The relationship between chronic type III acromioclavicular joint dislocation and cervical spine pain

<p>Abstract</p> <p>Background</p> <p>This study was aimed at evaluating whether or not patients with chronic type III acromioclavicular dislocation develop cervical spine pain and degenerative changes more frequently than normal subjects.</p> <p>Methods</p> <p>The cervical spine of 34 patients with chronic type III AC dislocation was radiographically evaluated. Osteophytosis presence was registered and the narrowing of the intervertebral disc and cervical lordosis were evaluated. Subjective cervical symptoms were investigated using the Northwick Park Neck Pain Questionnaire (NPQ). One-hundred healthy volunteers were recruited as a control group.</p> <p>Results</p> <p>The rate and distribution of osteophytosis and narrowed intervertebral disc were similar in both of the groups. Patients with chronic AC dislocation had a lower value of cervical lordosis. NPQ score was 17.3% in patients with AC separation (100% = the worst result) and 2.2% in the control group (p < 0.05). An inverse significant nonparametric correlation was found between the NPQ value and the lordosis degree in the AC dislocation group (p = 0.001) wheras results were not correlated (p = 0.27) in the control group.</p> <p>Conclusions</p> <p>Our study shows that chronic type III AC dislocation does not interfere with osteophytes formation or intervertebral disc narrowing, but that it may predispose cervical hypolordosis. The higher average NPQ values were observed in patients with chronic AC dislocation, especially in those that developed cervical hypolordosis.</p

Central Role of SREBP-2 in the Pathogenesis of Osteoarthritis

Background: Recent studies have implied that osteoarthritis (OA) is a metabolic disease linked to deregulation of genes involved in lipid metabolism and cholesterol efflux. Sterol Regulatory Element Binding Proteins (SREBPs) are transcription factors regulating lipid metabolism with so far no association with OA. Our aim was to test the hypothesis that SREBP-2, a gene that plays a key role in cholesterol homeostasis, is crucially involved in OA pathogenesis and to identify possible mechanisms of action. Methodology/Principal Findings: We performed a genetic association analysis using a cohort of 1,410 Greek OA patients and healthy controls and found significant association between single nucleotide polymorphism (SNP) 1784G>C in SREBP-2 gene and OA development. Moreover, the above SNP was functionally active, as normal chondrocytes’ transfection with SREBP-2-G/C plasmid resulted in interleukin-1β and metalloproteinase-13 (MMP-13) upregulation. We also evaluated SREBP-2, its target gene 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR), phospho-phosphoinositide3-kinase (PI3K), phospho-Akt, integrin-alphaV (ITGAV) and transforming growth factor-$\beta$ (TGF-$\beta$) mRNA and protein expression levels in osteoarthritic and normal chondrocytes and found that they were all significantly elevated in OA chondrocytes. To test whether TGF-$\beta$ alone can induce SREBP-2, we treated normal chondrocytes with TGF-$\beta$ and found significant upregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13. We also showed that TGF-$\beta$ activated aggrecan (ACAN) in chondrocytes only through Smad3, which interacts with SREBP-2. Finally, we examined the effect of an integrin inhibitor, cyclo-RGDFV peptide, on osteoarthritic chondrocytes, and found that it resulted in significant upregulation of ACAN and downregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13 expression levels. Conclusions/Significance: We demonstrated, for the first time, the association of SREBP-2 with OA pathogenesis and provided evidence on the molecular mechanism involved. We suggest that TGF-$\beta$ induces SREBP-2 pathway activation through ITGAV and PI3K playing a key role in OA and that integrin blockage may be a potential molecular target for OA treatment

Efficacy of intra-articular hyaluronan (Synvisc®) for the treatment of osteoarthritis affecting the first metatarsophalangeal joint of the foot (hallux limitus): study protocol for a randomised placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis of the first metatarsophalangeal joint (MPJ) of the foot, termed <it>hallux limitus</it>, is common and painful. Numerous non-surgical interventions have been proposed for this disorder, however there is limited evidence for their efficacy. Intra-articular injections of hyaluronan have shown beneficial effects in case-series and clinical trials for the treatment of osteoarthritis of the first metatarsophalangeal joint. However, no study has evaluated the efficacy of this form of treatment using a randomised placebo controlled trial. This article describes the design of a randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc^®) to reduce pain and improve function in people with hallux limitus.</p> <p>Methods</p> <p>One hundred and fifty community-dwelling men and women aged 18 years and over with hallux limitus (who satisfy inclusion and exclusion criteria) will be recruited.</p> <p>Participants will be randomised, using a computer-generated random number sequence, to receive a single intra-articular injection of up to 1 ml hyaluronan (Synvisc^®) or sterile saline (placebo) into the first MPJ. The injections will be performed by an interventional radiologist using fluoroscopy to ensure accurate deposition of the hyaluronan in the joint. Participants will be given the option of a second and final intra-articular injection (of Synvisc^®or sterile saline according to the treatment group they are in) either 1 or 3 months post-treatment if there is no improvement in pain and the participant has not experienced severe adverse effects after the first injection. The primary outcome measures will be the pain and function subscales of the Foot Health Status Questionnaire. The secondary outcome measures will be pain at the first MPJ (during walking and at rest), stiffness at the first MPJ, passive non-weightbearing dorsiflexion of the first MPJ, plantar flexion strength of the toe-flexors of the hallux, global satisfaction with the treatment, health-related quality of life (assessed using the Short-Form-36 version two questionnaire), magnitude of symptom change, use of pain-relieving medication and changes in dynamic plantar pressure distribution (maximum force and peak pressure) during walking. Data will be collected at baseline, then 1, 3 and 6 months post-treatment. Data will be analysed using the intention to treat principle.</p> <p>Discussion</p> <p>This study is the first randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc^®) for the treatment of osteoarthritis of the first MPJ (hallux limitus). The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if this form of treatment is found to be an effective treatment strategy.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry: ACTRN12607000654459</p

MOOD 2020: A public Benchmark for Out-of-Distribution Detection and Localization on medical Images

Detecting Out-of-Distribution (OoD) data is one of the greatest challenges in safe and robust deployment of machine learning algorithms in medicine. When the algorithms encounter cases that deviate from the distribution of the training data, they often produce incorrect and over-confident predictions. OoD detection algorithms aim to catch erroneous predictions in advance by analysing the data distribution and detecting potential instances of failure. Moreover, flagging OoD cases may support human readers in identifying incidental findings. Due to the increased interest in OoD algorithms, benchmarks for different domains have recently been established. In the medical imaging domain, for which reliable predictions are often essential, an open benchmark has been missing. We introduce the Medical-Out-Of-Distribution-Analysis-Challenge (MOOD) as an open, fair, and unbiased benchmark for OoD methods in the medical imaging domain. The analysis of the submitted algorithms shows that performance has a strong positive correlation with the perceived difficulty, and that all algorithms show a high variance for different anomalies, making it yet hard to recommend them for clinical practice. We also see a strong correlation between challenge ranking and performance on a simple toy test set, indicating that this might be a valuable addition as a proxy dataset during anomaly detection algorithm development

How the ear tunes in to sounds: a physics approach

Listening is a complex sound selection process thought to be located in the auditory cortex. A biophysically motivated Hopf model of the mammalian cochlea reveals that pitch, a main characteristic in the perception of sound, is already materialized at the level of the mammalian hearing sensor. Here, we provide evidence that major elements of listening may similarly be implemented at the auditory periphery by means of efferent connections to the cochlea that tune the hearing sensor towards an auditory object of interest. The cochlea model we use in our investigations is advocated by its performance quality, the simplicity by which efferent control can be implemented, and by the closeness of the control results compared to the biological data. We tune the Hopf parameters to target on a sound, using pitch as the guiding feature. How well we achieve our goal is tested on real-world sounds and measured by a specifically developed tuning-error measure. The results provide a first estimate of how much the peripheral hearing system can assist a listener in focusing on an auditory signal and, thus, what is contributed by the auditory cortex

Beyond scale-free small-world networks: Cortical columns for quick brains

We study to what extent cortical columns with their particular wiring boost neural computation. Upon a vast survey of columnar networks performing various real-world cognitive tasks, we detect no signs of enhancement. It is on a mesoscopic—intercolumnar—scale that the existence of columns, largely irrespective of their inner organization, enhances the speed of information transfer and minimizes the total wiring length required to bind distributed columnar computations towards spatiotemporally coherent results. We suggest that brain efficiency may be related to a doubly fractal connectivity law, resulting in networks with efficiency properties beyond those by scale-free networks

Increased Neural Activity in Mesostriatal Regions after Prefrontal Transcranial Direct Current Stimulation and L-DOPA Administration

Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n = 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (l-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n = 22) and compared the results between both studies. We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS- and l-DOPA-induced activation, and >100 neuronal receptor gene expression maps based on transcriptional data from the Allen Institute for Brain Science. In line with a specific activation of the dopaminergic system, we found that both interventions predominantly activated regions with high expression levels of the dopamine receptors D2 and D3