Evidence for cervical muscle morphometric changes on magnetic resonance images after whiplash: A systematic review and meta-analysis

INTRODUCTION Morphometric changes to cervical musculature in whiplash associated disorder have been reported in several studies with varying results. However, the evidence is not clear because only a limited number of cohorts have been studied and one cohort has been reported in multiple publications. The aim of this study was to assess the evidence for cervical muscle morphometric changes on magnetic resonance (MR) images after whiplash using a systematic review with meta-analysis. MATERIALS AND METHODS PubMed, MEDLINE and Cochrane Library were searched without language restriction using combinations of the MeSH terms "muscles", "whiplash injuries", and "magnetic resonance imaging". Studies of acute and chronic whiplash were included if they compared whiplash and control cervical spine muscle morphometry measurements from MR images. The search identified 380 studies. After screening, eight studies describing five cohorts (one acute, three chronic, one both acute and chronic) met the inclusion criteria. Participant characteristics and outcome measures were extracted using a standard extraction format. Quality of eligible studies was assessed using the Newcastle-Ottawa Scale. Muscle cross-sectional area (CSA) and fat infiltrate (MFI) for acute and chronic whiplash cohorts were compared using mean difference and 95% confidence intervals. Meta-analysis models were created when data from more than two eligible cohorts was available, using inverse-variance random-effects models (RevMan5 version 5.3.5). RESULTS Quality assessment was uniformly good but only two studies blinded the assessor. Analysis of the acute cohorts revealed no consensus with respect to CSA. MFI was not measured in the acute cohorts. Analysis of the chronic cohorts revealed CSA is probably increased in some muscles after whiplash but there is insufficient evidence to confirm whether MFI is also increased. Because the available data were limited, meta-analyses of only multifidus were performed. In chronic whiplash multifidus CSA was significantly increased at C5 (Z = 3.51, p < 0.01) and C6 (Z = 2.66, p < 0.01); and MFI was significantly increased at C7 only (Z = 2.52, p < 0.01) but the heterogeneity was unacceptably high (I2 = 83%). CONCLUSIONS The strength of the evidence for cervical muscle morphometric changes on MR images after whiplash is inconsistent for CSA and MFI. Future study designs should be standardised with quantification of three-dimensional muscle morphometry

The Impact of Depression, Anxiety and Personality Disorders on the Outcome of Patients with Functional Limb Weakness – Individual Patient Data Meta-Analysis

Objective: Psychiatric comorbidities such as depression, anxiety, and personality disorders are common in patients with functional limb weakness/paresis (FND-par). The impact of these conditions on the prognosis of FND-par has not been systematically reviewed. The aim of this study was to identify a potential prognostic effect of comorbid depression, anxiety, and/or personality disorder on prognosis in patients with FND-par. Methods: A systematic review was performed to identify studies that reported measures of baseline depression, anxiety, and/or personality disorder, and physical disability. An individual patient data meta-analysis was subsequently performed. Results: Eight studies comprising 348 individuals were included (7 prospective cohorts; 1 case-control study). There was heterogeneity in sample size, follow-up duration, and treatment modality. Depression and anxiety were present in 51.4% and 53.0% of FND-par patients, respectively. In individuals whose FND-par improved, there was no significant difference between those with versus without depression (52.6% vs 47.4%, p = 0.69) or those with versus without anxiety (50.3% vs 49.7%, p = 0.38). Meta-analysis showed no clear impact of baseline depression or anxiety per se [pooled OR for depression 0.85 (95%CI 0.50–1.45; p = 0.40) and anxiety 0.84 (95%CI 0.51–1.38; p = 0.91)]; and of depression or anxiety severity [pooled OR for depression 1.23 (95%CI 0.63–2.39; p = 0.91) and anxiety 1.40 (95%CI 0.70–2.78; p = 0.58)] on FND-par outcome. Insufficient data were available to assess the impact of personality disorders. Conclusion: We found no evidence that depression or anxiety influenced outcome in FND-par. Large-scale, prospective studies in FND-par, and other FND subtypes, are needed to fully contextualize the impact of concurrent mental health concerns on outcomes.</p

Effects of neuromuscular gait modification strategies on indicators of knee joint load in people with medial knee osteoarthritis:A systematic review and meta-analysis

OBJECTIVES: This systematic review aimed to determine the effects of neuromuscular gait modification strategies on indicators of medial knee joint load in people with medial knee osteoarthritis. METHODS: Databases (Embase, MEDLINE, Cochrane Central, CINAHL and PubMed) were searched for studies of gait interventions aimed at reducing medial knee joint load indicators for adults with medial knee osteoarthritis. Studies evaluating gait aids or orthoses were excluded. Hedges’ g effect sizes (ES) before and after gait retraining were estimated for inclusion in quality-adjusted meta-analysis models. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Seventeen studies (k = 17; n = 362) included two randomised placebo-controlled trials (RCT), four randomised cross-over trials, two case studies and nine cohort studies. The studies consisted of gait strategies of ipsilateral trunk lean (k = 4, n = 73), toe-out (k = 6, n = 104), toe-in (k = 5, n = 89), medial knee thrust (k = 3, n = 61), medial weight transfer at the foot (k = 1, n = 10), wider steps (k = 1, n = 15) and external knee adduction moment (KAM) biofeedback (k = 3, n = 84). Meta-analyses found that ipsilateral trunk lean reduced early stance peak KAM (KAM1, ES and 95%CI: -0.67, -1.01 to -0.33) with a dose-response effect and reduced KAM impulse (-0.37, -0.70 to -0.04) immediately after single-session training. Toe-out had no effect on KAM1 but reduced late stance peak KAM (KAM2; -0.42, -0.73 to -0.11) immediately post-training for single-session, 10 or 16-week interventions. Toe-in reduced KAM1 (-0.51, -0.81 to -0.20) and increased KAM2 (0.44, 0.04 to 0.85) immediately post-training for single-session to 6-week interventions. Visual, verbal and haptic feedback was used to train gait strategies. Certainty of evidence was very-low to low according to the GRADE approach. CONCLUSION: Very-low to low certainty of evidence suggests that there is a potential that ipsilateral trunk lean, toe-out, and toe-in to be clinically helpful to reduce indicators of medial knee joint load. There is yet little evidence for interventions over several weeks

Effect of Bioconjugation on the Reduction Potential of Heme Proteins

The modification of protein surfaces employing cationic and anionic species enables the assembly of these biomaterials into highly sophisticated hierarchical structures. Such modifications can allow bioconjugates to retain or amplify their functionalities under conditions in which their native structure would be severely compromised. In this work, we assess the effect of this type of bioconjugation on the redox properties of two model heme proteins, that is, cytochrome c (CytC) and myoglobin (Mb). In particular, the work focuses on the sequential modification by 3-dimethylamino propylamine (DMAPA) and 4-nonylphenyl 3-sulfopropyl ether (S1) anionic surfactant. Bioconjugation with DMAPA and S1 are the initial steps in the generation of pure liquid proteins, which remain active in the absence of water and up to temperatures above 150 °C. Thin-layer spectroelectrochemistry reveals that DMAPA cationization leads to a distribution of bioconjugate structures featuring reduction potentials shifted up to 380 mV more negative than the native proteins. Analysis based on circular dichroism, MALDI-TOF mass spectrometry, and zeta potential measurements suggest that the shift in the reduction potentials are not linked to protein denaturation, but to changes in the spin state of the heme. These alterations of the spin states originate from subtle structural changes induced by DMAPA attachment. Interestingly, electrostatic coupling of anionic surfactant S1 shifts the reduction potential closer to that of the native protein, demonstrating that the modifications of the heme electronic configuration are linked to surface charges

An Investigation of a Role for U2 snRNP Spliceosomal Components in Regulating Transcription

There is mounting evidence to suggest that the synthesis of pre-mRNA transcripts and their subsequent splicing are coordinated events. Previous studies have implicated the mammalian spliceosomal U2 snRNP as having a novel role in stimulating transcriptional elongation in vitro through interactions with the elongation factors P-TEFb and Tat-SF1; however, the mechanism remains unknown [1]. These factors are conserved in Saccharomyces cerevisiae, a fact that suggests that a similar interaction may occur in yeast to stimulate transcriptional elongation in vivo. To address this possibility we have looked for evidence of a role for the yeast Tat-SF1 homolog, Cus2, and the U2 snRNA in regulating transcription. Specifically, we have performed a genetic analysis to look for functional interactions between Cus2 or U2 snRNA and the P-TEFb yeast homologs, the Bur1/2 and Ctk1/2/3 complexes. In addition, we have analyzed Cus2-deleted or -overexpressing cells and U2 snRNA mutant cells to determine if they show transcription-related phenotypes similar to those displayed by the P-TEFb homolog mutants. In no case have we been able to observe phenotypes consistent with a role for either spliceosomal factor in transcription elongation. Furthermore, we did not find evidence for physical interactions between the yeast U2 snRNP factors and the P-TEFb homologs. These results suggest that in vivo, S. cerevisiae do not exhibit functional or physical interactions similar to those exhibited by their mammalian counterparts in vitro. The significance of the difference between our in vivo findings and the previously published in vitro results remains unclear; however, we discuss the potential importance of other factors, including viral proteins, in mediating the mammalian interactions

Hydrogel-immobilized supercharged proteins

The remarkable catalytic potential of enzymes in chemical synthesis, environ-mental bioremediation, and medical therapeutics is limited by their longevity and stability. Immobilization of enzymes on solid supports is demonstrated to improve the stability of biocatalysts but often relies on multiple chemical steps for covalent attachment and is limited by the physical properties of the various supports. Here, production of enzyme: hydrogel complexes is described via engineering of a cationic supercharged phosphotriesterase. These enzyme: hydrogel complexes are remarkably robust displaying no loss of catalytic activity after 80 d of use and up to 105 turnovers when used in a flow reactor at catalyst loadings as low as 0.0008 mol%. In addition, exceptional resilience to organic solvents is observed. The use of enzyme: hydrogel complexes is likely to be of value in a diverse range of applications such as enantioselective continuous-flow chemistry, detoxification of poisons, and the formation of functionalized biomaterials

Breaking Up the C Complex Spliceosome Shows Stable Association of Proteins with the Lariat Intron Intermediate

Spliceosome assembly requires several structural rearrangements to position the components of the catalytic core. Many of these rearrangements involve successive strengthening and weakening of different RNA∶RNA and RNA∶proteins interactions within the complex. To gain insight into the organization of the catalytic core of the spliceosome arrested between the two steps of splicing chemistry (C complex), we investigated the effects of exposing C complex to low concentrations of urea. We find that in the presence of 3M urea C complex separates into at least three sub-complexes. One sub-complex contains the 5′exon, another contains the intron-lariat intermediate, and U2/U5/U6 snRNAs likely comprise a third sub-complex. We purified the intron-lariat intermediate sub-complex and identified several proteins, including U2 snRNP and PRP19 complex (NTC) components. The data from our study indicate that U2 snRNP proteins in C complex are more stably associated with the lariat-intron intermediate than the U2 snRNA. The results also suggest a set of candidate proteins that hold the lariat-intron intermediate together in C complex. This information is critical for further interpreting the complex architecture of the mammalian spliceosome