A rare case of orbital osteogenic sarcoma

Osteogenic sarcoma is a malignant bony tumor of mesenchymal cell ori gin. The association of osteogenic sarcoma with Paget's disease of the bone (osteitis deformans) is well-known. However, orbital involvement is rare; only two other cases have been reported in all of the literature. Untreated, the tumor is lethal, with death usually occurring from extension into the cranial fossa

Variation in Vector Competence for Dengue Viruses Does Not Depend on Mosquito Midgut Binding Affinity

Several factors, such as mosquito and virus genetics and environmental variables, determine the ability of mosquitoes to transmit dengue viruses. In this report, we describe new and important information that in some ways contradicts what is in the literature. Midgut infection barriers have been described as important determinants of virus transmission in mosquitoes but we found that virus binding to these midgut cells does not vary. When we compared binding of 8 different, low passage dengue viruses to mosquito midguts that were dissected out of Aedes aegypti mosquitoes (the main vectors of dengue) from Mexico and Texas, we found that there were no differences. Previously, we (and others) had shown that these same viruses differed significantly in replication and dissemination throughout the rest of the mosquito body, including the salivary glands, and therefore they differed greatly in their potential to be transmitted to humans. Thus, the data presented here are important considerations for future studies of vector competence and in determining strategies for control of dengue viruses in the vector

Protocol: Personality assessment as a support for referral and case-work in treatment for substance use disorders (PASRC-study)

<p>Abstract</p> <p>Background</p> <p>Assessment of co-morbid personality disorders in substance use disorders may lead to important insights concerning individual patients. However, little is known about the potential value of routine personality disorder assessment in a clinical context.</p> <p>Methods</p> <p>Patients are adults with past-year substance dependence seeking treatment at a centralized intake unit for substance abusers in the City of Copenhagen. A randomized controlled trial of assessment of personality disorders and individual feedback vs. a general life situation interview. Patients are followed at 3 and 6 months post-treatment</p> <p>Discussion</p> <p>If routine personality assessment improves outcomes of substance abuse treatment, the clinical implication is to increase the use of personality disorder assessment in substance abuse treatment settings.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN39851689</p

The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

The original publication is available at http://www.jnrbm.com/content/10/1/12Includes bibliographyAbstract Background The gene family KCNE1-5, which encode modulating β-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic disease associated with an improper hypertrophic response. Results The coding regions of KCNE1, KCNE2, KCNE3, KCNE4, and KCNE5 were examined, by direct DNA sequencing, in a cohort of 93 unrelated HCM probands and 188 blood donor controls. Fifteen genetic variants, four previously unknown, were identified in the HCM probands. Eight variants were non-synonymous and one was located in the 3'UTR-region of KCNE4. No disease-causing mutations were found and no significant difference in the frequency of genetic variants was found between HCM probands and controls. Two variants of likely functional significance were found in controls only. Conclusions Mutations in KCNE genes are not a common cause of HCM and polymorphisms in these genes do not seem to be associated with a propensity to develop arrhythmiaPeer Reviewe

The Intermediate Filament Network in Cultured Human Keratinocytes Is Remarkably Extensible and Resilient

The prevailing model of the mechanical function of intermediate filaments in cells assumes that these 10 nm diameter filaments make up networks that behave as entropic gels, with individual intermediate filaments never experiencing direct loading in tension. However, recent work has shown that single intermediate filaments and bundles are remarkably extensible and elastic in vitro, and therefore well-suited to bearing tensional loads. Here we tested the hypothesis that the intermediate filament network in keratinocytes is extensible and elastic as predicted by the available in vitro data. To do this, we monitored the morphology of fluorescently-tagged intermediate filament networks in cultured human keratinocytes as they were subjected to uniaxial cell strains as high as 133%. We found that keratinocytes not only survived these high strains, but their intermediate filament networks sustained only minor damage at cell strains as high as 100%. Electron microscopy of stretched cells suggests that intermediate filaments are straightened at high cell strains, and therefore likely to be loaded in tension. Furthermore, the buckling behavior of intermediate filament bundles in cells after stretching is consistent with the emerging view that intermediate filaments are far less stiff than the two other major cytoskeletal components F-actin and microtubules. These insights into the mechanical behavior of keratinocytes and the cytokeratin network provide important baseline information for current attempts to understand the biophysical basis of genetic diseases caused by mutations in intermediate filament genes

Substance abuse and psychiatric co-morbidity as predictors of premature mortality in Swedish drug abusers a prospective longitudinal study 1970 - 2006

<p>Abstract</p> <p>Background</p> <p>Few longitudinal cohort studies have focused on the impact of substances abused and psychiatric disorders on premature mortality. The aim of the present study was to identify predictors of increased risk of drug related death and non drug related death in substance abusers of opiates, stimulants, cannabis, sedatives/hypnotics, hallucinogens and alcohol over several decades.</p> <p>Methods</p> <p>Follow-up study of a consecutive cohort of 561 substance abusers, admitted to a detoxification unit January 1970 to February 1978 in southern Sweden, and followed up in 2006. Demographic and clinical data, substance diagnoses and three groups of psychiatric diagnoses were identified at first admission. Causes of death were coded according to ICD-10 and classified as drug related deaths or non drug related deaths. To identify the incidence of some probable risk factors of drug related premature death, the data were subjected to a competing risks Cox regression analysis.</p> <p>Results</p> <p>Of 561 patients in the cohort, 11 individuals had either emigrated or could not be located, and 204/561 patients (36.4%) were deceased by 2006. The cumulative risk of drug related death increased more in the first 15 years and leveled out later on when non drug related causes of death had a similar incidence. In the final model, male gender, regular use of opiates or barbiturates at first admission, and neurosis were associated with an increased risk of drug related premature death, while cannabis use and psychosis were associated with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death.</p> <p>Conclusions</p> <p>The cohort of drug abusers had an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates and depression and anxiety disorders at first admission. The predicted cumulative incidence of drug related death was significantly higher in opiate and barbiturate abusers over the observed period of 37 years, while stimulant abuse did not have any impact. Alcohol contributed to non drug related death.</p

Host Alternation Is Necessary to Maintain the Genome Stability of Rift Valley Fever Virus

Arthropod-borne viruses are transmitted among vertebrate hosts by insect vectors. Unusually, Rift Valley fever virus (RVFV) can also be transmitted by direct contacts of animals/humans with infectious tissues. What are the molecular mechanisms and evolutionary events leading to adopt one mode of transmission rather than the other? Viral replication is implied to be different in a vertebrate host and an invertebrate host. The alternating host cycle tends to limit virus evolution by adopting a compromise fitness level for replication in both hosts. To test this hypothesis, we used a cell culture model system to study the evolution of RVFV. We found that freeing RVFV from alternating replication in mammalian and mosquito cells led to large deletions in the NSs gene carrying the virulence factor. Resulting NSs-truncated viruses were able to protect mice from a challenge with a virulent RVFV. Thus, in nature, virulence is likely maintained by continuous alternating passages between vertebrates and insects. Thereby, depending on the mode of transmission adopted, the evolution of RVFV will be of major importance to predict the outcome of outbreaks

Evaluation of porcine epidemic diarrhea virus transmission and the immune response in growing pigs

Citation: Crawford, K., Lager, K., Miller, L., Opriessnig, T., Gerber, P., & Hesse, R. (2015). Evaluation of porcine epidemic diarrhea virus transmission and the immune response in growing pigs. Veterinary Research, 46, 9. doi:10.1186/s13567-015-0180-5Clinical disease associated with porcine epidemic diarrhea virus (PEDV) infection in naive pigs is well chronicled; however, information on endemic PEDV infection is limited. To characterize chronic PEDV infection, the duration of infectious virus shedding and development of protective immunity was determined. On Day 0 (D0), a growing pig was challenged with PEDV and 13 contacts were commingled. On D7, 9 contact pigs (principal virus group (PG)), were selected, moved to a separate room and commingled with one sentinel pig (S1). This process was repeated weekly with S2, S3 and S4. The PG was PEDV-positive by PCR from D3-11, with some pigs intermittently positive to D42. Pigs S1 and S2 were PEDV-positive within 24 hours of commingling. Antibodies were detected in all PG by D21 and by 7 days post-contact in S1 and S2. Pigs S3 and S4 were PCR and antibody negative following commingling. To evaluate protective immunity, 5 naive pigs (N) and the PG were challenged (N/C, PG/C) with homologous virus on D49. All N/C pigs were PEDV PCR-positive by D52 with detection out to D62 in 3/5 N/C pigs. All PG/C pigs were PEDV PCR-negative post-challenge. By D63, all N/C seroconverted. Although PEDV RNA was demonstrated in pigs after primary infection until D42, infectious PEDV capable of horizontal transmission to naive pigs was only shed 14-16 days after infection to age-matched pigs. Homologous re-challenge 49 days post initial PEDV exposure did not result in re-infection of the pigs. This demonstrates potential for an effective PEDV vaccine

Causal Measures of Structure and Plasticity in Simulated and Living Neural Networks

A major goal of neuroscience is to understand the relationship between neural structures and their function. Recording of neural activity with arrays of electrodes is a primary tool employed toward this goal. However, the relationships among the neural activity recorded by these arrays are often highly complex making it problematic to accurately quantify a network's structural information and then relate that structure to its function. Current statistical methods including cross correlation and coherence have achieved only modest success in characterizing the structural connectivity. Over the last decade an alternative technique known as Granger causality is emerging within neuroscience. This technique, borrowed from the field of economics, provides a strong mathematical foundation based on linear auto-regression to detect and quantify “causal” relationships among different time series. This paper presents a combination of three Granger based analytical methods that can quickly provide a relatively complete representation of the causal structure within a neural network. These are a simple pairwise Granger causality metric, a conditional metric, and a little known computationally inexpensive subtractive conditional method. Each causal metric is first described and evaluated in a series of biologically plausible neural simulations. We then demonstrate how Granger causality can detect and quantify changes in the strength of those relationships during plasticity using 60 channel spike train data from an in vitro cortical network measured on a microelectrode array. We show that these metrics can not only detect the presence of causal relationships, they also provide crucial information about the strength and direction of that relationship, particularly when that relationship maybe changing during plasticity. Although we focus on the analysis of multichannel spike train data the metrics we describe are applicable to any stationary time series in which causal relationships among multiple measures is desired. These techniques can be especially useful when the interactions among those measures are highly complex, difficult to untangle, and maybe changing over time