Prospective study of the primary evaluation of 1016 horses with clinical signs of abdominal pain by veterinary practitioners, and the differentiation of critical and non‑critical cases

Background: The majority of research on the evaluation of horses with colic is focused on referral hospital populations. Early identification of critical cases is important to optimise outcome and welfare. The aim of this prospective study was to survey the primary evaluation of horses with clinical signs of abdominal pain by veterinary practitioners, and compare the initial presentation of critical and non-critical cases. Results: Data from 1016 primary evaluations of horses presenting with clinical signs of colic were submitted by 167 veterinary practitioners across the United Kingdom over a 13 month period. The mean age of the study population was 13.5 years (median 12.0, range 0–42). Mean heart rate on primary presentation was 47 beats/min (median 44, range 18–125), mean respiratory rate was 20 breaths/min (median 16, range 6–100), and median gastrointestinal auscultation score (0–12, minimum–maximum) was 5 (range 0–12). Clinical signs assessed using a behavioural severity score (0–17, minimum–maximum), were between 0 and 6 in 70.4 % of cases, and 7 12 for 29.6 % of cases. Rectal examination was performed in 73.8 % of cases. Cases that responded positively to simple medical treatment were categorised retrospectively as ‘non-critical’; cases that required intensive medical treatment, surgical intervention, died or were euthanased were categorised as ‘critical’. Eight-hundred-and-twenty- two cases met these criteria; 76.4 % were ‘non-critical’ and 23.6 % were ‘critical’. Multivariable logistic regression was used to identify features of the clinical presentation associated with critical cases. Five variables were retained in the final multivariable model: combined pain score: (OR 1.19, P 2.5 s (OR 3.21, P = 0.046, 95 % CI 1.023–10.09), weak pulse character (OR 2.90, P = 0.004, 95 % CI 1.39–5.99) and absence of gut sounds in ≥1 quadrant (OR 3.65, P < 0.001, 95 % CI 2.08–6.41). Conclusions: This is the first study comparing the primary presentation of critical and non-critical cases of abdominal pain. Pain, heart rate, gastrointestinal borborygmi and simple indicators of hypovolaemia were significant indicators of critical cases, even at the primary veterinary examination, and should be considered essential components of the initial assessment and triage of horses presenting with colic

Tools to Support Policy Decisions Related to Treatment Strategies and Surveillance of Schistosomiasis Japonica towards Elimination

Immunodiagnostic assays are widely applied in the field to control schistosomiasis in P.R. China as the prevalence and infection intensity of schistosome infections decrease. Field evaluations are urgently needed before they can be adopted to support policy decisions of the national programme for the control and elimination of schistosomiasis in P.R. China. We carried out a large scale cross-sectional survey in field settings with different transmission situations to validate immunodiagnostic tools that can be used to formulate new schistosomiasis elimination strategy in P.R. China. Regarding stool examination as gold reference, the validity and screening efficacy of each immunodiagnostic kit were calculated and compared with each other. The association of the prevalence of schistosomiasis and antibody positive rates determined by immunoassays were analyzed using Pearson's correlation coefficient values. The study indicates that which test to use with the elimination strategy is dependent on the purpose of testing, the endemic status of community and the resources available. And more sensitive methods need to be explored and used to target infected individuals for treatment or to eliminate schistosomiasis

Systemic virus distribution and host responses in brain and intestine of chickens infected with low pathogenic or high pathogenic avian influenza virus

<p>Abstract</p> <p>Background</p> <p>Avian influenza virus (AIV) is classified into two pathotypes, low pathogenic (LP) and high pathogenic (HP), based on virulence in chickens.</p> <p>Differences in pathogenicity between HPAIV and LPAIV might eventually be related to specific characteristics of strains, tissue tropism and host responses.</p> <p>Methods</p> <p>To study differences in disease development between HPAIV and LPAIV, we examined the first appearance and eventual load of viral RNA in multiple organs as well as host responses in brain and intestine of chickens infected with two closely related H7N1 HPAIV or LPAIV strains.</p> <p>Results</p> <p>Both H7N1 HPAIV and LPAIV spread systemically in chickens after a combined intranasal/intratracheal inoculation. In brain, large differences in viral RNA load and host gene expression were found between H7N1 HPAIV and LPAIV infected chickens. Chicken embryo brain cell culture studies revealed that both HPAIV and LPAIV could infect cultivated embryonic brain cells, but in accordance with the absence of the necessary proteases, replication of LPAIV was limited. Furthermore, TUNEL assay indicated apoptosis in brain of HPAIV infected chickens only. In intestine, where endoproteases that cleave HA of LPAIV are available, we found minimal differences in the amount of viral RNA and a large overlap in the transcriptional responses between HPAIV and LPAIV infected chickens. Interestingly, brain and ileum differed clearly in the cellular pathways that were regulated upon an AI infection.</p> <p>Conclusions</p> <p>Although both H7N1 HPAIV and LPAIV RNA was detected in a broad range of tissues beyond the respiratory and gastrointestinal tract, our observations indicate that differences in pathogenicity and mortality between HPAIV and LPAIV could originate from differences in virus replication and the resulting host responses in vital organs like the brain.</p

Mosquito Infection Responses to Developing Filarial Worms

Human lymphatic filariasis is a mosquito-vectored disease caused by the nematode parasites Wuchereria bancrofti, Brugia malayi and Brugia timori. These are relatively large roundworms that can cause considerable damage in compatible mosquito vectors. In order to assess how mosquitoes respond to infection in compatible mosquito-filarial worm associations, microarray analysis was used to evaluate transcriptome changes in Aedes aegypti at various times during B. malayi development. Changes in transcript abundance in response to the different stages of B. malayi infection were diverse. At the early stages of midgut and thoracic muscle cell penetration, a greater number of genes were repressed compared to those that were induced (20 vs. 8). The non-feeding, intracellular first-stage larvae elicited few differences, with 4 transcripts showing an increased and 9 a decreased abundance relative to controls. Several cecropin transcripts increased in abundance after parasites molted to second-stage larvae. However, the greatest number of transcripts changed in abundance after larvae molted to third-stage larvae and migrated to the head and proboscis (120 induced, 38 repressed), including a large number of putative, immunity-related genes (∼13% of genes with predicted functions). To test whether the innate immune system of mosquitoes was capable of modulating permissiveness to the parasite, we activated the Toll and Imd pathway controlled rel family transcription factors Rel1 and Rel2 (by RNA interference knockdown of the pathway's negative regulators Cactus and Caspar) during the early stages of infection with B. malayi. The activation of either of these immune signaling pathways, or knockdown of the Toll pathway, did not affect B. malayi in Ae. aegypti. The possibility of LF parasites evading mosquito immune responses during successful development is discussed

Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?

The laboratory mouse has been widely used to test the efficacy of schistosome vaccines and a long list of candidates has emerged from this work, many of them abundant internal proteins. These antigens do not have an additive effect when co-administered, or delivered as SWAP homogenate, a quarter of which comprises multiple candidates; the observed protection has an apparent ceiling of 40–50 %. We contend that the low level of maturation of penetrating cercariae (~32 % for Schistosoma mansoni) is a major limitation of the model since 68/100 parasites fail to mature in naïve mice due to natural causes. The pulmonary capillary bed is the obstacle encountered by schistosomula en route to the portal system. The fragility of pulmonary capillaries and their susceptibility to a cytokine-induced vascular leak syndrome have been documented. During lung transit schistosomula burst into the alveolar spaces, and possess only a limited capacity to re-enter tissues. The acquired immunity elicited by the radiation attenuated (RA) cercarial vaccine relies on a pulmonary inflammatory response, involving cytokines such as IFNγ and TNFα, to deflect additional parasites into the alveoli. A principal difference between antigen vaccine protocols and the RA vaccine is the short interval between the last antigen boost and cercarial challenge of mice (often two weeks). Thus, after antigen vaccination, challenge parasites will reach the lungs when both activated T cells and cytokine levels are maximal in the circulation. We propose that “protection” in this situation is the result of physiological effects on the pulmonary blood vessels, increasing the proportion of parasites that enter the alveoli. This hypothesis will explain why internal antigens, which are unlikely to interact with the immune response in a living schistosomulum, plus a variety of heterologous proteins, can reduce the level of maturation in a non-antigen-specific way. These proteins are “successful” precisely because they have not been selected for immunological silence. The same arguments apply to vaccine experiments with S. japonicum in the mouse model; this schistosome species seems a more robust parasite, even harder to eliminate by acquired immune responses. We propose a number of ways in which our conclusions may be tested

Reassessing the Evidence Hierarchy in Asthma: Evaluating Comparative Effectiveness

Classical randomized controlled trials are the gold standard in medical evidence because of their high internal validity. However, their necessarily strict design can limit their external validity and the ability to extrapolate these data to real world patients. Therefore, alternatively designed studies may play a complementary role in evaluating the comparative effectiveness of therapies in nonidealized patients in more naturalistic, real world settings. Observational studies have high external validity and can evaluate real world outcomes. Their strength lies in hypothesis generation and testing and in identifying areas in which further clinical trials may be required. Pragmatic trials are designed to maximize applicability of trial results to usual care settings by relying on clinically important outcomes and enrolling a wide range of participants. A combination of these approaches is preferable and necessary

H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

<p>Abstract</p> <p>Background</p> <p>The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.</p> <p>Results</p> <p>Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in <it>Saccharomyces cerevisiae</it>. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an <it>htb-K123R </it>mutation, leads to synthetic lethality.</p> <p>Conclusion</p> <p>These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.</p

Transfusion-transmitted infections

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens