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Background: Single-legged hop tests are frequently used in substantiating return to sport decisions following lower extremity injury. Evidence for using the non-injured leg as a reference for the injured leg in the return to sport decision-making at the criterion-based point of return to sport following lower extremity injury is lacking., Purpose: To compare absolute values in single-legged hop tests between the non-injured leg of athletes returning to high-impact sports after lower extremity injury and the matched leg of healthy athletes., Study Design: Cross-sectional study., Methods: One hundred and sixty-nine athletes returning to high-impact sports after lower extremity injury and 169 matched healthy athletes executed five single-legged hop tests. Differences between athletes returning to high-impact sports after lower extremity injury and matched healthy athletes on five single-legged hop tests were analyzed using paired t-tests., Results: There were no statistically significant differences between the non-injured leg of athletes returning to sport and the matched leg of healthy athletes. Effect sizes ranged from 0.05 to 0.14 indicating negligible effects., Conclusion: Clinicians can use the non-injured leg as a reference for the injured leg in single-legged hop tests for deciding on return to high-impact sports after lower extremity injuries., Level of Evidence: 3b., Competing Interests: All authors declare that they have no conflicts of interest relevant to the content of this manuscript.

Background and purpose - Quantitative T2 mapping MRI of cartilage has proven value for the assessment of early osteoarthritis changes in research. We evaluated knee cartilage T2 relaxation times in a clinical population with knee complaints and its association with patients and disease characteristics and clinical symptoms.Patients and methods - In this cross-sectional study, T2 mapping knee scans of 109 patients with knee pain who were referred for an MRI by an orthopedic surgeon were collected. T2 relaxation times were calculated in 6 femoral and tibial regions of interest of full-thickness tibiofemoral cartilage. Its associations with age, sex, BMI, duration of complaints, disease onset (acute/chronic), and clinical symptoms were assessed with multivariate regression analysis. Subgroups were created of patients with abnormalities expected to cause predominantly medial or lateral tibiofemoral cartilage changes.Results - T2 relaxation times increased statistically significantly with higher age and BMI. In patients with expected medial cartilage damage, the medial femoral T2 values were significantly higher than the lateral; in patients with expected lateral cartilage damage the lateral tibial T2 values were significantly higher. A traumatic onset of knee complaints was associated with an acute elevation. No significant association was found with clinical symptoms.Interpretation - Our study demonstrates age, BMI, and type of injury-dependent T2 relaxation times and emphasizes the importance of acknowledging these variations when performing T2 mapping in a clinical population.

Objectives: To assess the impact of acute physical fatigue on traditional and neurocognitive functional performance tests in recreational athletes., Design: randomized counterbalanced cross-over study, pre-post design SETTING: laboratory PARTICIPANTS: Twenty recreational athletes (age = 24 ± 3 years) MAIN OUTCOME MEASURES: We evaluated fatigue impairments following a 30 s all-out effort in three traditional and one neurocognitive functional performance test. The traditional functional performance tests encompassed the single leg hop for distance (SLH), countermovement jump (CMJ) and Y-balance test (YBT). The neurocognitive functional performance test encompassed the reactive balance test (RBT). A 30 s modified Wingate was used to induce acute physical fatigue., Results: Acute physical fatigue was successfully induced as indicated by a significant increase in heart rate, systolic blood pressure, blood lactate levels and rating of perceived exertion (p < 0.001). Acute physical fatigue induced significant decreases in RBT accuracy (p = 0.004) and SLH performance (p < 0.001). YBT, CMJ and RBT visuomotor reaction time remained unaffected by acute physical fatigue., Conclusions: Acute physical fatigue impairs SLH performance and decreases accuracy in the RBT. YBT and CMJ performance remained unaffected by acute physical fatigue. Clinicians should be aware of this divergent neurocognitive functional impairments caused by one all-out effort to allow well-informed selection of functional performance tests., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest relevant to the content of this manuscript. The authors declare that the results are presented clearly, honestly, and without falsification, fabrication, or inappropriate data manipulation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: T 2 mapping is increasingly used to quantify cartilage degeneration in knee osteoarthritis (OA), yet reproducibility studies in a multicenter setting are limited. The purpose of this study was to determine the longitudinal reproducibility and multicenter variation of cartilage T 2 mapping, using various MRI equipment and acquisition protocols., Methods: In this prospective multicenter study, four traveling, healthy human subjects underwent T 2 mapping twice at five different centers with a 6-month-interval. Centers had various MRI scanners, field strengths, and T 2 mapping acquisition protocols. Mean T 2 values were calculated in six cartilage regions of interest (ROIs) as well as an average value per patient. A phantom was scanned once at each center. To evaluate longitudinal reproducibility, intraclass correlation coefficients (ICC), root-mean-square coefficient of variation (RMS-CV), and a Bland-Altman plot were used. To assess the variation of in vivo and phantom T 2 values across centers, ANOVA was performed., Results: ICCs of the T 2 mapping measurements per ROI and the ROI's combined ranged from 0.73 to 0.91, indicating good to excellent longitudinal reproducibility. RMS-CVs ranged from 1.1% to 1.5% (per ROI) and 0.6% to 1.6% (ROIs combined) across the centers. A Bland-Altman plot did not reveal a systematic error. Evident, but consistent, discrepancies in T 2 values were observed across centers, both in vivo and in the phantom., Conclusions: The results of this study suggest that T 2 mapping can be used to longitudinal assess cartilage degeneration in multicenter studies. Given the differences in absolute cartilage T 2 values across centers, absolute T 2 values derived from various centers in multicenter multivendor trials should not be pooled., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-674). EHGO serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. The authors have no other conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: The reactive balance test (RBT) is a recently developed neurocognitive balance test. The aim of this study was to determine test-retest, intra- and inter-rater reliability of the RBT in healthy recreational athletes., Design: Reliability study design., Setting: Primary., Participants: Twenty-one volunteers (age = 22 ± 1 years, height = 175 ± 9 cm, weight = 69 ± 7 kg) participated., Interventions: The two experimental trials were separated by an average of 33 ± 15 days. During experimental trials participants performed the Y-balance test (to determine maximal reach distances), and RBT once., Main Outcome Measures: Visuomotor response time and accuracy. Test-retest, intra- and inter-rater reliability were estimated for both these RBT outcome measures., Results: Excellent intra- and inter-rater reliability was observed for visuomotor response time and accuracy. Test-retest reliability for visuomotor response time was considered good, while moderate test-retest reliability was found for accuracy., Conclusions: Our results indicate that overall test-retest, intra- and inter-rater reliability of the RBT was moderate to excellent. Thus, the RBT possesses acceptable reliability to use in group level analyses. Future research should further determine the clinimetric properties of the RBT in specific populations and research the RBT along the sport injury continuum., Competing Interests: Declaration of competing interest The authors declare to not have any conflicts of interest or to have received any external source of funding for this study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In this experiment, we compared changes in visuomotor performance and motor control after a single session of differential learning (DL) and contextual interference (CI) in a reaching task to mimic goalkeeping. Subjects (n DL  = n CI  = 16) stood in front of a wall with six LED-light targets that flashed on in a random order and subjects had to move their hand in front of it as fast as possible in order to extinguish the target. After the pre-test subjects followed a DL or CI training session, followed immediately by a post-test, followed by one hour of rest and a retention test. Performance and motor control were measured respectively by visuomotor response time (VMRT) and an Index of Motor Abundance (IMA; reflecting the strength of movement synergies) calculated with Uncontrolled Manifold analysis. A mixed-effects Bayesian ANOVA model was used to evaluate differences in changes in both parameters between both training groups. Averaged over the six targets, the decrease in VMRT was stronger for DL than CI at the post-test (interference effect) but not at retention. The IMA was on average increased at post- and retention test in both groups, indicating stronger synergies between the degrees-of-freedom. While the ANOVA for IMA was not conclusive, the changes were likely not different between both learning methods. Thus, while an interference effect was found for CI but not DL in terms of performance on the task, no such effect was observed on the behavioural level in terms of the strength of movement synergies.

Purpose: Mental fatigue impairs psychomotor skill performance by affecting visuomotor reaction time, accuracy, and decision-making. Recently, neurocognitive functional performance tests (FPT) that integrate these outcomes have been developed. The aim of this study was to assess the effect of mental fatigue on traditional and neurocognitive FPT in healthy adults., Methods: Fourteen volunteers (four women; mean ± SD age, 22 ± 1 yr; height, 176.9 ± 8.4 cm; weight, 69.7 ± 10.4 kg) participated in a randomized counterbalanced crossover design. A 100% incongruent Stroop color word test of 90 min was used to induce mental fatigue and the control task encompassed watching a 90-min documentary. Traditional FPT comprised a single-leg hop for distance, countermovement jump, and Y-balance test, whereas the neurocognitive FPT encompassed the reactive balance test (RBT). All FPTs were evaluated pre-post the 90-min task. Mental fatigue was assessed using the Stroop task, visual analog scale for mental fatigue, and the Eriksen-Flanker task., Results: Mental fatigue was successfully induced, as shown by a significant increase in visual analog scale for mental fatigue (P < 0.001), with no decrease in performance on the Stroop and Eriksen-Flanker task. No interaction effect of mental fatigue was found for the Y-balance test, single-leg hop, and countermovement jump. For the RBT accuracy, a significant interaction effect of mental fatigue and time was observed (P = 0.024), with participants performing significantly worse when mentally fatigued. No interaction effect or main effect of condition and time was observed when considering the effect of mental fatigue on visuomotor reaction time in the RBT., Conclusions: Mental fatigue negatively affects a neurocognitive FPT, indicated by a decreased accuracy in response to visual stimuli in the RBT. Traditional FPT remained unaffected by mental fatigue.

After lower extremity injury, only half of the injured athletes return to their pre-injury sports level. Even though functional performance tests are often used to make return to sport decisions, it is unknown whether functional performance is associated with return to performance after such injuries. The aim of this systematic review was to identify, critically appraise, and analyze studies that investigated the association of functional performance tests with return to performance after lower extremity injuries in athletes participating in high-impact sports. MEDLINE, Embase, Web of Science, and CINAHL were systematically searched for relevant studies. Articles were independently screened by two authors and data were obtained from each included study using a data extraction form. Two authors independently scored methodological quality using the Quality In Prognosis Studies tool. A qualitative best evidence synthesis was conducted. Eight studies reported the association of functional performance with return to performance after lower extremity injuries, involving 1,246 athletes after anterior or posterior cruciate ligament reconstruction. No studies were found on the association of functional performance with return to performance for lower extremity injuries other than after anterior or posterior cruciate ligament reconstruction. All included studies had a high risk of bias. Two studies found significant but small associations for selected hop tests after anterior cruciate ligament reconstruction. Low evidence of association between functional performance and return to performance was present after anterior cruciate ligament reconstruction for the triple hop for distance, the 6-meter timed hop, the side hop in female athletes, and for the combination of the single and crossover hop for distance. In athletes after posterior cruciate ligament reconstruction, the vertical jump showed a significant but small association with return to performance. There is no high-quality evidence that functional performance is associated with return to performance after lower extremity injuries in athletes practicing high-impact sports. Low quality evidence suggests small associations after anterior and posterior cruciate ligament reconstruction. No evidence exists for lower extremity injuries other than after anterior or posterior cruciate ligament reconstruction. Therefore, research on functional performance associated with return to performance is recommended in high-quality prospective cohort studies including athletes with any type of lower extremity injury., (© Journal of Sports Science and Medicine.)

Objective: Subchondral bone changes, characterized by increased bone turnover and vascularity, are believed to stimulate progression and pain in knee osteoarthritis (OA). The objective of this study was to evaluate the bone perfusion in knee OA using quantitative dynamic contrast enhanced MRI (DCE-MRI)., Design: Unicompartmental knee OA patients were included and underwent 3 Tesla DCE-MRI and T2-weighted MRI. Quantitative DCE-MRI analysis of Ktrans and Kep, representing perfusion parameters, was performed to evaluate differences between the most and least affected knee compartment. First, DCE-MRI parameter differences between epimetaphyseal and subchondral bone in both femur and tibia were assessed. Second, DCE-MRI parameters in subchondral bone marrow lesions (BMLs) were compared to surrounding subchondral bone without BMLs., Results: Twenty-three patients were analyzed. Median Ktrans and Kep in epimetaphyseal bone were significantly higher (p < 0.05) in the most affected (Ktrans: 0.014; Kep: 0.054 min -1 ) compared to least affected (Ktrans: 0.010; Kep: 0.016 min -1 ) compartment. For subchondral bone, DCE-MRI parameters were significantly higher (p < 0.05) in the most affected (Ktrans: 0.019; Kep: 0.091 min -1 ) compared to least affected (Ktrans: 0.014; Kep: 0.058 min -1 ) compartment as well. Subchondral BMLs detected on fat-saturated T2-weighted images were present in all patients. Median Ktrans (0.091 vs 0.000 min -1 ) and Kep (0.258 vs 0.000 min -1 ) were significantly higher within subchondral BMLs compared to surrounding subchondral bone without BMLs (p < 0.001)., Conclusions: Increased perfusion parameters in epimetaphyseal bone, subchondral bone and BMLs are observed in unicompartmental knee OA. BMLs likely account for most of the effect of the higher bone perfusion in knee OA., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Acute fatigue is hypothesized to alter lower extremity injury risk profiles by affecting intrinsic risk factors (i.e. single leg postural control, hamstring strength). However, no systematic overview exists that merges the insights into prospective lower extremity injury risk profiling with the effect of acute fatigue on functional test performance., Objective: The objective of this review is to identify the influence of acute fatigue on prospectively determined modifiable intrinsic risk factors for lower extremity injuries., Design: Systematic review., Methods: PubMed (MEDLINE), Web of Science, PEDro, and Cochrane Library were searched until 29 May 2019. Studies were eligible when the study outcomes encompassed intrinsic modifiable risk factors for lower extremity injury, an acute fatigue intervention, and included healthy athletes or physically active people. Intrinsic modifiable risk factors were identified through recent systematic reviews and meta-analyses, and the referenced original research papers were used to determine outcome measures associated with increased injury risk., Results: Forty-three studies reported acute fatigue effects on modifiable risk factors, with eight studies matching all criteria for data-extraction. Acute fatigue can decrease single leg postural control, decrease ankle joint position sense, decrease isokinetic strength of hamstring and quadriceps muscles and can affect isokinetic hamstring:quadriceps ratios., Conclusion: Acute fatigue affects prospective intrinsic modifiable risk factors for lower extremity injury, indicating an altered injury risk profile for lateral ankle sprain, patellofemoral pain syndrome and hamstring injuries. Future research should allow for individual fatiguability as a relevant outcome, and merge insights from athlete-centred injury risk profiling and fatigue.

Purpose: The importance of the brain in sports was recently confirmed by the negative effect of mental fatigue (MF) on sport-specific psychomotor skills. Creatine supplementation improves strength but can also improve cognitive functioning. To explore the role of creatine in combating MF, we evaluated whether creatine supplementation counteracts the MF-associated impairment in sport-specific psychomotor skills., Methods: In 23°C, 14 healthy participants (4 females, 10 males; mean ± SD, age = 24 ± 3 yr, mass = 74 ± 13 kg, height = 179 ± 9 cm) performed a 90-min mentally fatiguing task (counterbalanced, crossover, and double-blinded; i.e., Stroop task) in two different conditions: after a 7-d creatine supplementation (CR; 20 g·d) and after a 7-d calcium lactate supplementation (placebo [PLAC]), separated by a 5-wk washout. In both conditions, a 7-min sport-specific visuomotor task, a dynamic handgrip strength endurance task, and a 3-min Flanker task was performed before and after the mentally fatiguing task. Physiological and perceptual responses were measured throughout the protocol., Results: Handgrip strength endurance was higher in CR compared with PLAC (P = 0.022). MF impaired visuomotor response time (+4.4%; P = 0.022) and Flanker accuracy (-5.0%; P = 0.009) in both conditions. Accuracy on the Stroop task was higher in CR compared with PLAC (+4.9%; P = 0.026). Within the perceptual and physiological parameters, only motivation and vigor (P ≤ 0.027) were lower in CR compared with PLAC., Conclusion: Creatine supplementation improved physical (strength endurance) and prolonged cognitive (Stroop accuracy) performance, yet it did not combat MF-induced impairments in short sport-specific psychomotor or cognitive (Flanker) performance. These results warrant further investigation in the potential role of creatine in combating the MF-associated decrements in prolonged (e.g., 90-min soccer game) sport performance and suggest a role of brain phosphocreatine in MF.

Background: Malaria (Plasmodium spp) remains a top cause of travel-associated morbidity among European residents. Here, we describe recent trends of imported malaria to Belgium and characterize the first cases of P.falciparum failure to artemisinin-based combination therapy (ACT)., Methods: National surveillance data and registers from national reference laboratory were used to investigate malaria cases and ACT failures in the past 20 years. Recurrent infections were confirmed by pfmsp genotyping and polymorphisms in drug resistance-associated genes pfk13, pfcrt, pfmdr1, pfpm2, pfap2mu and pfubp1 were determined by sequencing or quantitative PCR., Results: Annual malaria cases steadily increased in the last decade, reaching 428 in 2017 (all species). An estimated 15% of P.falciparum cases were severe. Between 2014 and 2017, 727 P.falciparum cases were reported and six non-immune travellers presented late recurrence. Five had hyperparasitaemia and/or signs of severe malaria at initial consultation. No mutations in ACT drug resistance markers were detected, although pfcrt-pfmdr1 haplotypes associated with lumefantrine tolerance were common., Conclusions: The upward trend in imported malaria, the substantial proportion of severe cases and the emergence of ACT failures are sources of concern, although late failures were infrequent. Genetic analysis did not support parasitological resistance to ACT, suggesting prospective pharmacokinetic studies should assess adequacy of partner drug dosage and duration of treatment in non-immune populations., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate in vivo T 2 mapping as quantitative, imaging-based biomarker for meniscal degeneration in humans, by studying the correlation between T 2 relaxation time and degree of histological degeneration as reference standard., Methods: In this prospective validation study, 13 menisci from seven patients with radiographic knee osteoarthritis (median age 67 years, three males) were included. Menisci were obtained during total knee replacement surgery. All patients underwent pre-operative magnetic resonance imaging using a 3-T MR scanner which included a T 2 mapping pulse sequence with multiple echoes. Histological analysis of the collected menisci was performed using the Pauli score, involving surface integrity, cellularity, matrix organization, and staining intensity. Mean T 2 relaxation times were calculated in meniscal regions of interest corresponding with the areas scored histologically, using a multi-slice multi-echo postprocessing algorithm. Correlation between T 2 mapping and histology was assessed using a generalized least squares model fit by maximum likelihood., Results: The mean T 2 relaxation time was 22.4 ± 2.7 ms (range 18.5-27). The median histological score was 10, IQR 7-11 (range 4-13). A strong correlation between T 2 relaxation time and histological score was found (r s  = 0.84, CI 95% 0.64-0.93)., Conclusion: In vivo T 2 mapping of the human meniscus correlates strongly with histological degeneration, suggesting that T 2 mapping enables the detection and quantification of early compositional changes of the meniscus in knee OA., Key Points: • Prospective histology-based study showed that in vivo T 2 mapping of the human meniscus correlates strongly with histological degeneration. • Meniscal T 2 mapping allows detection and quantifying of compositional changes, without need for contrast or special MRI hardware. • Meniscal T 2 mapping provides a biomarker for early OA, potentially allowing early treatment strategies and prevention of OA progression.

Background: Balance tests are commonly used in clinical practice with applicability in injury prevention and return to sport decisions. While most sports injuries occur in a changing environment where reacting to a non-planned stimulus is of great importance, these balance tests only evaluate pre-planned movements without taking these dynamics environmental aspects into account. Therefore, the goal of this paper was to develop a clinician-friendly test that respects these contextual interactions and to describe the test protocol of an adapted Y-balance test that includes environmental perception and decision-making., Methods: Within the theoretical construct of balance and adaptability, balance errors were selected as outcome measures for balance ability and, visuomotor reaction time and accuracy are selected as outcome measures for adaptability. A reactive balance task was developed and described using the Y-balance test for the balance component, while the FitLight training system TM was chosen for the environmental perception and decision-making component of the test., Results: This paper describes the test protocol of a reactive balance test as an adapted Y-balance test. The LED-lights of the FitLight training systemTM are placed at 80% of the maximal reach distance for each axis along the Y-Balance test kitTM. To induce cognitive load within the visuomotor task, colours were fixed to a corresponding axis, and both the order of the visual stimuli as the interstimulus time were randomised to integrate environmental perception and decision-making., Conclusion: The reactive balance test is a functional test that allows clinicians to score balance ability and athlete adaptability easily., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose: To compare bloodpool SPECT with planar imaging in bone SPECT/CT of painful total knee arthroplasty (TKA) with respect to inter-rater agreement, confidence, prosthesis outcome, and biomechanical functioning., Methods: Retrospective study of bloodpool SPECT and planar control images. Four raters used the validated Bruderholz scheme and a 5-point scale to grade uptake. Inter-rater agreement and overall confidence scores were calculated. Variable cluster analysis was performed to identify patterns of uptake, and associations between patterns and prosthesis outcome and biomechanical functioning were examined., Results: In all, 55 knees in 43 patients were analyzed (median follow-up 17 months; revision rate 21.8%). SPECT significantly improved inter-rater agreement in 24% of regions (all P < 0.05) and overall confidence by 20% (P < 0.001). Regional uptake cluster analysis showed improved antero-posterior separation with SPECT, and distinct patterns associated with prosthesis survival in lateral femoral (P = 0.041) and medial tibial (P < 0.001) regions. The prognostic value of SPECT outperformed planar imaging for tibial (P < 0.001), patellar (P = 0.009), and synovial (P = 0.040) assessment. Internal femoral malrotation resulted in increased uptake in posteromedial (P = 0.042) and anterolateral (P = 0.016) femoral, and lateral patellar (P = 0.011) regions. Internal tibial malrotation increased uptake in posterolateral (P = 0.026) and posteromedial tibial (P = 0.005), and medial patellar regions (P = 0.004). Bloodpool SPECT improved the prognostic value of late-phase SPECT/CT for the assessment of the medial tibial region., Conclusions: Bloodpool SPECT outperforms planar assessment of painful TKAs and the identification of distinct uptake patterns make it a potentially clinically relevant biomarker of prosthesis survival and biomechanical functioning.

Objective: The aim of this systematic review was to identify prospective studies that used a criteria-based return to sport (RTS) decision-making process for patients with lateral ankle sprain (LAS) injury., Design: Systematic review and narrative synthesis., Data Sources: The PubMed (MEDLINE), Web of Science, PEDro, Cochrane Library, SPORTDiscus (EBSCO), ScienceDirect, and Scopus databases were searched to 23 November 2018., Eligibility Criteria for Selecting Studies: Studies were included if they prospectively applied a criteria-based RTS decision-making process for patients with LAS injury, but were excluded if they merely gathered outcome measures at the RTS time point. Studies were also excluded if patients were recovering from ankle fracture, high ankle sprain, medial ankle sprain, chronic ankle instability or complex ankle injury., Results: No studies were identified that used a criteria-based RTS decision-making process for patients with LAS injury. We were unable to conduct a quantitative synthesis or meta-analysis, therefore we provide a narrative synthesis of relevant questionnaires, as well as clinical and functional assessments commonly used in studies retrieved in the search., Conclusion: There are currently no published evidence-based criteria to inform RTS decisions for patients with an LAS injury. Based on our narrative synthesis, we propose a number of variables that could be used to develop a criteria-based RTS decision paradigm. Future research should aim to reach consensus on these variables and apply them to actual RTS decisions within prospective study designs. Furthermore, we suggest that complex systems theory and the RTS continuum could be used to inform the development of an RTS decision-making paradigm for athletes with LAS injury.

Background: The Belgian Reference Laboratory for Plasmodium offers a free-of-charge reference testing of malaria-positive or doubtful samples to clinical laboratories., Methods: The final malaria diagnosis from the Reference Laboratory (microscopy, rapid diagnostic tests (RDTs) and Plasmodium species-specific PCR) were compared with the final diagnosis from peripheral Belgian laboratories. The Reference Laboratory reports were analysed for all samples submitted between 2013 and 2017. Criteria assessed included the diagnosis of malaria, Plasmodium species identification including mixed infections, and in case of Plasmodium falciparum, the parasite density and the presence of sexual and asexual stages., Results: A total of 947 non-duplicate samples were included. Reference testing confirmed 96.3% (893/927) and 90.0% (18/20) samples submitted as positive and negative, respectively, the two missed diagnoses were samples with Plasmodium ovale and Plasmodium malariae. Submitting laboratories had correctly identified P. falciparum in 95.1% (508/534) samples with P. falciparum single infection. They had correctly diagnosed the species in 62.9% (95/151) single non-falciparum samples and had reported 'non-falciparum' in another 26 (17.2%) samples; most errors occurred among P. malariae (n = 8/21, 38.1%) and P. ovale (n = 14/51, 27.5%). Only one of the 21 mixed Plasmodium species infections had been diagnosed as such by the submitting laboratories; in three of them, P. falciparum had been overlooked. Taken single and mixed infections together, P. falciparum was diagnosed in 98.6% (546/554) samples. Among 471 single P. falciparum samples available for comparison, laboratories had correctly reported parasite densities above 2% in 87.5% (70/80) samples; they had incorrectly reported parasite densities > 2% in an extra 52 (8.9%) samples. Laboratories had correctly reported P. falciparum schizonts and gametocytes in 25.6% (11/43) and 56.7% (17/30) samples, respectively., Conclusion: Diagnostic laboratories in a malaria non-endemic setting provided excellent diagnosis of malaria and P. falciparum, reasonably good diagnosis of non-falciparum infections and acceptable calculation of P. falciparum parasite density.

Background: Amebiasis is a protozoal infection caused by Entamoeba histolytica, while the morphologically indistinguishable E. dispar is considered as non-pathogenic. Polymerase chain reaction (PCR) assays are necessary to differentiate both species. The most common clinical presentations of E. histolytica disease are amebic colitis and amebic liver abscess, but asymptomatic infection is also possible. We assessed the frequency and pattern of clinical symptoms and microscopic features in travelers/migrants associated with E. histolytica intestinal infection and compared them to those found in individuals with E. dispar infection., Methods: We conducted a retrospective study at the travel clinic of the Institute of Tropical Medicine, Antwerp, Belgium on travelers/migrants found from 2006 to 2016 positive for Entamoeba histolytica/dispar through antigen detection and/or through microscopy confirmed by PCR. All files of individuals with a positive PCR for E. histolytica (= cases) and a random selection of an equal number of Entamoeba dispar carriers (= controls) were reviewed. We calculated the sensitivity, specificity and likelihood ratios (LRs) of clinical symptoms (blood in stool, mucus in stool, watery diarrhea, abdominal cramps, fever or any of these 5 symptoms) and of microscopic features (presence of trophozoites in direct and in sodium acetate-acetic acid-formalin (SAF)-fixed stool smears) to discriminate between E. histolytica and E. dispar infection., Results: Of all stool samples positive for Entamoeba histolytica/dispar for which PCR was performed (n = 810), 30 (3.7%) were true E. histolytica infections, of which 39% were asymptomatic. Sensitivity, specificity and positive LRs were 30%, 100% and 300 (p 0.007) for presence of blood in stool; 22%, 100% and 222 (p 0.03) for mucus in stool; 44%, 90% and 4.7 (p 0.009) for cramps and 14%, 97% and 4.8 (p = 0.02) for trophozoites in direct smears. For watery diarrhea, fever and for trophozoites in SAF fixated smears results were non-significant., Conclusions: E. histolytica infection was demonstrated in a small proportion of travelers/migrants with evidence of Entamoeba histolytica/dispar infection. In this group, history of blood and mucus in stool and cramps had good to strong confirming power (LR+) for actual E. histolytica infection. Trophozoites were also predictive for true E. histolytica infection but in direct smears only., Competing Interests: All the authors declare that no competing interests exist.

T2-mapping is a widely used quantitative MRI technique in osteoarthritis research. An important challenge for its application in the context of high tibial osteotomy (HTO) is the presence of metallic fixation devices. In this study, we evaluated the possibility of performing T2-mapping after a HTO, by assessing the extent of magnetic susceptibility artifacts and the influence on T2 relaxation times caused by two commonly used fixation devices. T2-mapping with a 3D fast spin-echo sequence at three Tesla was performed on 11 human cadaveric knee joints before and after implantation of a titanium plate and screws (n = 5) or cobalt chrome staples (n = 6). Mean T2 relaxation times were calculated in six cartilage regions, located in the distal and posterior cartilage of femoral condyles and the cartilage of tibial plateaus, both medially and laterally. T2 relaxation times before and after the implantation were compared with paired t-tests and Wilcoxon rank tests. Due to the extent of the magnetic susceptibility artifact, it was not possible to segment the knee cartilage and thus calculate T2 relaxation times in the lateral weight-bearing femoral and tibial cartilage regions only in the cobalt chrome group. In all cartilage regions of the titanium implanted knees and those unaffected by artifacts due to cobalt chrome implants, T2 relaxation times did not significantly differ between the two scans. Our results suggest that accurate T2-mapping after a HTO procedure is possible in all areas after implantation of a titanium fixation device and in most areas after implantation of a cobalt chrome fixation device. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1206-1212, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Purpose: Acetabular deficiencies in young patients can be restored in several ways during total hip arthroplasty. Currently, cementless cups are most frequently used. Impaction bone grafting of acetabular defects is a more biological approach, but is it cost-effective in young patients on the long term?, Methods: We designed a decision model for a cost-utility analysis of a cemented cup with acetabular impaction bone grafting versus an uncemented cup, in terms of cost per quality-adjusted life year (QALY) for the young adult with acetabular bone deficiency, in need for a primary total hip arthroplasty. Outcome probabilities and effectiveness were derived from the Radboud University Nijmegen Medical Centre and the Norwegian Hip Register. Multiple sensitivity analyses were used to assess the contribution of the included variables in the model's outcome., Results: Cemented cups with impaction bone grafting were more cost-effective compared to the uncemented option in terms of costs per QALY. A scenario suggesting equal primary survival rates of both cemented and uncemented cups still showed an effect gain of the cemented cup with impaction bone grafting, but at higher costs., Conclusions: Based on this model, the first choice of treatment of the acetabular bone deficient osteoarthritic hip in a young patient is reconstruction with impaction bone grafting and a cemented cup.

Purpose: Microscopy is the diagnostic reference standard for the detection of parasites, but it is labor-intensive and requires experience. Rapid diagnostic tests (RDTs) can provide an alternative to microscopy., Methods: RDTs from four different manufacturers were compared to enzyme-linked immunosorbent assay (ELISA), microscopy and/or parasite-specific real-time PCR: ImmunoCardSTAT!®CGE (Meridian Bioscience Inc., Cincinnati, Ohio, USA) (A), Crypto/Giardia Duo-Strip (Coris Bioconcepts, Gembloux, Belgium) (B), RIDA®QUICK Cryptosporidium/Giardia/Entamoeba Combi (R-BioPharm, Darmstadt, Germany) (C) and Giardia/Cryptosporidium Quik Chek (Techlab Inc., Blacksburg, Virginia, USA) (D)., Results: Thirty frozen samples were analyzed retrospectively. For Giardia lamblia (n=12) and Cryptosporidium (n=12) sensitivities ranged from 58% (B), over 83% (A, C) to 100% (D) and from 92% (B) to 100% (A, C, D), respectively. Specificity for both G. lamblia and Cryptosporidium was 100% for all RDT brands. Sensitivity for Entamoeba histolytica (n=5) was 100%, while specificity reached 80% (A) to 88% (C). In a prospective study, fresh samples were tested. For G. lamblia (n=30), sensitivity ranged from 66% (B), over 79% (A) and 83% (C) to 100% (D) and specificity varied between 94% (D) and 100% (A, B, C). For Cryptosporidium (n=3), sensitivity was 100% for all brands except (B) (67%) and specificities were 95% (A, B), 98% (C) and 100% (D). E. histolytica (n=1) was detected by both (A) and (C), while specificity was 81% and 87% respectively., Conclusion: RDTs can be a valuable tool when microscopic expertise is poor and in remote and outbreak settings where other techniques are often not available and rapid diagnosis is required., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Importance: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting the motor system, with extramotor involvement to a variable extent. Biomarkers for early differential diagnosis and prognosis are needed. An autosomal dominant hexanucleotide (GGGGCC) expansion in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent genetic cause of ALS, but its metabolic pattern has not been studied systematically., Objectives: To evaluate the use of 18fluorodeoxyglucose-positron-emission tomography as a marker of ALS pathology and investigate whether a specific metabolic signature is present in patients with C9orf72 mutations., Design, Setting, and Participants: In total, 81 patients with a suspected diagnosis of ALS at University Hospital Leuven were prospectively investigated. All underwent detailed neurological examination and electrodiagnostic and genetic testing for the major known genetic causes of ALS (C9orf72, SOD1, TARDBP, and FUS). A diagnosis of ALS was made in 70 of 81 patients. Of these, 11 were C9orf72 positive and 59 were C9orf72 negative. In 7 patients, the diagnosis of primary lateral sclerosis was made; 4 patients had progressive muscular atrophy. A screened healthy control population was used for comparison., Main Outcomes and Measures: Positron-emission tomographic data were spatially normalized and analyzed using a predefined volume of interest and a voxel-based analysis (SPM8). Discriminant analysis was done both volume of interest based and voxel based using a support vector machine approach., Results: Compared with control participants, 18fluorodeoxyglucose-positron-emission tomography showed perirolandic and variable prefrontal hypometabolism in most patients. Patients with primary lateral sclerosis showed a similar pattern. Patients with C9orf72-positive ALS had discrete relative hypometabolism in the thalamus and posterior cingulate compared with those with C9orf72-negative ALS. A posteriori-corrected discriminant analysis was able to correctly classify 95% of ALS cases and 71% of primary lateral sclerosis cases. Prefrontal hypometabolism was associated with reduced clinical functioning (ALS Functional Rating Scale). Extensive hypometabolism in the prefrontal or anterior temporal areas was present in 10% of patients and associated with significantly shorter survival as an independent factor (n = 63, P < .001). Patients who were C9orf72 positive did not differ in survival compared with those who were C9orf72 negative., Conclusions and Relevance: 18Fluorodeoxyglucose-positron-emission tomography is a useful early diagnostic and prognostic marker for ALS. Amyotrophic lateral sclerosis that is positive for C9orf72 is characterized by only mild cerebral metabolic differences that show no prognostic difference.

Aim: Injuries of the lower extremity tend to be associated with jump-landing movements. This review provides an overview of the kinematic variables and malalignments during jump-landing, which could be attributed to overuse or acute injury occurrence., Methods: We searched ISI Web of Knowledge, SPORTDiscus, PubMed, EMBASE and SCOPUS for all studies, published before October 2012, which looked at the relation between kinematic risk factors and malalignments of jump-landing and injuries. An article was included 1) if the article was an observational, retrospective or prospective study; 2) if the article investigated the relationship between injuries and the visible and easily measurable kinematic variables or malalignments of the jump-landing technique; 3) if the article met a predefined quality cut-off score., Results: Ten studies met all inclusion criteria. Literature shows that several kinematic factors are related to lower acute and overuse injuries., Conclusion: A stiffer jump-landing technique is a risk factor in the development of overuse injuries and acute injuries. This is caused by less active motion in the lower extremity joints and by the increased valgus position of the knee during the jump-landing maneuver which creates an unfavorable alignment of the lower extremity. A valgus position of the knee during landing was also a predictor of acute lower extremity injuries. Future intervention programs should focus on the jump-landing technique and the performance of the athlete.

Songbirds are well known for their ability to learn their vocalizations by imitating conspecific adults. This uncommon skill has led to many studies examining the behavioral and neurobiological processes involved in vocal learning. Canaries display a variable, seasonally dependent, vocal behavior throughout their lives. This trait makes this bird species particularly valuable to study the functional relationship between the continued plasticity in the singing behavior and alterations in the anatomy and physiology of the brain. In order to optimally interpret these types of studies, a detailed understanding of the brain anatomy is essential. Because traditional 2-dimensional brain atlases are limited in the information they can provide about the anatomy of the brain, here we present a 3-dimensional MRI-based atlas of the canary brain. Using multiple imaging protocols we were able to maximize the number of detectable brain regions, including most of the areas involved in song perception, learning, and production. The brain atlas can readily be used to determine the stereotactic location of delineated brain areas at any desirable head angle. Alternatively the brain data can be used to determine the ideal orientation of the brain for stereotactic injections, electrophysiological recordings, and brain sectioning. The 3-dimensional canary brain atlas presented here is freely available and is easily adaptable to support many types of neurobiological studies, including anatomical, electrophysiological, histological, explant, and tracer studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to determine the influence of five different recovery strategies on repeated simulated time trial (TT) performance on a stationary cycle ergometer., Methods: Study 1 (n=8, male, club-level trained; V˙O2max: 56.9 ± 3.8 mL·min·kg) investigated the influence of passive rest with or without upper leg cooling (cooling device set at 0 °C or 10 °C) and compression after a first time trial (TT1) on a second time trial (TT2). Study 2 (n=9, male, club-level trained; V˙O2max: 53.3 ± 5.2 mL·min·kg) examined the influence of active recovery (AR) with or without upper leg cooling (cooling device set at 0 °C) applied after TT1 on TT2. Exhaustive exercise consisted of a cycle exercise at 55% Wmax lasting 30 min, immediately followed by a TT in which subjects had to complete a preset amount of work, equal to 30 min at 75% Wmax, as fast as possible. Immediately after TT1, a different recovery intervention was used for 20 min, and then subjects passively rested for 100 min before starting TT2. TT performance and physiological parameters were registered during the experiments., Results: In both studies, we observed that TT performance did not significantly change for either of the recovery interventions. During the cooling interventions, skin temperatures significantly decreased (P<0.05). AR + cooling + compression versus AR (study 2) clearly showed a significantly (P<0.05) faster decrease of the blood lactate concentration ([BLa]) during the recovery period after TT1 and a lower [BLa] during TT2., Conclusions: Twenty minutes after cooling (device set at 0 °C or 10 °C), AR or the combined recovery method had comparable effects as passive recovery on the maintenance of TT2 performance 120 min after the first TT (TT1). After AR, however, subjects seemed to perform slightly better during TT2., (© 2011 by the American College of Sports Medicine)

Background: Cell transplantation is likely to become an important therapeutic tool for the treatment of various traumatic and ischemic injuries to the central nervous system (CNS). However, in many pre-clinical cell therapy studies, reporter gene-assisted imaging of cellular implants in the CNS and potential reporter gene and/or cell-based immunogenicity, still remain challenging research topics., Results: In this study, we performed cell implantation experiments in the CNS of immunocompetent mice using autologous (syngeneic) luciferase-expressing bone marrow-derived stromal cells (BMSC-Luc) cultured from ROSA26-L-S-L-Luciferase transgenic mice, and BMSC-Luc genetically modified using a lentivirus encoding the enhanced green fluorescence protein (eGFP) and the puromycin resistance gene (Pac) (BMSC-Luc/eGFP/Pac). Both reporter gene-modified BMSC populations displayed high engraftment capacity in the CNS of immunocompetent mice, despite potential immunogenicity of introduced reporter proteins, as demonstrated by real-time bioluminescence imaging (BLI) and histological analysis at different time-points post-implantation. In contrast, both BMSC-Luc and BMSC-Luc/eGFP/Pac did not survive upon intramuscular cell implantation, as demonstrated by real-time BLI at different time-points post-implantation. In addition, ELISPOT analysis demonstrated the induction of IFN-gamma-producing CD8+ T-cells upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating that BMSC-Luc and BMSC-Luc/eGFP/Pac are immune-tolerated in the CNS. However, in our experimental transplantation model, results also indicated that reporter gene-specific immune-reactive T-cell responses were not the main contributors to the immunological rejection of BMSC-Luc or BMSC-Luc/eGFP/Pac upon intramuscular cell implantation., Conclusion: We here demonstrate that reporter gene-modified BMSC derived from ROSA26-L-S-L-Luciferase transgenic mice are immune-tolerated upon implantation in the CNS of syngeneic immunocompetent mice, providing a research model for studying survival and localisation of autologous BMSC implants in the CNS by real-time BLI and/or histological analysis in the absence of immunosuppressive therapy.

Introduction: In vivo bioluminescence imaging (BLI) is a promising technique for non-invasive tumour imaging. D: -luciferin can be administrated intraperitonealy or intravenously. This will influence its availability and, therefore, the bioluminescent signal. The aim of this study is to compare the repeatability of BLI measurement after IV versus IP administration of D: -luciferin and assess the correlation between photon emission and histological cell count both in vitro and in vivo., Materials and Methods: Fluc-positive R1M cells were subcutaneously inoculated in nu/nu mice. Dynamic BLI was performed after IV or IP administration of D: -luciferin. Maximal photon emission (PE(max)) was calculated. For repeatability assessment, every acquisition was repeated after 4 h and analysed using Bland-Altman method. A second group of animals was serially imaged, alternating IV and IP administration up to 21 days. When mice were killed, PE(max) after IV administration was correlated with histological cell number., Results: The coefficients of repeatability were 80.2% (IV) versus 95.0% (IP). Time-to-peak is shorter, and its variance lower for IV (p < 0.0001). PE(max) was 5.6 times higher for IV. A trend was observed towards lower photon emission per cell in larger tumours., Conclusion: IV administration offers better repeatability and better sensitivity when compared to IP. In larger tumours, multiple factors may contribute to underestimation of tumour burden. It might, therefore, be beneficial to test novel therapeutics on small tumours to enable an accurate evaluation of tumour burden.

Background: Head-up tilt testing is a useful test for investigating vasovagal syncope. The determination of early, accurate, predictive criteria for a negative result would permit a reduction in the duration of the tilt test., Methods and Results: Patients with no drug use and no illnesses other than recurrent unexplained syncope were recruited. In an initial study (110 consecutive patients), we aimed to determine a predictive criterion based on heart rate variations during the first minutes of upright tilting that could distinguish between patients with positive and negative tilt tests (patients with an early continual decrease in heart rate or blood pressure were excluded). Then we tested the predictive value of the established criterion in a second independent sample of patients with unexplained syncope (109 consecutive patients). An early sustained increase in heart rate < or = 18 bpm during the first 6 minutes of upright tilting at a 60 degree angle allowed us to predict negative tilt tests with 100% specificity, 100% positive predictive value, and 88.6% sensitivity. This criterion was validated in the second, prospective arm of the study (96.4% specificity, 98.4% positive predictive value, and 87.3% sensitivity), even with subsequent use of isoproterenol in low doses., Conclusions: In patients with no drug use and no illnesses other than recurrent unexplained syncope, a simple clinical criterion identifies patients who will not develop syncope during a prolonged upright tilt.