We should not forget the foot: relations between signs and symptoms, damage, and function in rheumatoid arthritis

We studied rheumatoid arthritis (RA) patients with foot complaints to address the associations between clinical signs and symptoms, radiographic changes, and function in connection with disease duration. Secondly, we describe the contribution of several foot segments to the clinical presentation and function. In 30 RA patients with complaints of their feet, attributed to either signs of arthritis and/or radiographic damage, we compared radiographic, ultrasound, clinical, and functional parameters of the feet and ankle. Pain and swelling of the ankle were correlated weakly but statistically significantly with limitation and disability (0.273 to 0.293) as measured on the 5-Foot Function Index (FFI). The clinical signs of the forefoot joints did not influence any of the functional outcome measures. Radiographic scores for both forefeet (SvdH) and hindfeet (Larsen) were correlated with the total Health Assessment Questionnaire Disability Index (HAQ DI) and the 5-FFI limitation subscale. Pain and disease duration, more than radiographic damage, influence the total HAQ DI significantly. With the progression of time, structural damage and function of the rheumatic foot worsen in RA patients. Pain and swelling of the ankle contribute more to disability than radiographic damage of the foot and ankle

Comparison of Statistical Population Reconstruction Using Full and Pooled Adult Age-Class Data

BACKGROUND: Age-at-harvest data are among the most commonly collected, yet neglected, demographic data gathered by wildlife agencies. Statistical population construction techniques can use this information to estimate the abundance of wild populations over wide geographic areas and concurrently estimate recruitment, harvest, and natural survival rates. Although current reconstruction techniques use full age-class data (0.5, 1.5, 2.5, 3.5, … years), it is not always possible to determine an animal's age due to inaccuracy of the methods, expense, and logistics of sample collection. The ability to inventory wild populations would be greatly expanded if pooled adult age-class data (e.g., 0.5, 1.5, 2.5+ years) could be successfully used in statistical population reconstruction. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the performance of statistical population reconstruction models developed to analyze full age-class and pooled adult age-class data. We performed Monte Carlo simulations using a stochastic version of a Leslie matrix model, which generated data over a wide range of abundance levels, harvest rates, and natural survival probabilities, representing medium-to-big game species. Results of full age-class and pooled adult age-class population reconstructions were compared for accuracy and precision. No discernible difference in accuracy was detected, but precision was slightly reduced when using the pooled adult age-class reconstruction. On average, the coefficient of variation (i.e., SE(θ)/θ) increased by 0.059 when the adult age-class data were pooled prior to analyses. The analyses and maximum likelihood model for pooled adult age-class reconstruction are illustrated for a black-tailed deer (Odocoileus hemionus) population in Washington State. CONCLUSIONS/SIGNIFICANCE: Inventorying wild populations is one of the greatest challenges of wildlife agencies. These new statistical population reconstruction models should expand the demographic capabilities of wildlife agencies that have already collected pooled adult age-class data or are seeking a cost-effective method for monitoring the status and trends of our wild resources

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Resistance to Wheat streak mosaic virus identified in synthetic wheat lines

Citation: Shoup Rupp, J. L., Simon, Z. G., Gillett-Walker, B., & Fellers, J. P. (2014). Resistance to Wheat streak mosaic virus identified in synthetic wheat lines. Retrieved from http://krex.ksu.eduWheat streak mosaic virus (WSMV) is an important pathogen in wheat that causes significant yield losses each year. WSMV is typically controlled using cultural practices such as the removal of volunteer wheat. Genetic resistance is limited. Until recently, no varieties have been available with major resistance genes to WSMV. Two resistance genes have been derived from Thinopyrum intermedium through chromosome engineering, while a third gene was transferred from bread wheat through classical breeding. New sources of resistance are needed and synthetic wheat lines provide a means of accessing genetic variability in wheat progenitors. A collection of wheat synthetic lines was screened for WSMV resistance. Four lines, 07-SYN-27, -106, -164, and -383 had significant levels of resistance. Resistance was effective at 18 °C and virus accumulation was similar to the resistant control, WGGRC50 containing Wsm1. At 25 °C, resistance was no longer effective and virus accumulation was similar to the susceptible control, Tomahawk

Attribution of 2012 extreme climate events: does air-sea interaction matter?

In 2012, extreme anomalous climate conditions occurred around the globe. Large areas of North America experienced an anomalously hot summer, with large precipitation deficits inducing severe drought. Over Europe, the summer of 2012 was marked by strong precipitation anomalies with the UK experiencing its wettest summer since 1912 while Spain suffered severe drought. What caused these extreme climate conditions in various regions in 2012? This study compares attribution conclusions for 2012 climate anomalies relative to a baseline period (1964–1981) based on two sets of parallel experiments with different model configurations (with coupling to an ocean mixed layer model or with prescribed sea surface temperatures) to assess whether attribution conclusions concerning the climate anomalies in 2012 are sensitive to the representation of air-sea interaction. Modelling results indicate that attribution conclusions for large scale surface air temperature (SAT) changes in both boreal winter and summer are generally robust and not very sensitive to air-sea interaction. This is especially true over southern Europe, Eurasia, North America, South America, and North Africa. Some other responses also appear to be insensitive to air-sea interaction: for example, forced increases in precipitation over northern Europe and Sahel, and reduced precipitation over North America and the Amazon in boreal summer. However, the attribution of circulation and precipitation changes for some other regions exhibits a sensitivity to air-sea interaction. Results from the experiments including coupling to an ocean mixed layer model show a positive NAO-like circulation response in the Atlantic sector in boreal winter and weak changes in the East Asian summer monsoon and precipitation over East Asia. With prescribed sea surface temperatures, some different responses arise over these two regions. Comparison with observed changes indicates that the coupled simulations generally agree better with observations, demonstrating that attribution methods based on atmospheric general circulation models have limitations and may lead to erroneous attribution conclusions for regional anomalies in circulation, precipitation and surface air temperature

Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens

<div><p>Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle.</p></div

DNA methylation and methyl-CpG binding proteins: developmental requirements and function

DNA methylation is a major epigenetic modification in the genomes of higher eukaryotes. In vertebrates, DNA methylation occurs predominantly on the CpG dinucleotide, and approximately 60% to 90% of these dinucleotides are modified. Distinct DNA methylation patterns, which can vary between different tissues and developmental stages, exist on specific loci. Sites of DNA methylation are occupied by various proteins, including methyl-CpG binding domain (MBD) proteins which recruit the enzymatic machinery to establish silent chromatin. Mutations in the MBD family member MeCP2 are the cause of Rett syndrome, a severe neurodevelopmental disorder, whereas other MBDs are known to bind sites of hypermethylation in human cancer cell lines. Here, we review the advances in our understanding of the function of DNA methylation, DNA methyltransferases, and methyl-CpG binding proteins in vertebrate embryonic development. MBDs function in transcriptional repression and long-range interactions in chromatin and also appear to play a role in genomic stability, neural signaling, and transcriptional activation. DNA methylation makes an essential and versatile epigenetic contribution to genome integrity and function

Keratin and S100 calcium-binding proteins are major constituents of the bovine teat canal lining

The bovine teat canal provides the first-line of defence against pathogenic bacteria infecting the mammary gland, yet the protein composition and host-defence functionality of the teat canal lining (TCL) are not well characterised. In this study, TCL collected from six healthy lactating dairy cows was subjected to two-dimensional electrophoresis (2-DE) and mass spectrometry. The abundance and location of selected identified proteins were determined by western blotting and fluorescence immunohistochemistry. The variability of abundance among individual cows was also investigated. Two dominant clusters of proteins were detected in the TCL, comprising members of the keratin and S100 families of proteins. The S100 proteins were localised to the teat canal keratinocytes and were particularly predominant in the cornified outermost layer of the teat canal epithelium. Significant between-animal variation in the abundance of the S100 proteins in the TCL was demonstrated. Four of the six identified S100 proteins have been reported to have antimicrobial activity, suggesting that the TCL has additional functionality beyond being a physical barrier to invading microorganisms. These findings provide new insights into understanding host-defence of the teat canal and resistance of cows to mastitis