Human and livestock diseases can be difficult to control where infection persists in wildlife populations. For three decades, European badgers (Meles meles) have been culled by the British government ...in a series of attempts to limit the spread of Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Despite these efforts, the incidence of TB in cattle has risen consistently, re-emerging as a primary concern for Britain's cattle industry. Recently, badger culling has attracted controversy because experimental studies have reached contrasting conclusions (albeit using different protocols), with culled areas showing either markedly reduced or increased incidence of TB in cattle. This has confused attempts to develop a science-based management policy. Here we use data from a large-scale, randomized field experiment to help resolve these apparent differences. We show that, as carried out in this experiment, culling reduces cattle TB incidence in the areas that are culled, but increases incidence in adjoining areas. These findings are biologically consistent with previous studies but will present challenges for policy development.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To estimate prevalence and number of people visually impaired or blind due to cataract.
Based on the Global Burden of Diseases Study 2010 and ongoing literature research, we examined how many people ...were affected by moderate to severe vision impairment (MSVI; presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60) due to cataract.
In 2010, of overall 32.4 million blind and 191 million vision impaired, 10.8 million people were blind and 35.1 million were visually impaired due to cataract. Cataract caused worldwide 33.4% of all blindness in 2010, and 18.4% of all MSVI. These figures were lower in the high-income regions (<15%) and higher (>40%) in South and Southeast Asia and Oceania. From 1990 to 2010, the number of blind or visually impaired due to cataract decreased by 11.4% and by 20.2%, respectively; the age-standardized global prevalence of cataract-related blindness and MSVI reduced by 46% and 50%, respectively, and the worldwide crude prevalence of cataract-related blindness and MSVI reduced by 32% and 39%, respectively. The percentage of global blindness and MSVI caused by cataract decreased from 38.6% to 33.4%, and from 25.6% to 18.4%, respectively. This decrease took place in almost all world regions, except East Sub-Saharan Africa.
In 2010, one in three blind people was blind due to cataract, and one of six visually impaired people was visually impaired due to cataract. Despite major improvements in terms of reduction of prevalence, cataract remains a major public health problem.
Docking scoring functions are notoriously weak predictors of binding affinity. They typically assign a common set of weights to the individual energy terms that contribute to the overall energy ...score; however, these weights should be gene family dependent. In addition, they incorrectly assume that individual interactions contribute toward the total binding affinity in an additive manner. In reality, noncovalent interactions often depend on one another in a nonlinear manner. In this paper, we show how the use of support vector machines (SVMs), trained by associating sets of individual energy terms retrieved from molecular docking with the known binding affinity of each compound from high-throughput screening experiments, can be used to improve the correlation between known binding affinities and those predicted by the docking program eHiTS. We construct two prediction models: a regression model trained using IC50 values from BindingDB, and a classification model trained using active and decoy compounds from the Directory of Useful Decoys (DUD). Moreover, to address the issue of overrepresentation of negative data in high-throughput screening data sets, we have designed a multiple-planar SVM training procedure for the classification model. The increased performance that both SVMs give when compared with the original eHiTS scoring function highlights the potential for using nonlinear methods when deriving overall energy scores from their individual components. We apply the above methodology to train a new scoring function for direct inhibitors of Mycobacterium tuberculosis (M.tb) InhA. By combining ligand binding site comparison with the new scoring function, we propose that phosphodiesterase inhibitors can potentially be repurposed to target M.tb InhA. Our methodology may be applied to other gene families for which target structures and activity data are available, as demonstrated in the work presented here.
We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The ...approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today's most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the 'TB-drugome'. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable and could serve as novel anti-tubercular targets. Furthermore, a detailed analysis of the TB-drugome has shed new light on the controversial issues surrounding drug-target networks 1-3. Indeed, our results support the idea that drug-target networks are inherently modular, and further that any observed randomness is mainly caused by biased target coverage. The TB-drugome (http://funsite.sdsc.edu/drugome/TB) has the potential to be a valuable resource in the development of safe and efficient anti-tubercular drugs. More generally the methodology may be applied to other pathogens of interest with results improving as more of their structural proteomes are determined through the continued efforts of structural biology/genomics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Patient-controlled analgesia is a widely used and effective method of controlling pain after THA. This method is associated with substantial undesirable side effects. Local infiltration ...has been introduced in an attempt to reduce opioid requirements postoperatively, but its ability to reduce pain without complications is still questioned.
Questions/Purposes
We evaluated patient-controlled analgesia use, pain and satisfaction scores, complication rates, and ropivacaine levels associated with the use of periarticular multimodal drug infiltration in THA.
Patients and Methods
We randomized 64 patients undergoing THA to receive a periarticular intraoperative multimodal drug injection or to receive no injection. All patients received patient-controlled analgesia for 24 hours after surgery. The final assessment was at 6 weeks.
Results
Patients receiving the periarticular injection used less patient-controlled analgesia 6 hours postoperatively. The 24-hour patient-controlled analgesia requirement postsurgery also was less. The visual analog scale score for pain on activity in the postanesthetic care unit was less for patients who received an injection. The visual analog scale satisfaction score was similar in the two groups throughout the followup period. Recorded unbound ropivacaine levels were 2.5 times lower than toxic levels.
Conclusions
Periarticular intraoperative injection with multimodal drugs can reduce postoperative patient-controlled analgesia requirements and pain on activity in patients undergoing THA with no apparent increase in risk.
Level of Evidence
Level I, therapeutic study. See the guidelines online for a complete description of level of evidence.
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Human and livestock diseases can be difficult to control where infection persists in wildlife populations. In Britain, European badgers (Meles meles) are implicated in transmitting Mycobacterium ...bovis, the causative agent of bovine tuberculosis (TB), to cattle. Badger culling has therefore been a component of British TB control policy for many years. However, large-scale field trials have recently shown that badger culling has the capacity to cause both increases and decreases in cattle TB incidence. Here, we show that repeated badger culling in the same area is associated with increasing prevalence of M. bovis infection in badgers, especially where landscape features allow badgers from neighboring land to recolonize culled areas. This impact on prevalence in badgers might reduce the beneficial effects of culling on cattle TB incidence, and could contribute to the detrimental effects that have been observed. Additionally, we show that suspension of cattle TB controls during a nationwide epidemic of foot and mouth disease, which substantially delayed removal of TB-affected cattle, was associated with a widespread increase in the prevalence of M. bovis infection in badgers. This pattern suggests that infection may be transmitted from cattle to badgers, as well as vice versa. Clearly, disease control measures aimed at either host species may have unintended consequences for transmission, both within and between species. Our findings highlight the need for policymakers to consider multiple transmission routes when managing multihost pathogens.
Due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. As a continuation of our research ...in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against Bacillus anthracis. The structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an N-acryloyl-substituted 1,2-dihydrophthalazine ring. Various changes were made at the C1 stereocenter of the dihydrophthalazine moiety in the structure, and the biological activity was assessed by measurement of the MIC and K(i) values to identify the most potent drug candidate.
Objective To improve the interpretation of future studies in women who are initially diagnosed with a pregnancy of unknown location (PUL), we propose a consensus statement with definitions of ...population, target disease, and final outcome. Design A review of literature and a series of collaborative international meetings were used to develop a consensus for definitions and final outcomes of women initially diagnosed with a PUL. Result(s) Global differences were noted in populations studied and in the definitions of outcomes. We propose to define initial ultrasound classification of findings into five categories: definite ectopic pregnancy (EP), probable EP, PUL, probable intrauterine pregnancy (IUP), and definite IUP. Patients with a PUL should be followed and final outcomes should be categorized as visualized EP, visualized IUP, spontaneously resolved PUL, and persisting PUL. Those with the transient condition of a persisting PUL should ultimately be classified as nonvisualized EP, treated persistent PUL, resolved persistent PUL, or histologic IUP. These specific categories can be used to characterize the natural history or location (intrauterine vs. extrauterine) of any early gestation where the initial location is unknown. Conclusion(s) Careful definition of populations and classification of outcomes should optimize objective interpretation of research, allow objective assessment of future reproductive prognosis, and hopefully lead to improved clinical care of women initially identified to have a PUL.
BioJava is an open-source project for processing of biological data in the Java programming language. We have recently released a new version (3.0.5), which is a major update to the code base that ...greatly extends its functionality.
BioJava now consists of several independent modules that provide state-of-the-art tools for protein structure comparison, pairwise and multiple sequence alignments, working with DNA and protein sequences, analysis of amino acid properties, detection of protein modifications and prediction of disordered regions in proteins as well as parsers for common file formats using a biologically meaningful data model.
BioJava is an open-source project distributed under the Lesser GPL (LGPL). BioJava can be downloaded from the BioJava website (http://www.biojava.org). BioJava requires Java 1.6 or higher. All inquiries should be directed to the BioJava mailing lists. Details are available at http://biojava.org/wiki/BioJava:MailingLists.
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