Compliance with Australian stroke guideline recommendations for outdoor mobility and transport training by post-inpatient rehabilitation services: an observational cohort study

Background: Community participation is often restricted after stroke, due to reduced confidence and outdoor mobility. Australian clinical guidelines recommend that specific evidence-based interventions be delivered to target these restrictions, such as multiple escorted outdoor journeys. The aim of this study was to describe post-inpatient outdoor mobility and transport training delivered to stroke survivors in New South Wales, Australia and whether therapy differed according to type, sector or location of service provider. Methods: Using an observational retrospective cohort study design, 24 rehabilitation service providers were audited. Provider types included outpatient (n = 8), day therapy (n = 9), home-based rehabilitation (n = 5) and transitional aged care services (TAC, n = 2). Records of 15 stroke survivors who had received post-hospital rehabilitation were audited per service, for wait time, duration, amount of therapy and outdoor-related therapy. Results: A total of 311 records were audited. Median wait time for post-hospital therapy was 13 days (IQR, 5–35). Median duration of therapy was 68 days (IQR, 35–109), consisting of 11 sessions (IQR 4–19). Overall, a median of one session (IQR 0–3) was conducted outdoors per person. Outdoor-related therapy was similar across service providers,except that TAC delivered an average of 5.4 more outdoor-related sessions (95 % CI 4.4 to 6.4), and 3.5 more outings into public streets (95 % CI 2.8 to 4.3) per person, compared to outpatient services. Conclusion: The majority of service providers in the sample delivered little evidence-based outdoor mobility and travel training per stroke participant, as recommended in national stroke guidelines

Human Cytomegalovirus UL29/28 Protein Interacts with Components of the NuRD Complex Which Promote Accumulation of Immediate-Early RNA

Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate-early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate-early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs

Histone deacetylases in viral infections

Chromatin remodeling and gene expression are regulated by histone deacetylases (HDACs) that condense the chromatin structure by deacetylating histones. HDACs comprise a group of enzymes that are responsible for the regulation of both cellular and viral genes at the transcriptional level. In mammals, a total of 18 HDACs have been identified and grouped into four classes, i.e., class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10), class III (Sirt1–Sirt7), and class IV (HDAC11). We review here the role of HDACs on viral replication and how HDAC inhibitors could potentially be used as new therapeutic tools in several viral infections

Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis

Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH

Is Meta-Analysis for Utility Values Appropriate Given the Potential Impact Different Elicitation Methods Have on Values?

A growing number of published articles report estimates from meta-analysis or meta-regression on health state utility values (HSUVs), with a view to providing input into decision-analytic models. Pooling HSUVs is problematic because of the fact that different valuation methods and different preference-based measures (PBMs) can generate different values on exactly the same clinical health state. Existing meta-analyses of HSUVs are characterised by high levels of heterogeneity, and meta-regressions have identified significant (and substantial) impacts arising from the elicitation method used. The use of meta-regression with few utility values and inclusion criteria that extend beyond the required utility value has not helped. There is the potential to explore greater use of mapping between different PBMs and valuation methods prior to data synthesis, which could support greater use of pooling values. Researchers wishing to populate decision-analytic models have a responsibility to incorporate all high-quality evidence available. In relation to HSUVs, greater understanding of the differences between different methods and greater consistency of methodology is required before this can be achieved