Reliability of knee joint position sense measurement: a comparison between goniometry and image capture methods

Aims: Evaluate the intra-rater and inter-rater reliability of hand-held goniometry compared to image capture (IMC) in the assessment of joint position sense (JPS) in healthy participants. Methodology: Repeated-measures observational study design was undertaken with 36 asymptomatic university students of both genders aged between 18 to 45 years. JPS in the knee was assessed by two assessors over two sessions (one-week interval) using hand-held goniometry and IMC methods. Joint position sense was assessed at four target knee flexion angles. Intra- and inter-rater reliability was assessed with absolute error (AE), relative error (RE) and intra-class correlation coefficient. Findings: Inter-rater reliability for goniometry was poor to substantial (ICC: 0.00 to 0.64) and was poor to moderate (ICC: 0.00 to 0.47) for IMC. Intra-rater reliability for goniometry was poor to moderate (ICC: 0.00 to 0.42) and poor to moderate for IMC (ICC: 0.00 to 0.41). AE for goniometry ranged from 3.2° to 8.6°, with RE from 0.1°-8.3°. For IMC, AE for goniometry was 5.3° to 12.5°, with RE ranging from 0.1° to 11.1°. Principal Conclusions: Neither goniometry nor IMC appeared superior to the other in JPS assessment. Caution should be made when considering the reliability for goniometry and IMC before clinical assessment is made

Auditory Function in the Tc1 Mouse Model of Down Syndrome Suggests a Limited Region of Human Chromosome 21 Involved in Otitis Media

Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21) in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR) measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs) were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K+ currents characteristic of control hair cells. However, the size of the large conductance (BK) Ca2+ activated K+ current (IK,f), which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active

Neuromuscular training to enhance sensorimotor and functional deficits in subjects with chronic ankle instability: A systematic review and best evidence synthesis

<p>Abstract</p> <p>Objective</p> <p>To summarise the available evidence for the efficacy of neuromuscular training in enhancing sensorimotor and functional deficits in subjects with chronic ankle instability (CAI).</p> <p>Design</p> <p>Systematic review with best evidence synthesis.</p> <p>Data Sources</p> <p>An electronic search was conducted through December 2009, limited to studies published in the English language, using the Pubmed, CINAHL, Embase, and SPORTDiscus databases. Reference screening of all included articles was also undertaken.</p> <p>Methods</p> <p>Studies were selected if the design was a RCT, quasi RCT, or a CCT; the patients were adolescents or adults with confirmed CAI; and one of the treatment options consisted of a neuromuscular training programme. The primary investigator independently assessed the risk of study bias and extracted relevant data. Due to clinical heterogeneity, data was analysed using a best-evidence synthesis.</p> <p>Results</p> <p>Fourteen studies were included in the review. Meta-analysis with statistical pooling of data was not possible, as the studies were considered too heterogeneous. Instead a best evidence synthesis was undertaken. There is limited to moderate evidence to support improvements in dynamic postural stability, and patient perceived functional stability through neuromuscular training in subjects with CAI. There is limited evidence of effectiveness for neuromuscular training for improving static postural stability, active and passive joint position sense (JPS), isometric strength, muscle onset latencies, shank/rearfoot coupling, and a reduction in injury recurrence rates. There is limited evidence of no effectiveness for improvements in muscle fatigue following neuromuscular intervention.</p> <p>Conclusion</p> <p>There is limited to moderate evidence of effectiveness in favour of neuromuscular training for various measures of static and dynamic postural stability, active and passive JPS, isometric strength, muscle onset latencies, shank/rearfoot coupling and injury recurrence rates. Strong evidence of effectiveness was lacking for all outcome measures. All but one of the studies included in the review were deemed to have a high risk of bias, and most studies were lacking sufficient power. Therefore, in future we recommend conducting higher quality RCTs using appropriate outcomes to assess for the effectiveness of neuromuscular training in overcoming sensorimotor deficits in subjects with CAI.</p

Improving Coping Skills for Self-management of Treatment Side Effects Can Reduce Antiretroviral Medication Nonadherence among People Living with HIV

BackgroundHuman immunodeficiency virus (HIV) treatment side effects have a deleterious impact on treatment adherence, which is necessary to optimize treatment outcomes including morbidity and mortality.PurposeTo examine the effect of the Balance Project intervention, a five-session, individually delivered HIV treatment side effects coping skills intervention on antiretroviral medication adherence.MethodsHIV+ men and women (N = 249) on antiretroviral therapy (ART) with self-reported high levels of ART side effect distress were randomized to intervention or treatment as usual. The primary outcome was self-reported ART adherence as measured by a combined 3-day and 30-day adherence assessment.ResultsIntent-to-treat analyses revealed a significant difference in rates of nonadherence between intervention and control participants across the follow-up time points such that those in the intervention condition were less likely to report nonadherence. Secondary analyses revealed that intervention participants were more likely to seek information about side effects and social support in efforts to cope with side effects.ConclusionsInterventions focusing on skills related to ART side-effects management show promise for improving ART adherence among persons experiencing high levels of perceived ART side effects

The epigenetic regulator Histone Deacetylase 1 promotes transcription of a core neurogenic programme in zebrafish embryos

<p>Abstract</p> <p>Background</p> <p>The epigenetic regulator Histone Deacetylase 1 (Hdac1) is required for specification and patterning of neurones and myelinating glia during development of the vertebrate central nervous system (CNS). This co-ordinating function for Hdac1 is evolutionarily conserved in zebrafish and mouse, but the mechanism of action of Hdac1 in the developing CNS is not well-understood.</p> <p>Results</p> <p>A genome-wide comparative analysis of the transcriptomes of Hdac1-deficient and wild-type zebrafish embryos was performed, which identified an extensive programme of gene expression that is regulated by Hdac1 in the developing embryo. Using time-resolved expression profiling of embryos, we then identified a small subset of 54 genes within the Hdac1-regulated transcriptome that specifically exhibit robust and sustained Hdac1-dependent expression from early neurogenesis onwards. 18 of these 54 stringently Hdac1-regulated genes encode DNA-binding transcription factors that are implicated in promoting neuronal specification and CNS patterning, including the proneural bHLH proteins Ascl1a and Ascl1b, as well as Neurod4 and Neurod. Relatively few genes are strongly repressed by Hdac1 but expression of the Notch target gene <it>her6 </it>is attenuated by Hdac1 in specific sub-regions of the developing CNS, from early stages of neurogenesis onwards. Selected members of the stringently Hdac1-regulated group of genes were tested for Hdac1 binding to their promoter-proximal <it>cis</it>-regulatory elements. Surprisingly, we found that Hdac1 is specifically and stably associated with DNA sequences within the promoter region of <it>ascl1b </it>during neurogenesis, and that this Hdac1-<it>ascl1b </it>interaction is abolished in <it>hdac1 </it>mutant embryos.</p> <p>Conclusions</p> <p>We conclude that Hdac1 regulates histone acetylation and methylation in the developing zebrafish embryo and promotes the sustained, co-ordinate transcription of a small set of transcription factor genes that control expansion and diversification of cell fates within the developing CNS. Our <it>in vivo </it>chromatin immunoprecipitation results also suggest a specific function for Hdac1 in directly regulating transcription of a key member of this group of genes, <it>ascl1b</it>, from the beginning of neurogenesis onwards. Taken together, our observations indicate a novel role for Hdac1 as a positive regulator of gene transcription during development of the vertebrate CNS, in addition to its more well-established function in transcriptional repression.</p

Fix Your Eyes in the Space You Could Reach: Neurons in the Macaque Medial Parietal Cortex Prefer Gaze Positions in Peripersonal Space

Interacting in the peripersonal space requires coordinated arm and eye movements to visual targets in depth. In primates, the medial posterior parietal cortex (PPC) represents a crucial node in the process of visual-to-motor signal transformations. The medial PPC area V6A is a key region engaged in the control of these processes because it jointly processes visual information, eye position and arm movement related signals. However, to date, there is no evidence in the medial PPC of spatial encoding in three dimensions. Here, using single neuron recordings in behaving macaques, we studied the neural signals related to binocular eye position in a task that required the monkeys to perform saccades and fixate targets at different locations in peripersonal and extrapersonal space. A significant proportion of neurons were modulated by both gaze direction and depth, i.e., by the location of the foveated target in 3D space. The population activity of these neurons displayed a strong preference for peripersonal space in a time interval around the saccade that preceded fixation and during fixation as well. This preference for targets within reaching distance during both target capturing and fixation suggests that binocular eye position signals are implemented functionally in V6A to support its role in reaching and grasping

“Biological Geometry Perception”: Visual Discrimination of Eccentricity Is Related to Individual Motor Preferences

In the continuum between a stroke and a circle including all possible ellipses, some eccentricities seem more “biologically preferred” than others by the motor system, probably because they imply less demanding coordination patterns. Based on the idea that biological motion perception relies on knowledge of the laws that govern the motor system, we investigated whether motorically preferential and non-preferential eccentricities are visually discriminated differently. In contrast with previous studies that were interested in the effect of kinematic/time features of movements on their visual perception, we focused on geometric/spatial features, and therefore used a static visual display.In a dual-task paradigm, participants visually discriminated 13 static ellipses of various eccentricities while performing a finger-thumb opposition sequence with either the dominant or the non-dominant hand. Our assumption was that because the movements used to trace ellipses are strongly lateralized, a motor task performed with the dominant hand should affect the simultaneous visual discrimination more strongly. We found that visual discrimination was not affected when the motor task was performed by the non-dominant hand. Conversely, it was impaired when the motor task was performed with the dominant hand, but only for the ellipses that we defined as preferred by the motor system, based on an assessment of individual preferences during an independent graphomotor task.Visual discrimination of ellipses depends on the state of the motor neural networks controlling the dominant hand, but only when their eccentricity is “biologically preferred”. Importantly, this effect emerges on the basis of a static display, suggesting that what we call “biological geometry”, i.e., geometric features resulting from preferential movements is relevant information for the visual processing of bidimensional shapes

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands