Background and Purpose
PEDro (the Physiotherapy Evidence Database) is a widely used, comprehensive, freely available, online database that indexes studies of the effectiveness of physiotherapy ...interventions. We have recently built another database, called DiTA, on the same platform as PEDro. DiTA provides a comprehensive index of studies of the accuracy of diagnostic tests used by physiotherapists. This study aims to describe the number and scope of such studies.
Methods
A comprehensive search was conducted for studies of the accuracy of diagnostic tests. The search was conducted on the MEDLINE, EMBASE and CINAHL databases from their inceptions to November 2018. Subsequently, monthly searches have updated the database. To be included on DiTA, studies need to investigate (a) both a pathology and patients that a physiotherapist could assess in clinical practice, and (b) an index test that a physiotherapist would perform themselves rather than one which they would request.
Results
To date, the searches have yielded 44,884 titles. Screening has identified 1,419 reports that meet the inclusion criteria. The most frequently studied subdisciplines are “musculoskeletal” (1,050/1,419; 74.0%) and “cardiothoracics” (241; 17.0%); the most frequently studied categories of pathologies are joint pathologies (463; 32.6%) and nervous system pathologies (175; 12.3%); and the most frequently studied body part is the “lower leg or knee” (232; 16.3%). Most studies investigate index tests which are “physical examination” procedures (851; 60.0%); fewer investigate “questions or questionnaires” (420; 29.6%) and “health technologies” (351; 24.7%).
Discussion
There is a rapidly growing body of evidence on the accuracy of diagnostic tests relevant to most physiotherapy subdisciplines. While the volume of evidence is substantial, it is not yet clear how much of the evidence is of good enough quality to support clinical decision‐making.
TGFβ superfamily ligands greatly outnumber their receptors. Thus, receptors are shared between ligands and individual ligands can bind multiple receptors. Bone morphogenetic proteins (BMPs) bind and ...signal via both BMP type II (BMPR2) and activin type II (ACVR2) receptors. We hypothesized that, in addition to its canonical receptor ACVR2, activin A might similarly bind and signal via BMPR2. First, using surface plasmon resonance, we showed that activin A binds to the BMPR2 extracellular domain (ECD), though with lower affinity compared to the ACVR2-ECD. We confirmed these results in cells, where radiolabeled activin A bound to ACVR2 and BMPR2, but not to other type II receptors (AMHR2 or TGFBR2). Using homology modeling and site-directed mutagenesis, we identified key residues in BMPR2 that mediate its interaction with activin A. The soluble ECDs of ACVR2 or BMPR2 dose-dependently inhibited activin A-, but not TGFβ-induced signaling in cells, suggesting that activin binding to BMPR2 could have functional consequences. To address this idea, we altered BMPR2 expression levels in immortalized murine gonadotrope-like cells, LβT2, in which activins potently stimulate follicle-stimulating hormone β (Fshb) subunit transcription. BMPR2 expression potentiated activin A responses whereas depletion of endogenous BMPR2 with short interfering RNAs attenuated activin A-stimulated Fshb transcription. Additional data suggest, for the first time, that BMPR2 may form functional complexes with the canonical activin type I receptor, activin receptor-like kinase 4. Collectively, our data show that BMPR2, along with ACVR2, functions as a bona fide activin type II receptor in gonadotrope-like cells, thereby broadening our understanding of mechanisms of activin action.
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•Activin A binds BMPR2 with nanomolar affinity.•Activins signal via BMPR2 in gonadotrope-like cells.•BMPR2 complexes with ALK4 (ACVR1B) to regulate Fshb promoter activity.•BMPR2 is a functional activin type II receptor in gonadotrope-like cells.
Streptococcus suis is an important swine pathogen that causes meningitis, endocarditis, arthritis and septicaemia. As a zoonotic agent, S. suis also causes similar diseases in humans. Binding of ...pathogenic bacteria to extracellular matrix components enhances their adhesion to and invasion of host cells. In the present study we isolated and identified a novel fibronectin-binding protein from S. suis. The native protein (designated SsEno) possessed not only high homology with other bacterial enolases but also enolase activity. We cloned, expressed and purified SsEno and showed that it is ubiquitously expressed by all S. suis serotypes and we identified its surface localization using immunoelectron microscopy. ELISA demonstrated that SsEno binds specifically to fibronectin and plasminogen in a lysine-dependent manner. Additional surface plasmon resonance assays demonstrated that SsEno binds to fibronectin or plasminogen with low nanomolar affinity. Inhibition experiments with anti-SsEno antibodies also showed that bacterial SsEno is important for the adhesion to and invasion of brain microvascular endothelial cells by S. suis. Overall, the present work is the first study, to our knowledge, to demonstrate a fibronectin-binding activity of a bacterial enolase, and shows that, similar to other bacterial fibronectin-binding proteins, SsEno may contribute to the virulence of S. suis.
Potato is a major global crop that has an important role to play in food security, reducing poverty and improving human nutrition. Productivity in potato however is limited in many environments by ...its sensitivity to abiotic stresses such as elevated temperature, drought, frost, and salinity. In this chapter we focus on the effects of elevated temperature on potato yields as high temperature is the most important uncontrollable factor affecting growth and yield of potato. We describe some of the physiological impacts of elevated temperature and review recent findings about response mechanisms. We describe genetic approaches that could be used to identify allelic variants of genes that may be useful to breed for increased climate resilience, an approach that could be deployed with recent advances in potato breeding.
Bud break in raspberry (Rubus idaeus L.) is often poor and uneven, with many of the subapical buds remaining in a dormant state. In order to determine the dormancy status of raspberry buds, an ...empirical measure of bud burst in a growth-permissive environment following exposure to chilling (4 °C cold storage) was developed. For cv. Glen Ample, percentage bud burst in intact canes and isolated nodes was recorded after 14 d. Isolated nodes (a measure of endodormancy) achieved 100% bud burst after ∼1500 h chilling whereas buds on intact plants (combined endo- and paradormancy) required an additional 1000 h chilling. A microarray approach was used to follow changes in gene expression that occurred during dormancy transition. The probes for the microarrays were obtained from endodormant and paradormant raspberry bud cDNA libraries. The expression profiles of 5300 clones from these libraries were subjected to principal component analysis to determine the most significant expression patterns. Sequence analysis of these clones, in many cases, enabled their functional categorization and the development of hypotheses concerning the mechanisms of bud dormancy release. Thus a set of novel candidates for key dormancy-related genes from raspberry buds have been identified. Bud dormancy is fundamental to the study of plant developmental processes and, in addition, its regulation is of significant economic importance to fruit and horticultural industries.
CS31A, a K88-related surface antigen specified by the clp operon, is a member of the type P family of adhesive factors and plays a key role in the establishment of disease caused by septicemic and ...enterotoxigenic Escherichia coli strains. Its expression is under the control of methylation-dependent transcriptional regulation, for which the leucine-responsive regulatory protein (Lrp) is essential. CS31A is preferentially in the OFF state and exhibits distinct regulatory features compared to the regulation of other P family members. In the present study, surface plasmon resonance and DNase I protection assays showed that Lrp binds to the distal moiety of the clp regulatory region with low micromolar affinity compared to its binding to the proximal moiety, which exhibits stronger, nanomolar affinity. The complex formation was also influenced by the addition of PapI or FooI, which increased the affinity of Lrp for the clp distal and proximal regions and was required to induce phase variation. The influence of PapI or FooI, however, was predominantly associated with a more complete shutdown of clp expression, in contrast to what has previously been observed with AfaF (a PapI ortholog). Taken together, these results suggest that the preferential OFF state observed in CS31A cells is mainly due to the weak interaction of the leucine-responsive regulatory protein with the clp distal region and that the PapI homolog favors the OFF phase. Within the large repertoire of fimbrial variants in the P family, our study illustrates that having a fimbrial operon that lacks its own PapI ortholog allows it to be more flexibly regulated by other orthologs in the cell.
Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology ...(BSG) guidelines as a reference point.
We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey.
Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4-6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab.
We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel.
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