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20860786

Testing the feasibility of the Dignity Therapy interview: adaptation for the Danish culture.

'Dignity Therapy' (DT) is a brief, flexible intervention, which allows patients plete an interview and create a document regarding their life, identity and what they want to leave in writing for their loved ones. DT is based on the DT Question Protocol. Developed and tested in English speaking settings, DT has proven to be a feasible and effective way to enhance patient dignity, while diminishing suffering and depression. The aim of this study was to test the acceptability and feasibility of the DT Question Protocol among Danish health professionals and cancer patients, and to obtain preliminary estimates of patient uptake for DT. These results will be used to inform a larger evaluation study.

20860787

Patient safety in surgical environments: cross-countries comparison of psychometric properties and results of the Norwegian version of the Hospital Survey on Patient Safety.

How hospital health care personnel perceive safety climate has been assessed in several countries by using the Hospital Survey on Patient Safety (HSOPS). Few studies have examined safety climate factors in surgical departments per se. This study examined the psychometric properties of a Norwegian translation of the HSOPS and pared safety climate factors from a surgical setting to hospitals in the United States, the Netherlands and Norway.

20860789

Inter-rater agreement and reliability of the COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) checklist.

The COSMIN checklist is a tool for evaluating the methodological quality of studies on measurement properties of health-related patient-reported es. The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist (n = 114).

20860788

Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF) rat.

Early markers of diabetic autonomic neuropathy (DAN) in an electrocardiogram (ECG) include elevated R wave amplitudes, widening of QTc intervals and decreased heart rate variability (HRV). The severity of DAN has a direct relationship with mortality risk. Aerobic exercise training is mon mendation for the delay and possible reversal of cardiac dysfunction. Limited research exists on ECG measures for the evaluation of aerobic exercise training in Zucker Diabetic Fatty (ZDF) rat, a model of type 2 diabetes. The objective of this study was to assess whether aerobic exercise training may attenuate diabetes induced ECG changes.

20860790

ModuleOrganizer: detecting modules in families of transposable elements.

Most known eukaryotic genomes contain mobile copied elements called transposable elements. In some species, these elements account for the majority of the genome sequence. They have been subject to many mutations and other genomic events (copies, deletions, captures) during transposition. The identification of these transformations remains a difficult issue. The study of families of transposable elements is generally founded on a multiple alignment of their sequences, a critical step that is adapted to transposons containing mostly localized nucleotide mutations. Many transposons that have lost their protein-coding capacity have undergone plex rearrangements, needing the development of plex methods in order to characterize the architecture of sequence variations.

20860791

Relating underrepresented genomic DNA patterns and tiRNAs: the rule behind the observation and beyond.

One of the central problems of post-genomic biology is the understanding of regulatory network of genes. Traditionally the problem is approached from the protein-DNA interaction perspective. In recent years various types of noncoding RNAs appeared on the scene as new potent players of the game. The exact role of these molecules in gene expression control is mostly unknown at present, while their importance is generally recognized.

20860793

Statistical inference of the time-varying structure of gene-regulation networks.

Biological networks are highly dynamic in response to environmental and physiological cues. This variability is in contrast to conventional analyses of biological networks, which have overwhelmingly employed static graph models which stay constant over time to describe biological systems and their underlying molecular interactions.

20860794

Prediction and classification of aminoacyl tRNA synthetases using PROSITE domains.

Aminoacyl tRNA synthetases (aaRSs) catalyse the first step of protein synthesis in all organisms. They are responsible for the precise attachment of amino acids to their cognate transfer RNAs. There are twenty different types of aaRSs, unique for each amino acid. These aaRSs have been divided into two classes, prising ten enzymes. It is important to predict and classify aaRSs in order to understand protein synthesis.

20860792

BOLD cardiovascular magnetic resonance at 3.0 tesla in myocardial ischemia.

The purpose of this study was to determine the ability of blood oxygen level dependent (BOLD) cardiovascular magnetic resonance (CMR) to detect stress-inducible myocardial ischemic reactions in the presence of angiographically significant coronary artery disease (CAD).

20860795

Use of a highly sensitive strand-specific quantitative PCR to identify abortive replication in the mouse model of respiratory syncytial virus disease.

The BALB/c mouse monly used to study RSV infection and disease. However, despite the many advantages of this well-characterised model, the inoculum is large, viral replication is restricted and only a very small amount of virus can be recovered from infected animals. A key question in this model is the fate of the administered virus. Is replication really being measured or is the model measuring the survival of the virus over time? To answer these questions we developed a highly sensitive strand-specific quantitative PCR (QPCR) able to accurately quantify the amount of RSV replication in the BALB/c mouse lung, allowing characterisation of RSV negative and positive strand RNA dynamics.

20860797

Integrin α2-deficient mice provide insights into specific functions of collagen receptors in the kidney.

Integrins are important cellular receptors for collagens. Within the glomerulus, podocytes regulate the integrity of the glomerular basement membrane (GBM) by sensing the presence of collagen and regulating collagen IV synthesis. The present study evaluates the role of integrin α2 (ITGA2) in cell-matrix interaction.

20860796

Enhanced chlorhexidine skin penetration with eucalyptus oil.

Chlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic.

20860798

P-cadherin counteracts myosin II-B function: implications in melanoma progression.

Malignant transformation of melanocytes is frequently attended by a switch in cadherin expression profile as shown for E- and N-cadherin. For P-cadherin, downregulation in metastasizing melanoma has been demonstrated, and over-expression of P-cadherin in melanoma cell lines has been shown to inhibit invasion. The strong invasive and metastatic nature of cutaneous melanoma implies a deregulated interplay between intercellular adhesion and migration-related molecules

20860799

The first-generation Daphnia magna linkage map.

Daphnia magna is a well-established model species in ecotoxicology, ecology and evolution. Several new genomics tools are presently under development for this species; among them, a linkage map is a first requirement for estimating the genetic background of phenotypic traits in quantitative trait loci (QTL) studies and is also very useful in assembling the genome. It also parative studies between D. magna and D. pulex, for which a linkage map already exists.

20860801

Analysis of simultaneous space-time clusters of Campylobacter spp. in humans and in broiler flocks using a multiple dataset approach.

Campylobacteriosis is the most frequently reported zoonosis in the EU and the epidemiology of sporadic campylobacteriosis, especially the routes of transmission, is to a great extent unclear. Poultry easily e colonised with Campylobacter spp., being symptom-less intestinal carriers. Earlier it was estimated that internationally between 50% and 80% of the cases could be attributed to chicken as a reservoir. In a Norwegian surveillance programme all broiler flocks under 50 days of age were tested for Campylobacter spp. The aim of the current study was to identify simultaneous local space-time clusters each year from 2002 to 2007 for human cases of campylobacteriosis and for broiler flocks testing positive for Campylobacter spp. using a multivariate spatial scan statistic method. A cluster occurring simultaneously in humans and broilers could indicate the presence mon factors associated with the dissemination of Campylobacter spp. for both humans and broilers.

20860802

FragViz: visualization of fragmented networks.

Researchers in systems biology use network visualization to summarize the results of their analysis. Such networks often include ponents, which popular network alignment algorithms place arbitrarily with respect to the rest of the network. This can lead to misinterpretations due to the proximity of otherwise unrelated elements.

20860800

Purinergic receptors are involved in tooth-pulp evoked nocifensive behavior and brainstem neuronal activity.

To evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X3 and P2X2/3 receptor agonist α,β-methyleneATP (α,β-meATP) was applied to the molar tooth pulp and nocifensive behavior and extracellular-signal regulated kinase (ERK) phosphorylation in trigeminal spinal subnucleus caudalis (Vc), trigeminal spinal subnucleus interpolaris (Vi), upper cervical spinal cord (C1/C2) and paratrigeminal nucleus (Pa5) neurons were analyzed in rats.

20860803

Completeness and timeliness of Salmonella notifications in Ireland in 2008: a cross sectional study.

In Ireland, salmonellosis is the second mon cause of bacterial gastroenteritis. A new electronic system for reporting (Computerised Infectious Disease Reporting--CIDR) of Salmonella cases was established in 2004. It collates clinical (and/or laboratory) data on confirmed and probable Salmonella cases. The authors studied pleteness and the timeliness of Salmonella notifications in 2008.

20860804

Newly discovered KI, WU, and Merkel cell polyomaviruses: no evidence of mother-to-fetus transmission.

Three* human polyomaviruses have been discovered recently, KIPyV, WUPyV and MCPyV. These viruses appear to circulate ubiquitously; however, their clinical significance beyond Merkel cell carcinoma is pletely unknown. In particular, nothing is known about their preponderance in vertical transmission. The aim of this study was to investigate the frequency of fetal infections by these viruses. We sought the three by PCR, and MCPyV also by real-time quantitative PCR (qPCR), from 535 fetal autopsy samples (heart, liver, placenta) from intrauterine fetal deaths (IUFDs) (N = 169), miscarriages (120) or induced abortions (246). We also measured the MCPyV IgG antibodies in the corresponding maternal sera (N = 462) mostly from the first trimester.

20860805

Variations in autologous neutralization and CD4 dependence of b12 resistant HIV-1 clade C env clones obtained at different time points from antiretroviral naïve Indian patients with recent infection.

Limited information is available on HIV-1 Indian clade C sensitivities to autologous antibodies during the course of natural infection. In the present study, a total of plete envelope clones (Env) were amplified at different time points predominantly from the plasma of five Indian patients with recent HIV-1 infection and envelope-pseudotyped viruses were examined for their magnitude of sensitivity to autologous plasma antibodies during natural course of infection.

20860807

Urbanization, ethnicity and cardiovascular risk in a population in transition in Nakuru, Kenya: a population-based survey.

Cardiovascular disease (CVD) is the leading cause of death among older people in Africa. This study aimed to investigate the relationship of urbanization and ethnicity with CVD risk markers in Kenya.

20860806

Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region.

Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes.

20860809

Cost-effectiveness analysis of malaria chemoprophylaxis for travellers to West-Africa.

The importation of malaria to non-endemic countries remains a major cause of travel-related morbidity and a leading cause of travel-related hospitalizations. Currently they are three priority medications for malaria prophylaxis to West Africa: mefloquine, atovaquone/proguanil and doxycycline. We investigate the cost effectiveness of a partial reimbursement of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers to high risk areas of malaria pared with the current situation of no reimbursement.

20860808

Neurorehabilitation using the virtual reality based Rehabilitation Gaming System: methodology, design, psychometrics, usability and validation.

Stroke is a frequent cause of adult disability that can lead to enduring impairments. However, given the life-long plasticity of the brain one could assume that recovery could be facilitated by the harnessing of mechanisms underlying neuronal reorganization. Currently it is not clear how this reorganization can be mobilized. Novel technology based neurorehabilitation techniques hold promise to address this issue. Here we describe a Virtual Reality (VR) based system, the Rehabilitation Gaming System (RGS) that is based on a number of hypotheses on the neuronal mechanisms underlying recovery, the structure of training and the role of individualization. We investigate the psychometrics of the RGS in stroke patients and healthy controls.

20860811

Evolutionary history of mammalian sucking lice (Phthiraptera: Anoplura).

Sucking lice (Phthiraptera: Anoplura) are obligate, permanent ectoparasites of eutherian mammals, parasitizing members of 12 of the 29 recognized mammalian orders and approximately 20% of all mammalian species. These host specific, blood-sucking insects are morphologically adapted for life on mammals: they are wingless, dorso-ventrally flattened, possess tibio-tarsal claws for clinging to host hair, and have piercing mouthparts for feeding. Although there are more than 540 described species of Anoplura and despite the potential economical and medical implications of sucking louse infestations, this study represents the first attempt to examine higher-level anopluran relationships using molecular data. In this study, we use molecular data to reconstruct the evolutionary history of 65 sucking louse taxa with phylogenetic analyses pare the results to findings based on morphological data. We also estimate divergence times among anopluran taxa pare our results to host (mammal) relationships.

20860810

The effects of oligomerization on Saccharomyces cerevisiae Mcm4/6/7 function.

Minichromosome maintenance proteins (Mcm) 2, 3, 4, 5, 6 and 7 are related by sequence and form a variety plexes that unwind DNA, including Mcm4/6/7. A Mcm4/6/7 trimer forms one half of the Mcm2-7 hexameric ring and can be thought of as the catalytic core of Mcm2-7, the replicative helicase in eukaryotic cells. Oligomeric analysis of Mcm4/6/7 suggests that it forms a hexamer containing two Mcm4/6/7 trimers, however, under certain conditions trimeric Mcm4/6/7 has also been observed. The functional significance of the different Mcm4/6/7 oligomeric states has not been assessed. The results of such an assessment would have implications for studies of both Mcm4/6/7 and Mcm2-7.

20860812

A successfully treated case of herpes simplex encephalitis complicated by subarachnoid bleeding: a case report.

Histopathologically, herpes simplex virus type 1 causes hemorrhagic necrosis. Overt hemorrhage is infrequent in herpes simplex virus encephalitis but can lead to poor es. This report describes a successfully treated case of herpes simplex virus encephalitis associated with subarachnoid bleeding in which real-time polymerase chain reaction was useful for diagnosis.

20860813

Therapeutic angiogenesis by transplantation of induced pluripotent stem cell-derived Flk-1 positive cells.

Induced pluripotent stem (iPS) cells are the novel stem cell population induced from somatic cells. It is anticipated that iPS will be used in the expanding field of regenerative medicine. Here, we investigated whether implantation of fetal liver kinase-1 positive (Flk-1+) cells derived from iPS cells could improve angiogenesis in a mouse hind limb model of ischemia.

20860814

A structural-based statistical approach suggests a cooperative activity of PUM1 and miR-410 in human 3'-untranslated regions.

Micro prise a large family of small non-coding RNAs that are thought to regulate a large fraction of protein-coding genes. Generally, miRNAs downregulate messenger (m)RNA expression by binding to the 3' untranslated regions (UTRs) of the RNA molecules. An important factor for binding specificity is the matching in the seed region. In addition, target site accessibility is thought to be crucial for efficient repression of miRNA targets. Several recent studies indicated that miRNA repression can be facilitated by RNA-binding proteins. In this study, we examine the conjecture that RNA-binding proteins are involved in ushering miRNAs to bind targets that are initially less accessible.

20860815

Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition.

Dysregulation of epidermal growth factor and insulin-like growth factor signaling play important roles in human hepatocellular carcinoma (HCC), leading to frequent activation of their downstream targets, the ras/raf/extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K)/Akt/mammalian Target of Rapamycin (mTOR) pathways. Salirasib is an S-prenyl-cysteine analog that has been shown to block ras and/or mTOR activation in several non hepatic tumor cell lines. We investigated in vitro the effect of salirasib on cell growth as well as its mechanism of action in human hepatoma cell lines (HepG2, Huh7, and Hep3B) and its in vivo effect in a subcutaneous xenograft model with HepG2 cells.

20860816

Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer.

Fibronectin 1 (FN1) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of FN1 in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.

20860817

Whey protein isolate attenuates strength decline after eccentrically-induced muscle damage in healthy individuals.

We examined the effects of short-term consumption of whey protein isolate on muscle proteins and force recovery after eccentrically-induced muscle damage in healthy individuals.

20860818

Distribution of polycyclic aromatic hydrocarbons in subcellular root tissues of ryegrass (Lolium multiflorum Lam.).

Because of the increasing quantity and high toxicity to humans of polycyclic aromatic hydrocarbons (PAHs) in the environment, several bioremediation mechanisms and protocols have been investigated to restore PAH-contaminated sites. The transport of organic contaminants among plant cells via tissues and their partition in roots, stalks, and leaves resulting from transpiration and lipid content have been extensively investigated. However, information about PAH distributions in intracellular tissues is lacking, thus limiting the further development of a mechanism-based phytoremediation strategy to improve treatment efficiency.

20860819

Detection of DNA fusion junctions for BCR-ABL translocations by Anchored ChromPET.

Anchored ChromPET, a technique to capture and interrogate targeted sequences in the genome, has been developed to identify chromosomal aberrations and define breakpoints. Using this method, we could define the BCR-ABL1 translocation DNA breakpoint to a base-pair resolution in Philadelphia chromosome-positive samples. This DNA-based method is highly sensitive and can detect the fusion junction using samples from which it is hard to obtain RNA or cells where the RNA expression has been silenced.

20860820

The RISAP-study: a complex intervention in risk communication and shared decision-making in general practice.

General practitioners (GPs) and patients find it difficult to talk about risk of future disease, especially when patients have asymptomatic conditions, and treatment options are unlikely to cause immediate perceptible improvements in well-being. Further studies in munication training are needed.

20860821

MicroRNA signature of the human developing pancreas.

MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study.

20860822

Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults.

Untreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain.

20860824

Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway.

Treatment strategies for Retinoblastoma (RB), the mon primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K+ channels.

20860825

Increased serum kallistatin levels in type 1 diabetes patients with vascular complications.

Kallistatin, a serpin widely produced throughout the body, has vasodilatory, anti-angiogenic, anti-oxidant, and anti-inflammatory effects. Effects of diabetes and its plications on serum kallistatin levels are unknown.

20860823

Duplicate dmbx1 genes regulate progenitor cell cycle and differentiation during zebrafish midbrain and retinal development.

The Dmbx1 gene is important for the development of the midbrain and hindbrain, and mouse gene targeting experiments reveal that this gene is required for mediating postnatal and adult feeding behaviours. A single Dmbx1 gene exists in terrestrial vertebrate genomes, while teleost genomes have at least two paralogs. pared the loss of function of the zebrafish dmbx1a and dmbx1b genes in order to gain insight into the molecular mechanism by which dmbx1 regulates neurogenesis, and to begin to understand why these duplicate genes have been retained in the zebrafish genome.

20860826

Impact of pericardial adhesions on diastolic function as assessed by vortex formation time, a parameter of transmitral flow efficiency.

Pericardial adhesions are a pathophysiological marker of constrictive pericarditis (CP), which impairs cardiac filling by limiting the total cardiac pliance and diastolic filling function. We studied diastolic transmitral flow efficiency as a new parameter of filling function in a pericardial adhesion animal model. We hypothesized that vortex formation time (VFT), an index of optimal efficient diastolic transmitral flow, is altered by patchy pericardial-epicardial adhesions.

20860827

Doubling the number of health graduates in Zambia: estimating feasibility and costs.

The Ministry of Health (MoH) in Zambia is operating with fewer than half of the human resources for health (HRH) necessary to meet basic population health needs. Responding urgently to address this HRH crisis, the MoH plans to double the annual number of health training graduates in the next five years to increase the supply of health workers. The feasibility and costs of achieving this initiative, however, are unclear.

20860828

Changes in cortical cytoskeletal and extracellular matrix gene expression in prostate cancer are related to oncogenic ERG deregulation.

The cortical cytoskeleton network connects the actin cytoskeleton to various membrane proteins, influencing cell adhesion, polarity, migration and response to extracellular signals. Previous studies have suggested changes in the expression of ponents in prostate cancer, especially of 4.1 proteins (encoded by EPB41 genes) which form nodes in this network.

20860829

The use of insecticide-treated nets for reducing malaria morbidity among children aged 6-59 months, in an area of high malaria transmission in central Côte d'Ivoire.

Long-lasting insecticidal nets (LLINs) are an important tool for controlling malaria. Much attention has been devoted to determine both the effect of LLINs on the reduction of Plasmodium infection rate and on clinically-confirmed malaria cases in sub-Saharan Africa. We carried out an epidemiological study to investigate whether LLINs impact on Plasmodium prevalence rate and the proportion of clinically-confirmed malaria cases, in five villages in the district of Toumodi, central Côte d'Ivoire.

20860830

A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases.

Giant cell tumor (GCT) of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated as. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT.

20860831

Expression profiling in canine osteosarcoma: identification of biomarkers and pathways associated with outcome.

a (OSA) spontaneously arises in the appendicular skeleton of large breed dogs and shares many physiological and molecular biological characteristics with human OSA. The standard treatment for OSA in both species is amputation or limb-sparing surgery, followed by chemotherapy. Unfortunately, OSA is an aggressive cancer with a high metastatic rate. Characterization of OSA with regard to its metastatic potential and chemotherapeutic resistance will improve both prognostic capabilities and treatment modalities.

20860832

Aquaporins: relevance to cerebrospinal fluid physiology and therapeutic potential in hydrocephalus.

The discovery of a family of membrane water channel proteins called aquaporins, and the finding that aquaporin 1 was located in the choroid plexus, has prompted interest in the role of aquaporins in cerebrospinal fluid (CSF) production and consequently hydrocephalus. While the role of aquaporin 1 in choroidal CSF production has been demonstrated, the relevance of aquaporin 1 to the pathophysiology of hydrocephalus remains debated. This has been further hampered by the lack of a non-toxic specific pharmacological blocking agent for aquaporin 1. In recent times aquaporin 4, the most abundant aquaporin within the brain itself, which has also been shown to have a role in brain water physiology and relevance to brain oedema in trauma and tumours, has e an alternative focus of attention for hydrocephalus research. This review summarises current knowledge and concepts in relation to aquaporins, specifically aquaporin 1 and 4, and hydrocephalus. It also examines the relevance of aquaporins as potential therapeutic targets in hydrocephalus and other CSF circulation disorders.

20860833

Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model.

The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) is widely expressed throughout the vertebrate nervous system, including the pain processing neuraxis. Inhibitors of NAAG peptidases are analgesic in animal models of pain. However, the brain regions involved in NAAG's analgesic action have not been rigorously defined. Group II metabotropic glutamate receptors (mGluR2/3) play a role in pain processing in the laterocapsular part of the central nucleus of the amygdala (CeLC). Given the high concentration of NAAG in the amygdala and its activation of group II mGluRs (mGluR3 > mGluR2), this study was undertaken using the mouse formalin model of inflammatory pain to test the hypothesis that NAAG influences pain processing in the amygdala. Evoked excitatory postsynaptic currents (eEPSCs) were studied in neurons in the CeLC of mouse brain slices following stimulation of the spinoparabrachial amygdaloid afferents.

20860836

Prediction of early race starts in Norwegian-Swedish Coldblooded Trotters.

Less than a third of Norwegian-Swedish Coldblooded Trotters (NSCTs) have started racing as three year olds since the year 2000 despite the fact that large sums are paid out as price-money in the three year season. Recruitment races are arranged by the Norwegian Trotting Association (NTA) to stimulate early training. The management of young horses varies considerably and a large majority is reared by amateurs. The aim of the present study was to identify predictors of early race starts in young NSCT horses under field conditions.

20860835

Traditional birth attendants lack basic information on HIV and safe delivery practices in rural Mysore, India.

There is little research on HIV awareness and practices of traditional birth attendants (TBA) in India. This study investigated knowledge and attitudes among rural TBA in Karnataka as part of a project examining how traditional birth attendants could be integrated into prevention-of-mother-to-child transmission of HIV (PMTCT) programs in India.

20860834

Prognostic value of radical cystoprostatectomy in men with bladder cancer infiltrating prostate versus co-existing prostate cancer: a research study.

The aim of the following study is to evaluate the advancement of incidentally diagnosed prostate cancer in specimen after cystoprostatectomies caused by muscle-invasive bladder cancer. Secondly we assessed the survival in patients after radical cystoprostatectomy whose postoperative specimen was characterized by the presence of co-existing prostate cancer or prostate infiltration by urothelial bladder cancer.

20860837

Validity of the work productivity and activity impairment questionnaire--general health version in patients with rheumatoid arthritis.

The Work Productivity and Activity Impairment (WPAI) questionnaire is a well validated instrument to measure impairments in work and activities. However, its validation among patients with rheumatoid arthritis (RA) has not been well established. The present study's purpose is to evaluate the construct validity of the WPAI-general health version among RA patients and its ability to differentiate between RA patients with varying health status.

20860839

The use of reference gene selection programs to study the silvering transformation in a freshwater eel Anguilla australis: a cautionary tale.

Quantitative real-time PCR (qPCR) has been the method of choice for the quantification of mRNA. Due to the various artifactual factors that may affect the accuracy of qPCR, internal reference genes are most often used to normalize qPCR data. Recently, many studies have puter programs such as GeNorm, BestKeeper and NormFinder in selecting reference genes, but very few statistically validate the es of these programs. Thus, in this study, we selected reference genes for qPCR of liver and ovary samples of yellow (juvenile), migratory (silver) and 11-KT treated juveniles of New Zealand shortfinned eels (Anguilla australis) using the puter programs and validate the selected genes statistically using REST 2009 software and the Mann-Whitney test. We also tested for the repeatability of use for the best reference genes by applying them to a data set obtained in a similar experiment conducted the previous year.

20860838

P190B RhoGAP has pro-tumorigenic functions during MMTV-Neu mammary tumorigenesis and metastasis.

Rho GTPases are overexpressed and hyperactivated in human breast cancers. Deficiency of p190B RhoGAP, a major inhibitor of the Rho GTPases, inhibits mouse mammary tumor virus long terminal repeat (MMTV)-Neu/ErbB2 mammary tumor formation and progression in part through effects within the stromal environment, suggesting that p190B function is pro-tumorigenic. To further investigate the potential pro-tumorigenic actions of p190B, we examined the effects of exogenous p190B expression within the mammary epithelium on MMTV-Neu tumor formation and progression.

20860840

Improving performance of mammalian microRNA target prediction.

MicroRNAs (miRNAs) are single-stranded non-coding RNAs known to regulate a wide range of cellular processes by silencing the gene expression at the protein and/or mRNA levels. Computational prediction of miRNA targets is essential for elucidating the detailed functions of miRNA. However, the prediction specificity and sensitivity of the existing algorithms are still poor to generate meaningful, workable hypotheses for subsequent experimental testing. Constructing a richer and more reliable training data set and developing an algorithm that properly exploits this data set would be the key to improve the performance current prediction algorithms.

20860843

Evaluation of blood reservation and use for caesarean sections in a tertiary maternity unit in south western Nigeria.

Haemorrhage from obstetric causes is the mon cause of maternal mortality in the developing world. Prevention of mortality from haemorrhage will necessarily involve prompt blood transfusions among other life saving measures. There are however limited stocks of fresh or stored blood in many health care facilities in Sub Saharan Africa. Caesarean section has been identified as mon indication for blood transfusion in obstetrics practice and its performance is often delayed by non availability of blood in our centre. An evaluation of blood reservation and use at caesarean sections in a tertiary maternity unit in Lagos, south western Nigeria should therefore assist in formulating the most rational blood transfusion policies.

20860841

Phosphatases in the cellular response to DNA damage.

In the last fifteen years, rapid progress has been made in delineating the cellular response to DNA damage. The DNA damage response network posed of a large number of proteins with different functions that detect and signal the presence of DNA damage in order to coordinate DNA repair with a variety of cellular processes, notably cell cycle progression. This signal, which radiates from the chromatin template, is driven primarily by phosphorylation events, mainly on serine and threonine residues. While we have accumulated detailed information about kinases and their substrates our understanding of the role of phosphatases in the DNA damage response is still preliminary. Identifying the phosphatases and their regulation will be instrumental to obtain plete picture of the dynamics of the DNA damage response. Here we give an overview of the DNA damage response in mammalian cells and then review the data on the role of different phosphatases and discuss their biological relevance.

20860844

A bi-ordering approach to linking gene expression with clinical annotations in gastric cancer.

In the study of cancer genomics, gene expression microarrays, which measure thousands of genes in a single assay, provide abundant information for the investigation of interesting genes or biological pathways. However, in order to analyze the large number of noisy measurements in microarrays, effective and efficient bioinformatics techniques are needed to identify the associations between genes and relevant phenotypes. Moreover, systematic tests are needed to validate the statistical and biological significance of those discoveries.

20860845

Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival.

Triple-negative breast cancers (TNBCs) and basal-like breast cancers (BLBCs) are known as poor e subtypes with a lack of targeted therapy. Previous studies have shown conflicting results regarding the difference of prognostic significance between TNBCs and BLBCs. In this study, we aimed to characterize the prognostic features of TNBCs, in view of BLBCs and quintuple-negative breast cancers (QNBC/5NPs).

20860842

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye.

Reactivation of Epstein-Barr virus (EBV) infection may cause serious, plications in promised individuals. EBV DNA is often detected in EBV-associated disease states, with viral load believed to be a reflection of virus activity. Two separate real-time quantitative polymerase chain reaction (QPCR) assays using SYBR Green I dye and a single quantification standard containing two EBV genes, Epstein-Barr nuclear antigen-1 (EBNA-1) and BamHI fragment H rightward open reading frame-1 (BHRF-1), were developed to detect and measure absolute EBV DNA load in patients with various EBV-associated diseases. EBV DNA loads and viral capsid antigen (VCA) IgG antibody titres were also quantified on a population sample.

20860846

Association of CACNG6 polymorphisms with aspirin-intolerance asthmatics in a Korean population.

Aspirin-intolerant asthma (AIA) occurs in the lower and upper airways through excessive production of leukotrienes upon administration of non-steroidal anti-inflammatory drugs (NSAIDs). One of the three symptoms of AIA is nasal polyposis, a chronic inflammatory disease that is related to the function of calcium ion in recruitment of immune cells during airway inflammation. It has been implicated that bronchodilation in the airway is related to Ca(2+) regulation. The calcium channel, voltage-dependent, gamma subunit 6 (CACNG6) gene encodes a protein that stabilizes the calcium channel.

20860848

A wild derived quantitative trait locus on mouse chromosome 2 prevents obesity.

The genetic architecture of multifactorial traits such as obesity has been poorly understood. Quantitative trait locus (QTL) analysis is widely used to localize loci affecting multifactorial traits on chromosomal regions. However, large confidence intervals and small phenotypic effects of identified QTLs and closely linked loci are impeding the identification of causative genes that underlie the QTLs. Here we developed five subcongenic mouse strains with overlapping and non-overlapping wild-derived genomic regions from an F2 intercross of a previously developed congenic strain, B6.Cg-Pbwg1, and its genetic background strain, C57BL/6J (B6). The subcongenic strains developed were phenotyped on low-fat standard chow and a high-fat diet to fine-map a previously identified obesity QTL. Microarray analysis was performed with Affymetrix GeneChips to search for candidate genes of the QTL.

20860847

Predictive factors of radiation-induced skin toxicity in breast cancer patients.

To assess the factors affecting the incidence of radiation-induced dermatitis in breast cancer patients treated with adjuvant 3 D conformal radiotherapy by the analysis of dosimetry and topical treatments.

20860849

An alternative surgical approach to subclavian and innominate stenosis: a case series.

We report three cases of symptomatic stenosis of the great vessels or supra-aortic trunks successfully treated surgically with aorto-subclavian and aorto-innominate bypass. Two were performed via manubriotomy and a third case via standard median sternotomy because of itant coronary revascularisation. There plete symptomatic relief on follow-up, and radiological imaging confirmed good flow in the grafts and post-stenotic arteries.

20860851

Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research.

There is heterogeneity between depression in childhood, adolescence and adulthood in terms of the position of affected cases, prevalence, rates of recurrence and risk factors. This plex questions for refining the phenotype for molecular genetic studies of depression and the selection of appropriate proband groups. This article aims to provide a review of issues arising from family, twin and adoption studies of relevance to molecular genetic studies, and to summarize molecular genetic findings on childhood/adolescent depression. While retrospective studies of adults suggest greater familial aggregation among those with an earlier age of onset, prospective studies do not confirm this association. In fact, taken together, evidence from family and twin studies suggests that prepubertal depression is more strongly associated with psychosocial adversity, is less heritable and shows lower levels of continuity with adult depression than either adolescent or adult depression. Adolescent depressive symptoms and disorder show similar levels of heritability to depression in adult life, although there is only one twin study of adolescent depressive disorder, and heritability estimates of depressive symptoms vary widely between studies. This variability in heritability estimates is partly attributable to age and informant effects. Adoption studies and other intergenerational transmission designs show that the transmission of depression between parents and children involves genetic and environmental processes, with converging evidence that environmental processes are most important. Molecular genetic studies of childhood/adolescent depression have to date used a candidate gene approach and focused on genes already examined in adult studies. Prospective longitudinal studies munity and high-risk samples are needed to clarify issues of etiological heterogeneity in depression, and these should in turn inform the planning of molecular genetic studies.

20860850

Detecting variants with Metabolic Design, a new software tool to design probes for explorative functional DNA microarray development.

Microorganisms display vast diversity, and each one has its own set of genes, ponents and metabolic reactions. To assess their huge unexploited metabolic potential in different ecosystems, we need high throughput tools, such as functional microarrays, that allow the simultaneous analysis of thousands of genes. However, most classical functional microarrays use specific probes that monitor only known sequences, and so fail to cover the full microbial gene diversity present plex environments. We have thus developed an algorithm, implemented in the user-friendly program Metabolic Design, to design efficient explorative probes.

20860853

Norepinephrine: more of a neurohormone than a vasopressor.

Septic shock causes unpredictable cardiovascular responses through adrenoreceptor-mediated changes in cardiac function and vascular responsiveness. The use of norepinephrine should be regarded as neurohormonal augmentation therapy to defend pensating haemodynamic function rather than as a rescue therapy to treat shock. Recent trials represent a perceptible change in clinical practice to preferentially use norepinephrine early in resuscitation to defend the mean arterial pressure and to use norepinephrine as a neurohormone rather than as a vasopressor.

20860854

Methods in Mammary Gland Development and Cancer: the second ENDBC meeting--intravital imaging, genomics, modeling and metastasis.

The second meeting of the European Network for Breast Development and Cancer (ENBDC) on 'Methods in Mammary Gland Development and Cancer' was held in April 2010 in Weggis, Switzerland. The focus was on genomics and bioinformatics, extracellular matrix and stroma-epithelial cell interactions, intravital imaging, the search for metastasis founder cells and mouse models of breast cancer.

20860855

Pharmacogenetics and pharmacogenomics: practical applications in routine medical practice.

A report of the 3rd joint European Science Foundation and University of Barcelona Conference in Biomedicine, San Feliu de Guixols, Catalonia, Spain, 6-11 June 2010.

20860856

Diet, exercise and gut mucosal immunity.

Diet and exercise are primary strategies mended for the control of the obesity epidemic. Considerable attention is being paid to the effect of both on the immune system. However, little research has been done on the effect of diet, nutrients or exercise on the mucosal immune system. The gastrointestinal tract (gut) is not only responsible for the entry of nutrients into the organism, but also for triggering the primary immune response to orally ingested antigens. The gut-associated lymphoid tissue contains a large amount of immune cells, disseminated all along the intestine in Peyer's patches and lamina propria. Specific nutrients or binations, as well as the microflora, are capable of modulating the immune system through cell activation, production of signalling molecules or gene expression. We have observed an increase in T-cells as well as a decrease in B-cells from Peyer's patches, induced by diets high in fats or carbohydrates in Balb/c mice. It has also been demonstrated that exercise modulates the immune system, where moderate levels may improve its function by increasing the proliferation of lymphocytes from various sites, including gut-associated lymphoid tissue, whereas exhaustive acute exercise may cause immunosuppression. High-fat bined with exercise are able to induce an increase in CD3+ lymphocytes due to increased CD8+ cells and a decrease in B-cells. Explanations and consequences of the effects of diet and exercise on the gut mucosal immunity are still being explored.

20860858

Food security: increasing yield and improving resource use efficiency.

Food production and security will be a major issue for supplying an increasing world population. The problem will almost certainly be exacerbated by climate change. There is a projected need to double food production by 2050. In recent times, the trend has been for incremental modest yield increases for most crops. There is an urgent need to develop integrated and sustainable approaches that will significantly increase both production per unit land area and the resource use efficiency of crops. This review considers some key processes involved in plant growth and development with some examples of ways in which molecular technology, plant breeding and genetics may increase the yield and resource use efficiency of wheat. The successful application of biotechnology to breeding is essential to provide the major increases in production required. However, each crop and each specific agricultural situation presents specific requirements and targets for optimisation. Some increases in production e about as new varieties are developed which are able to produce satisfactory crops on marginal land presently not considered appropriate for arable crops. Other new varieties will be developed to increase both yield and resource use efficiency on the best land.

20860857

Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses.

The thymus gland, where T lymphocyte development occurs, is targeted in malnutrition secondary to protein energy deficiency. There is a severe thymic atrophy, resulting from massive thymocyte apoptosis (particularly affecting the immature CD4+CD8+ cell subset) and decrease in cell proliferation. The thymic microenvironment (the partment that drives intrathymic T-cell development) is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production, as well as an increase of intrathymic contents of extracellular proteins. Profound changes in the thymus can also be seen in deficiencies of vitamins and trace elements. Taking Zn deficiency as an example, there is a substantial thymic atrophy. Importantly, marginal Zn deficiency in AIDS subjects, children with diarrhoea and elderly persons, significantly impairs the host's immunity, resulting in an increased risk of opportunistic infections and mortality; effects that are reversed by Zn supplementation. Thymic changes also occur in acute infectious diseases, including a severe thymic atrophy, mainly due to the depletion of CD4+CD8+ thymocytes, decrease in thymocyte proliferation, in parallel to densification of the epithelial network and increase in the extracellular matrix contents, with consequent disturbances in thymocyte migration and export. In conclusion, the thymus is targeted in several conditions of malnutrition as well as in acute infections. These changes are related to the impaired peripheral immune response seen in malnourished and infected individuals. Thus, strategies inducing thymus replenishment should be considered as adjuvant therapeutics to improve immunity in malnutrition and/or acute infectious diseases.

20860859

Providing optimal nutritional support on the intensive care unit: key challenges and practical solutions.

Many patients in the intensive care unit are malnourished or unable to eat. Feeding them correctly has the potential to reduce morbidity and even mortality but is a plex procedure. The inflammatory response induced by surgery, trauma or sepsis will alter metabolism, change the ability to utilise nutrients and can lead to rapid loss of lean mass. Both overfeeding and underfeeding macronutrients can be harmful but generally it would seem optimal to give less during metabolic stress and immobility and increase in recovery. Physical intolerance of feeding such as diarrhoea or delayed gastric emptying mon in the intensive care unit. Diarrhoea can be treated with fibre or peptide feeds and anti-diarrhoeal drugs; however, the use of probiotics is controversial. Gastric dysfunction problems can often be e with prokinetic drugs or small bowel feeding tubes. New feeds with nutrients such as n-3 fatty acids that have the potential to attenuate excessive inflammatory responses show great promise in favourably improving metabolism and substrate utilisation. The importance of changing nutrient provision according to metabolic and physical tolerance cannot be understated and although expert groups have produced many guidelines on nutritional support of the critically ill, correct interpretation and implementation can be difficult without a dedicated nutrition health care professional such as a dietitian or a multidisciplinary nutritional support team.

20860860

Informing food policy: balancing the evidence.

The paper considers some of the reasons why governments develop food policies, gives examples of what is in food policies at the Scottish and UK levels and explores ways of effectively providing balanced evidence for policy development. It discusses the challenges of exchanging knowledge between the science and munities, given their different languages and cultures, highlighting the need for greater mutual understanding of roles and responsibilities. It draws on experience in the Scottish Government of developing the government's 'Recipe for Success - Scotland's National Food and Drink Policy' through engagement with stakeholders, scientists and analysts and touches on the plex nature of the Department for International Development's contribution to meeting the first Millennium Development Goal. pares the need for collation and analysis of existing evidence during the development of policy, with the desirability of providing policy direction for longer-term strategic research and the challenges of connecting the policy expectations with researchable questions. The paper concludes by emphasising the need to focus research in the short-term on mitigation of climate change through decreasing greenhouse gas emissions associated with the production of food, while also taking an account of economic, health and broader environmental sustainability objectives. A further challenge is plexity and uncertainty in ways which enable decision-makers from the consumer to policy-makers to make informed choices. Longer-term research needs to focus on the opportunities and risks associated with adapting to climate change.

20860861

Risk-benefit analysis of mineral intakes: case studies on copper and iron.

Dietary reference values for essential trace elements are designed to meet requirements with minimal risk of deficiency and toxicity. Risk-benefit analysis requires data on habitual dietary intakes, an estimate of variation and effects of deficiency and excess on health. For some nutrients, the range between the upper and lower limits may be extremely narrow and even overlap, which creates difficulties when setting safety margins. A new approach for estimating optimal intakes, taking into account several health biomarkers, has been developed and applied to selenium, but at present there are insufficient data to extend this technique to other micronutrients. The existing methods for deriving reference values for Cu and Fe are described. For Cu, there are no sensitive biomarkers of status or health relating to marginal deficiency or toxicity, despite the well-characterised genetic disorders of Menkes and Wilson's disease which, if untreated, lead to lethal deficiency and overload, respectively. For Fe, the wide variation in bioavailability confounds the relationship between intake and status plicates risk-benefit analysis. As with Cu, health effects associated with deficiency or toxicity are not easy to quantify, therefore status is the most accessible variable for risk-benefit analysis. Serum ferritin reflects Fe stores but is affected by infection/inflammation, and therefore additional biomarkers are generally employed to measure and assess Fe status. Characterising the relationship between health and dietary intake is problematic for both these trace elements due to the confounding effects of bioavailability, inadequate biomarkers of status and a lack of sensitive and specific biomarkers for health es.

20860862

Ethnic isolation and psychosis: re-examining the ethnic density effect.

Elevated incidence of psychotic illness has been consistently shown among migrant populations. Ethnic density, the proportion of an ethnic group in a defined area, is cited as one factor with a reduced risk of psychosis where ethnicity is shared. However, UK studies have shown mixed results. We set out to re-examine the ethnic density effect at a greater level of geographic detail than previous studies.

20860863

Contrasting prototypes and dimensions in the classification of personality pathology: evidence that dimensions, but not prototypes, are robust.

DSM-5 may mark the shift from a categorical classification of personality pathology to a dimensional system. Although dimensional and categorical conceptualizations of personality pathology are often viewed peting, it is possible to develop categories (prototypes) binations of dimensions. Robust prototypes could bridge dimensions and categories within a single classification system.

20860865

Long-term cognitive and emotional consequences of mild traumatic brain injury.

The objective of this study was to investigate long-term cognitive and emotional sequelae of mild traumatic brain injury (mTBI), as previous research has remained inconclusive with respect to their prevalence and extent.

20860866

Familial transmission of depression and antisocial behavior symptoms: disentangling the contribution of inherited and environmental factors and testing the mediating role of parenting.

Genetic and environmental influences on child psychopathology have been studied extensively through twin and adoption designs. We offer a novel methodology to examine genetic and environmental influences on the intergenerational transmission of psychopathology using a sample of parents and children conceived through in vitro fertilization (IVF).

20860868

A cross-ethnic comparison on incidence of suicide.

Suicide rates vary widely across nations and ethnic groups. This study aims to explore potential factors contributing to inter-ethnic differences in suicide rates.

20860869

Increased risk of schizophrenia following traumatic brain injury: a 5-year follow-up study in Taiwan.

Whether traumatic brain injury (TBI) is an independent risk factor for the subsequent development of schizophrenia has evoked considerable controversy. No evidence has been previously reported from Asia. This study estimated the risk of schizophrenia during a 5-year period following hospital admission for TBI relative to parison group of non-TBI patients during the same period in Taiwan.

20860867

Mechanisms of functional improvement in a 2-year trial of cognitive enhancement therapy for early schizophrenia.

Cognitive rehabilitation has emerged as an effective treatment for addressing cognitive impairments and functional disability in schizophrenia; however, the degree to which changes in various social and non-social cognitive processes translate into improved functioning during treatment remains unclear. This research sought to identify the neurocognitive and social-cognitive mechanisms of functional improvement during a 2-year trial of cognitive enhancement therapy (CET) for early-course schizophrenia.

20860870

Intellectual functioning and the long-term course of schizophrenia-spectrum illness.

Recent neurodevelopmental models of schizophrenia, together with substantial evidence of neurocognitive dysfunction among people with schizophrenia, have led to a widespread view that general cognitive deficits are a central aspect of schizophrenic pathology. However, the temporal relationships between intellectual functioning and schizophrenia-spectrum illness remain unclear.

20860871

Decision making in euthymic bipolar I and bipolar II disorders.

The main aim of this study was pare a large population of patients with bipolar disorder (BD) types I and II strictly defined as euthymic with healthy controls on measures of decision making. An additional aim was pare performance on a decision-making task between patients with and without a history of suicide attempt.

20860872

What kinds of things are psychiatric disorders?

This essay explores four answers to the question 'What kinds of things are psychiatric disorders?' Essentialist kinds are classes whose members share an essence from which their defining features arise. Although elegant and appropriate for some physical (e.g. atomic elements) and medical (e.g. Mendelian disorders) phenomena, this model is inappropriate for psychiatric disorders, which are multi-factorial and 'fuzzy'. Socially constructed kinds are classes whose members are defined by the cultural context in which they arise. This model excludes the importance of shared physiological mechanisms by which the same disorder could be identified across different cultures. Advocates of practical kinds put off metaphysical questions about 'reality' and focus on defining classes that are useful. Practical kinds models for psychiatric disorders, implicit in the DSM nosologies, do not require that diagnoses be grounded in shared causal processes. If psychiatry seeks to tie disorders to etiology and underlying mechanisms, a model first proposed for biological species, mechanistic property cluster (MPC) kinds, can provide a useful framework. MPC kinds are defined not in terms of essences but in terms plex, mutually reinforcing networks of causal mechanisms. We argue that psychiatric disorders are objectively grounded features of the causal structure of the mind/brain. MPC kinds are fuzzy sets defined by mechanisms at multiple levels that act and interact to produce the key features of the kind. Like species, psychiatric disorders are populations with central paradigmatic and more marginal members. The MPC view is the best current answer to 'What kinds of things are psychiatric disorders?'

20860874

Optical genetic mapping defines regions of chromosomal variation in serovars of S. enterica subsp. enterica of concern for human and animal health.

Infections involving Salmonella enterica subsp. enterica serovars have serious animal and human health implications; causing gastroenteritis in humans and clinical symptoms, such as diarrhoea and abortion, in livestock. In this study an optical genetic mapping technique was used to screen 20 field isolate strains from four serovars implicated in disease outbreaks. The technique was able to distinguish between the serovars and the available sequenced strains and group them in agreement with similar data from microarrays and PFGE. The optical maps revealed variation in genome maps associated with antimicrobial resistance and prophage content in S. Typhimurium, and separated the S. Newport strains into two clear geographical lineages defined by the presence of prophage sequences. The technique was also able to detect novel insertions that may have had effects on the central metabolism of some strains. Overall optical mapping allowed a greater level of differentiation of genomic content and spatial information than more traditional typing methods.

20860873

Risk factors, pre-morbid functioning and episode correlates of neurological soft signs in drug-naive patients with schizophrenia-spectrum disorders.

There is a lack of consistent evidence regarding associations of neurological soft signs (NSS) with illness-related variables in schizophrenia. This study examined NSS in first-episode psychotic patients with respect to their factor structure and associations with risk factors, pre-morbid characteristics, psychopathology and spontaneous extrapyramidal syndromes.

20860875

Oestrogen: an overlooked mediator in the neuropsychopharmacology of treatment response?

Major depression (MD) and anorexia nervosa (AN) often orbidly and both share some affective symptoms, despite obvious phenotypic differences. In the illness phase, pathophysiological evidence indicates similar abnormalities in both clinical groups including dysfunction in the serotonin (5-HT) system (of which some abnormalities persist following recovery) and between 60% and 80% of patients in both groups present with significant hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis. First-line approach to treatment for MD involves modulation of the 5-HT system using selective serotonin reuptake inhibitors (SSRIs). For AN, treatment with SSRIs has been shown to be considerably less pared to MD. Both illnesses show marked dysregulation in the HPA axis. A consequence of SSRI treatment is a reduction and/or normalization of indices of the HPA axis [i.e. cortisol, adrenocorticotropic hormone (ACTH)], which is consistent with recovery levels in both clinical groups. Oestrogen (in high doses) has been shown to exert antidepressant effects and positively impact on MD symptoms as a treatment in its own right, or bination with antidepressants, in women of menopausal age. It is proposed that bination of SSRIs and oestrogen therapy may facilitate physiological normalization in MD in women of non-menopausal age and in AN. Preliminary evidence suggests oestrogen treatment alone is of some benefit to patients and it is proposed that bination of SSRI and oestrogen will precipitate and potentially accelerate symptomatic remission. Should this approach be successful, it offers the capacity for improvement over traditional antidepressant use in women diagnosed with MD and a novel strategy for the treatment of AN, a serious clinical illness associated with the highest mortality of any psychiatric condition.

20860876

Alterations in the central CRF system of two different rat models of comorbid depression and functional gastrointestinal disorders.

Clinical evidence orbidity between depression and irritable bowel syndrome (IBS). Early-life stress and genetic predisposition are key factors in the pathophysiology of both IBS and depression. Thus, neonatal maternal separation (MS), and the Wistar-Kyoto (WKY) rat, a genetically stress-sensitive rat strain, are two animal models of depression that display increased visceral hypersensitivity and alterations in the hypothalamic-pituitary-adrenal axis. Corticotrophin-releasing factor (CRF) is the primary peptide regulating this axis, acting through two receptors: CRF1 and CRF2. The central CRF system is also a key regulator in the stress response. However, there is a paucity of studies investigating alterations in the central CRF system of adult MS or WKY animals. Using in-situ hybridization we demonstrate that CRF mRNA is increased in the paraventricular nucleus (PVN) of WKY rats and the dorsal raphé nucleus (DRN) of MS pared to Sprague-Dawley and non-separated controls, respectively. Additionally, CRF1 mRNA was higher in the PVN, amygdala and DRN of both animal models, along with high levels of CRF1 mRNA in the hippocampus of WKY pared to control animals. Finally, CRF2 mRNA was lower in the DRN of MS and WKY pared to control animals, and in the hippocampus and amygdala of MS rats. These results show that the central CRF system is altered in both animal models. Such alterations may affect HPA axis regulation, contribute to behavioural changes associated with stress-related disorders, and alter the ponent of visceral pain modulation, which is enhanced in IBS patients.

20860877

Higher BDNF serum levels predict slower cognitive decline in Alzheimer's disease patients.

The neurotrophin brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal survival, synaptic plasticity, and memory. Several recent studies have demonstrated altered BDNF serum levels in Alzheimer's disease (AD) patients. However, the association of BDNF serum levels with the rate of cognitive decline in AD patients is still unclear. We demonstrate that BDNF serum levels are significantly decreased in AD patients with fast cognitive decline [decrease of Mini-Mental State Examination (MMSE) score >4/yr; pared to AD patients with slow cognitive decline (decrease of MMSE score ≤4/yr, n=28) and show a significant correlation with the rate of cognitive decline during 1 yr follow-up. These results suggest that higher BDNF serum levels are associated with a slower rate of cognitive decline in AD patients. Further longitudinal studies are necessary to elucidate the kinetics and the potential role of serum BDNF as a surrogate marker of disease progression in AD patients.

20860878

Association study of a functional catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and suicide attempts in patients with alcohol dependence.

Alcohol dependence is frequently associated with aggressive and suicidal behaviour. Genetic factors contribute to both behaviours. Candidate genes, related to suicide and aggression, include genes involved in serotonin, norepinephrine and dopamine pathways. The enzyme catechol-O-methyl transferase (COMT) degrades dopamine, epinephrine and norepinephrine. The functional polymorphism (COMT Val108/158Met) affects COMT activity, with the valine (Val) variant associated with higher and the methionine (Met) variant with lower COMT activity. This polymorphism is associated with aggressive and suicidal behaviour, but the literature data on this relationship is contradictory and inconsistent. The hypothesis of this study was that Met allele carriers with alcohol dependence will have a higher frequency of suicide pared to other genotypes. Participants were 312 male and 81 female medication-free patients with alcohol dependence and 487 male and 122 female unrelated, non-suicidal medication-free Caucasian healthy subjects. Our results showed significant (χ2 test with standardized residuals) differences in the frequencies of COMT variants in all alcoholics, alcoholics with orbid diagnoses, and in male but not in female alcoholics, with or without suicide attempts. Male alcoholic suicide pared to male non-attempters, had the higher frequency of Met/Met genotype or Met allele, and significantly (Kruskal-Wallis ANOVA on ranks and Mann-Whitney test) higher aggression and depression scores. These results confirmed the associations between Met allele and aggressive behaviour or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158 Met might be used as an independent biomarker of suicidal behaviour across different psychopathologies.

20860879

Ethical considerations in clinical training, care and research in psychopharmacology.

Psychopharmacology is a powerful tool in psychiatry; however, it is one that demands responsibility in order to deal with the plexities that pany advances in the field. It is important that questions are asked and that ethical mindfulness and sensitivity are developed along with clinical skills. In order to cultivate and deepen ethical awareness and subsequently solve issues in optimal fashion, investment should be made in the development of an ethical decision-making process as well as in education in the ethics of psychopharmacology to trainees in the field at all stages of their educational development. A clear approach to identifying ethical problems, engaging various ethical concepts in considering solutions and then applying these principles in problem resolution is demanded. An openness in identifying and exploring issues has e crucial to the future development and maturation of psychopharmacologists, both research and clinical. Consideration must be given to the social implications of psychopharmacological practice, with the best interests of patients always paramount. From both a research and clinical perspective, psychopharmacology has to be practised with fairness, sensitivity and ethical relevance to all. While ethical issues related to psychopharmacological practice are varied and plentiful, this review focuses on advances in technology and biological sciences, personal integrity, special populations, and education and training.

20860881

Effect of risperidone on high-affinity state of dopamine D2 receptors: a PET study with agonist ligand [11C](R)-2-CH3O-N-n-propylnorapomorphine.

The increased proportion of the high-affinity state of dopamine D2/3 receptors (D2,high) is assumed to correlate with dopamine hypersensitivity, implying a relationship with psychotic symptoms observed in psychiatric disorders such as schizophrenia. [11C](R)-2-CH3O-N-n-propylnorapomorphine ([11C]MNPA), which has an agonistic property to dopamine D2 receptors (D2Rs), is expected to bind preferentially to D2,high. The occupancy of dopamine D2Rs by antagonists to receptors has not been investigated using [11C]MNPA. pared dopamine D2R occupancies by risperidone, an antagonist to receptors, between [11C]MNPA and [11C]raclopride to confirm whether risperidone occupies D2,high and D2,low at almost identical proportions. PET studies were performed on 11 healthy men under resting condition and following oral administration of a single dose of risperidone (0.5-2.0 mg). Striatal receptor occupancy for each radioligand was calculated. The relationship between dose or plasma concentration of risperidone and dopamine D2R occupancy was calculated. Striatal dopamine D2R occupancies measured with [11C]MNPA and [11C]raclopride were 22-65% and 24-69%, respectively. In the striatum, ED50 values measured with [11C]MNPA and [11C]raclopride were 0.98 and 1.03 mg, respectively. The striatal ED50 values as calculated from plasma concentration were 9.15 ng/ml and 8.01 ng/ml, respectively. Almost identical occupancies and ED50 values were observed between the two radioligands, indicating that risperidone bound to D2,high and D2,low at almost identical proportions in a dose-dependent manner.

20860882

Mass spectrometry-based proteomics in biomedical research: emerging technologies and future strategies.

In recent years, the technology and methods widely available for mass spectrometry (MS)-based proteomics have increased in power and potential, allowing the study of protein-level processes occurring in biological systems. Although these methods remain an active area of research, established techniques are already helping answer biological questions. Here, this recent evolution of MS-based proteomics and its applications are reviewed, including standard methods for protein and peptide separation, biochemical fractionation, quantitation, targeted MS approaches such as selected reaction monitoring, data analysis and bioinformatics. Recent research in many of these areas reveals that proteomics has moved beyond simply cataloguing proteins in biological systems and is finally living up to its initial potential - as an essential tool to aid related disciplines, notably health research. From here, there is great potential for MS-based proteomics to move beyond basic research, into clinical research and diagnostics.

20860880

Increased medial temporal lobe and striatal grey-matter volume in a rare disorder of androgen excess: a voxel-based morphometry (VBM) study.

Major questions remain about how sex hormones influence human brain development and cognition. Studies in humans and animals suggest a strong impact of androgen on the structure and function of the medial temporal lobe (MTL) and striatum. Using voxel-based morphometry (DARTEL), pared MTL and striatal structures in 13 [mean age (±S.D.) 12.7±3.2 yr, mean bone age 14.8±3.2 yr] boys with familial male precocious puberty (FMPP), characterized by early excess androgen secretion, and 39 healthy age-matched boys (mean age 14.3±2.5 yr). The FMPP group showed significantly larger grey-matter volume (GMV) in parahippocampal and fusiform gyri as well as putamen relative to controls. parison, larger GMV for controls relative to patients was only apparent in the precentral gyrus. Exploratory regression analyses that examined the impact of age on the current findings revealed a significant increase of GMV in the putamen with age in patients suffering from excess androgen but not in controls. Finally, current levels of free testosterone were obtained in the patient group. Analyses revealed a significant negative association indicating that FMPP boys with low levels of bioavailable testosterone exhibited high GMV in the bilateral striatum. The findings suggest a critical influence of androgen on human brain development and are discussed in relation to male-dominant psychiatric childhood disorders.

20860883

Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet.

Our genome adapts slowly to changing conditions of existence. Many diseases of civilisation result from mismatches between our Paleolithic genome and the rapidly changing environment, including our diet. The objective of the present study was to reconstruct multiple Paleolithic diets to estimate the ranges of nutrient intakes upon which humanity evolved. A database of, predominantly East African, plant and animal foods (meat/fish) was used to model multiple Paleolithic diets, using two pathophysiological constraints (i.e. protein < 35 energy % (en%) and linoleic acid (LA) >1.0 en%), at known hunter-gatherer plant/animal food intake ratios (range 70/30-30/70 en%/en%). We investigated selective and non-selective savannah, savannah/aquatic and aquatic hunter-gatherer/scavenger foraging strategies. We found (range of medians in en%) intakes of moderate-to-high protein (25-29), moderate-to-high fat (30-39) and moderate carbohydrates (39-40). The fatty position was SFA (11.4-12.0), MUFA (5.6-18.5) and PUFA (8.6-15.2). The latter was high in α-linolenic acid (ALA) (3.7-4.7 en%), low in LA (2.3-3.6 en%), and high in long-chain PUFA (LCP; 4.75-25.8 g/d), LCP n-3 (2.26-17.0 g/d), LCP n-6 (2.54-8.84 g/d), ALA/LA ratio (1.12-1.64 g/g) and LCP n-3/LCP n-6 ratio (0.84-1.92 g/g). Consistent with the wide range of employed variables, nutrient intakes showed wide ranges. We conclude pared with Western diets, Paleolithic diets contained consistently higher protein and LCP, and lower LA. These are likely to contribute to the known beneficial effects of Paleolithic-like diets, e.g. through increased satiety/satiation. Disparities between Paleolithic, contemporary and mended intakes might be important factors underlying the aetiology mon Western diseases. Data on Paleolithic diets and lifestyle, rather than the investigation of single nutrients, might be useful for the rational design of clinical trials.

20860884

Food & health forum meeting: evidence-based nutrition.

The present report summarises a meeting held by the Food & Health Forum at the Royal Society of Medicine, London, on 27 May 2010. The objective of the meeting was to review the problems associated with the use of evidence-based nutrition and to discuss what constitutes the efficacy for foods and food constituents and how the strength and consistency of the evidence can be assessed and adapted to circumstances in which health claims are to be used on food products. The meeting highlighted the limitations with the present evidence-based nutrition models with the prospect that this may have long-term consequences for nutrition science and ultimately the consumer who may not benefit from new science that could have an impact on health.

20860886

To what extent have sweetened beverages contributed to the obesity epidemic?

A systematic literature review was conducted to determine whether sweetened beverage intake increases the risk for obesity, and the extent to which it has contributed to recent increases in energy intake and adiposity in the USA.

20860885

The process of setting micronutrient recommendations: a cross-European comparison of nutrition-related scientific advisory bodies.

To examine the workings of the nutrition-related scientific advisory bodies in Europe, paying particular attention to the internal and external contexts within which they operate.

20860887

Essential actions for caterers to promote healthy eating out among European consumers: results from a participatory stakeholder analysis in the HECTOR project.

To identify and assess actions by which the catering sector could be engaged in strategies for healthier eating out in Europe.