes & Control : CCC. Aug, 2009  |  Pubmed ID: 19184473

The objective of this retrospective cohort study was to evaluate cancer risk among rheumatoid arthritis (RA) patients in California.

Epidemiology of Cancer-related Venous Thromboembolism

Best Practice & Research. Clinical Haematology. Mar, 2009  |  Pubmed ID: 19285269

Recent studies have better defined the epidemiology of venous thromboembolism (VTE) in cancer patients. The incidence is highest in patients who have metastatic disease at the time of presentation and who have fast growing, biologically aggressive cancers associated with a poor prognosis. The incidence is also high in patients with haematological cancers. Other specific risk factors that affect the incidence of VTE include undergoing invasive neurosurgery, the number of underlying chronic co-morbid conditions, and being of Asian/Pacific Islander decent (lower incidence). The incidence is highest in the first few months after diagnosis, which may reflect the biology of the cancer or medical interventions such as major surgery or start of chemotherapy. The development of VTE is clearly associated with decreased survival, and this effect is greater among patients initially diagnosed with local- or regional-stage cancer compared with patients with metastatic cancer, probably because VTE reflects the presence of a biologically aggressive cancer. Finally, a small percentage of patients with idiopathic VTE and no clinical or laboratory evidence of cancer may harbour an aggressive but 'occult' malignancy likely causally linked to the development of VTE.

Venous Thromboembolism (VTE) in Patients with Cancer: Epidemiology and Risk Factors

Cancer Investigation. 2009  |  Pubmed ID: 19291526

Although cancer is recognized as a major risk factor for venous thromboembolism, the exact magnitude of the problem and specific risk factors most strongly associated with the development of VTE is not well defined. Several recent studies have shown that the incidence of VTE is highest in patients who present with metastatic cancer, particularly cancers associated with a high one-year mortality rate, such as pancreatic cancer. The incidence rate of VTE is highest in the first few months after the diagnosis of cancer, and it decreases over time thereafter. For most cancers, it is not clear to what extent undergoing major surgery adds to the already high risk of VTE associated with the presence of the cancer. However, patients with glioma clearly have a very high incidence of VTE soon after they undergo any invasive neurosurgical procedure. Active chemotherapy, the use of erythropoetin agents, and the use of certain anti-cancer therapies such as thalidomide, high-dose steroids, and anti-angiogenic therapy also increase the risk of thrombosis. Similar to patients without cancer, the risk of VTE is higher in patients with coexisting chronic medical illnesses. Development of VTE is clearly associated with decreased survival and this effect is greater among patients initially diagnosed with local or regional stage cancer compared to patients with metastatic cancer.

Essential Role of the 90-kilodalton Heat Shock Protein in Mediating Nongenomic Estrogen Signaling in Coronary Artery Smooth Muscle

The Journal of Pharmacology and Experimental Therapeutics. Jun, 2009  |  Pubmed ID: 19293389

Under normal physiological conditions, estrogen is a coronary vasodilator, and this response involves production of NO from endothelial cells. In addition, estrogen also stimulates NO production in coronary artery smooth muscle (CASM); however, the molecular basis for this nongenomic effect of estrogen is unclear. The purpose of this study was to investigate a potential role for the 90-kDa heat shock protein (Hsp90) in estrogen-stimulated neuronal nitric-oxide synthase (nNOS) activity in coronary artery smooth muscle. 17Beta-estradiol produced a concentration-dependent relaxation of endothelium-denuded porcine coronary arteries in vitro, and this response was attenuated by inhibiting Hsp90 function with 1 microM geldanamycin (GA) or 100 microg/ml radicicol (RAD). These inhibitors also prevented estrogen-stimulated NO production in human CASM cells and reversed the stimulatory effect of estrogen on calcium-activated potassium (BK(Ca)) channels. These functional studies indicated a role for Hsp90 in coupling estrogen receptor activation to NOS stimulation in CASM. Furthermore, coimmunoprecipitation studies demonstrated that estrogen stimulates bimolecular interaction of immunoprecipitated nNOS with Hsp90 and that either GA or RAD could inhibit this association. Blocking estrogen receptors with ICI182780 (fulvestrant) also prevented this association. These findings indicate an essential role for Hsp90 in nongenomic estrogen signaling in CASM and further suggest that Hsp90 might represent a prospective therapeutic target to enhance estrogen-stimulated cardiovascular protection.

Digital PCR Provides Sensitive and Absolute Calibration for High Throughput Sequencing

BMC Genomics. 2009  |  Pubmed ID: 19298667

Next-generation DNA sequencing on the 454, Solexa, and SOLiD platforms requires absolute calibration of the number of molecules to be sequenced. This requirement has two unfavorable consequences. First, large amounts of sample-typically micrograms-are needed for library preparation, thereby limiting the scope of samples which can be sequenced. For many applications, including metagenomics and the sequencing of ancient, forensic, and clinical samples, the quantity of input DNA can be critically limiting. Second, each library requires a titration sequencing run, thereby increasing the cost and lowering the throughput of sequencing.

Effects of Race and Ethnicity on the Incidence of Venous Thromboembolism

Thrombosis Research. 2009  |  Pubmed ID: 19303496

Although there is strong evidence that the prevalence of venous thrombo-embolism (VTE) varies significantly among different ethnic/racial groups, the genetic, physiologic and/or clinical basis for these differences remain largely undefined. African-American patients have a significantly higher rate of incident VTE, particularly following exposure to a provoking risk factor such as surgery, medical illness, trauma, etc. In addition, African-Americans are more likely to be diagnosed with pulmonary embolism (PE) than deep-vein thrombosis (DVT) compared to Caucasian and other racial groups. On the other extreme, Asians/Pacific Islanders have a 70% lower prevalence of VTE and this is true for both idiopathic VTE and provoked, or 'secondary', VTE. Hispanics have a significantly lower prevalence of VTE compared to Caucasians, but higher than Asians/Pacific Islanders. The incidence of recurrent VTE varies depending on gender, type of thromboembolic event and race. Further research is needed in order to determine the fundamental differences between racial/ethnic groups that explain the observed differences in the prevalence of VTE. Race/ethnicity should be considered an important factor in the risk-stratification of patients with suspected VTE or patients at some risk for developing VTE.

The Pain Quality Response Profile of Oxymorphone Extended Release in the Treatment of Low Back Pain

The Clinical Journal of Pain. Feb, 2009  |  Pubmed ID: 19333156

In controlled trials of analgesics, the primary outcome variable is most often a measure of global pain intensity. However, because pain is associated with a variety of pain sensations, the effects of analgesic treatments on different sensations could go undetected if specific pain qualities are not assessed. This study sought to evaluate the utility of assessing the multiple components of non-neuropathic pain in an analgesic clinical trial.

Venous Ultrasound Testing for Suspected Thrombosis: Incidence of Significant Non-thrombotic Findings

The Journal of Emergency Medicine. Jan, 2009  |  Pubmed ID: 18325713

Duplex ultrasound (US) is used to "rule out" deep venous thrombosis (DVT), but can also diagnose other causes of leg pain or swelling in Emergency Department (ED) patients. Recent literature suggests that US imaging is unnecessary among patients with low or moderate clinical probability of DVT with a normal D-dimer. We attempted to determine the incidence of clinically important incidental findings detected using venous US imaging in patients with suspected lower extremity DVT. We conducted a retrospective chart review of all ultrasounds performed by the non-invasive vascular laboratory on ED patients > 18 years old. Results were classified: normal, DVT, or incidental finding. The latter were classified as clinically significant major findings if the diagnosis led to immediate and specific treatment to prevent morbidity, or clinically significant minor findings. A total of 484 US studies were reviewed; 179 were excluded (arterial studies, penetrating trauma, upper extremity US). Findings among 305 studies were: 238 (78%) normal, 28 (9%) DVT, and 39 (12%) incidental findings. Among 39 incidental findings, 10 were clinically significant major findings and 29 clinically significant minor findings. Clinically significant major findings included: pseudoaneurysm, arterial occlusive disease, vascular graft complication, compartment syndrome, and tumor. Among 38 abnormal US studies that required immediate treatment, DVT comprised 74% (95% confidence interval 59%-85%) and important major incidental findings 26% (95% confidence interval 14%-41%). Among ED patients who underwent US to evaluate leg pain and swelling, 26% of positive studies showed clinically important findings other than DVT. Further research is needed to determine if D-dimer plus a clinical probability tool will include or exclude the patients with clinically significant major findings.

RhoA/Rho-kinase Signaling: a Therapeutic Target in Pulmonary Hypertension

Vascular Health and Risk Management. 2009  |  Pubmed ID: 19707285

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of the pulmonary vasculature. Both animal and clinical studies suggest that ROCK inhibitors are effective for treatment of severe PAH with minimal risk, which supports the premise that ROCKs are important therapeutic targets in pulmonary hypertension and that ROCK inhibitors are a promising new class of drugs for this devastating disease.

Chemical Genetic Screening in the Zebrafish Embryo

Nature Protocols. 2009  |  Pubmed ID: 19745824

Chemical genetic screening can be described as a discovery approach in which chemicals are assayed for their effects on a defined biological system. The zebrafish, Danio rerio, is a well-characterized and genetically tractable vertebrate model organism that produces large numbers of rapidly developing embryos that develop externally. These characteristics allow for flexible, rapid and scalable chemical screen design using the zebrafish. We describe a protocol for screening compounds from a chemical library for effects on early zebrafish development using an automated in situ based read-out. As screenings are carried out in the context of a complete, developing organism, this approach allows for a more comprehensive analysis of the range of a chemical's effects than that provided by, for example, a cell culture-based or in vitro biochemical assay. Using a 24-h chemical treatment, one can complete a round of screening in 6 d.

How Valid is the ICD-9-CM Based AHRQ Patient Safety Indicator for Postoperative Venous Thromboembolism?

Medical Care. Dec, 2009  |  Pubmed ID: 19786907

Hospital administrative data are being used to identify patients with postoperative venous thromboembolism (VTE), either pulmonary embolism (PE) or deep-vein thrombosis (DVT). However, few studies have evaluated the accuracy of these ICD-9-CM codes across multiple hospitals.

Tissue Viability and the Quality Accounts Agenda

British Journal of Nursing (Mark Allen Publishing). Nov 12-25, 2009  |  Pubmed ID: 20081670

Re: Does Aspirin Have a Role in Venous Thromboembolism Prophylaxis in Total Knee Arthroplasty Patients?

The Journal of Arthroplasty. Jun, 2010  |  Pubmed ID: 20097038

Variations in Perioperative Warfarin Management: Outcomes and Practice Patterns at Nine Hospitals

The American Journal of Medicine. Feb, 2010  |  Pubmed ID: 20103023

Before surgery, most patients receiving oral anticoagulation require temporary cessation of treatment. Physicians sometimes substitute heparin or low-molecular-weight heparin for oral anticoagulation in the perioperative setting ("bridging therapy"). We sought to characterize rates of bridging therapy use at 9 clinical centers to determine the extent to which the use of bridging is explained by clinical characteristics of patients (vs physician style) and to determine the 30-day incidence of thrombotic and bleeding complications.

Leveling the Field: Addressing Health Disparities Through Diabetes Disease Management

The American Journal of Managed Care. Jan, 2010  |  Pubmed ID: 20148604

To examine the relationships among patient characteristics, labor inputs, and improvement in glycosylated hemoglobin (A1C) level in a successful primary care-based diabetes disease management program (DDMP).

Effect of Turfgrass Establishment Practices and Composted Biosolids on Water Quality

Journal of Environmental Quality. Mar-Apr, 2010  |  Pubmed ID: 20176842

Land application of composted municipal biosolids (CMB) enhances soil physical properties and turf establishment. Yet large, volume-based rates of CMB can increase nonpoint source losses of sediment and nutrients from urban soils to surface waters. The objectives were (i) to compare runoff losses of sediment, N, P, and organic C among contrasting establishment treatments for bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy, var. Tifway] and (ii) to evaluate relationships between runoff and soil measurements of N, P, and organic C. Three replications of seven establishment treatments were installed on an excavated slope (8.5%) under field conditions. Five treatments comprised sod transplanted from Tifway bermudagrass grown with and without CMB on soil with and without incorporation of CMB. Two other treatments were composed of Tifway sprigged in soil with and without CMB. Runoff from seven natural rain events was channeled into collection tanks for sampling and analysis. Runoff concentrations and mass loss of dissolved P and organic C forms were greater for CMB-amended sod than for sprigs planted in soil with or without CMB or treatments comprising sod established without CMB. In addition, a linear relationship (R(2) = 0.87) was observed between water extractable soil P of sodded and sprigged treatments and concentrations and mass losses of dissolved P in runoff. Transplanted sod reduced sediment loss compared with sprigged treatments and incorporation of CMB reduced sediment loss from sprigged treatments. Incorporation of CMB within soil on which sod grown without CMB was transplanted proved the best option for achieving benefits of CMB while reducing nutrient runoff loss compared to sod transplanted from Tifway grown with CMB.

Research Design Considerations for Confirmatory Chronic Pain Clinical Trials: IMMPACT Recommendations

Pain. May, 2010  |  Pubmed ID: 20207481

There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain.

Reproductive History, Hormone Replacement, and Incidence of Venous Thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology

British Journal of Haematology. May, 2010  |  Pubmed ID: 20230397

Numerous studies have established that hormone replacement therapy increases the risk of venous thromboembolism (VTE), but an association of endogenous oestrogen exposure with the incidence of VTE is not fully established. Using a prospective design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, we studied the 12-year risk of VTE in relation to hormone replacement therapy use, age at menopause, parity number, and type of menopause in 8236 post-menopausal women. There were no significant associations of age at menopause, parity number, or type of menopause with incidence of VTE. Women currently using hormone replacement had a 1.6-times higher multivariate-adjusted rate ratio (RR) of VTE compared with those without hormone use in the time-dependent model (RR=1.60, 95% confidence interval [CI], 1.06-2.36; Population attributable fraction=6.7%, 95%CI, 1.0-10.3). When we excluded women with 1-year or more duration of hormone therapy at baseline, the association was stronger (RR=2.02, 95%CI, 1.31-3.12). The multivariate-adjusted RRs of VTE for current users tended to be higher in those with idiopathic VTE (RR=2.40, 95%CI, 1.40-4.12) than those with secondary VTE (RR=1.08, 95%CI, 0.63-1.85). Hormone replacement therapy is associated with increased risk of VTE, but reproductive history markers of endogenous oestrogen exposure were not associated with VTE.

Surveillance for Deep Vein Thrombosis and Pulmonary Embolism: Recommendations from a National Workshop

American Journal of Preventive Medicine. Apr, 2010  |  Pubmed ID: 20331950

Deep vein thrombosis (DVT) and pulmonary embolism (PE), known collectively as venous thromboembolism (VTE), affect an estimated 900,000 people in the U.S. each year, resulting in several hundred thousand hospitalizations and about 300,000 deaths. Despite this substantial public health burden, no systematic collection of VTE-related morbidity and mortality data exists in the U.S. The available information about disease prevalence and incidence consists of estimates based mainly on population-based epidemiologic studies and analysis of hospital discharge or health insurance claims databases. The limited scope of the available data has raised the question of whether a systematic surveillance system for VTE should be established. To help answer this question and to make recommendations for the next steps toward better surveillance of VTE, the CDC asked the American Society of Hematology (ASH) to convene a national workshop of stakeholders representing relevant federal agencies, experts in VTE epidemiology and treatment, public health experts in VTE, and patient representatives. These groups were assembled by ASH for a 1-day meeting in Washington DC. The subspecialty experts included representatives from internal medicine, cardiovascular diseases, adult and pediatric hematology, surgery, obstetrics and gynecology, radiology, emergency medicine and trauma care, hospital practice and critical care, and geriatrics. Experts in epidemiology, healthcare quality, and health policy also participated. During the workshop, experts discussed their perspectives on the burden of disease from VTE and its diagnosis, treatment, and prevention. The workshop also focused on the advisability and feasibility of establishing systematic surveillance for VTE and included preliminary discussion of the advantages and disadvantages of various approaches. The workshop concluded that (1) improved utilization in clinical practice of existing, proven-effective preventive measures is critical to reducing the disease burden from VTE; (2) systematic surveillance of DVT and PE is needed to provide nationally representative data on the prevalence and annual incidence of DVT and PE in the U.S.; (3) tracking and documenting changes in the incidence of DVT and PE through systematic surveillance will be important to enhance prevention efforts; and (4) the CDC should convene a second group of experts to advise the agency in detail on the strengths, weaknesses, and feasibility of possible approaches to systematic surveillance for DVT and PE.

The Incidence of Venous Thromboembolism and Its Effect on Survival Among Patients with Primary Bladder Cancer

Cancer. Jun, 2010  |  Pubmed ID: 20336780

The incidence, risk factors, time course, and impact on survival of venous thromboembolism (VTE) in a large, population-based study of patients with bladder cancer have not been identified previously.

The Relationship of Changes in Pain Quality to Pain Interference and Sleep Quality

The Journal of Pain : Official Journal of the American Pain Society. Aug, 2010  |  Pubmed ID: 20338817

Pain is a complex multidimensional experience that includes overall intensity/magnitude, unpleasantness/bothersomeness (affect), location, and quality. However, there is a paucity of research examining the importance of pain quality to patient functioning; most research focuses only on the intensity and affective components of pain. This study sought to address this gap by examining, in a sample of patients with carpal tunnel syndrome (CTS), the associations between pain quality and 2 domains of patient functioning: pain interference and sleep quality. We found that measures of pain quality contributed to the prediction of pain interference and sleep quality over and above the effects of global pain intensity and unpleasantness. In our sample, both throbbing and itchy pain emerged as contributing the most unique variance to the prediction of patient functioning. The findings indicate that the presence of pain described as throbbing or itchy, regardless of the overall magnitude of pain, may make patients with CTS particularly vulnerable to the negative impact of pain on quality of life. The findings support the need for experimental studies to determine if treatments can be identified that address these 2 pain qualities, and if effective treatments for these qualities in particular result in significant improvement in the quality of life of patients with CTS. PERSPECTIVE: A growing body of research supports the importance of assessing multiple domains of pain in clinical and research settings. The current findings suggest the possibility that, in patients with carpal tunnel syndrome, itchy and throbbing pain may play key roles in patient functioning above and beyond global pain intensity and unpleasantness. More research is needed to confirm this finding, and whether treatments can be identified that address these pain qualities specifically.

Implementing the Quality Accounts Agenda in Tissue Viability

Nursing Standard (Royal College of Nursing (Great Britain) : 1987). Feb 17-23, 2010  |  Pubmed ID: 20359078

This article attempts to summarise and interpret recent quality initiatives from the Department of Health to improve tissue viability nursing services across England. It is directed towards nurses responsible for the planning and delivery of tissue viability services, and to nursing management at trust level. Quality initiatives are aimed at encouraging trust board members and service providers to assess, and make public, the quality and standards of care that they provide in the form of quality accounts. All healthcare service providers will have to produce a quality account in 2010. This article offers guidance on the use of quality indicators or nursing metrics to measure quality, and prepare quality accounts in tissue viability.

Food Security: Fossil Fuels

Science (New York, N.Y.). Apr, 2010  |  Pubmed ID: 20378802

HIV Transmission Risk Through Anal Intercourse: Systematic Review, Meta-analysis and Implications for HIV Prevention

International Journal of Epidemiology. Aug, 2010  |  Pubmed ID: 20406794

The human immunodeficiency virus (HIV) infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention.

Evaluation of the Predictive Value of ICD-9-CM Coded Administrative Data for Venous Thromboembolism in the United States

Thrombosis Research. Jul, 2010  |  Pubmed ID: 20430419

To determine the positive predictive value of International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) discharge codes for acute deep vein thrombosis or pulmonary embolism.

Venous Thromboembolism in Patients with Acute Leukemia, Lymphoma, and Multiple Myeloma

Thrombosis Research. Apr, 2010  |  Pubmed ID: 20434017

The association of malignancies and venous thromboembolism (VTE) is a long held axiom in medicine. A growing number of studies have demonstrated that the risk of VTE associated with the hematological malignancies acute leukemia, lymphoma, and multiple myeloma is considerable. In fact, the incidence associated with these malignancies exceeds that for many solid tumors. Contributing factors include malignancy associated hypercoagulable factors; antineoplastic therapies such as high dose corticosteroids, L-asparaginase, and new immunomodulatory agents; central venous catheters; and hematopoietic growth factors. Primary and secondary pharmacological prophylaxis can be problematic in these patients who are often thrombocytopenic. Strategies to prevent VTE, especially upper extremity catheter-associated thrombosis need to be developed.

The D5 Dopamine Receptor Mediates Large-conductance, Calcium- and Voltage-activated Potassium Channel Activation in Human Coronary Artery Smooth Muscle Cells

The Journal of Pharmacology and Experimental Therapeutics. Feb, 2010  |  Pubmed ID: 19864616

Large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channels hyperpolarize coronary artery smooth muscle cells, causing vasorelaxation. Dopamine activates BK(Ca) channels by stimulating D(1)-like receptor-mediated increases in cAMP in porcine coronary artery myocytes. There are two D(1)-like receptors (R), D(1)R and D(5)R. We hypothesize that the specific D(1)-like receptor involved in BK(Ca) channel activation in human coronary artery smooth muscle cells (HCASMCs) is the D(5)R and that activation occurs via cAMP cross-activation of cGMP-dependent protein kinase (PKG), rather than cAMP-dependent protein kinase (PKA). The effects of D(1)-like receptor agonists and antagonists on BK(Ca) channel opening in HCASMCs were examined in the presence and absence of PKG/PKA inhibition by cell-attached patch clamp. In the absence of commercially available ligands specific for D(1)R or D(5)R, D(1)R or D(5)R protein was down-regulated by transfecting HCASMCs with human D(1)R or D(5)R antisense oligonucleotides, respectively: cells transfected with scrambled oligonucleotides and nontransfected HCASMCs served as controls. The predominant ion channel conducting outward currents in nontransfected HCASMCs was identified as the large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channel, which was activated by D(1)-like receptor agonists despite PKA inhibition with (9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid (KT 5720) (300 nM), but was abolished by inhibiting PKG with 9-methoxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b-11a-triazadibenzo(a,g) cycloocta(cde)-trinden-1-one (KT 5823) (300 nM). D(1)-like receptor agonists activated BK(Ca) channels in all transfected cells except those transfected with D(5)R antisense oligonucleotides. Thus, the dopamine (D(1)-like) receptor mediates activation of BK(Ca) channels in HCASMCs by D(5)R, not D(1)R, and via PKG, not PKA. This is the first report of differential D(1)-like receptor regulation of vascular smooth muscle function in human cells.

Calibration of Disease Simulation Model Using an Engineering Approach

Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. Jan-Feb, 2010  |  Pubmed ID: 19883406

Concurrency is More Complex Than It Seems

AIDS (London, England). Jan, 2010  |  Pubmed ID: 19898215

Arteriovenous Fistula of a Colic Branch of the Superior Mesenteric Artery: Endovascular Therapy

Cardiovascular and Interventional Radiology. Aug, 2010  |  Pubmed ID: 19641958

Arteriovenous fistulae (AVF) of the superior mesenteric artery and its branches are exceedingly rare. We report an unusual case of a patient who was found to be symptomatic from such an AVF, with diarrhea and terminal ileal thickening. We describe the findings from magnetic resonance imaging, computed tomography and catheter angiography and discuss the endovascular management.

Inhalation Exposure Systems for the Development of Rodent Models of Sulfur Mustard-induced Pulmonary Injury

Toxicology Mechanisms and Methods. Jan, 2010  |  Pubmed ID: 20025432

Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg x min/m(3) resulted in homogeneous lung injury with no nasal degeneration.

Estrogen and Oxidative Stress: A Novel Mechanism That May Increase the Risk for Cardiovascular Disease in Women

Steroids. Nov, 2010  |  Pubmed ID: 20060403

Although early studies demonstrated that exogenous estrogen lowered a woman's risk of cardiovascular disease, recent trials indicate that HRT actually increases the risk of coronary heart disease or stroke. However, there is no clear explanation for this discrepancy. Is estrogen a helpful or a harmful hormone in terms of cardiovascular function? This review discusses some recent findings that propose a novel mechanism which may shed significant light upon this controversy. We propose that nitric oxide synthase (NOS) expressed within the vascular wall is a target of estrogen action. Under normal conditions in younger women, the primary product of estrogen action is NO, which produces a number of beneficial effects on vascular biology. As a woman ages, however, there is evidence for loss of important molecules essential for NO production (e.g., tetrahydrobiopterin, l-arginine). As these molecules are depleted, NOS becomes increasingly "uncoupled" from NO production, and instead produces superoxide, a dangerous reactive oxygen species. We propose that a similar uncoupling and reversal of estrogen response occurs in diabetes. Therefore, we propose that estrogen is neither "good" nor "bad", but simply stimulates NOS activity. It is the biochemical environment around NOS that will determine whether estrogen produces a beneficial (NO) or deleterious (superoxide) product, and can account for this dual and opposite nature of estrogen pharmacology. Further, this molecular mechanism is consistent with recent analyses revealing that HRT produces salutary effects in younger women, but mainly increases the risk of cardiovascular dysfunction in older postmenopausal women.

Measuring Aortic Pulse Wave Velocity Using High-field Cardiovascular Magnetic Resonance: Comparison of Techniques

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2010  |  Pubmed ID: 20459799

The assessment of arterial stiffness is increasingly used for evaluating patients with different cardiovascular diseases as the mechanical properties of major arteries are often altered. Aortic stiffness can be noninvasively estimated by measuring pulse wave velocity (PWV). Several methods have been proposed for measuring PWV using velocity-encoded cardiovascular magnetic resonance (CMR), including transit-time (TT), flow-area (QA), and cross-correlation (XC) methods. However, assessment and comparison of these techniques at high field strength has not yet been performed. In this work, the TT, QA, and XC techniques were clinically tested at 3 Tesla and compared to each other.

Tissue Viability Can Tackle the Financial Burden of Wounds

Nursing Times. Apr 27-May 3, 2010  |  Pubmed ID: 20462105

ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance: a Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents

Circulation. Jun, 2010  |  Pubmed ID: 20479157

ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance: a Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents

Journal of the American College of Cardiology. Jun, 2010  |  Pubmed ID: 20513610

Giant Virchow-Robin Spaces: Functional Magnetic Resonance Imaging and Tractography

Archives of Neurology. Jun, 2010  |  Pubmed ID: 20558401

Embedding the Quality Agenda into Tissue Viability and Wound Care

British Journal of Nursing (Mark Allen Publishing). Jun 10-23, 2010  |  Pubmed ID: 20622789

The vision for the NHS over the next 5 years is to go from 'good to great', with the government's 5-year plan mapping the journey for the NHS while focusing on improving quality and productivity, using innovation and prevention to drive and connect them. The Department of Health's 2010 report Frontline Care. Report of the Prime Minister's Commission on the Future of Nursing and Midwifery in England identified the need to develop national nursing indicators that measure nurse quality and their impact on patient outcomes and satisfaction. This article explores the impact that the quality agenda will have on tissue viability and wound care, and discusses the development of effective and achievable metrics. The importance of the multidisciplinary team working together to develop metrics and achieve quality outcomes for patients is further identified and discussed.

Therapeutics. Review: Heparin and Mechanical Compression Are Similar in Reducing Postsurgical VTE Risk, but Heparin Increases Bleeding

Annals of Internal Medicine. Jul, 2010  |  Pubmed ID: 20643985

Polygyny and Symmetric Concurrency: Comparing Long-duration Sexually Transmitted Infection Prevalence Using Simulated Sexual Networks

Sexually Transmitted Infections. Dec, 2010  |  Pubmed ID: 20656724

To compare the effects of polygyny (only men can form concurrent partnerships) and gender-symmetric concurrency (both genders can form concurrent partnerships) on prevalence of long-duration sexually transmitted infections (STIs) using a dynamic stochastic network model.

Risk of Recurrent Venous Thromboembolism After a First Oestrogen-associated Episode. Data from the REVERSE Cohort Study

Thrombosis and Haemostasis. Sep, 2010  |  Pubmed ID: 20539910

The use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3-6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged immobilisation. Our objective was to assess the risk of recurrent VTE in women after a first unprovoked episode on oestrogen. The REVERSE study is a cohort study of patients with a first unprovoked VTE treated with anticoagulant treatment for 5-7 months. The risk of recurrent VTE during follow-up was compared between women users and non users of oestrogen at the time of index VTE. Among the 646 patients included, 314 were women, of them 67 were current users of oestrogen at the time of their VTE: 49 were on oral contraceptives and 18 on post-menopausal hormone replacement therapy (HRT). No significant association was found between oestrogen exposure, either oral contraceptives or HRT, and a lower risk of recurrent VTE after adjustment for age, or analysis restricted to women in the same age range as oestrogen contraceptives and HRT users, respectively. The risk of recurrent VTE is low in women after a first otherwise unprovoked oestrogen-associated VTE. However, this risk is not significantly lower than in women whose VTE was not related to oestrogen use.

Design and Optimization of Fiber Optical Parametric Oscillators for Femtosecond Pulse Generation

Optics Express. Aug, 2010  |  Pubmed ID: 20721117

In this paper, we use a genetic algorithm and pulse-propagation analysis to design and optimize optical parametric oscillators based on soft-glass microstructured optical fibers. The maximum parametric gain, phase-match, walk-off between pump (1560 nm) and signal (880 nm) pulses, signal feedback ratio and signal-pump synchronization of the cavity are optimized. Pulse propagation analysis suggests that one can implement a fiber optical parametric oscillator capable of generating approximately 200-fs pulses at 880 nm with 43% peak-power conversion, high output pulse quality (time-bandwidth product approximately 0.43) and a wavelength tuning range that is limited only by the glass transmission windows.

Off-pump Bypass Surgery and Postoperative Stroke: California Coronary Bypass Outcomes Reporting Program

The Annals of Thoracic Surgery. Sep, 2010  |  Pubmed ID: 20732490

Coronary artery bypass surgery (CABG) is associated with a significant risk of stroke. Some studies suggest that off-pump CABG (OPCAB) may reduce postoperative stroke rate. We performed this study to evaluate the relationship between postoperative stroke and OPCAB compared with conventional on-pump CABG (CCB) in a recent, large cohort of patients.

Relation of Elevated Plasma Renin Activity at Baseline to Cardiac Events in Patients with Angiographically Proven Coronary Artery Disease

The American Journal of Cardiology. Sep, 2010  |  Pubmed ID: 20816114

Plasma renin activity (PRA) is a measure of renin-angiotensin system activity and is associated with cardiovascular outcomes in patients with heart failure (HF). We conducted a prospective analysis to assess whether elevated baseline PRA is associated with cardiovascular outcomes in 1,165 patients with coronary artery disease (> or =70% stenosis on the coronary angiogram) enrolled in the Intermountain Heart Collaborative Study. The exclusion criteria included previous myocardial infarction (MI) or HF, ejection fraction < or =45%, and a discharge diagnosis of MI/beta-blocker treatment. Baseline PRA measurements were evaluated as risk categories (< or =0.50, 0.51 to 2.30, and >2.30 ng/ml/h) and as tertiles (< or =0.40, 0.41 to 1.90, and > or =1.90 ng/ml/h). Predefined cardiovascular outcomes were assessed for a minimum follow-up of 3 years (mean 6.4 +/- 3.2, maximum 14.6) using Cox regression analysis to adjust for the baseline characteristics. The mean patient age was 64.4 years; most patients were men (73.1%) and hypertensive (63.2%). Elevated baseline PRA (high vs low category; >2.30 vs < or =0.50 ng/ml/h) was associated with a significantly increased risk of 3-year cardiac morbidity/mortality (hazard ratio 1.96; p = 0.004), MI (hazard ratio 2.41; p = 0.02), HF hospitalization (hazard ratio 4.39; p = 0.03), and all-cause death (hazard ratio 1.80; p = 0.01). Elevated baseline PRA was also associated with longer-term HF hospitalization (hazard ratio 2.12; p = 0.004) and all-cause death (hazard ratio 1.56; p = 0.002). Similar results were observed for the PRA tertiles. The association of PRA with outcomes was observed after correction for hypertension, hyperlipidemia, diabetes, a family history of cardiovascular events, smoking, renal failure, and the use of statins. In conclusion, elevated baseline PRA is associated with cardiac morbidity and mortality in patients with coronary artery disease but normal left ventricular function and no previous MI or HF.

Infectiousness of HIV-infected Homosexual Men in the Era of Highly Active Antiretroviral Therapy

AIDS (London, England). Sep, 2010  |  Pubmed ID: 20827059

A Population-based Study of Inferior Vena Cava Filters in Patients with Acute Venous Thromboembolism

Archives of Internal Medicine. Sep, 2010  |  Pubmed ID: 20837832

Our study objective was to describe the frequency, indications, and outcomes after inferior vena cava (IVC) filter placement in a population-based sample of residents of the Worcester, Massachusetts, metropolitan area who had been diagnosed as having acute venous thromboembolism (VTE) in 1999, 2001, and 2003.

T-lymphoblastic Lymphoma Cells Express High Levels of BCL2, S1P1, and ICAM1, Leading to a Blockade of Tumor Cell Intravasation

Cancer Cell. Oct, 2010  |  Pubmed ID: 20951945

The molecular events underlying the progression of T-lymphoblastic lymphoma (T-LBL) to acute T-lymphoblastic leukemia (T-ALL) remain elusive. In our zebrafish model, concomitant overexpression of bcl-2 with Myc accelerated T-LBL onset while inhibiting progression to T-ALL. The T-LBL cells failed to invade the vasculature and showed evidence of increased homotypic cell-cell adhesion and autophagy. Further analysis using clinical biopsy specimens revealed autophagy and increased levels of BCL2, S1P1, and ICAM1 in human T-LBL compared with T-ALL. Inhibition of S1P1 signaling in T-LBL cells led to decreased homotypic adhesion in vitro and increased tumor cell intravasation in vivo. Thus, blockade of intravasation and hematologic dissemination in T-LBL is due to elevated S1P1 signaling, increased expression of ICAM1, and augmented homotypic cell-cell adhesion.

Allograft Compared with Autograft Infection Rates in Primary Anterior Cruciate Ligament Reconstruction

The Journal of Bone and Joint Surgery. American Volume. Oct, 2010  |  Pubmed ID: 20962190

Injuries to the anterior cruciate ligament are the most common surgically treated knee ligament injury. There is no consensus regarding the optimal graft choice between allograft and autograft tissue. Postoperative septic arthritis is an uncommon complication after anterior cruciate ligament reconstruction. The purpose of this study was to compare infection rates between procedures with use of allograft and autograft tissue in primary anterior cruciate ligament reconstruction.

Surface Composition, Chemistry, and Structure of Polystyrene Modified by Electron-beam-generated Plasma

Langmuir : the ACS Journal of Surfaces and Colloids. Jun, 2010  |  Pubmed ID: 20369866

Polystyrene (PS) surfaces were treated by electron-beam-generated plasmas in argon/oxygen, argon/nitrogen, and argon/sulfur hexafluoride environments. The resulting modifications of the polymer surface energy, morphology, and chemical composition were analyzed by a suite of complementary analytical techniques: contact angle goniometry, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and reflection electron energy loss spectroscopy (REELS). The plasma treatments produced only minimal increases in the surface roughness while introducing the expected chemical modifications: oxygen-based after Ar/O(2) plasma, oxygen- and nitrogen-based after Ar/N(2) plasma, and fluorine-based after Ar/SF(6) plasma. Fluorinated PS surfaces became hydrophobic and did not significantly change their properties over time. In contrast, polymer treated in Ar/O(2) and Ar/N(2) plasmas initially became hydrophilic but underwent hydrophobic recovery after 28 days of aging. The aromatic carbon chemistry in the top 1 nm of these aged surfaces clearly indicated that the hydrophobic recovery was produced by reorientation/diffusion of undamaged aromatic polymer fragments from the bulk rather than by contamination. Nondestructive depth profiles of aged plasma-treated PS films were reconstructed from parallel angle-resolved XPS (ARXPS) measurements using a maximum-entropy algorithm. The salient features of reconstructed profiles were confirmed by sputter profiles obtained with 200 eV Ar ions. Both types of depth profiles showed that the electron-beam-generated plasma modifications are confined to the topmost 3-4 nm of the polymer surface, while valence band measurements and unsaturated carbon signatures in ARXPS and REELS data indicated that much of the PS structure was preserved below 9 nm.

Silver-containing Dressings: Availability Concerns

Ostomy/wound Management. Aug, 2010  |  Pubmed ID: 21495446

Addressing Health Literacy and Numeracy to Improve Diabetes Education and Care

Diabetes Spectrum : a Publication of the American Diabetes Association. Oct, 2010  |  Pubmed ID: 21297890

The Dual Role of TNF in Pulmonary Edema

Journal of Cardiovascular Disease Research. Jan, 2010  |  Pubmed ID: 21188088

-Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectin-like domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema. ABBREVIATIONS: -tumor necrosis factor (TNF); acute lung injury (ALI); acute respiratory distress syndrome (ARDS); positive end-expiratory pressure (PEEP);epithelial sodium channel (ENaC);neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2);serum and glucocorticoid dependent kinase (Sgk-1);insulin-like growth factor 1 (IGF-1);Protein Kinase C (PKC);reactive oxygen species (ROS);myosin light chain (MLC);pneumolysin (PLY);listeriolysin (LLO);interleukin (IL);bronchoalveolar lavage fluids (BALF);Bacillus Calmette-Guerin (BCG);TNF receptor type 1 (TNFR1); TNF receptor type 2 (TNF-R2);

ACR Appropriateness Criteria® on Chest Pain, Suggestive of Acute Coronary Syndrome

Journal of the American College of Radiology : JACR. Jan, 2011  |  Pubmed ID: 21211759

Acute chest pain suggestive of acute coronary syndrome is a frequent complaint in the emergency department. Acute coronary syndromes include myocardial infarction and unstable angina. Being able to establish the diagnosis rapidly and accurately may be lifesaving. A cardiac workup is indicated in this subset of patients in the acute setting, even if there are no ischemic changes on electrocardiography. If the clinical examination and initial cardiac workup suggest that a patient is having myocardial ischemia, the patient will usually be urgently referred for invasive coronary angiography and revascularization. In stable patients without evidence of ST elevation and ongoing myocardial ischemia, an initially conservative approach is sometimes considered. Cardiac risk stratification of this subgroup of patients who are at low and intermediate risk for coronary artery disease is recommended before discharge, and imaging is necessary to exclude ischemia as an etiology. Noninvasive cardiac imaging modalities include chest radiography, single photon-emission CT myocardial perfusion imaging, echocardiography, multidetector CT, PET, and MRI. Noncardiac etiologies of chest pain include aortic dissection, aortic aneurysm, pulmonary embolism, pericardial disease, and lung parenchymal disease. Noninvasive cardiac imaging in patients who are at low and intermediate risk for coronary artery disease may improve confidence regarding the safety of discharge from the emergency department. In addition to risk stratification, noncoronary etiologies for chest pain can be established with imaging.

Cost Effectiveness of Treatments for Wet Age-related Macular Degeneration

PharmacoEconomics. Feb, 2011  |  Pubmed ID: 21244102

Age-related macular degeneration (AMD) is a leading cause of blindness in people aged ≥50 years. Wet AMD in particular has a major impact on patient quality of life and imposes substantial burdens on healthcare systems. This systematic review examined the cost-effectiveness data for current therapeutic options for wet AMD. PubMed and EMBASE databases were searched for all articles reporting original cost-effectiveness analyses of wet AMD treatments. The Centre for Reviews and Dissemination and Cochrane Library databases were searched for all wet AMD health technology assessments (HTAs). Overall, 44 publications were evaluated in full and included in this review. A broad range of cost-effectiveness analyses were identified for the most commonly used therapies for wet AMD (pegaptanib, ranibizumab and photodynamic therapy [PDT] with verteporfin). Three studies evaluated the cost effectiveness of bevacizumab in wet AMD. A small number of analyses of other treatments, such as laser photocoagulation and antioxidant vitamins, were also found. Ranibizumab was consistently shown to be cost effective for wet AMD in comparison with all the approved wet AMD therapies (four of the five studies identified showed ranibizumab was cost effective vs usual care, PDT or pegaptanib); however, there was considerable variation in the methodology for cost-effectiveness modelling between studies. Findings from the HTAs supported those from the PubMed and EMBASE searches; of the seven HTAs that included ranibizumab, six (including HTAs for Australia, Canada and the UK) concluded that ranibizumab was cost effective for the treatment of wet AMD; most compared ranibizumab with PDT and/or pegaptanib. By contrast, HTAs at best generally recommended pegaptanib or PDT for restricted use in subsets of patients with wet AMD. In the literature analyses, pegaptanib was found to be cost effective versus usual/best supportive care (including PDT) or no treatment in one of five studies; the other four studies found pegaptanib was of borderline cost effectiveness depending on the stage of disease and time horizon. PDT was shown to be cost effective versus usual/best supportive care or no treatment in five of nine studies; two studies showed that PDT was of borderline cost effectiveness depending on baseline visual acuity, and two showed that PDT was not cost effective. We identified no robust studies that properly evaluated the cost effectiveness of bevacizumab in wet AMD.

Antiretroviral Therapy and Sexual Behavior in Uganda: a Cohort Study

AIDS (London, England). Mar, 2011  |  Pubmed ID: 21252634

To assess evidence for sexual behavior change in response to antiretroviral therapy (ART) among members of a Ugandan clinical cohort. Secondarily, to examine factors associated with both sexual behavior and ART independently, that may help to assess the impact that ART is likely to have on the HIV epidemic.

Expression of GPR30, ERα and ERβ in Endometrium During Window of Implantation in Patients with Polycystic Ovary Syndrome: a Pilot Study

Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. Apr, 2011  |  Pubmed ID: 21269226

Women with polycystic ovary syndrome (PCOS) exhibit a lower pregnancy rate, which may be related to decreased estrogen receptor (ER) expression or endometrial receptivity. We measured expression of ERα, ERβ and the novel G protein-coupled ER (GPR30) in endometrium during window of implantation (WOI) in PCOS patients. Fifteen Chinese women with PCOS were compared to 15 normal subjects. Serial trans-vaginal ultrasonic scanner (TVUS) examinations detected follicular development, and endometrial thickness and pattern were assessed via TVUS on the day of ovulation. GPR30 expression was detected in the cytoplasm of endometrial epithelial cells, and was significantly lower in the PCOS group (p < 0.05). ERα and ERβ expression was lower in the PCOS group, and was detected mainly in the nucleus of endometrial epithelial cells. There was no significant difference in endometrium thickness (p > 0.05), but there was a significant difference in the ultrasonic pattern (p < 0.05). Endometrial expression of GPR30, ERα and ERβ was decreased during WOI in PCOS patients, and was accompanied by poor endometrial receptivity, low pregnancy rate and higher spontaneous abortions. We propose that restored receptor expression might improve endometrial receptivity and help lower infertility associated with PCOS.

Arytenoid Lateralization for Management of Combined Laryngeal Paralysis and Laryngeal Collapse in Small Dogs

Veterinary Surgery : VS. Nov, 2011  |  Pubmed ID: 22103399

OBJECTIVE: To identify combined laryngeal paralysis and collapse in small dogs and describe postoperative outcome after arytenoid lateralization. STUDY DESIGN: Case series. ANIMALS: Small nonbrachycephalic breed dogs with laryngeal paralysis and collapse (n = 6). METHODS: Medical records of small breed dogs with airway problems and undergoing laryngeal surgery (January-December 2008) were reviewed. Dogs with combined laryngeal paralysis and laryngeal collapse (LPLC) had arytenoid lateralization. The immediate, 4 week and 6 month postoperative outcomes were described. RESULTS: Direct visual laryngeal exam under a light plane of anesthesia revealed bilateral failure of arytenoid and vocal fold movement and concurrent bilateral medial folding with contact of the cuneiform processes in all dogs. None of the dogs had intra- or immediate postoperative complications after arytenoid lateralization. Two dogs required a 2nd contralateral procedure. Follow-up after 6 months revealed marked improvement in clinical signs related to upper airway obstruction, but all dogs continued to have mild respiratory noise. CONCLUSION: Concurrent laryngeal paralysis and collapse should be considered as part of the differential diagnosis for small, nonbrachycephalic dogs with upper airway disease. Arytenoid lateralization resulted in improvement of clinical signs related to obstructive airway disease.

Antiretroviral Treatment Cohort Analysis Using Time-updated CD4 Counts: Assessment of Bias with Different Analytic Methods

PloS One. 2011  |  Pubmed ID: 22114687

Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported.

Role of Acute Infection in HIV Transmission

Lancet. Dec, 2011  |  Pubmed ID: 22137836

Zebrafish Fukutin Family Proteins Link the Unfolded Protein Response with Dystroglycanopathies

Human Molecular Genetics. May, 2011  |  Pubmed ID: 21317159

Allelic mutations in putative glycosyltransferase genes, fukutin and fukutin-related protein (fkrp), lead to a wide range of muscular dystrophies associated with hypoglycosylation of α-dystroglycan, commonly referred to as dystroglycanopathies. Defective glycosylation affecting dystroglycan-ligand interactions is considered to underlie the disease pathogenesis. We have modelled dystroglycanopathies in zebrafish using a novel loss-of-function dystroglycan allele and by inhibition of Fukutin family protein activities. We show that muscle pathology in embryos lacking Fukutin or FKRP is different from loss of dystroglycan. In addition to hypoglycosylated α-dystroglycan, knockdown of Fukutin or FKRP leads to a notochord defect and a perturbation of laminin expression before muscle degeneration. These are a consequence of endoplasmic reticulum stress and activation of the unfolded protein response (UPR), preceding loss of dystroglycan-ligand interactions. Together, our results suggest that Fukutin family proteins may play important roles in protein secretion and that the UPR may contribute to the phenotypic spectrum of some dystroglycanopathies in humans.

Operative Risk of Staged Bilateral Knee Arthroplasty is Underestimated in Retrospective Studies

The Journal of Arthroplasty. Dec, 2011  |  Pubmed ID: 21392934

To find a safer surgical option, a number of studies have compared postoperative complications after bilateral total knee arthroplasty vs staged total knee arthroplasty (STKA) by contrasting postoperative complications collected retrospectively. However, we believe that a comparison based on retrospective studies could be biased. The purpose of this study was to demonstrate the misclassification bias associated with a retrospective study in comparing operative outcomes. Our analysis indicates that any conclusions based simply on retrospective analysis of subjects who successfully completed STKA is biased because it includes only cases that recovered after the first operation, rather than all of the patients who had planned STKA. In the absence of a prospective study to date, published studies should be interpreted with caution.

Determinism and Stochasticity During Maturation of the Zebrafish Antibody Repertoire

Proceedings of the National Academy of Sciences of the United States of America. Mar, 2011  |  Pubmed ID: 21393572

It is thought that the adaptive immune system of immature organisms follows a more deterministic program of antibody creation than is found in adults. We used high-throughput sequencing to characterize the diversifying antibody repertoire in zebrafish over five developmental time points. We found that the immune system begins in a highly stereotyped state with preferential use of a small number of V (variable) D (diverse) J (joining) gene segment combinations, but that this stereotypy decreases dramatically as the zebrafish mature, with many of the top VDJ combinations observed in 2-wk-old zebrafish virtually disappearing by 1 mo. However, we discovered that, in the primary repertoire, there are strong correlations in VDJ use that increase with zebrafish maturity, suggesting that VDJ recombination involves a level of deterministic programming that is unexpected. This stereotypy is masked by the complex diversification processes of antibody maturation; the variation and lack of correlation in full repertoires between individuals appears to be derived from randomness in clonal expansion during the affinity maturation process. These data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to better understand how the adaptive immune system achieves diversity.

DHODH Modulates Transcriptional Elongation in the Neural Crest and Melanoma

Nature. Mar, 2011  |  Pubmed ID: 21430780

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation.

The Role of N-methyl-D-aspartate Receptor Activation in Homocysteine-induced Death of Retinal Ganglion Cells

Investigative Ophthalmology & Visual Science. Jul, 2011  |  Pubmed ID: 21436276

Elevated plasma homocysteine has been implicated in glaucoma, a vision disorder characterized by retinal ganglion cell death. The toxic potential of homocysteine to ganglion cells is known, but the mechanisms are not clear. A mechanism of homocysteine-induced death of cerebral neurons is via N-methyl-D-aspartate (NMDA) receptor overstimulation, leading to excess calcium influx and oxidative stress. This study examined the role of the NMDA receptor in homocysteine-mediated ganglion cell death.

The Banning of Psychosurgery in NSW

Australasian Psychiatry : Bulletin of Royal Australian and New Zealand College of Psychiatrists. Apr, 2011  |  Pubmed ID: 21443401

Estrogen Signaling in Microvascular Arteries: Parturition Reduces Vasodilation by Reducing 17β-estradiol and NNOS

Steroids. Sep-Oct, 2011  |  Pubmed ID: 21458475

Few studies have examined the potential effects of childbirth on the responses of the female vasculature--especially the resistance microvasculature of non-reproductive tissues. In the present study we have investigated the response of mesenteric microvascular resistance vessels to estrogen (E2), an important vasoactive hormone. Vessels were obtained from either nulliparous or postpartum female Sprague-Dawley rats, and isometric tension studies were performed. We found that E2 induced a concentration-dependent, endothelium-independent relaxation of microvessels precontracted with 10(-5) M phenylephrine; however, E2-induced relaxation was reduced by nearly half in vessels from postpartum animals compared to nulliparous controls. Inhibiting nitric oxide synthase activity with 10(-4) M L-NMMA or L-NPA (which exhibits selectivity for type 1 or nNOS) attenuated the relaxation effect of E2 on arteries from nulliparous animals. In contrast, L-NPA had little effect on arteries from postpartum animals, suggesting a reduced influence of nNOS after parturition. Moreover, expression of nNOS protein in microvessels was decreased 39% in the postpartum state compared to arteries from nulliparous animals. We propose that the impaired E2-induced relaxation response of microvessels from postpartum animals reflects a downregulation of NO production due to lower nNOS expressed in vascular smooth muscle cells. We measured a 73% decrease in serum E2 levels in the postpartum state compared to nulliparous animals. Because E2 has been shown to increase nNOS protein expression, we propose that lower E2 levels after parturition decrease expression of nNOS, leading to a reduced vasodilatory capacity of resistance microvessels.

Low Prevalence of JAK2 V617F Mutation in Patients with First Unprovoked Venous Thromboembolism

British Journal of Haematology. Nov, 2011  |  Pubmed ID: 21517823

Rift Valley Fever Epidemiology, Surveillance, and Control: What Have Models Contributed?

Vector Borne and Zoonotic Diseases (Larchmont, N.Y.). Jun, 2011  |  Pubmed ID: 21548763

Rift Valley fever (RVF) is an emerging vector-borne zoonotic disease that represents a threat to human health, animal health, and livestock production, particularly in Africa. The epidemiology of RVF is not well understood, so that forecasting RVF outbreaks and carrying out efficient and timely control measures remains a challenge. Various epidemiological modeling tools have been used to increase knowledge on RVF epidemiology and to inform disease management policies.

Low-volume Ultrasound-guided Nerve Block Provides Inferior Postoperative Analgesia Compared to a Higher-volume Landmark Technique

Regional Anesthesia and Pain Medicine. Jul-Aug, 2011  |  Pubmed ID: 21610557

Ultrasound guidance reduces the required local anesthetic volume for successful peripheral nerve blockade, but it is unclear whether this impacts postoperative analgesia. This prospective, randomized, observer-blinded study tested the hypothesis that a low-volume ultrasound-guided ankle block would provide similar analgesia after foot surgery compared with a conventional-volume surface landmark technique.

Gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma

The New England Journal of Medicine. Jun, 2011  |  Pubmed ID: 21631324

Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone.

Skin Tumor Responsiveness to Interleukin-2 Treatment and CD8 Foxp3+ T Cell Expansion in an Immunocompetent Mouse Model

Cancer Immunology, Immunotherapy : CII. Sep, 2011  |  Pubmed ID: 21638127

Recombinant human interleukin-2 (rhIL-2) therapy is approved for treating patients with advanced melanoma yet significant responses are observed in only 10-15% of patients. Interleukin-2 induces Foxp3 expression in activated human CD8 T cells in vitro and expands circulating CD8 Foxp3+ T cells in melanoma patients. Employing IL-2 responsive (B16-F1, B16-BL6, JB/MS, MCA-205) and nonresponsive (JB/RH, B16-F10) subcutaneous tumor mouse models, we evaluated CD8 Foxp3+ T cell distribution and changes in response to rhIL-2 (50,000 U, i.p. or s.q., twice daily for 5 days). In tumor-free mice and subcutaneous tumor-bearing mouse models, CD8 Foxp3+ T cells were a rare but naturally occurring cell subset. Primarily located in skin-draining lymph nodes, CD8 Foxp3+ T cells expressed both activated T cell (CD28(+), CD44(+)) and Treg (CTLA4(+), PD1(lo/var), NKG2A(+/var)) markers. Following treatment with rhIL-2, a dramatic increase in CD8 Foxp3+ T cell prevalence was observed in the circulation and tumor-draining lymph nodes (TD.LNs) of animals bearing IL-2 nonresponsive tumors, while no significant changes were observed in the circulation and TD.LNs of animals bearing IL-2 responsive tumors. These findings suggest expansion of CD8 Foxp3+ T cell population in response to rhIL-2 treatment may serve as an early marker for tumor responsiveness to immunotherapy in an immune competent model. Additionally, these data may provide insight to predict response in patients with melanoma undergoing rhIL-2 treatment.

Cancer Immunotherapy

Surgical Oncology Clinics of North America. Jul, 2011  |  Pubmed ID: 21640920

Immune-based therapies for cancer are now commonplace. Cytokine therapy, including interferon and interleukin-2, is safe in the community setting. The US Food and Drug Administration has recently approved sipuleucel-T for the treatment of advanced prostate cancer, the first therapeutic cancer vaccine to meet this level of efficacy. The therapeutic use of monoclonal antibodies directed against proteins controlling various cell functions, including growth and modulation of immune response, has become so pervasive that the oncologist, whether surgeon or medical oncologist, must be familiar with indications, contraindications, and the associated toxicities.

Assessment of Pulmonary Artery Stiffness Using Velocity-encoding Magnetic Resonance Imaging: Evaluation of Techniques

Magnetic Resonance Imaging. Sep, 2011  |  Pubmed ID: 21641745

The loss of pulmonary artery (PA) compliance has significant pathophysiological effect on the right ventricle. Noninvasive and reliable assessment of PA wall stiffness would be an essential determiner of right heart load and a clinically useful factor to assess cardiovascular risk. Two MRI techniques have been proposed for assessing PA stiffness by measuring pulse wave velocity (PWV): transit time (TT) and flow area (QA). However, no data are available that compares the two techniques and evaluates their performance, especially over a wide range of PWV values or at 3.0-T, which is the purpose of the present study. Thirty-three patients with different heart conditions were imaged using optimized high-temporal resolution and high-spatial resolution velocity-encoding MRI sequences. Statistical analysis was conducted to study intermethod, interobserver and intraobserver variabilities. The PWV measurements using TT and QA techniques showed good agreement (P>0.1). The Bland-Altman analysis showed negligible differences between the two methods (mean±S.D.=0.11±0.35 m/s, correlation coefficient r=0.94). The repeated measurements showed low interobserver and intraobserver variabilities, although the S.D. of the differences was larger in the QA technique. The mean±S.D. of the TT/QA measurement differences were -0.05±0.2/0.0±0.36 m/s and 0.02±0.26/0.02±0.39 m/s for the interobserver and intraobserver differences, respectively. In conclusion, each technique has its own advantages and disadvantages. The two techniques result in similar measurements, although the QA method is more subjective due to its dependency on operator intervention.

Factors Predictive of the Status of Sentinel Lymph Nodes in Melanoma Patients from a Large Multicenter Database

Annals of Surgical Oncology. Dec, 2011  |  Pubmed ID: 21647761

Numerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database.

Venous Thromboembolism in Uterine Cancer

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Jul, 2011  |  Pubmed ID: 21666485

To determine the incidence, time course, and risk factors associated with the development of venous thromboembolism (VTE) and the effect of VTE on survival in women with uterine cancer.

Detection of Pulmonary Emboli with 99mTc-labeled Anti-D-dimer (DI-80B3)Fab' Fragments (ThromboView)

American Journal of Respiratory and Critical Care Medicine. Sep, 2011  |  Pubmed ID: 21680946

We report a new method to diagnose acute pulmonary embolism (PE) by single photon emission computerized tomography (SPECT) after administration of (99m)Tc-labeled anti-D-dimer (DI-80B3) monoclonal antibody Fab' fragments. This novel technique provides an additional approach to diagnosing PE in patients for whom other methods are nondiagnostic or contraindicated. Objectives: We performed a prospective, multicenter study to investigate the sensitivity and specificity of (99m)Tc-DI-80B3/SPECT in patients with suspected acute PE.

Cascaded Raman Shifting of High-peak-power Nanosecond Pulses in As₂S₃ and As₂Se₃ Optical Fibers

Optics Letters. Jun, 2011  |  Pubmed ID: 21686017

We report efficient cascaded Raman scattering of near-IR nanosecond pulses in large-core (65 μm diameter) As₂S₃ and As₂Se₃ optical fibers. Raman scattering dominates other spectral broadening mechanisms, such as four-wave mixing, modulation instability, and soliton dynamics, because the fibers have large normal group-velocity dispersion in the spectral range of interest. With ~2 ns pump pulses at a wavelength of 1.9 μm, four Stokes peaks, all with peak powers greater than 1 kW, have been measured.

Development and Validation of a Spanish Diabetes-specific Numeracy Measure: DNT-15 Latino

Diabetes Technology & Therapeutics. Sep, 2011  |  Pubmed ID: 21714674

Although deficits in health literacy and numeracy have been described among Latinos, the impact of low numeracy on diabetes outcomes has not been studied. Study objectives were (1) to establish the reliability and validity of a 15-item Spanish, diabetes-specific numeracy measure (Diabetes Numeracy Test [DNT]-15 Latino) and (2) to examine the relationship between diabetes-specific numeracy and diabetes-related outcomes among a sample of Latino adults with diabetes.

Photosynthetic Photon Flux Density and Phytochrome B Interact to Regulate Branching in Arabidopsis

Plant, Cell & Environment. Nov, 2011  |  Pubmed ID: 21726239

Branching is regulated by environmental signals including phytochrome B (phyB)-mediated responses to the ratio of red to far red light. While the mechanisms associated with phytochrome regulation of branching are beginning to be elucidated, there is little information regarding other light signals, including photosynthetic photon flux density (PPFD) and how it influences phytochrome-mediated responses. This study shows that Arabidopsis (Arabidopsis thaliana) branching is modified by both varying PPFD and phyB status and that significant interactions occur between these variables. While phyB deficiency decreased branching when the PPFD was low, the effect was suppressed by high PPFD and some branching aspects were actually promoted. Photosynthesis measurements showed that PPFD may influence branching in phyB-deficient plants at least partially through a specific signalling pathway rather than directly through energy effects on the shoot. The expression of various genes in unelongated buds of phyB-deficient and phyB-sufficient plants grown under high and low PPFD demonstrated potential roles for several hormones, including auxin, cytokinins and ABA, and also showed imperfect correlation between expression of the branching regulators BRC1 and BRC2 and bud fate. These results may implicate additional undiscovered bud autonomous mechanisms and/or components contributing to bud outgrowth regulation by environmental signals.

Debridement and Wound Biofilms

Journal of Wound Care. Jun, 2011  |  Pubmed ID: 21739682

Attaining Realistic and Substantial Reductions in HIV Incidence: Model Projections of Combining Microbicide and Male Circumcision Interventions in Rural Uganda

Sexually Transmitted Infections. Dec, 2011  |  Pubmed ID: 21768615

This study simulates the potential impact of male circumcision and female microbicide interventions, singularly and in combination, in rural Uganda.

Activation of G Protein-coupled Estrogen Receptor Induces Endothelium-independent Relaxation of Coronary Artery Smooth Muscle

American Journal of Physiology. Endocrinology and Metabolism. Nov, 2011  |  Pubmed ID: 21791623

Estrogens can either relax or contract arteries via rapid, nongenomic mechanisms involving classic estrogen receptors (ER). In addition to ERα and ERβ, estrogen may also stimulate G protein-coupled estrogen receptor 1 (GPER) in nonvascular tissue; however, a potential role for GPER in coronary arteries is unclear. The purpose of this study was to determine how GPER activity influenced coronary artery reactivity. In vitro isometric force recordings were performed on endothelium-denuded porcine arteries. These studies were augmented by RT-PCR and single-cell patch-clamp experiments. RT-PCR and immunoblot studies confirmed expression of GPER mRNA and protein, respectively, in smooth muscle from either porcine or human coronary arteries. G-1, a selective GPER agonist, produced a concentration-dependent relaxation of endothelium-denuded porcine coronary arteries in vitro. This response was attenuated by G15, a GPER-selective antagonist, or by inhibiting large-conductance calcium-activated potassium (BK(Ca)) channels with iberiotoxin, but not by inhibiting NO signaling. Last, single-channel patch-clamp studies demonstrated that G-1 stimulates BK(Ca) channel activity in intact smooth muscle cells from either porcine or human coronary arteries but had no effect on channels isolated in excised membrane patches. In summary, GPER activation relaxes coronary artery smooth muscle by increasing potassium efflux via BK(Ca) channels and requires an intact cellular signaling mechanism. This novel action of estrogen-like compounds may help clarify some of the controversy surrounding the vascular effects of estrogens.

History of Military Service and the Risk of Suicidal Ideation: Findings from the 2008 National Survey on Drug Use and Health

Suicide & Life-threatening Behavior. Oct, 2011  |  Pubmed ID: 21883410

Studies of completed suicide by history of military service have produced inconsistent findings; no representative population-based study has compared the risk of nonfatal suicidal behavior among veterans with risk among nonveterans. The objective of this study was to examine whether male veterans of the U.S. military are at heightened risk of suicidal ideation, compared with males who never served in the U.S. military. A total of 17,641 adult men completed the 2008 National Survey on Drug Use and Health (NSDUH). Subjects provided information about history of ever having served in the U.S. armed forces, past suicidal ideation, alcohol and drug abuse and dependence, measures of psychological distress, and sociodemographic data. Overall, men who had ever served in the armed forces were no more likely than men who had never served to report having seriously considered suicide over the prior 12 months. Military status was not differentially associated with other known suicide risk factors assessed by NSDUH, including psychiatric disorders. Our findings suggest that evidence-based suicide prevention strategies applicable to the general population should be employed to reduce suicide risk among the veteran population as well.

The Relationship Between Aortic Stiffness and E/A Filling Ratio and Myocardial Strain in the Context of Left Ventricular Diastolic Dysfunction in Heart Failure with Normal Ejection Fraction: Insights from Magnetic Resonance Imaging

Magnetic Resonance Imaging. Nov, 2011  |  Pubmed ID: 21907518

The purpose of this study is to investigate the relationship between aortic stiffness and diastolic dysfunction in heart failure with normal ejection fraction (HFNEF) and compare the results to normal subjects using magnetic resonance imaging (MRI). Sixteen human subjects (eight HFNEF and eight volunteers) were scanned on a 3.0-T MRI system. Aortic stiffness was assessed using pulse wave velocity (PWV). Left ventricle (LV) diastolic function was assessed by the early/atrial (E/A) filling ratio and different myocardial strain components. The results showed that, in HFNEF, a major part of LV filling occurred later during the atrial filling phase. The E/A ratio was less than 1 in HFNEF and greater than 1 in volunteers. Left ventricular myocardial dynamic strain range (difference between end-diastolic and end-systolic strains) was reduced in HFNEF, with less relaxation (strain rate) during the diastolic phase. Aortic PWV was higher in HFNEF than in volunteers due to less vessel compliance. The E/A ratio and myocardial strain measurements showed inverse correlations with aortic stiffness in HFNEF. The resulting inter- and intraobserver variabilities showed no bias between repeated cardiovascular measurements. In conclusion, a comprehensive MRI exam was developed for assessing patients with HFNEF. Heart failure with normal EF is associated with impaired LV diastolic function and significant ventricular and aortic stiffening. The degree of aortic stiffness involvement suggests reduced aortic compliance as a major factor in HFNEF.

Prognostic Value of Routine Cardiac Magnetic Resonance Assessment of Left Ventricular Ejection Fraction and Myocardial Damage: an International, Multicenter Study

Circulation. Cardiovascular Imaging. Nov, 2011  |  Pubmed ID: 21911738

Cardiac magnetic resonance (CMR) is considered the reference standard for assessment of left ventricular ejection fraction (LVEF) and myocardial damage. However, few studies have evaluated the relationship between CMR findings and patient outcome, and of these, most are small and none multicenter. We performed an international, multicenter study to assess the prognostic importance of routine CMR in patients with known or suspected heart disease.

Population Density, Water Supply, and the Risk of Dengue Fever in Vietnam: Cohort Study and Spatial Analysis

PLoS Medicine. Aug, 2011  |  Pubmed ID: 21918642

Aedes aegypti, the major vector of dengue viruses, often breeds in water storage containers used by households without tap water supply, and occurs in high numbers even in dense urban areas. We analysed the interaction between human population density and lack of tap water as a cause of dengue fever outbreaks with the aim of identifying geographic areas at highest risk.

Attempting to Explain Heterogeneous HIV Epidemics in Sub-Saharan Africa: Potential Role of Historical Changes in Risk Behaviour and Male Circumcision

Sexually Transmitted Infections. Dec, 2011  |  Pubmed ID: 21926115

A key conclusion of the Four Cities Study, carried out to explore reasons for heterogeneity in the HIV epidemic between two cities in sub-Saharan Africa with relatively low prevalence (Cotonou and Yaoundé) and two with high prevalence (Kisumu and Ndola), was that differences in biological cofactors outweighed differences in sexual risk behaviours. The authors explore an alternative hypothesis, that risk behaviours were historically higher in the high-prevalence cities. They also investigate the effects of different prevalence of male circumcision on the HIV epidemics in the four cities.

Mathematical Models for the Study of HIV Spread and Control Amongst Men Who Have Sex with Men

European Journal of Epidemiology. Sep, 2011  |  Pubmed ID: 21932033

For a quarter of century, mathematical models have been used to study the spread and control of HIV amongst men who have sex with men (MSM). We searched MEDLINE and EMBASE databases up to the end of 2010 and reviewed this literature to summarise the methodologies used, key model developments, and the recommended strategies for HIV control amongst MSM. Of 742 studies identified, 127 studies met the inclusion criteria. Most studies employed deterministic modelling methods (80%). Over time we saw an increase in model complexity regarding antiretroviral therapy (ART), and a corresponding decrease in complexity regarding sexual behaviours. Formal estimation of model parameters was carried out in only a small proportion of the studies (22%) while model validation was considered by an even smaller proportion (17%), somewhat reducing confidence in the findings from the studies. Nonetheless, a number of common conclusions emerged, including (1) identification of the importance of assumptions regarding changes in infectivity and sexual contact rates on the impact of ART on HIV incidence, that subsequently led to empirical studies to gather these data, and (2) recommendation that multiple strategies would be required for effective HIV control amongst MSM. The role of mathematical models in studying epidemics is clear, and the lack of formal inference and validation highlights the need for further developments in this area. Improved methodologies for parameter estimation and systematic sensitivity analysis will help generate predictions that more fully express uncertainty, allowing better informed decision making in public health.

Health Literacy Explains Racial Disparities in Diabetes Medication Adherence

Journal of Health Communication. 2011  |  Pubmed ID: 21951257

Although low health literacy and suboptimal medication adherence are more prevalent in racial/ethnic minority groups than Whites, little is known about the relationship between these factors in adults with diabetes, and whether health literacy or numeracy might explain racial/ethnic disparities in diabetes medication adherence. Previous work in HIV suggests health literacy mediates racial differences in adherence to antiretroviral treatment, but no study to date has explored numeracy as a mediator of the relationship between race/ethnicity and medication adherence. This study tested whether health literacy and/or numeracy were related to diabetes medication adherence, and whether either factor explained racial differences in adherence. Using path analytic models, we explored the predicted pathways between racial status, health literacy, diabetes-related numeracy, general numeracy, and adherence to diabetes medications. After adjustment for covariates, African American race was associated with poor medication adherence (r = -0.10, p < .05). Health literacy was associated with adherence (r = .12, p < .02), but diabetes-related numeracy and general numeracy were not related to adherence. Furthermore, health literacy reduced the effect of race on adherence to nonsignificance, such that African American race was no longer directly associated with lower medication adherence (r = -0.09, p = .14). Diabetes medication adherence promotion interventions should address patient health literacy limitations.

Transplantation in Zebrafish

Methods in Cell Biology. 2011  |  Pubmed ID: 21951540

Tissue or cell transplantation has been an extremely valuable technique for studying developmental potential of certain cell population, dissecting cell-environment interaction relationship, identifying stem cells, and many other applications. One key technical requirement for performing transplantation assay is the capability of distinguishing the transplanted donor cells from the endogenous host cells, and tracing the donor cells over time. Zebrafish has emerged as an excellent model organism for performing transplantation assay, thanks to the transparency of embryos during development and even certain adults. Using transgenic techniques and fast-evolving imaging technology, fluorescence-labeled donor cells can be easily identified and studied in vivo. In this chapter, we will first discuss the rationale of different types of zebrafish transplantation in both embryos and adults, and then focus on detailed methods of three types of transplantation: blastula/gastrula transplantation for mosaic analysis, stem cell transplantation, and tumor transplantation.

ACR Appropriateness Criteria® Chronic Chest Pain--high Probability of Coronary Artery Disease

Journal of the American College of Radiology : JACR. Oct, 2011  |  Pubmed ID: 21962781

Imaging is valuable in determining the presence, extent, and severity of myocardial ischemia and the severity of obstructive coronary lesions in patients with chronic chest pain in the setting of high probability of coronary artery disease. Imaging is critical for defining patients best suited for medical therapy or intervention, and findings can be used to predict long-term prognosis and the likely benefit from various therapeutic options. Chest radiography, radionuclide single photon-emission CT, radionuclide ventriculography, and conventional coronary angiography are the imaging modalities historically used in evaluating suspected chronic myocardial ischemia. Stress echocardiography, PET, cardiac MRI, and multidetector cardiac CT have all been more recently shown to be valuable in the evaluation of ischemic heart disease. Other imaging techniques may be helpful in those patients who do not present with signs classic for angina pectoris or in those patients who do not respond as expected to standard management. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

A Multiinstitutional, Multidisciplinary Model for Developing and Teaching Translational Research in Health Disparities

Clinical and Translational Science. Dec, 2011  |  Pubmed ID: 22212225

Health disparities may affect any person in any community in the world, resulting from a multitude of factors including socioeconomic status, race, ethnicity, environment, and genetics. The impact of health disparities is felt by affected individuals, their families, communities, and the greater health care system. There is a critical need to increase health disparities research activities. This may be achieved by expanding and strengthening the training, education and career development of motivated clinicians, physicians and basic scientists, engaging them in clinical and translational research. Translational research relies on collaboration across disciplines, facilitating the dissemination and transfer of knowledge to populations for the overall improvement of health while decreasing the economic burden of health care. The University of Puerto Rico Medical Sciences Campus (UPR-MSC), Schools of Health Professions and Medicine joint initiatives, Clinical Research Education and Career Development (CRECD) and Hispanics in Research Capability (HiREC) programs, convened health disparities experts, faculty and scholars from multiple disciplines, cultural backgrounds and institutions. Together, they created a model for teaching translational research in health disparities that spans disciplines without boundaries.

Periodic Active Case Finding for TB: when to Look?

PloS One. 2011  |  Pubmed ID: 22216182

To investigate the factors influencing the performance and cost-efficacy of periodic rounds of active case finding (ACF) for TB.

HElp3 Directly Modulates the Expression of HSP70 Gene in HeLa Cells Via HAT Activity

PloS One. 2011  |  Pubmed ID: 22216241

Human Elongator complex, which plays a key role in transcript elongation in vitro assay, is incredibly similar in either components or function to its yeast counterpart. However, there are only a few studies focusing on its target gene characterization in vivo. We studied the effect of down-regulation of the human elongation protein 3 (hELP3) on the expression of HSP70 through antisense strategy. Transfecting antisense plasmid p1107 into HeLa cells highly suppressed hELP3 expression, and substantially reduced expression of HSP70 mRNA and protein. Furthermore, chromatin immunoprecipitation assay (ChIP Assay) revealed that hElp3 participates in the transcription elongation of HSPA1A in HeLa cells. Finally, complementation and ChIP Assay in yeast showed that hElp3 can not only complement the growth and slow activation of HSP70 (SSA3) gene transcription, but also directly regulates the transcription of SSA3. On the contrary, these functions are lost when the HAT domain is deleted from hElp3. These data suggest that hElp3 can regulate the transcription of HSP70 gene, and the HAT domain of hElp3 is essential for this function. These findings now provide novel insights and evidence of the functions of hELP3 in human cells.

Risk Assessment Models for Cancer-associated Venous Thromboembolism

Cancer. Nov, 2011  |  Pubmed ID: 22086826

Venous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high-risk patients to prevent incident (first-time) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as well as ambulatory cancer patients receiving thalidomide or lenalidomide in combination with high-dose dexamethasone or chemotherapy, in the absence of contraindications to anticoagulation. However, the majority of cancer patients are ambulatory, and currently primary thromboprophylaxis is not recommended for these patients, even those considered at very high risk. In this concise review, the authors discuss risk stratification models that have been specifically developed to identify cancer patients at high risk for VTE, and thus might be useful in future studies designed to determine the potential benefit of primary thromboprophylaxis. Cancer 2011;. © 2011 American Cancer Society.

Fasciculations and Cramps: How Benign? Report of Four Cases Progressing to ALS

Journal of Neurology. Apr, 2011  |  Pubmed ID: 20967550

Clinical diagnosis of amyotrophic lateral sclerosis (ALS) in patients presenting with cramps and fasciculations may not be evident at the first consultation. Sequential reviews, clinical and neurophysiological, form an important part of clinical practice in such cases. Recent attempts to delineate a more benign group with cramps and fasciculations have lacked information on the long term profile, both clinical and neurophysiological. Four patients who were initially diagnosed as suffering from benign cramps and fasciculations, but who subsequently progressed to ALS, are described. We propose that a diagnosis of benign cramps and fasciculations should not be considered secure without a minimum follow up of 4-5 years.

A Comparison of Two Implant Systems in Restoration of Hip Geometry in Arthroplasty

Clinical Orthopaedics and Related Research. Feb, 2011  |  Pubmed ID: 21082363

Restoration of hip offset and leg length during THA is often limited by available implant geometries. The recent introduction of femoral components with a modular junction at the base of the neck (two modular junction components) has expanded the options to restore femoral offset and leg length.

Sentinel Lymph Node Biopsy After Neo-adjuvant Chemotherapy in Breast Cancer

The Breast Journal. Jan-Feb, 2011  |  Pubmed ID: 21129099

The timing of sentinel node biopsy in the setting of neo-adjuvant chemotherapy for breast cancer is controversial. Sentinel node biopsy performed after neo-adjuvant chemotherapy may save patients with a nodal response the morbidity of an axillary lymph node dissection. A retrospective review of prospectively collected data compared sentinel node biopsies performed after patients had received neo-adjuvant chemotherapy with patients who had not received neo-adjuvant chemotherapy. Demographic factors, tumor characteristics, and the results of the sentinel node biopsies and completion lymph node dissections (when applicable) were compared. A total of 231 axillary procedures (224 patients) were evaluated. The patients who received neo-adjuvant chemotherapy (NEO; N=52) were younger, had higher grade tumors, were more likely to have a mastectomy, and were more likely to have ER-negative and HER-2/neu positive tumors than the patients who did not receive neo-adjuvant chemotherapy (NON; N=179). The mean clinical tumor size in the neo-adjuvant group was 4.5cm (±1.8) prior to chemotherapy; the post-chemotherapy pathologic size was 1.4cm (±1.3). A sentinel node was identified in all cases. There were no significant differences between the groups in the mean number of sentinel nodes removed (NEO=3.3; NON=3.1; p=0.545), the percentage of positive axillae (NEO=24%; NON=21%; p=0.776) or the mean number of positive sentinel nodes (NEO=1.3; NON=1.5; p=0.627). There was no difference in the percentage of completion lymph node dissections with additional positive nodes (NEO=20%; NON=35%; p=0.462); there was a difference in the number of nodes removed in the completion lymph node dissections (mean NEO=12.0; NON=16.4; p=0.047). Sentinel node biopsy performed after neo-adjuvant chemotherapy appears to be an oncologically sound procedure and may save some patients the morbidity of a complete lymph node dissection.

Input/output Pulse Operation of ZnO Nanowire Threshold Integrators

Nanotechnology. Jan, 2011  |  Pubmed ID: 21139191

Integrating more functionality into individual nano-components is a key step to exploit alternative architectures for energy-efficient computation, such as, for instance, neuromorphic computing. Here, we show how to configure ZnO nanowire field-effect transistors as light pulse integrators with programmable threshold. We demonstrate that these single-component devices can be operated as both synchronous and asynchronous neuron-like structures, where the firing threshold and the form of the output signal, either step-like or spiked, can be controlled by using several operational parameters, including the environment in which the device operates. A detailed study showing how environmental variables, such as relative humidity, ambient light and temperature, affect device operation is presented.

Calibrating Models in Economic Evaluation: a Seven-step Approach

PharmacoEconomics. Jan, 2011  |  Pubmed ID: 21142277

In economic evaluation, mathematical models have a central role as a way of integrating all the relevant information about a disease and health interventions, in order to estimate costs and consequences over an extended time horizon. Models are based on scientific knowledge of disease (which is likely to change over time), simplifying assumptions and input parameters with different levels of uncertainty; therefore, it is sensible to explore the consistency of model predictions with observational data. Calibration is a useful tool for estimating uncertain parameters, as well as more accurately defining model uncertainty (particularly with respect to the representation of correlations between parameters). Calibration involves the comparison of model outputs (e.g. disease prevalence rates) with empirical data, leading to the identification of model parameter values that achieve a good fit. This article provides guidance on the theoretical underpinnings of different calibration methods. The calibration process is divided into seven steps and different potential methods at each step are discussed, focusing on the particular features of disease models in economic evaluation. The seven steps are (i) Which parameters should be varied in the calibration process? (ii) Which calibration targets should be used? (iii) What measure of goodness of fit should be used? (iv) What parameter search strategy should be used? (v) What determines acceptable goodness-of-fit parameter sets (convergence criteria)? (vi) What determines the termination of the calibration process (stopping rule)? (vii) How should the model calibration results and economic parameters be integrated? The lack of standards in calibrating disease models in economic evaluation can undermine the credibility of calibration methods. In order to avoid the scepticism regarding calibration, we ought to unify the way we approach the problems and report the methods used, and continue to investigate different methods.

The Role of the Natural Epidemic Dynamics and Migration in Explaining the Course of the HIV Epidemic in Rural Uganda: a Modelling Study

International Journal of Epidemiology. Apr, 2011  |  Pubmed ID: 21147847

Human immunodeficiency virus (HIV) prevalence in Uganda fell during the 1990s and has risen since 2000. The changing trends since 2000 may be due to changing risky sexual behaviour, but other factors may also contribute. We explore the possible impact that two factors may have on cohort trends: natural epidemic dynamics and local migration. We simultaneously fit a mathematical model to the contrasting prevalence trends by age/gender in a southwest Ugandan cohort, which has never been done before.

Identifying and Relating Biological Concepts in the Catalogue of Life

Journal of Biomedical Semantics. 2011  |  Pubmed ID: 22004596

ABSTRACT:

Evaluation of the Role of Location and Distance in Recruitment in Respondent-driven Sampling

International Journal of Health Geographics. 2011  |  Pubmed ID: 22008416

Respondent-driven sampling(RDS) is an increasingly widely used variant of a link tracing design for recruiting hidden populations. The role of the spatial distribution of the target population has not been robustly examined for RDS. We examine patterns of recruitment by location, and how they may have biased an RDS study findings.

Evidence of a Robust Resident Bacteriophage Population Revealed Through Analysis of the Human Salivary Virome

The ISME Journal. Dec, 2011  |  Pubmed ID: 22158393

Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host-virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.

A Population-based Comparison of the Incidence of Adverse Outcomes After Simultaneous-bilateral and Staged-bilateral Total Knee Arthroplasty

The Journal of Bone and Joint Surgery. American Volume. Dec, 2011  |  Pubmed ID: 22159856

It is unclear whether simultaneous-bilateral total knee arthroplasty is as safe as staged-bilateral arthroplasty is. We are aware of no randomized trials comparing the safety of these surgical strategies. The purpose of this study was to retrospectively compare these two strategies, with use of an intention-to-treat approach for the staged-bilateral arthroplasty cohort.

Driving Down the Detection Limit in Microstructured Fiber-Based Chemical Dip Sensors

Sensors (Basel, Switzerland). 2011  |  Pubmed ID: 22163778

We present improvements to fluorescence sensing in soft-glass microstructured optical fibers that result in significantly improved sensitivity relative to previously published results. Concentrations of CdSe quantum dots down to 10 pM levels have been demonstrated. We show that the primary limitation to the sensitivity of these systems is the intrinsic fluorescence of the glass itself.

Defense Mechanisms Against Herbivory in Picea: Sequence Evolution and Expression Regulation of Gene Family Members in the Phenylpropanoid Pathway

BMC Genomics. Dec, 2011  |  Pubmed ID: 22177423

ABSTRACT: BACKGROUND: In trees, a substantial amount of carbon is directed towards production of phenolics for development and defense. This metabolic pathway is also a major factor in resistance to insect pathogens in spruce. In such gene families, environmental stimuli may have an important effect on the evolutionary fate of duplicated genes, and different expression patterns may indicate functional diversification. RESULTS: Gene families in spruce (Picea) have expanded to superfamilies, including O-methyltransferases, cytochrome-P450, and dirigents/classIII-peroxidases. Neo-functionalization of superfamily members from different clades is reflected in expression diversification. Genetical genomics can provide new insights into the genetic basis and evolution of insect resistance in plants. Adopting this approach, we merged genotype data (252 SNPs in a segregating pedigree), gene expression levels (for 428 phenylpropanoid-related genes) and measures of susceptibility to Pissodes stobi, using a partial-diallel crossing-design with white spruce (Picea glauca). Thirty-eight expressed phenylpropanoid-related genes co-segregated with weevil susceptibility, indicating either causative or reactive effects of these genes to weevil resistance. We identified eight regulatory genomic regions with extensive overlap of quantitative trait loci from susceptibility and growth phenotypes (pQTLs) and expression QTL (eQTL) hotspots. In particular, SNPs within two different CCoAOMT loci regulate phenotypic variation from a common set of 24 genes and three resistance traits. CONCLUSIONS: Pest resistance was associated with individual candidate genes as well as with trans-regulatory hotspots along the spruce genome. Our results showed that specific genes within the phenylpropanoid pathway have been duplicated and diversified in the conifer in a process fundamentally different from short-lived angiosperm species. These findings add to the information about the role of the phenylpropanoid pathway in the evolution of plant defense mechanisms against insect pests and provide substantial potential for the functional characterization of several not yet resolved alternative pathways in plant defenses.

Patient Management After Noninvasive Cardiac Imaging Results From SPARC (Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease)

Journal of the American College of Cardiology. Jan, 2012  |  Pubmed ID: 22281249

This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging.

Subtotal Vaginectomy for Management of Extensive Vaginal Disease in 11 Dogs

Veterinary Surgery : VS. Jan, 2012  |  Pubmed ID: 22292563

OBJECTIVE: To report (1) a surgical technique for subtotal vaginectomy using a combined abdominal and vestibular approach; (2) intra- and postoperative complications; and (3) long-term outcome. STUDY DESIGN: Retrospective case series. ANIMALS: Female dogs (n = 11) with extensive intramural vaginal disease. METHODS: Through a ventral median celiotomy, the cranial aspect of the vagina was freed and ovariohysterectomy (OVH) was performed in intact females. After episiotomy, the vaginal wall was incised at the vestibulovaginal junction cranial to the urethral orifice, and the vagina freed from any remaining pelvic attachments. Dogs were reexamined at 4 weeks and 6 months. Long-term outcome was evaluated by contacting the primary veterinarian by phone. RESULTS: Five dogs had benign vaginal disease and 6 had malignant vaginal neoplasia. A combined abdominal and vestibular approach permitted subtotal vaginectomy in all dogs; 6 dogs also had OVH. No major complications occurred and clinical signs had resolved by 4 weeks. One dog with malignant neoplasia was euthanatized 3 months later for metastatic disease and 1 dog developed postoperative urinary incontinence. Local recurrence or metastases were not identified in the other dogs. CONCLUSION: Combined abdominal and vestibular approach for subtotal vaginectomy allowed complete resection of extensive vaginal lesions, was not associated with major complications, and outcome was favorable.

Agonist of Growth Hormone-releasing Hormone Reduces Pneumolysin-induced Pulmonary Permeability Edema

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22308467

Aggressive treatment with antibiotics in patients infected with Streptococcus pneumoniae induces release of the bacterial virulence factor pneumolysin (PLY). Days after lungs are sterile, this pore-forming toxin can still induce pulmonary permeability edema in patients, characterized by alveolar/capillary barrier dysfunction and impaired alveolar liquid clearance (ALC). ALC is mainly regulated through Na(+) transport by the apically expressed epithelial sodium channel (ENaC) and the basolaterally expressed Na(+)/K(+)-ATPase in type II alveolar epithelial cells. Because no standard treatment is currently available to treat permeability edema, the search for novel therapeutic candidates is of high priority. We detected mRNA expression for the active receptor splice variant SV1 of the hypothalamic polypeptide growth hormone-releasing hormone (GHRH), as well as for GHRH itself, in human lung microvascular endothelial cells (HL-MVEC). Therefore, we have evaluated the effect of the GHRH agonist JI-34 on PLY-induced barrier and ALC dysfunction. JI-34 blunts PLY-mediated endothelial hyperpermeability in monolayers of HL-MVEC, in a cAMP-dependent manner, by means of reducing the phosphorylation of myosin light chain and vascular endothelial (VE)-cadherin. In human airway epithelial H441 cells, PLY significantly impairs Na(+) uptake, but JI-34 restores it to basal levels by means of increasing cAMP levels. Intratracheal instillation of PLY into C57BL6 mice causes pulmonary alveolar epithelial and endothelial hyperpermeability as well as edema formation, all of which are blunted by JI-34. These findings point toward a protective role of the GHRH signaling pathway in PLY-induced permeability edema.

Structural Brain Abnormalities and Suicidal Behavior in Borderline Personality Disorder

Journal of Psychiatric Research. Feb, 2012  |  Pubmed ID: 22336640

BACKGROUND: Structural brain abnormalities have been demonstrated in subjects with BPD in prefrontal and fronto-limbic regions involved in the regulation of emotion and impulsive behavior, executive cognitive function and episodic memory. Impairment in these cognitive functions is associated with increased vulnerability to suicidal behavior. We compared BPD suicide attempters and non-attempters, high and low lethality attempters to healthy controls to identify neural circuits associated with suicidal behavior in BPD. METHODS: Structural MRI scans were obtained on 68 BPD subjects (16 male, 52 female), defined by IPDE and DIB/R criteria, and 52 healthy controls (HC: 28 male, 24 female). Groups were compared by diagnosis, attempt status, and attempt lethality. ROIs were defined for areas reported to have structural or metabolic abnormalities in BPD, and included: mid-inf. orbitofrontal cortex, mid-sup temporal cortex, anterior cingulate, insula, hippocampus, amygdala, fusiform, lingual and parahippocampal gyri. Data were analyzed using optimized voxel-based morphometry implemented with DARTEL in SPM5, co-varied for age and gender, corrected for cluster extent (p < .001). RESULTS: Compared to HC, BPD attempters had significantly diminished gray matter concentrations in 8 of 9 ROIs, non-attempters in 5 of 9 ROIs. Within the BPD sample, attempters had diminished gray matter in Lt. insula compared to non-attempters. High lethality attempters had significant decreases in Rt. mid-sup. temporal gyrus, Rt. mid-inf. orbitofrontal gyrus, Rt. insular cortex, Lt. fusiform gyrus, Lt. lingual gyrus and Rt. parahippocampal gyrus compared to low lethality attempters. CONCLUSIONS: Specific structural abnormalities discriminate BPD attempters from non-attempters and high from low lethality attempters.

Graphene from Electrochemical Exfoliation and Its Direct Applications in Enhanced Energy Storage Devices

Chemical Communications (Cambridge, England). Jan, 2012  |  Pubmed ID: 22170354

Graphite was electrochemically exfoliated in mixtures of room temperature ionic liquids and deionized water containing lithium salts to produce functionalized graphenes and such an electrochemical exfoliation technique can be directly used in making primary battery electrodes with significantly enhanced specific energy capacity.

An Optical Platform for Cell Tracking in Adult Zebrafish

Cytometry. Part A : the Journal of the International Society for Analytical Cytology. Feb, 2012  |  Pubmed ID: 22162445

Adult zebrafish are being increasingly used as a model in cancer and stem cell research. Here we describe an integrated optical system that combines a laser scanning confocal microscope (LSCM) and an in vivo flow cytometer (IVFC) for simultaneous visualization and cell quantification. The system is set up specifically for non-invasive tracking of both stationary and circulating cells in adult zebrafish (casper) that have been engineered to be optically transparent. Confocal imaging in this instrument serves the dual purpose of visualizing fish tissue microstructure and an imaging-based guide to locate a suitable vessel for quantitative analysis of circulating cells by IVFC. We demonstrate initial testing of this novel instrument by imaging the transparent adult zebrafish casper vasculature and tracking circulating cells in CD41-GFP/Gata1-DsRed transgenic fish whose thrombocytes/erythrocytes express the green and red fluorescent proteins. In vivo measurements allow cells to be tracked under physiological conditions in the same fish over time, without drawing blood samples or sacrificing animals. We also discuss the potential applications of this instrument in biomedical research. © 2011 International Society for Advancement of Cytometry.

Assessment of Health Literacy and Numeracy Among Spanish-Speaking Parents of Young Children: Validation of the Spanish Parental Health Literacy Activities Test (PHLAT Spanish)

Academic Pediatrics. Jan-Feb, 2012  |  Pubmed ID: 22056223

To assess the health literacy and numeracy skills of Spanish-speaking parents of young children and to validate a new Spanish language health literacy assessment for parents, the Spanish Parental Health Literacy Activities Test (PHLAT Spanish).

Measurement of Distance Walked and Physiologic Responses to a 6-minute Walk Test on Level Ground and on a Treadmill: a Comparative Study

Journal of Geriatric Physical Therapy (2001). Jan-Mar, 2012  |  Pubmed ID: 22189948

: The 6-minute walk test (6MWT) is commonly used to test the functional capacity of individuals. However, in many practice settings, the long corridor needed to administer the test may not be available. Review of current literature revealed limited evidence regarding the use of a treadmill as an alternate method of performing a 6MWT.

Digital PCR Provides Absolute Quantitation of Viral Load for an Occult RNA Virus

Journal of Virological Methods. Jan, 2012  |  Pubmed ID: 21983150

Using a multiplexed LNA-based Taqman assay, RT-digital PCR (RT-dPCR) was performed in a prefabricated microfluidic device that monitored absolute viral load in native and immortalized cell lines, overall precision of detection, and the absolute detection limit of an occult RNA virus GB Virus Type C (GBV-C). RT-dPCR had on average a 10% lower overall coefficient of variation (CV, a measurement of precision) for viral load testing than RT-qPCR and had a higher overall detection limit, able to quantify as low as three 5'-UTR molecules of GBV-C genome. Two commercial high-yield in vitro transcription kits (T7 Ribomax Express by Promega and Ampliscribe T7 Flash by Epicentre) were compared to amplify GBV-C RNA genome with T7-mediated amplification. The Ampliscribe T7 Flash outperformed the T7 Ribomax Express in yield of full-length GBV-C RNA genome. THP-1 cells (a model of monocytic derived cells) were transfected with GBV-C, yielding infectious virions that replicated over a 120h time course and could be infected directly. This study provides the first evidence of GBV-C replication in monocytic derived clonal cells. Thus far, it is the only study using a microfluidic device that measures directly viral load of mammalian RNA virus in a digital format without need for a standard curve.

Testosterone-induced Relaxation of Coronary Arteries: Activation of BKCa Channels Via the CGMP-dependent Protein Kinase

American Journal of Physiology. Heart and Circulatory Physiology. Jan, 2012  |  Pubmed ID: 22081702

Androgens are reported to have both beneficial and detrimental effects on human cardiovascular health. The aim of this study was to characterize nongenomic signaling mechanisms in coronary artery smooth muscle (CASM) and define the ionic basis of testosterone (TES) action. TES-induced relaxation of endothelium-denuded porcine coronary arteries was nearly abolished by 20 nM iberiotoxin, a highly specific inhibitor of large-conductance, calcium-activated potassium (BK(Ca)) channels. Molecular patch-clamp studies confirmed that nanomolar concentrations of TES stimulated BK(Ca) channel activity by ∼100-fold and that inhibition of nitric oxide synthase (NOS) activity by N(G)-monomethyl-L-arginine nearly abolished this effect. Inhibition of nitric oxide (NO) synthesis or guanylyl cyclase activity also attenuated TES-induced coronary artery relaxation but did not alter relaxation due to 8-bromo-cGMP. Furthermore, we detected TES-stimulated NO production in porcine coronary arteries and in human CASM cells via stimulation of the type 1 neuronal NOS isoform. Inhibition of the cGMP-dependent protein kinase (PKG) attenuated TES-stimulated BK(Ca) channel activity, and direct assay determined that TES increased activity of PKG in a concentration-dependent fashion. Last, the stimulatory effect of TES on BK(Ca) channel activity was mimicked by addition of purified PKG to the cytoplasmic surface of a cell-free membrane patch from CASM myocytes (∼100-fold increase). These findings indicate that TES-induced relaxation of endothelium-denuded coronary arteries is mediated, at least in part, by enhanced NO production, leading to cGMP synthesis and PKG activation, which, in turn, opens BK(Ca) channels. These findings provide a molecular mechanism that could help explain why androgens have been reported to relax coronary arteries and relieve angina pectoris.

Evaluation of Respondent-driven Sampling

Epidemiology (Cambridge, Mass.). Jan, 2012  |  Pubmed ID: 22157309

Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total population data.

Hematopoietic Defects in Rps29 Mutant Zebrafish Depend Upon P53 Activation

Experimental Hematology. Mar, 2012  |  Pubmed ID: 22120640

Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Blackfan anemia, a rare congenital disease characterized by red cell aplasia and distinctive craniofacial anomalies. A zebrafish screen uncovered decreased hematopoietic stem cells in embryos with mutations in ribosomal protein rps29. Here, we determined that rps29(-/-) embryos also have red blood cell defects and increased apoptosis in the head. As the p53 pathway has been shown to play a role in other ribosomal protein mutants, we studied the genetic relationship of rps29 and p53. Transcriptional profiling revealed that genes upregulated in the rps29 mutant are enriched for genes upregulated by p53 after irradiation. p53 mutation near completely rescues the rps29 morphological and hematopoietic phenotypes, demonstrating that p53 mediates the effects of rps29 knockdown. We also identified neuronal gene orthopedia protein a (otpa) as one whose expression correlates with rps29 expression, suggesting that levels of expression of some genes are dependent on rps29 levels. Together, our studies demonstrate a role of p53 in mediating the cellular defects associated with rps29 and establish a role for rps29 and p53 in hematopoietic stem cells and red blood cell development.