DEP domains: structurally similar but functionally different.

The Dishevelled, EGL-10 and pleckstrin (DEP) domain is a globular protein domain that is present in about ten human protein families with well-defined structural features. A picture is emerging that DEP domains mainly function in the spatial and temporal control of diverse signal transduction events by recruiting proteins to the plasma membrane. DEP domains can interact with various partners at the membrane, including phospholipids and membrane receptors, and their binding is subject to regulation.

Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography (ECoG) and subthalamic local field potential (LFP) recordings were performed OFF therapy (N = 22), ON dopaminergic medication (N = 18) and ON subthalamic deep brain stimulation (N = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography (EMG). In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.

Baseline clinical and MRI risk factors for hamstring reinjury showing the value of performing baseline MRI and delaying return to play: a multicentre, prospective cohort of 330 acute hamstring injuries.

OBJECTIVES: Studies identifying clinical and MRI reinjury risk factors are limited by relatively small sample sizes. This study aimed to examine the association between baseline clinical and MRI findings with the incidence of hamstring reinjuries using a large multicentre dataset. METHODS: We merged data from four prospective studies (three randomised controlled trials and one ongoing prospective case series) from Qatar and the Netherlands. Inclusion criteria included patients with MRI-confirmed acute hamstring injuries (<7 days). We performed multivariable modified Poisson regression analysis to assess the association of baseline clinical and MRI data with hamstring reinjury incidence within 2 months and 12 months of follow-up. RESULTS: 330 and 308 patients were included in 2 months (31 (9%) reinjuries) and 12 months (52 (17%) reinjuries) analyses, respectively. In the 2-month analysis, the presence of discomfort during the active knee extension test was associated with reinjury risk (adjusted risk ratio (ARR) 3.38; 95% CI 1.19 to 9.64). In the 12 months analysis, the time to return to play (RTP) (ARR 0.99; 95% CI 0.97 to 1.00), straight leg raise angle on the injured leg (ARR 0.98; 95% CI 0.96 to 1.00), the presence of discomfort during active knee extension test (ARR 2.52; 95% CI 1.10 to 5.78), the extent of oedema anteroposterior on MRI (ARR 0.74; 95% CI 0.57 to 0.96) and myotendinous junction (MTJ) involvement on MRI (ARR 3.10; 95% CI 1.39 to 6.93) were independently associated with hamstring reinjury. CONCLUSIONS: Two clinical findings (the presence of discomfort during active knee extension test, lower straight leg raise angle on the injured leg), two MRI findings (less anteroposterior oedema, MTJ involvement) and shorter time to RTP were independently associated with increased hamstring reinjury risk. These findings may assist the clinician to identify patients at increased reinjury risk following acute hamstring injury. TRIAL REGISTRATION NUMBERS: NCT01812564; NCT02104258; NL2643; NL55671.018.16.

Acute clinical evaluation for the diagnosis of lateral ankle ligament injuries is useful: A comparison between the acute and delayed settings.

PURPOSE: To determine the diagnostic value of seven injury history variables, nine clinical tests (including the combination thereof) and overall clinical suspicion for complete discontinuity of the lateral ankle ligaments in the acute (0-2 days post-injury) and delayed setting (5-8 days post-injury). METHODS: All acute ankle injuries in adult athletes (≥18 years) presenting up to 2 days post-injury were assessed for eligibility. Athletes were excluded if imaging studies demonstrated a frank fracture or 3 T MRI could not be acquired within 10 days post-injury. Using standardized history variables and clinical tests, acute clinical evaluation was performed within 2 days post-injury. Delayed clinical evaluation was performed 5-8 days post-injury. Overall, clinical suspicion was recorded after clinical evaluation. MRI was used as the reference standard. RESULTS: Between February 2018 and February 2020, a total of 117 acute ankle injuries were screened for eligibility, of which 43 were included in this study. Complete discontinuity of lateral ankle ligaments was observed in 23 (53%) acute ankle injuries. In the acute setting, lateral swelling had 100% (95% confidence interval [CI]: 82-100) sensitivity, haematoma had 85% (95% CI: 61-96) specificity and the anterior drawer test had 100% (95% CI: 77-100) specificity. In the delayed setting, sensitivity for the presence of haematoma improved from 43% (95% CI: 24-65) to 91% (95% CI: 70-98; p < 0.01) and the sensitivity of the anterior drawer test improved from 21% (95% CI: 7-46) to 61% (95% CI: 39-80; p = 0.02). Clinical suspicion had a positive likelihood ratio (LR) of 4.35 (95% CI: 0.55-34.17) in the acute setting and a positive LR of 6.09 (95% CI: 1.57-23.60) in the delayed setting. CONCLUSIONS: In the acute setting, clinical evaluation can exclude complete discontinuity (e.g., absent lateral swelling) and identify athletes with a high probability of complete discontinuity (e.g., positive anterior drawer test) of the lateral ankle ligaments. In the delayed setting, the sensitivity of common clinical findings increases resulting in an improved diagnostic accuracy. In clinical practice, this study underlines the importance of meticulous clinical evaluation in the acute setting. LEVEL OF EVIDENCE: Level III.

A proteomics approach to identify COPD-related changes in lung fibroblasts.

Lung fibroblasts are implicated in abnormal tissue repair in chronic obstructive pulmonary disease (COPD). The exact mechanisms are unknown and comprehensive analysis comparing COPD- and control fibroblasts is lacking. The aim of this study is to gain insight into the role of lung fibroblasts in COPD pathology using unbiased proteomic and transcriptomic analysis. Protein and RNA were isolated from cultured parenchymal lung fibroblasts of 17 patients with stage IV COPD and 16 non-COPD controls. Proteins were analyzed using LC-MS/MS and RNA through RNA sequencing. Differential protein and gene expression in COPD was assessed via linear regression, followed by pathway enrichment, correlation analysis, and immunohistological staining in lung tissue. Proteomic and transcriptomic data were compared to investigate the overlap and correlation between both levels of data. We identified 40 differentially expressed (DE) proteins and zero DE genes between COPD and control fibroblasts. The most significant DE proteins were HNRNPA2B1 and FHL1. Thirteen of the 40 proteins were previously associated with COPD, including FHL1 and GSTP1. Six of the 40 proteins were related to telomere maintenance pathways, and were positively correlated with the senescence marker LMNB1. No significant correlation between gene and protein expression was observed for the 40 proteins. We hereby describe 40 DE proteins in COPD fibroblasts including previously described COPD proteins (FHL1, GSTP1) and new COPD research targets like HNRNPA2B1. Lack of overlap and correlation between gene and protein data supports the use of unbiased proteomics analysis and indicates that different types of information are generated with both methods.

Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up.

Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.

Emerging Quantitative Imaging Techniques in Sports Medicine.

This article describes recent advances in quantitative imaging of musculoskeletal extremity sports injuries, citing the existing literature evidence and what additional evidence is needed to make such techniques applicable to clinical practice. Compositional and functional MRI techniques including T2 mapping, diffusion tensor imaging, and sodium imaging as well as contrast-enhanced US have been applied to quantify pathophysiologic processes and biochemical compositions of muscles, tendons, ligaments, and cartilage. Dual-energy and/or spectral CT has shown potential, particularly for the evaluation of osseous and ligamentous injury (eg, creation of quantitative bone marrow edema maps), which is not possible with standard single-energy CT. Recent advances in US technology such as shear-wave elastography or US tissue characterization as well as MR elastography enable the quantification of mechanical, elastic, and physical properties of tissues in muscle and tendon injuries. The future role of novel imaging techniques such as photon-counting CT remains to be established. Eventual prediction of return to play (ie, the time needed for the injury to heal sufficiently so that the athlete can get back to playing their sport) and estimation of risk of repeat injury is desirable to help guide sports physicians in the treatment of their patients. Additional values of quantitative analyses, as opposed to routine qualitative analyses, still must be established using prospective longitudinal studies with larger sample sizes.

Diffusion tensor imaging and quantitative T2 mapping to monitor muscle recovery following hamstring injury.

MRI examinations are accurate for diagnosing sports-related acute hamstring injuries. However, sensitive imaging methods for assessing recovery of these injuries are lacking. Diffusion tensor imaging (DTI) and quantitative T2 (qT2) mapping have both shown promise for assessing recovery of muscle micro trauma and exercise effects. The purpose of this study was to explore the potential of DTI and qT2 mapping for monitoring the muscle recovery processes after acute hamstring injury. In this prospective study, athletes with an acute hamstring injury underwent a 3-T MRI examination of the injured and contralateral hamstrings including DTI and qT2 measurements at three time points: (1) within 1 week after sustaining the injury, (2) 2 weeks after time point 1, and (3) return to play (RTP). A linear mixed model was used for time-effect analysis and paired t-tests for the detection of differences between injured and uninjured muscles. Forty-one athletes (age 27.8 ± 7 years; two females and 39 males) were included. Mean RTP time was 50 (range 12-169) days. A significant time effect was found for mean diffusivity, radial diffusivity, and the second and third eigenvalues (p ≤ 0.001) in the injured muscles. Fractional anisotropy (p = 0.40), first eigenvalue (p = 0.02), and qT2 (p = 0.61) showed no significant time effect. All DTI indices, except for fractional anisotropy, were significantly elevated compared with control muscles right after the injury (p < 0.001). Values normalized during the recovery period, with no significant differences between control and injured muscles at RTP (p values ranged from 0.08 to 0.51). Mean qT2 relaxation times in injured muscles were not significantly elevated compared with control muscles at any time point (p > 0.04). In conclusion, DTI can be used to monitor recovery after an acute hamstring injury. Future work should explore the potential of DTI indices to predict RTP and recovery times in athletes after an acute strain injury.

Local Field Potentials Predict Motor Performance in Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment option for patients with Parkinson's disease (PD). However, clinical programming remains challenging with segmented electrodes. OBJECTIVE: Using novel sensing-enabled neurostimulators, we investigated local field potentials (LFPs) and their modulation by DBS to assess whether electrophysiological biomarkers may facilitate clinical programming in chronically implanted patients. METHODS: Sixteen patients (31 hemispheres) with PD implanted with segmented electrodes in the subthalamic nucleus and a sensing-enabled neurostimulator were included in this study. Recordings were conducted 3 months after DBS surgery following overnight withdrawal of dopaminergic medication. LFPs were acquired while stimulation was turned OFF and during a monopolar review of both directional and ring contacts. Directional beta power and stimulation-induced beta power suppression were computed. Motor performance, as assessed by a pronation-supination task, clinical programming and electrode placement were correlated to directional beta power and stimulation-induced beta power suppression. RESULTS: Better motor performance was associated with stronger beta power suppression at higher stimulation amplitudes. Across directional contacts, differences in directional beta power and the extent of stimulation-induced beta power suppression predicted motor performance. However, within individual hemispheres, beta power suppression was superior to directional beta power in selecting the contact with the best motor performance. Contacts clinically activated for chronic stimulation were associated with stronger beta power suppression than non-activated contacts. CONCLUSIONS: Our results suggest that stimulation-induced ß power suppression is superior to directional ß power in selecting the clinically most effective contact. In sum, electrophysiological biomarkers may guide programming of directional DBS systems in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Christmas-Related Reduction in Beta Activity in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus (STN) beta (13 - 35 Hz) activity is a biomarker reflecting motor state in Parkinson's disease (PD). Adaptive deep brain stimulation (DBS) aims to use beta activity for therapeutic adjustments, but many aspects of beta activity in real-life situations are unknown. OBJECTIVE: The aim was to investigate Christmas-related influences on beta activity in PD. METHODS: Differences in Christmas Day to nonfestive daily averages in chronic biomarker recordings in 4 PD patients with a sensing-enabled STN DBS implant were retrospectively analyzed. Sweet-spot and whole-brain network connectomic analyses were performed. RESULTS: Beta activity was significantly reduced on Christmas Eve in all patients (4.00-9.00 p.m.: -12.30 ± 10.78%, P = 0.015). A sweet spot in the dorsolateral STN connected recording sites to motor, premotor, and supplementary motor cortices. CONCLUSIONS: We demonstrate that festive events can reduce beta biomarker activity. We conclude that circadian and holiday-related changes should be considered when tailoring adaptive DBS algorithms to patient demands. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Past, present, and future in sports imaging: how to drive in a three-lane freeway.

KEY POINTS: • Morphological evaluation of SRIs is still nowadays the clinical standard in daily practice.• New functional imaging modalities show potential to add valuable physiopathological information about the insights of SRIs in specific clinical scenarios.• In the era of personalized medicine, AI algorithms may help athletes and all professionals involved in their care to improve the evaluation of SRIs through a definitive quantitative metric approach.

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2023-overview, and primary local imaging: how and where?

OBJECTIVES: Early, accurate diagnosis is crucial for the prognosis of patients with soft tissue sarcomas. To this end, standardization of imaging algorithms, technical requirements, and reporting is therefore a prerequisite. Since the first European Society of Musculoskeletal Radiology (ESSR) consensus in 2015, technical achievements, further insights into specific entities, and the revised WHO-classification (2020) and AJCC staging system (2017) made an update necessary. The guidelines are intended to support radiologists in their decision-making and contribute to interdisciplinary tumor board discussions. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements were scored online by level of agreement (0 to 10) during two iterative rounds. Either "group consensus," "group agreement," or "lack of agreement" was achieved. RESULTS: Eight sections were defined that finally contained 145 statements with comments. Overall, group consensus was reached in 95.9%, and group agreement in 4.1%. This communication contains the first part consisting of the imaging algorithm for suspected soft tissue tumors, methods for local imaging, and the role of tumor centers. CONCLUSION: Ultrasound represents the initial triage imaging modality for accessible and small tumors. MRI is the modality of choice for the characterization and local staging of most soft tissue tumors. CT is indicated in special situations. In suspicious or likely malignant tumors, a specialist tumor center should be contacted for referral or teleradiologic second opinion. This should be done before performing a biopsy, without exception. CLINICAL RELEVANCE: The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability both in individual patients and in future studies on individualized strategies. KEY POINTS: • Ultrasound remains the best initial triage imaging modality for accessible and small suspected soft tissue tumors. • MRI is the modality of choice for the characterization and local staging of soft tissue tumors in most cases; CT is indicated in special situations. Suspicious or likely malignant tumors should undergo biopsy. • In patients with large, indeterminate or suspicious tumors, a tumor reference center should be contacted for referral or teleradiologic second opinion; this must be done before a biopsy.

Molecular simulations of sliding on SDS surfactant films.

We use molecular dynamics simulations to study the frictional response of monolayers of the anionic surfactant sodium dodecyl sulfate and hemicylindrical aggregates physisorbed on gold. Our simulations of a sliding spherical asperity reveal the following two friction regimes: at low loads, the films show Amonton's friction with a friction force that rises linearly with normal load, and at high loads, the friction force is independent of the load as long as no direct solid-solid contact occurs. The transition between these two regimes happens when a single molecular layer is confined in the gap between the sliding bodies. The friction force at high loads on a monolayer rises monotonically with film density and drops slightly with the transition to hemicylindrical aggregates. This monotonous increase of friction force is compatible with a traditional plowing model of sliding friction. At low loads, the friction coefficient reaches a minimum at the intermediate surface concentrations. We attribute this behavior to a competition between adhesive forces, repulsion of the compressed film, and the onset of plowing.

Inter-examiner reliability of the Doha agreement meeting classification system of groin pain in male athletes.

The Doha agreement classification is used to classify groin pain in athletes. We evaluated the inter-examiner reliability of this classification system. We prospectively recruited 48 male athletes (66 symptomatic sides) with groin pain between 10-2017 and 03-2020 at a sports medicine hospital in Qatar. Two examiners (23 and 10 years of clinical experience) performed history taking, and a standardized clinical examination blinded to each other's findings. Examiners classified groin pain using the Doha agreement terminology (adductor-, inguinal-, iliopsoas-, pubic-, hip-related groin pain, or other causes of groin pain). Multiple entities were ranked in order of perceived clinical importance. Each side was classified separately for bilateral groin pain. Inter-examiner reliability was calculated using Cohen's Kappa statistic (κ). Inter-examiner reliability was slight to moderate for adductor- (κ = 0.40), inguinal- (κ = 0.44), iliopsoas- (κ = 0.57), and pubic-related groin pain (κ = 0.12), substantial for hip-related groin pain (κ = 0.62), and slight for "other causes of groin pain" (κ = 0.13). Ranking entities in order of perceived clinical importance improved inter-examiner reliability for adductor-, inguinal-, and iliopsoas-related groin pain (κ = 0.52-0.65), but not for pubic (κ = 0.12), hip (κ = 0.51), and "other causes of groin pain" (κ = 0.03). For participants with unilateral groin pain classified with a single entity (n = 7), there was 100% agreement between the two examiners. Inter-examiner reliability of the Doha agreement meeting classification system varied from slight to substantial, depending on the clinical entity. Agreement between examiners was perfect when athletes were classified with a single clinical entity of groin pain, but lower when athletes were classified with multiple clinical entities.

Activity distribution among the hamstring muscles during high-speed running: A descriptive multichannel surface EMG study.

PURPOSE: This study assessed activity distribution among the hamstring muscles during high-speed running. The objective was to compare within and between muscle activity, relative contribution and hip and knee joint angles at peak muscle activity during high-speed running. METHODS: Through multichannel electromyography, we measured muscle activity in male basketball players during high-speed running on a treadmill at 15 locations: five for biceps femoris long head, four for semitendinosus, and six for semimembranosus. Muscle activity was calculated for each location within each hamstring muscle individually for each percent of a stride cycle. RESULTS: Twenty-nine non-injured basketball players were included (mean age: 17 ± 1 years; mass, 85 ± 9 kg; height, 193 ± 9 cm). Heterogeneous activity was found for all individual hamstring muscles across multiple events of the stride cycle. In the late-swing phase, muscle activity and relative contribution of the semimembranosus was significantly higher than of the semitendinosus. There was no significant difference in hip and knee joint angles at instant of peak muscle activity, assessed locally within individual hamstring muscles, as well as in general over the whole hamstring muscle. CONCLUSION: Hamstring muscles were most active in the late-swing phase during high-speed running. In this phase, the semimembranosus was most active and the semitendinosus was least active. Within the biceps femoris long head, the most proximal region was significantly more active in the late-swing phase, compared to other muscle regions. For each muscle and location, peak muscle activity occurred at similar hip and knee joint angles.

Effect of two eccentric hamstring exercises on muscle architectural characteristics assessed with diffusion tensor MRI.

OBJECTIVES: To evaluate the effect of a Nordic hamstring exercise or Diver hamstring exercise intervention on biceps femoris long head, semitendinosus and semimembranosus muscle's fascicle length and orientation through diffusion tensor imaging (DTI) with magnetic resonance imaging. METHODS: In this three-arm, single-center, randomized controlled trial, injury-free male basketball players were randomly assigned to a Nordic, Diver hamstring exercise intervention or control group. The primary outcome was the DTI-derived fascicle length and orientation of muscles over 12 weeks. RESULTS: Fifty-three participants were included for analysis (mean age 22 ± 7 years). Fascicle length in the semitendinosus over 12 weeks significantly increased in the Nordic-group (mean [M]: 20.8 mm, 95% confidence interval [95% CI]: 7.8 to 33.8) compared with the Control-group (M: 0.9 mm, 95% CI: -7.1 to 8.9), mean between-groups difference: 19.9 mm, 95% CI: 1.9 to 37.9, p = 0.026. Fascicle orientation in the biceps femoris long head over 12 weeks significantly decreased in the Diver-group (mean: -2.6°, 95% CI: -4.1 to -1.0) compared with the Control-group (mean: -0.2°, 95% CI: -1.4 to 1.0), mean between-groups difference: -2.4°, 95% CI: -4.7 to -0.1, p = 0.039. CONCLUSION: The Nordic hamstring exercise intervention did significantly increase the fascicle length of the semitendinosus and the Diver hamstring exercise intervention did significantly change the orientation of fascicles of the biceps femoris long head. As both exercises are complementary to each other, the combination is relevant for preventing hamstring injuries.

Skin and respiratory exposure to soluble lead, cobalt, nickel, copper, arsenic and silver at two South African precious metals refineries.

OBJECTIVES: Precious metals refinery workers are exposed to soluble platinum group metals (PGMs) during PGM-refining but may also be exposed to hazardous non-PGMs (Pb, Co, Ni, Cu, As and Ag) still present in the matte following base metals refining. The aim of this article was to report the skin and respiratory exposure of workers to soluble non-PGMs during PGM-refining. METHODS: Skin and respiratory exposure (of 40 workers at two precious metals refineries) were measured simultaneously over two consecutive shifts. Skin exposure was measured on the palm, wrist, neck and forehead using Ghostwipes™ and respiratory exposure was measured using the MDHS method 46/2 during which soluble metals were extracted using 0.07 M HCl and mechanical agitation, followed by ICP-MS analysis. RESULTS: The geometric means (GM) of average skin exposure to individual soluble metals on all anatomical areas was found in the order Cu (0.018 µg/cm2) > Ni (0.016 µg/cm2) > Pb (0.008 µg/cm2) > Ag (0.006 µg/cm2) > As (0.004 µg/cm2) > Co (0.0008 µg/cm2) with the palm being the highest exposed anatomical area. The order of the GM respiratory exposure was Pb (0.224 µg/m3) > Ag (0.201 µg/m3) > Cu (0.159 µg/m3) > As (0.079 µg/m3) > Ni (0.034 µg/m3) > Co (0.016 µg/m3) with exposure to As exceeding the South African occupational exposure limit (20 µg/m3) during concentrate handling (max 66.174 µg/m3). CONCLUSIONS: Workers were exposed to a mixture of toxic PGM and non-PGMs via the skin and inhalation. Exposure to these metals could lead to the development of diseases, such as contact dermatitis, occupational allergy, or occupational cancer. Non-PGMs must be included in hazardous chemical risk assessments and control strategies implemented at precious metals refineries.

What Is the Efficacy of Intra-articular Injections in the Treatment of Ankle Osteoarthritis? A Systematic Review.

BACKGROUND: Ankle osteoarthritis (OA) is painful and can impact a patient's physical and mental quality of life. Although intra-articular injections are commonly used to alleviate symptoms, there is conflicting evidence concerning their efficacy. Therefore, an updated systematic review would be informative. QUESTION/PURPOSE: In this systematic review, we asked: Are there clinically important benefits or harms associated with the use of intra-articular injections in the treatment of ankle OA? METHODS: We used PubMed, Embase, and the Cochrane Library to search for randomized controlled trials on intra-articular injections for the treatment of ankle OA in June 2021, and updated the search in January 2022; eligible dates were from the date of inception of each database through January 2022. Reference lists of eligible studies and previous reviews were manually screened. Two reviewers independently assessed studies for eligibility. We included seven studies. Three compared hyaluronic acid (HA) with saline, one compared HA with exercise, one compared four different regimens of HA [ 34 ], one compared platelet-rich plasma (PRP) with saline, and one compared botulinum toxin Type A (BoNT-A) with HA. A total of 340 patients were included: 141 in the HA arms, 48 in the PRP arm, 38 in the BoNT-A arm, and 113 in the saline arms. Across all studies, the mean age was 52 ± 21 years, and 35% were women (119 of 340 patients). Methodologic quality was assessed using the Cochrane Risk of Bias 2.0 tool. Of the included studies, the risk of bias was low in two studies, presented some concerns in one study, and was high in four studies. According to the Grading of Recommendations Assessment, Development, and Evaluation methodology, the level of evidence was very low for HA, moderate for PRP, and very low for BoNT-A. The level of heterogeneity was high, and we opted to perform a systematic review rather than a meta-analysis. A clinically relevant difference was based on whether the between-group difference surpassed the cutoff point determined as the minimum clinically important difference. RESULTS: No clinically relevant differences were found among HA, PRP, and BoNT-A and their control groups at 3, 6, or 12 months. No studies reported any serious adverse events in any treatment group. CONCLUSION: Given the lack of observed efficacy in this systematic review, these treatments should not be used in practice until or unless future high-quality studies find evidence of efficacy. LEVEL OF EVIDENCE: Level III, therapeutic study.

Towards a simplified fluid-sensitive MRI protocol in small joints of the hand in early arthritis patients: reliability between modified Dixon and regular Gadolinium enhanced TSE fat saturated MRI-sequences.

OBJECTIVE: MRI of small joints plays an important role in the early detection and early treatment of rheumatoid arthritis. Despite its sensitivity to demonstrate inflammation, clinical use is hampered by accessibility, long scan time, intravenous contrast, and consequent high costs. To improve the feasibility of MRI implementation in clinical practice, we introduce a modified Dixon sequence, which does not require contrast and reduces total acquisition time to 6 min. Because the reliability in relation to conventional MRI sequences is unknown, we determined this. METHODS: In 29 consecutive early arthritis patients, coronal and axial T2-weighted modified Dixon acquisitions on 3.0 T MRI scanner were acquired from metacarpophalangeal 2-5 to the wrist, followed by the standard contrast-enhanced protocol on 1.5 T extremity MRI. Two readers scored osteitis, synovitis and tenosynovitis (summed as total MRI-inflammation), and erosions (all summed as total Rheumatoid Arthritis MRI Score (RAMRIS)). Intraclass correlation coefficients (ICCs) between readers, and comparing the two sequences, were studied. Spearman correlations were determined. RESULTS: Performance between readers was good/excellent. Comparing modified Dixon and conventional sequences revealed good/excellent reliability: ICC for total MRI-inflammation score was 0.84 (95% CI:0.70-0.92), for erosions 0.90 (95% CI:0.79-0.96), and for the total RAMRIS score 0.88 (95% CI:0.77-0.94). The scores of total MRI-inflammation, total erosions, and total RAMRIS were highly correlated (ρ = 0.80, ρ = 0.81, ρ = 0.82, respectively). CONCLUSION: The modified Dixon protocol is reliable compared to the conventional MRI protocol, suggesting it is accurate to detect MRI inflammation. The good correlation may be the first step towards a patient-friendly, short and affordable MRI protocol, which can facilitate the implementation of MRI for early detection of inflammation in rheumatology practice.