Do physical interventions improve outcomes following concussion : A systematic review and meta-analysis?

Objective To investigate the effect of physical interventions (subthreshold aerobic exercise, cervical, vestibular and/or oculomotor therapies) on days to recovery and symptom scores in the management of concussion. Design A systematic review and meta-analysis. Data sources Medline, CINAHL, Embase, SportDiscus, Cochrane library, Scopus and PEDro. Eligibility criteria Randomised controlled trials of participants with concussion that evaluated the effect of subthreshold aerobic exercise, cervical, vestibular and/or oculomotor therapies on days to recovery/return to activity, symptom scores, balance, gait and/or exercise capacity. Results Twelve trials met the inclusion criteria: 7 on subthreshold aerobic exercise, 1 on vestibular therapy, 1 on cervical therapy and 3 on individually tailored multimodal interventions. The trials were of fair to excellent quality on the PEDro scale. Eight trials were included in the quantitative analysis. Subthreshold aerobic exercise had a significant small to moderate effect in improving symptom scores (standardised mean difference (SMD)=0.43, 95% CI 0.18 to 0.67, p=0.001, I2=0%) but not in reducing days to symptom recovery in both acutely concussed individuals and those with persistent symptoms (SMD=0.19, 95% CI −0.54 to 0.93, p=0.61, I2=52%). There was limited evidence for stand-alone cervical, vestibular and oculomotor therapies. Concussed individuals with persistent symptoms (>2 weeks) were approximately 3 times more likely to have returned to sport by 8 weeks (relative risk=3.29, 95% CI 0.30 to 35.69, p=0.33, I2=83%) if they received individually tailored, presentation-specific multimodal interventions (cervical, vestibular and oculo-motor therapy). In addition, the multimodal interventions had a moderate effect in improving symptom scores (SMD=0.63, 95% CI 0.11 to 1.15, p=0.02, I2=0%) when compared with control. Conclusions Subthreshold aerobic exercise appears to lower symptom scores but not time to recovery in concussed individuals. Individually tailored multimodal interventions have a worthwhile effect in providing faster return to sport and clinical improvement, specifically in those with persistent symptoms. PROSPERO registration number CRD42020108117

Tension of the ulnar, median, and radial nerves during ulnar nerve neurodynamic testing : Observational cadaveric study

Background: The ulnar nerve upper limb neurodynamic test (ULNT3) uses upper limb positioning to investigate symptoms arising from the ulnar nerve. It is proposed to selectively increase tension of the nerve; however, this property of the test is not well established. Objective: The aim of this study was to determine the upper limb position that results in: (1) the greatest tension of the ulnar nerve and (2) the greatest difference in tension between the ulnar nerve and the other 2 major nerves of the upper limb: median and radial. Design: This was an observational cadaver study. Methods: Tension (in newtons) of the ulnar, median, and radial nerves was measured simultaneously using 3 buckle force transducers in 5 upper limb positions in 10 embalmed human cadavers (N=20 limbs). Repeated-measures analysis of variance (ANOVA) with Bonferroni post hoc tests determined differences in tension among nerves and among limb positions. Results: The addition of shoulder horizontal abduction (H.Abd; 12.62 N; 95% confidence interval [95% CI]=10.76, 14.47) and combined shoulder abduction and internal rotation (H.Abd+IR; 11.86 N; 95% CI=9.96, 13.77) to ULNT3 (scapular depression, shoulder abduction and external rotation, elbow flexion, forearm pronation, and wrist and finger extension) produced significantly greater ulnar nerve tension compared with the ULNT3 alone (8.71 N; 95% CI=7.25, 10.17). The ULNT3+H.Abd test demonstrated the greatest difference in tension among nerves (mean difference between ulnar and median nerves=11.87 N; 95% CI=9.80, 13.92; mean difference between ulnar and radial nerves=8.47 N; 95% CI=6.41, 10.53). Limitations: These results pertain only to the biomechanical plausibility of the ulnar nerve neurodynamic test and do not account for other factors that may affect the clinical application of this test. Conclusions: The ULNT3+H.Abd is a biomechanically plausible test for detecting peripheral neuropathic pain related to the ulnar nerve. In situations where the shoulder complex will not tolerate the combination of shoulder external rotation in abduction, performing upper limb neurodynamic tests with internal rotation instead of external rotation is a biomechanically plausible alternative

Efficacy of manual therapy treatments for people with cervicogenic dizziness and pain : Protocol of a randomised controlled trial

BACKGROUND: Cervicogenic dizziness is a disabling condition characterised by postural unsteadiness that is aggravated by cervical spine movements and associated with a painful and/or stiff neck. Two manual therapy treatments (Mulligan’s Sustained Natural Apophyseal Glides (SNAGs) and Maitland’s passive joint mobilisations) are used by physiotherapists to treat this condition but there is little evidence from randomised controlled trials to support their use. The aim of this study is to conduct a randomised controlled trial to compare these two forms of manual therapy (Mulligan glides and Maitland mobilisations) to each other and to a placebo in reducing symptoms of cervicogenic dizziness in the longer term and to conduct an economic evaluation of the interventions. METHODS: Participants with symptoms of dizziness described as imbalance, together with a painful and/or stiff neck will be recruited via media releases, advertisements and mail-outs to medical practitioners in the Hunter region of NSW, Australia. Potential participants will be screened by a physiotherapist and a neurologist to rule out other causes of their dizziness. Once diagnosed with cervciogenic dizziness, 90 participants will be randomly allocated to one of three groups: Maitland mobilisations plus range-of-motion exercises, Mulligan SNAGs plus self-SNAG exercises or placebo. Participants will receive two to six treatments over six weeks. The trial will have unblinded treatment but blinded outcome assessments. Assessments will occur at baseline, post-treatment, six weeks, 12 weeks, six months and 12 months post treatment. The primary outcome will be intensity of dizziness. Other outcome measures will be frequency of dizziness, disability, intensity of cervical pain, cervical range of motion, balance, head repositioning, adverse effects and treatment satisfaction. Economic outcomes will also be collected. DISCUSSION: This paper describes the methods for a randomised controlled trial to evaluate the effectiveness of two manual therapy techniques in the treatment of people with cervicogenic dizziness for which there is limited established evidence-based treatment. TRIAL REGISTRATION: ACTRN1261100007390

Evaluation of spontaneous generation of allelic variation in soybean in response to sexual hybridization and stress

Intra-cultivar variation reported in pure lines of soybean has been hypothesized to result from genetic mechanisms contributing to de novo genetic variation. In this study we have detected allele switching by following segregation pattern of Aconitase-4 isozyme in sexual crosses and pure lines. In sexual crosses, one F2 plant showed switch at the Aconitase- 4 (Aco4) locus from the expected heterozygous genotype Aco4-ac to Aco4-ab. In the pure lines grown in a honeycomb planting design and treated with an accelerated aging test, multiple cases of allele switching were detected at the Aco4 locus. Both single and double switches were detected that were stable and heritable. These findings indicate that the generation of endogenous variation continues in pure lines as a result of intrinsic genetic mechanisms. With a long-term goal of understanding the genetic nature of the changes, we genetically mapped the Aco4 gene to a 3.3 cM region on Chromosome 11. The corresponding physical region is ~293 kb with 39 predicated genes. Of these, Glyma.11g080600 is of particular interest, as it shows 93% and 88% identity to Medicago truncatula and Arabidopsis aconitase genes, respectively. Further characterization of the soybean Aco4 gene may shed light on genetic mechanisms responsible for allele switching

Sec24p and Sec16p cooperate to regulate the GTP cycle of the COPII coat

Vesicle budding from the endoplasmic reticulum (ER) employs a cycle of GTP binding and hydrolysis to regulate assembly of the COPII coat. We have identified a novel mutation (sec24‐m11) in the cargo‐binding subunit, Sec24p, that specifically impacts the GTP‐dependent generation of vesicles in vitro. Using a high‐throughput approach, we defined genetic interactions between sec24‐m11 and a variety of trafficking components of the early secretory pathway, including the candidate COPII regulators, Sed4p and Sec16p. We defined a fragment of Sec16p that markedly inhibits the Sec23p‐ and Sec31p‐stimulated GTPase activity of Sar1p, and demonstrated that the Sec24p‐m11 mutation diminished this inhibitory activity, likely by perturbing the interaction of Sec24p with Sec16p. The consequence of the heightened GTPase activity when Sec24p‐m11 is present is the generation of smaller vesicles, leading to accumulation of ER membranes and more stable ER exit sites. We propose that association of Sec24p with Sec16p creates a novel regulatory complex that retards the GTPase activity of the COPII coat to prevent premature vesicle scission, pointing to a fundamental role for GTP hydrolysis in vesicle release rather than in coat assembly/disassembly

Secondary school pupils' preferences for different types of structured grouping practices

The aim of this paper is to explore pupils’ preferences for particular types of grouping practices an area neglected in earlier research focusing on the personal and social outcomes of ability grouping. The sample comprised over 5,000 year 9 pupils (aged 13-14 years) in 45 mixed secondary comprehensive schools in England. The schools represented three levels of ability grouping in the lower school (years 7 to 9). Pupils responded to a questionnaire which explored the types of grouping that they preferred and the reasons for their choices. The majority of pupils preferred setting, although this was mediated by their set placement, type of school, socio-economic status and gender. The key reason given for this preference was that it enabled work to be matched to learning needs. The paper considers whether there are other ways of achieving this avoiding the negative social and personal outcomes of setting for some pupils

A phase 1b/pharmacokinetic trial of PTC299, a novel post-transcriptional VEGF inhibitor, for AIDS-related Kaposi’s sarcoma: AIDS Malignancy Consortium trial 059

Vascular endothelial growth factor (VEGF) plays an important role in Kaposi’s sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received three different doses of PTC299. Adverse events typically observed with VEGF-inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KSHV DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KSHV proliferation

Gene Co-Expression Network Analysis Identifies Vitamin D-Associated Gene Modules in Adult Normal Rectal Epithelium Following Supplementation

Colorectal cancer (CRC) is a common, multifactorial disease. While observational studies have identified an association between lower vitamin D and higher CRC risk, supplementation trials have been inconclusive and the mechanisms by which vitamin D may modulate CRC risk are not well understood. We sought to perform a weighted gene co-expression network analysis (WGCNA) to identify modules present after vitamin D supplementation (when plasma vitamin D level was sufficient) which were absent before supplementation, and then to identify influential genes in those modules. The transcriptome from normal rectal mucosa biopsies of 49 individuals free from CRC were assessed before and after 12 weeks of 3200IU/day vitamin D (Fultium-D3) supplementation using paired-end total RNAseq. While the effects on expression patterns following vitamin D supplementation were subtle, WGCNA identified highly correlated genes forming gene modules. Four of the 17 modules identified in the post-vitamin D network were not preserved in the pre-vitamin D network, shedding new light on the biochemical impact of supplementation. These modules were enriched for GO terms related to the immune system, hormone metabolism, cell growth and RNA metabolism. Across the four treatment-associated modules, 51 hub genes were identified, with enrichment of 40 different transcription factor motifs in promoter regions of those genes, including VDR:RXR. Six of the hub genes were nominally differentially expressed in studies of vitamin D effects on adult normal mucosa organoids: LCN2, HLA-C, AIF1L, PTPRU, PDE4B and IFI6. By taking a gene-correlation network approach, we have described vitamin D induced changes to gene modules in normal human rectal epithelium in vivo, the target tissue from which CRC develops