Are HCAHPS Scores Higher for Private vs Double-Occupancy Inpatient Rooms in Total Joint Arthroplasty Patients?

BACKGROUND: Private hospital rooms have a number of potential advantages compared to shared rooms, including reduced noise and increased control over the hospital environment. However, the association of room type with patient experience metrics in total joint arthroplasty (TJA) patients is currently unclear. METHODS: For private versus shared rooms, we compared our institutional Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores in patients who underwent primary TJA over a 2-year period. Regression model odds ratios (ORs) were adjusted for surgeon, date of surgery, and length of stay. RESULTS: Patients in private rooms were more likely to report a top-box score for overall hospital rating (85.6% vs 79.4%, OR = 1.53, P = .011), hospital recommendation (89.3% vs 83.0%, OR = 1.78, P = .002), call button help (76.0% vs 68.7%, OR = 1.40, P = .028), and quietness (70.4% vs 59.0%, OR = 1.78, P < .001). There were no significant differences on surgeon metrics including listening (P = .225), explanations (P = .066), or treatment with courtesy and respect (P = .396). CONCLUSION: For patients undergoing TJA, private hospital rooms were associated with superior performance on patient experience metrics. This association appears specific for global and hospital-related metrics, with little impact on surgeon evaluations. With the utilization of HCAHPS data in value-based initiatives, placement of TJA patients in private rooms may lead to increased reimbursement and higher hospital rankings. LEVEL OF EVIDENCE: Level III, retrospective cohort.

Proteins interacting with CreA and CreB in the carbon catabolite repression network in Aspergillus nidulans.

In Aspergillus nidulans, carbon catabolite repression (CCR) is mediated by the global repressor protein CreA. The deubiquitinating enzyme CreB is a component of the CCR network. Genetic interaction was confirmed using a strain containing complete loss-of-function alleles of both creA and creB. No direct physical interaction was identified between tagged versions of CreA and CreB. To identify any possible protein(s) that may form a bridge between CreA and CreB, we purified both proteins from mycelia grown in media that result in repression or derepression. The purified proteins were analysed by LC/MS and identified using MaxQuant and Mascot databases. For both CreA and CreB, 47 proteins were identified in repressing and derepressing conditions. Orthologues of the co-purified proteins were identified in S. cerevisiae and humans. Gene ontology analyses of A. nidulans proteins and yeast and human orthologues were performed. Functional annotation analysis revealed that proteins that preferentially interact with CreA in repressing conditions include histones and histone transcription regulator 3 (Hir3). Proteins interacting with CreB tend to be involved in cellular transportation and organization. Similar findings were obtained using yeast and human orthologues, although the yeast background generated a number of other biological processes involving Mig1p which were not present in the A. nidulans or human background analyses. Hir3 was present in repressing conditions for CreA and in both growth conditions for CreB, suggesting that Hir3, or proteins interacting with Hir3, could be a possible target of CreB.

The CreB deubiquitinating enzyme does not directly target the CreA repressor protein in Aspergillus nidulans.

Ubiquitination/deubiquitination pathways are now recognized as key components of gene regulatory mechanisms in eukaryotes. The major transcriptional repressor for carbon catabolite repression in Aspergillus nidulans is CreA, and mutational analysis led to the suggestion that a regulatory ubiquitination/deubiquitination pathway is involved. A key unanswered question is if and how this pathway, comprising CreB (deubiquitinating enzyme) and HulA (ubiquitin ligase) and other proteins, is involved in the regulatory mechanism. Previously, missense alleles of creA and creB were analysed for genetic interactions, and here we extended this to complete loss-of-function alleles of creA and creB, and compared morphological and biochemical phenotypes, which confirmed genetic interaction between the genes. We investigated whether CreA, or a protein in a complex with it, is a direct target of the CreB deubiquitination enzyme, using co-purifications of CreA and CreB, first using strains that overexpress the proteins and then using strains that express the proteins from their native promoters. The Phos-tag system was used to show that CreA is a phosphorylated protein, but no ubiquitination was detected using anti-ubiquitin antibodies and Western analysis. These findings were confirmed using mass spectrometry, which confirmed that CreA was differentially phosphorylated but not ubiquitinated. Thus, CreA is not a direct target of CreB, and nor are proteins that form part of a stable complex with CreA a target of CreB. These results open up new questions regarding the molecular mechanism of CreA repressing activity, and how the ubiquitination pathway involving CreB interacts with this regulatory network.

The CreB deubiquitinating enzyme does not directly target the CreA repressor protein in Aspergillus nidulans.

Ubiquitination/deubiquitination pathways are now recognized as key components of gene regulatory mechanisms in eukaryotes. The major transcriptional repressor for carbon catabolite repression in Aspergillus nidulans is CreA, and mutational analysis led to the suggestion that a regulatory ubiquitination/deubiquitination pathway is involved. A key unanswered question is if and how this pathway, comprising CreB (deubiquitinating enzyme) and HulA (ubiquitin ligase) and other proteins, is involved in the regulatory mechanism. Previously, missense alleles of creA and creB were analysed for genetic interactions, and here we extended this to complete loss-of-function alleles of creA and creB, and compared morphological and biochemical phenotypes, which confirmed genetic interaction between the genes. We investigated whether CreA, or a protein in a complex with it, is a direct target of the CreB deubiquitination enzyme, using co-purifications of CreA and CreB, first using strains that overexpress the proteins and then using strains that express the proteins from their native promoters. The Phos-tag system was used to show that CreA is a phosphorylated protein, but no ubiquitination was detected using anti-ubiquitin antibodies and Western analysis. These findings were confirmed using mass spectrometry, which confirmed that CreA was differentially phosphorylated but not ubiquitinated. Thus, CreA is not a direct target of CreB, and nor are proteins that form part of a stable complex with CreA a target of CreB. These results open up new questions regarding the molecular mechanism of CreA repressing activity, and how the ubiquitination pathway involving CreB interacts with this regulatory network.

Role of HxkC, a mitochondrial hexokinase-like protein, in fungal programmed cell death.

Apoptosis is a form of programmed cell death (PCD) that occurs during animal development and is also triggered by a variety of signals including nutrient or oxidative stress, hypoxia, DNA damage, viral infection and oncogenic transformation. Though apoptotic-like PCD also occurs in plants and fungi, genes encoding several of the key players in mammalian apoptosis (p53 and BH-domain proteins) have not been identified in these kingdoms. In this report we investigated whether HxkC, a mitochondrial hexokinase-like protein, and XprG, a putative p53-like transcription factor similar to Ndt80, play a role in programmed cell death in the filamentous fungus Aspergillus nidulans. We show that a mutant lacking HxkC is more sensitive to oxidative stress. Autolysis, a form of fungal programmed cell death triggered by carbon starvation, is accelerated in the hxkCΔ1 mutant but not the hxkCΔ1 xprGΔ1 double mutant. In the absence of nutrient stress, the hxkCΔ1 mutant displays XprG-dependent DNA fragmentation typical of apoptosis and elevated levels of intracellular protease. HxkC and XprG are required for catabolism of N-acetylglucosamine, as in Trichoderma reesei. We show that XprG is present in the nucleus. We conclude that, like mammalian mitochondrial hexokinase, HxkC has anti-apoptotic activity and the XprG transcription factor has a pro-apoptotic role in filamentous fungi.

A second component of the SltA-dependent cation tolerance pathway in Aspergillus nidulans.

The transcriptional response to alkali metal cation stress is mediated by the zinc finger transcription factor SltA in Aspergillus nidulans and probably in other fungi of the pezizomycotina subphylum. A second component of this pathway has been identified and characterized. SltB is a 1272 amino acid protein with at least two putative functional domains, a pseudo-kinase and a serine-endoprotease, involved in signaling to the transcription factor SltA. Absence of SltB activity results in nearly identical phenotypes to those observed for a null sltA mutant. Hypersensitivity to a variety of monovalent and divalent cations, and to medium alkalinization are among the phenotypes exhibited by a null sltB mutant. Calcium homeostasis is an exception and this cation improves growth of sltΔ mutants. Moreover, loss of kinase HalA in conjunction with loss-of-function sltA or sltB mutations leads to pronounced calcium auxotrophy. sltA sltB double null mutants display a cation stress sensitive phenotype indistinguishable from that of single slt mutants showing the close functional relationship between these two proteins. This functional relationship is reinforced by the fact that numerous mutations in both slt loci can be isolated as suppressors of poor colonial growth resulting from certain null vps (vacuolar protein sorting) mutations. In addition to allowing identification of sltB, our sltB missense mutations enabled prediction of functional regions in the SltB protein. Although the relationship between the Slt and Vps pathways remains enigmatic, absence of SltB, like that of SltA, leads to vacuolar hypertrophy. Importantly, the phenotypes of selected sltA and sltB mutations demonstrate that suppression of null vps mutations is not dependent on the inability to tolerate cation stress. Thus a specific role for both SltA and SltB in the VPS pathway seems likely. Finally, it is noteworthy that SltA and SltB have a similar, limited phylogenetic distribution, being restricted to the pezizomycotina subphylum. The relevance of the Slt regulatory pathway to cell structure, intracellular trafficking and cation homeostasis and its restricted phylogenetic distribution makes this pathway of general interest for future investigation and as a source of targets for antifungal drugs.

Novel heparan sulfate assay by using automated high-throughput mass spectrometry: Application to monitoring and screening for mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) are caused by deficiency of one of a group of specific lysosomal enzymes, resulting in excessive accumulation of glycosaminoglycans (GAGs). We previously developed GAG assay methods using liquid chromatography tandem mass spectrometry (LC-MS/MS); however, it takes 4-5 min per sample for analysis. For the large numbers of samples in a screening program, a more rapid process is desirable. The automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) integrates a solid phase extraction robot to concentrate and desalt samples prior to direction into the MS/MS without chromatographic separation; thereby allowing each sample to be processed within 10s (enabling screening of more than one million samples per year). The aim of this study was to develop a higher throughput system to assay heparan sulfate (HS) using HT-MS/MS, and to compare its reproducibility, sensitivity and specificity with conventional LC-MS/MS. HS levels were measured in the blood (plasma and serum) from control subjects and patients with MPS II, III, or IV and in dried blood spots (DBS) from newborn controls and patients with MPS I, II, or III. Results obtained from HT-MS/MS showed 1) that there was a strong correlation of levels of disaccharides derived from HS in the blood, between those calculated using conventional LC-MS/MS and HT-MS/MS, 2) that levels of HS in the blood were significantly elevated in patients with MPS II and III, but not in MPS IVA, 3) that the level of HS in patients with a severe form of MPS II was higher than that in an attenuated form, 4) that reduction of blood HS level was observed in MPS II patients treated with enzyme replacement therapy or hematopoietic stem cell transplantation, and 5) that levels of HS in newborn DBS were elevated in patients with MPS I, II or III, compared to those of control newborns. In conclusion, HT-MS/MS provides much higher throughput than LC-MS/MS-based methods with similar sensitivity and specificity in an HS assay, indicating that HT-MS/MS may be feasible for diagnosis, monitoring, and newborn screening of MPS.

Selective acceptance of acute whiplash guidelines: a qualitative analysis of perceptions of health professionals in Australia.

PURPOSE: To explore health professionals' acceptance of the guidelines for acute whiplash associated disorders (WAD), and to identify barriers and facilitators to adherence. MATERIALS AND METHODS: Qualitative descriptive study involving focus group discussions among health professionals who treat people with WAD in primary and secondary care settings in New South Wales and Queensland, Australia. Twenty-eight health professionals (physiotherapists = 19; chiropractors = 6; osteopaths = 3) participated in six semi-structured focus group discussions that were held in independent offices in Sydney and Brisbane, Australia between September and December 2015. Discussions were audio recorded and verbatim, de-identified transcripts produced. Thematic analysis was conducted using an inductive approach to identify commonly held beliefs. RESULTS: Acceptance of guideline recommendations appeared to be influenced by factors related to the guideline itself, practitioner and practice characteristics, and patient-related factors. Specifically, acceptance was hindered by conflicting belief systems, ambiguity in guideline recommendations, and patient characteristics and expectations. CONCLUSIONS: Practitioners demonstrated a positive attitude towards the use of the guidelines in general; however, in some cases, acceptance of key recommendations appeared selective. Future guideline revision and implementation might focus on explaining the underlying principles of the guidelines, providing more detailed recommendations, and involving strategies that challenge inconsistent beliefs and promote informed decision-making. IMPLICATIONS FOR REHABILITATIONSelective acceptance of guideline recommendations in favour of those not requiring practice change may present a challenge for the implementation of evidence-based practice in the management of whiplash.Participants demonstrated variable, sometimes polar attitudes to guideline key messages and recommendations.Guideline developers need to focus more strongly on changing practitioner beliefs and attitudes, as well as better explaining the underlying principles of the guidelines, and providing more detailed recommendations.

"It made you feel like you've still got it": experiences of people with chronic low back pain undertaking a single session of body image training in virtual reality.

INTRODUCTION: Embodying fit avatars in virtual reality (VR) is proposed as a possible treatment for cortical body representations and pain-related self-perceptions. OBJECTIVE: To explore consumer perceptions of a novel VR intervention (VR-BiT) for chronic low back pain. METHODS: Adults (n = 17, mean age(SD) = 52(14)) with chronic low back pain who had undergone a single session of VR-BiT as part of a randomized controlled trial underwent a semi-structured interview using open-ended questions. Interviews were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: Data reduction identified four themes: clinically beneficial and beyond; helping and hindering use; desire for more; and individualized future. Participants experienced wide ranging effects, including improved physical self-efficacy, pain, ability to perform physical activity and psychological symptoms. The intervention was well tolerated, except for two reports of nausea, and a few participants indicating pain associated with unaccustomed movement. Most participants were motivated to use VR-BiT again, despite some having technical issues. Participants suggested that personalizing VR-BiT and regular use would be beneficial. CONCLUSIONS: There was strong consumer support for further use of VR-BiT. Future studies of VR-BiT effectiveness are warranted and should consider incorporating individual user preferences, including people with diverse pain presentations, and involving a multi-session design.

A randomized controlled pilot study examining immediate effects of embodying a virtual reality superhero in people with chronic low back pain.

PURPOSE: In virtual reality, avatar embodiment can spur perceptions and behaviours related the avatars' characteristics. We tested whether embodying superhero-like avatars can change self-perceptions in people with chronic low back pain (CLBP). DESIGN: A non-blinded pilot randomized controlled trial. METHODS: Participants were randomly allocated to embody a superhero (VR-SH, n = 20) or a neutral, non-superhero (VR-Play, n = 10) avatar. Primary outcomes related to body image (e.g., self-perceived vulnerability) and pain intensity were assessed at baseline, during exposure, immediately after and at one-week follow-up. Fear of movement, strength and patient impression of change were also recorded. RESULTS: The VR-SH group reported gains in body image during (p < .001, Î·p2=0.71) and immediately after (p < .001, Î·p2=0.66) VR, whereas the VR-Play group reported small gains during VR (p = .021, Î·p2=0.46) but not immediately after (p = .076, ηp2=0.31). Pain, strength and fear of movement did not change and there were no sustained effects at follow-up (all ps > .05). A greater proportion of people in the VR-SH group reported at least minimal improvement at follow-up (7/20 vs. 1/10). CONCLUSION: A VR-SH session produced temporary positive effects on body image. Future research may consider whether larger and sustained effects can be obtained with multisession exposures or explore combined interventions. Implications for rehabilitationPhysical confidence and bodily trust can be significantly enhanced in people with chronic back pain using virtual reality.These positive body image effects may have implications for rehabilitation, such as in enhancing confidence with movementWhether a multisession intervention might produce more robust effects and changes in pain is yet to be determined.

Disruption of Trichoderma reesei cre2, encoding an ubiquitin C-terminal hydrolase, results in increased cellulase activity.

BACKGROUND: The filamentous fungus Trichoderma reesei (Hypocrea jecorina) is an important source of cellulases for use in the textile and alternative fuel industries. To fully understand the regulation of cellulase production in T. reesei, the role of a gene known to be involved in carbon regulation in Aspergillus nidulans, but unstudied in T. reesei, was investigated. RESULTS: The T. reesei orthologue of the A. nidulans creB gene, designated cre2, was identified and shown to be functional through heterologous complementation of a creB mutation in A. nidulans. A T. reesei strain was constructed using gene disruption techniques that contained a disrupted cre2 gene. This strain, JKTR2-6, exhibited phenotypes similar to the A. nidulans creB mutant strain both in carbon catabolite repressing, and in carbon catabolite derepressing conditions. Importantly, the disruption also led to elevated cellulase levels. CONCLUSIONS: These results demonstrate that cre2 is involved in cellulase expression. Since the disruption of cre2 increases the amount of cellulase activity, without severe morphological affects, targeting creB orthologues for disruption in other industrially useful filamentous fungi, such as Aspergillus oryzae, Trichoderma harzianum or Aspergillus niger may also lead to elevated hydrolytic enzyme activity in these species.

Independent duplications of α-amylase in different strains of Aspergillus oryzae.

Aspergillus oryzae is a filamentous fungus that has arisen through the ancient domestication of Aspergillus flavus for making traditional oriental foods and beverages. In the many centuries A. oryzae has been used for fermenting the starch in rice to simple sugars, it has undergone selection for increased secretion of starch-degrading enzymes. In particular, all A. oryzae strains investigated thus far have two or more copies of a gene encoding α-amylase, whereas A. flavus has only one. Here we investigate the duplications leading to these copies in three A. oryzae strains. We find evidence of at least three separate duplications of α-amylase, an example of parallel evolution in a micro-organism under artificial selection. At least two of these duplications appear to be associated with activity of transposable elements of the Tc1/mariner class. Both involve a 9.1 kb element that terminates in inverted repeats, encodes a putative transposase and another putative protein of unknown function, and contains an unusual arrangement of four short internal imperfect repeats. Although "unusual Mariners" of this size have previously been identified in A. oryzae, Aspergillus fumigatus and Aspergillus nidulans, this is the first evidence we know of that at least some of them are active in modern times and that their activity can contribute to beneficial genetic changes.

Carbon Catabolite Repression Governs Diverse Physiological Processes and Development in Aspergillus nidulans.

Carbon catabolite repression (CCR) is a common phenomenon of microorganisms that enable efficient utilization of carbon nutrients, critical for the fitness of microorganisms in the wild and for pathogenic species to cause infection. In most filamentous fungal species, the conserved transcription factor CreA/Cre1 mediates CCR. Previous studies demonstrated a primary function for CreA/Cre1 in carbon metabolism; however, the phenotype of creA/cre1 mutants indicated broader roles. The global function and regulatory mechanism of this wide-domain transcription factor has remained elusive. Here, we applied two powerful genomics methods (transcriptome sequencing and chromatin immunoprecipitation sequencing) to delineate the direct and indirect roles of Aspergillus nidulans CreA across diverse physiological processes, including secondary metabolism, iron homeostasis, oxidative stress response, development, N-glycan biosynthesis, unfolded protein response, and nutrient and ion transport. The results indicate intricate connections between the regulation of carbon metabolism and diverse cellular functions. Moreover, our work also provides key mechanistic insights into CreA regulation and identifies CreA as a master regulator controlling many transcription factors of different regulatory networks. The discoveries for this highly conserved transcriptional regulator in a model fungus have important implications for CCR in related pathogenic and industrial species. IMPORTANCE The ability to scavenge and use a wide range of nutrients for growth is crucial for microorganisms' survival in the wild. Carbon catabolite repression (CCR) is a transcriptional regulatory phenomenon of both bacteria and fungi to coordinate the expression of genes required for preferential utilization of carbon sources. Since carbon metabolism is essential for growth, CCR is central to the fitness of microorganisms. In filamentous fungi, CCR is mediated by the conserved transcription factor CreA/Cre1, whose function in carbon metabolism has been well established. However, the global roles and regulatory mechanism of CreA/Cre1 are poorly defined. This study uncovers the direct and indirect functions of CreA in the model organism Aspergillus nidulans over diverse physiological processes and development and provides mechanistic insights into how CreA controls different regulatory networks. The work also reveals an interesting functional divergence between filamentous fungal and yeast CreA/Cre1 orthologues.

Mutations in genes encoding sorting nexins alter production of intracellular and extracellular proteases in Aspergillus nidulans.

XprG, a putative p53-like transcriptional activator, regulates production of extracellular proteases in response to nutrient limitation and may also have a role in programmed cell death. To identify genes that may be involved in the XprG regulatory pathway, xprG2 revertants were isolated and shown to carry mutations in genes which we have named sogA-C (suppressors of xprG). The translocation breakpoint in the sogA1 mutant was localized to a homolog of Saccharomyces cerevisiae VPS5 and mapping data indicated that sogB was tightly linked to a VPS17 homolog. Complementation of the sogA1 and sogB1 mutations and identification of nonsense mutations in the sogA2 and sogB1 alleles confirmed the identification. Vps17p and Vps5p are part of a complex involved in sorting of vacuolar proteins in yeast and regulation of cell-surface receptors in mammals. Protease zymograms indicate that mutations in sogA-C permit secretion of intracellular proteases, as in S. cerevisiae vps5 and vps17 mutants. In contrast to S. cerevisiae, the production of intracellular protease was much higher in the mutants. Analysis of serine protease gene expression suggests that an XprG-independent mechanism for regulation of extracellular protease gene expression in response to carbon starvation exists and is activated in the pseudorevertants.

Can in vitro metabolism-dependent covalent binding data distinguish hepatotoxic from nonhepatotoxic drugs? An analysis using human hepatocytes and liver S-9 fraction.

In vitro covalent binding studies in which xenobiotics are shown to undergo metabolism-dependent covalent binding to macromolecules have been commonly used to shed light on the biochemical mechanisms of xenobiotic-induced toxicity. In this paper, 18 drugs (nine hepatotoxins and nine nonhepatotoxins) were tested for their proclivity to demonstrate metabolism-dependent covalent binding to macromolecules in human liver S-9 fraction (9000 g supernatant) or human hepatocytes, as an extension to previous work that used human liver microsomes published in this journal [ Obach et al. ( 2008 ) Chem. Res. Toxicol. 21 , 1814 -1822 ]. In the S-9 fraction, seven out of the nine drugs in each category demonstrated some level of metabolism-dependent covalent binding. Inclusion of reduced glutathione, cofactors needed by conjugating enzymes, and other parameters (total daily dose and fraction of total intrinsic clearance comprised by covalent binding) improved the ability of the system to separate hepatotoxins from nonhepatotoxins to a limited extent. Covalent binding in human hepatocytes showed that six out of the nine hepatotoxins and four out of eight nonhepatotoxins demonstrated covalent binding. Taking into account estimates of total daily body burden of covalent binding from the hepatocyte data showed an improvement over other in vitro systems for distinguishing hepatotoxins from nonhepatotoxins; however, this metabolism system still displayed some false positives. Combined with the previous study using liver microsomes, these findings identify the limitations of in vitro covalent binding data for prospective prediction of hepatotoxicity for new drug candidates and highlight the need for a better understanding of the link between drug bioactivation, covalent adduct formation, and toxicity outcomes. Directly relating covalent binding to hepatotoxicity is likely an oversimplification of the process whereby adduct formation ultimately leads to toxicity. Understanding underlying complexities (e.g., which macromolecules are important covalent binding targets, interindividual differences in susceptibility, etc.) will be essential to any understanding of the problem of metabolism-dependent hepatotoxicity and predicting toxicity from in vitro experiments.

Agreement is very low between a clinical prediction rule and physiotherapist assessment for classifying the risk of poor recovery of individuals with acute whiplash injury.

BACKGROUND: A prognostic clinical prediction rule (whiplash CPR) has been validated for use in individuals with acute whiplash associated disorders (WAD). The clinical utility of this tool is unknown. OBJECTIVES: To investigate: 1) the level of agreement between physiotherapist- and whiplash CPR-determined prognostic risk classification of people with acute WAD; 2) which clinical findings are used by physiotherapists to classify prognostic risk; and 3) whether physiotherapists plan to differ the number of treatment sessions provided based on prognostic risk classification. DESIGN: Pragmatic, observational. METHOD: 38 adults with acute WAD were classified as low, medium, or high risk of poor recovery by their treating physiotherapist (n = 24) at the conclusion of the initial consultation. A weighted Cohen's kappa examined the agreement between physiotherapist estimated risk classification and the whiplash CPR. Physiotherapists' reasons for classification were provided and summarised descriptively. Kruskal-Wallis and post-hoc Dunn's tests compared projected number of treatment sessions between risk subgroups. RESULTS: Physiotherapist agreement with the whiplash CPR occurred in 29% of cases (n = 11/38), which was less than what is expected by chance (K = -0.03; 95%CI -0.17 to 0.12). Physiotherapists most frequently considered range of movement (n = 23/38, 61%), a premorbid pain condition (n = 14/38, 37%), response to initial physiotherapy treatment (n = 12/38, 32%), and pain intensity (n = 12/38, 32%) when classifying prognostic risk. The projected number of treatment sessions was not different between risk groups using classifications provided by the physiotherapists (χ2(2) = 2.69, p = 0.26). CONCLUSIONS: Physiotherapists should consider incorporating the whiplash CPR into current assessment processes to enhance accuracy in prognostic decision-making.

An Interactive Website for Whiplash Management (My Whiplash Navigator): Process Evaluation of Design and Implementation.

BACKGROUND: Whiplash is a health and economic burden worldwide. Contributing to this burden is poor guideline adherence and variable management by health care professionals (HCPs). Web-based tools that facilitate clinical pathways of care are an innovative solution to improve management. OBJECTIVE: The study aimed to develop, implement, and evaluate a Web-based tool to support whiplash management following a robust process. METHODS: This study followed the first 3 processes of a research translation framework (idea generation, feasibility, and efficacy) to inform the development, implementation, and evaluation of a website that supports HCPs in whiplash management. Development followed the idea generation and feasibility processes to inform the content, design, features, and functionality of the website. This involved stakeholder (eg, industry partners, website developers, and HCPs) consultations through face-to-face meetings, surveys, and focus group discussions. Implementation followed the feasibility process to determine the practicality of the website for clinical use and the most effective strategy to promote wider uptake. Implementation strategies included classroom education, educational meetings, educational outreach, reminders, and direct phone contact. The analysis of website use and practicality of implementation involved collection of website metrics. Evaluation followed the feasibility and efficacy processes to investigate the acceptability and extent to which the website assisted HCPs in gaining knowledge about whiplash management. Surveys were conducted among student, primary, and specialist HCPs to explore ease of access, use, and satisfaction with the website, as well as self-rated improvements in knowledge of risk assessment, management, and communication between HCPs. Website logs of specialist management decisions (eg, shared care, specialist care, and referred care) were also obtained to determine actual practice. RESULTS: The development process delivered an interactive, user-friendly, and acceptable website, My Whiplash Navigator, tailored to the needs of HCPs. A total of 260 registrations were recorded from June 2016 to March 2018, including 175 student, 65 primary, and 20 specialist HCPs. The most effective implementation strategies were classroom education for students (81% uptake, 175/215) and educational meetings for primary HCPs (43% uptake, 47/110). Popular pages visited included advice and exercises and risk assessment. Most HCPs agreed that their knowledge about risk management (79/97, 81%) and exercises (85/97, 88%) improved. The specialists' most common management decision was shared care, an improvement from a previous cohort. Areas to improve were navigation and access to outcome measures. CONCLUSIONS: A robust process resulted in an innovative, interactive, user-friendly, and acceptable website, the My Whiplash Navigator. Implementation with HCPs was best achieved through classroom education and educational meetings. Evaluation of the website showed improved knowledge and practice to be more consistent with a risk-based clinical care pathway for whiplash. The positive results provide sufficient evidence to scale implementation nationally and involve other target markets such as people with whiplash, insurers, and insurance regulators.

CreA-mediated repression in Aspergillus nidulans does not require transcriptional auto-regulation, regulated intracellular localisation or degradation of CreA.

The major regulatory protein in carbon repression in Aspergillus nidulans is CreA. Strains constitutively over-expressing creA show normal responses to carbon repression, indicating that auto-regulation of creA is not essential for CreA-mediated regulation. In these strains, high levels of CreA are present whether cells are grown in repressing or derepressing conditions, indicating large-scale degradation of CreA does not play a key role. CreA is located in the nucleus and cytoplasm in cells when grown in either repressing or derepressing conditions, and absence of CreB, CreD or AcrB does not affect either the localisation or amount of CreA. Therefore, CreA must require some modification or interaction to act as a repressor. Deletion analysis indicates that a region of CreA thought to be important for repression in Trichoderma reesei and Sclerotina sclerotiorum CreA homologues is not critical for function in Aspergillus nidulans.

Production of L(+)-lactic acid using acid-adapted precultures of Rhizopus arrhizus in a stirred tank reactor.

Cultivations of filamentous fungi in stirred tank reactors (STRs) to produce metabolites are often limited by insufficient mixing and mass transfer because of the formation of mycelial clumps inside the reactors. This study developed an acid-adapted preculture approach to control the morphology of filamentous Rhizopus arrhizus in a STR, consequently to enhance the production yield and productivity of L(+)-lactic acid efficiently using waste potato starch as substrate. Using the acid-adapted precultures as inoculum, the morphology of R. arrhizus was maintained as large clumps, coalesced loose small pellets, and freely dispersed small pellets. The highest lactic acid concentration of 85.7 g/L with a yield of 86% was obtained in association with the formation of coalesced loose small pellets. The results indicate that the use of the acid-adapted precultures as inoculum is a promising approach for lactic acid production in STRs.