Carbamazepine Ozonation Byproducts: Toxicity in Zebrafish (Danio rerio) Embryos and Chemical Stability.

Carbamazepine (CBZ) is an anticonvulsant medication with highly persistent properties in the aquatic environment, where it has the potential to affect nontarget biota. Because CBZ and many other pharmaceuticals are not readily removed in conventional sewage treatment plants (STP), additional STP effluent treatment technologies are being evaluated and implemented. Whole effluent ozonation is a prospective method to remove pharmaceuticals such as CBZ, yet knowledge on the toxicity of CBZ ozonation byproducts (OBPs) is lacking. This study presents, for the first time, in vivo individual and mixture toxicity of four putative OBPs, that is, carbamazepine 10,11-epoxide, 10,11-Dihydrocarbamazepine, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), and 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD) in developing zebrafish (Danio rerio) embryos. BQM and BQD were isolated from the ozonated solution as they were not commercially available. The study confirmed that the OBP mixture caused embryotoxic responses comparable to that of ozonated CBZ. Individual compound embryotoxicity assessment further revealed that BQM and BQD were the drivers of embryotoxicity. OBP chemical stability in ozonated CBZ water solution during 2 week dark storage at 22 °C was also assessed. The OBP concentrations remained over time, except for BQD which decreased by 94%. Meanwhile, ozonated CBZ persistently induced embryotoxicity over 2 week storage, potentially illustrating environmental concern.

Thyroid disruption properties of three indoor dust chemicals tested in Silurana tropicalis tadpoles.

Indoor dust contains a multitude of industrial chemicals, and ingestion of dust is considered an important exposure route to organic contaminants. Some of these contaminants have been shown to interfere with the thyroid system, which may result in significant consequences on public health. The amphibian metamorphosis is a thyroid hormone-dependent process, which can be used as an in vivo model for studies on thyroid hormone-disrupting potency. Three contaminants of indoor dust were tested on metamorphosing Silurana (Xenopus) tropicalis tadpoles. The tested chemicals were Tris (1,3-dichloroisopropyl) phosphate (TDCiPP), tetrabromobisphenol-A (TBBPA) and propylparaben (PrP). Measurements reflecting general growth, development progress and thyroid epithelial cell height were performed on the exposed tadpoles as well as chemical analyses of the exposure water. It was shown that TDCiPP acts as a thyroid hormone-disrupting chemical in metamorphosing tadpoles by causing increased epithelial cell height in thyroid glands after exposure to a nominal concentration of 0.010 mg/L and in higher concentrations. TBBPA caused reductions in general growth of tadpoles at the nominal concentration 0.125 mg/L, and PrP caused acute toxicity at the nominal concentration 12.5 mg/L. However, no evident indications of specific thyroid-disrupting effects caused by TBBPA or PrP were observed.

Wind turbine audibility and noise annoyance in a national U.S. survey: Individual perception and influencing factors.

With results from a nationwide survey sponsored by the U.S. Department of Energy, factors that affect outdoor audibility and noise annoyance of wind turbines were evaluated. Wind turbine and summer daytime median background sound levels were estimated for 1043 respondents. Wind turbine sound level was the most robust predictor of audibility yet only a weak, albeit significant, predictor of noise annoyance. For each 1 dB increase in wind turbine sound level (L1h-max), the odds of hearing a wind turbine on one's property increased by 31% [odds ratio (OR): 1.31; 95% CI (confidence interval): 1.25-1.38] and the odds of moving to the next level of annoyance increased by 9% (OR: 1.09; 95% CI: 1.02-1.16). While audibility was overwhelmingly dependent on turbine sound level, noise annoyance was best explained by visual disapproval (OR: 11.0; 95% CI: 4.8-25.4). The final models correctly predict audibility and annoyance level for 80% and 62% of individuals, respectively. The results demonstrate that among community members not receiving personal benefits from wind projects, the Community Tolerance Level of wind turbine noise for the U.S. aligns with the international average, further supporting observations that communities are less tolerant of wind turbine noise than other common environmental noise sources at equivalent A-weighted sound levels.

Reduction of absorption losses in MOVPE-grown AlGaAs Bragg mirrors.

Residual p-type doping from carbon has been identified as the root cause of excess absorption losses in (Al)GaAs/AlGaAs Bragg mirrors for high-finesse optical cavities when grown by metalorganic vapor phase epitaxy (MOVPE). Through optimization of the growth parameters with the aim of realizing low carbon uptake, we have shown a path for decreasing the parasitic background absorption in these mirrors from 100 to the 10 ppm range near 1064 nm. This significant reduction is realized via compensation of the carbon acceptors by intentional doping with the donor silicon in the uppermost layer pairs of 40-period GaAs/AlGaAs Bragg mirrors. Thus, we find that such compensation enables MOVPE-derived multilayer mirrors with the potential for a high cavity finesse (>100,000 in the near infrared) approaching the performance levels found with Bragg mirrors grown by molecular beam epitaxy (MBE).

Impaired learning of punishments in Parkinson's disease with and without impulse control disorder.

To document specific learning mechanisms in patients with Parkinson's disease (PD) with and without impulse control disorder (ICD). Thirty-two PD patients receiving dopamine replacement therapy (DRT) were investigated. Sixteen were diagnosed with ICD (ICD + ) and 16 PD patients matched for levodopa equivalence dosage, and DRT duration and severity of disease did not show impulsive behavior (non-ICD). Short-term learning of inhibitory control was assessed by an experimental procedure which was intended to mimic everyday life. Correct inhibition especially, had to be learned without reward (passive avoidance), and the failure to inhibit a response was punished (punishment learning). Results were compared to 16 healthy controls (HC) matched for age and sex. In ICD+ patients within-session learning of non-rewarded inhibition was at chance levels. Whereas healthy controls rapidly developed behavioral inhibition, non-ICD patients were also significantly impaired compared to HC, but gradually developed some degree of control. Both patient groups showed significantly decreased learning if the failure to withhold a response was punished. PD patients receiving DRT show impaired ability to acquire both punishment learning and passive avoidance learning, irrespective of whether or not ICD was developed. In ICD + PD patients, behavioral inhibition is nearly absent. Results demonstrate that by means of subtle learning paradigms it is possible to identify PD-DRT patients who show subtle alterations of punishment learning. This may be a behavioral measure for the identification of PD patients who are prone to develop ICD if DRT is continued.

Astigmatism-free high-brightness 1060 nm edge-emitting lasers with narrow circular beam profile.

1060 nm high-brightness vertical broad-area edge-emitting lasers providing anastigmatic high optical power into a narrow circular beam profile are demonstrated. Ridge-waveguide (RW) lasers yield record 2.2 W single-transverse mode power in the 1060-nm wavelength range under continuous-wave (cw) operation at room temperature with excellent beam quality factor M2 ≤ 2. Independent of operating current the astigmatism is only 2.5 µm. 3 mm long broad-area (BA) lasers produce a θvert as narrow as 9° full width at half maximum, which agrees well with our simulation results, being insensitive to drive current. 5 mm long BA lasers deliver highest ever reported cw 12 W multimode output power among lasers showing θvert <10° in the 1060-nm wavelength range. The emitted laser beams from both RW and BA lasers show a perfect circular shape with ≤10° divergence angle at record 2.1 W and 4.2 W cw-mode output power, respectively.

The association between dexterity and upper limb impairment during stroke recovery.

Introduction: Stroke-induced upper limb disabilities can be characterized by both motor impairments and activity limitations, commonly assessed using Fugl-Meyer Motor Assessment for Upper Extremity (FMMA-UE) and Action Research Arm Test (ARAT), respectively. The relationship between the two assessments during recovery is largely unstudied. Expectedly they diverge over time when recovery of impairment (restitution) plateaus, but compensation-driven improvements still occur. The objective of this study is to evaluate the alignment between FMMA-UE and ARAT in defining upper limb functional recovery categories by ARAT scores. We aimed to establish cut-off scores for both measures from the acute/early subacute, subacute and chronic stages of stroke recovery. Methods: Secondary analysis of four prospective cohort studies (acute/early subacute: n = 133, subacute: n = 113, chronic: n = 92) stages post-stroke. Receiver operating characteristic curves calculated the area under the curve (AUC) to establish optimal FMMA-UE cut-offs based on predefined ARAT thresholds distinguishing five activity levels from no activity to full activity. Weighted kappa was used to determine agreement between the two assessments. We used minimally clinically important difference (MCID) and minimal detectable change (MDC95) for comparison. Results: FMMA-UE and ARAT scores showed no relevant divergence across all recovery stages. Results indicated similar cut-off scores in all recovery stages with variability below MCID and MDC95 levels. Cut-off scores demonstrated robust AUC values from 0.77 to 0.86 at every recovery stage. Only in highly functional patients at the chronic stage, we found a reduced specificity of 0.55. At all other times sensitivity ranged between 0.68 and 0.99 and specificity between 0.71 and 0.99. Weighted kappa at the acute/early subacute, subacute and chronic stages was 0.76, 0.83, and 0.81, respectively. Discussion: Our research shows a strong alignment between FMMA-UE and ARAT cut-off scores throughout stroke recovery, except among the subgroup of highly recovered patients at the chronic stage. Discrepancies in specificity potentially stem from fine motor deficits affecting dexterity outcomes that are not captured by FMMA-UE. Additionally, the high congruence of both measures suggests they are not suited to distinguish between restitution and compensation. Calling for more comprehensive assessment methods to better understand upper limb functionality in rehabilitation.

Effects of moderate-intensity aerobic exercise on serum BDNF and motor learning in the upper-limb in patients after chronic-stroke: A randomized, controlled feasibility study with embedded health economic evaluation.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) promotes activity-dependent neuroplasticity and is released following aerobic-exercise. OBJECTIVE: Feasibility and efficacy of 1.Moderate-Intensity Cycle-Ergometer-Training (MI-ET) and 2.Low-Intensity Circuit-Training (LI-CT) on BDNF-serum-concentration in chronic-stroke and consequently efficacy of motor-learning in varying BDNF-concentrations (neuroplasticity being the substrate for motor-learning) via upper-limb robotic-training (RT) in both groups. METHODS: Randomised-control feasibility-study. 12-week, 3x/week intervention, 17 chronic-stroke-survivors randomized into: (1) MI-ET&RT or (2) LI-CT&RT. Both groups completed 40 mins MI-ET or LI-CT followed by 40 mins RT. Feasibility outcomes: (1) screening and enrollment-rates, (2) retention-rates, (3) adherence: (i) attendance-rates, (ii) training-duration, (4) adverse events. Primary clinical outcomes: 1. serum-BDNF changes pre-post training (immediate) and pre-training basal-levels over 12-weeks (long-term). 2.upper-limb performance with Action-Research-Arm-Test (ARAT). Additionally, feasibility of an embedded health economic evaluation (HEE) to evaluate health-costs and cost-effectiveness. OUTCOMES: cost-questionnaire return-rates, cost-of-illness (COI) and Health-Utitility-Index (HUI). RESULTS: 21.5% of eligible and contactable enrolled. 10 randomized to MI-ET and 7 to LI-CT. 85% of training-sessions were completed in MI-ET (306/360) and 76.3% in LI-CT-group (165/216). 12-weeks: Drop-outs MI-ET-10%, LI-CT-43%. CLINICAL OUTCOMES: No significant changes in immediate or long-term serum-BDNF in either group. Moderate-intensity aerobic-training did not increase serum-BDNF post-stroke. Individual but no group clinically-relevant changes in ARAT-scores. HEE outcomes at 12-weeks: 100% cost-questionnaires returned. Group-costs baseline and after treatment, consistently favouring MI-ET group. COI: (1-year-time-frame): MI-ET 67382 SD (43107) Swiss-Francs and LI-CT 95701(29473) Swiss-Francs. CONCLUSION: The study is feasible with modifications. Future studies should compare high-intensity versus moderate-intensity aerobic-exercise combined with higher dosage arm-training.

Individual Response to Botulinum Toxin Therapy in Movement Disorders: A Time Series Analysis Approach.

On a group level, satisfaction with botulinum neurotoxin (BoNT) treatment in neurological indications is high. However, it is well known that a relevant amount of patients may not respond as expected. The aim of this study is to evaluate the BoNT treatment outcome on an individual level using a statistical single-case analysis as an adjunct to traditional group statistics. The course of the daily perceived severity of symptoms across a BoNT cycle was analyzed in 20 cervical dystonia (CD) and 15 hemifacial spasm (HFS) patients. A parametric single-case autoregressive integrated moving average (ARIMA) time series analysis was used to detect individual responsiveness to BoNT treatment. Overall, both CD and HFS patients significantly responded to BoNT treatment with a gradual worsening of symptom intensities towards BoNT reinjection. However, only 8/20 CD patients (40%) and 5/15 HFS patients (33.3%) displayed the expected U-shaped curve of BoNT efficacy across a single treatment cycle. CD (but not HFS) patients who followed the expected outcome course had longer BoNT injection intervals, showed a better match to objective symptom assessments, and were characterized by a stronger certainty to control their somatic symptoms (i.e., internal medical locus of control). In addition to standard evaluation procedures, patients should be identified who do not follow the mean course-of-treatment effect. Thus, the ARIMA single-case time series analysis seems to be an appropriate addition to clinical treatment studies in order to detect individual courses of subjective symptom intensities.

External validation and extension of the Early Prediction of Functional Outcome after Stroke (EPOS) prediction model for upper limb outcome 3 months after stroke.

OBJECTIVE: The 'Early Prediction of Functional Outcome after Stroke' (EPOS) model was developed to predict the presence of at least some upper limb capacity (Action Research Am Test [ARAT] ≥10/57) at 6 months based on assessments on days 2, 5 and 9 after stroke. External validation of the model is the next step towards clinical implementation. The objective here is to externally validate the EPOS model for upper limb outcome 3 months poststroke in Switzerland and extend the model using an ARAT cut-off at 32 points. METHODS: Data from two prospective longitudinal cohort studies including first-ever stroke patients admitted to a Swiss stroke center were analyzed. The presence of finger extension and shoulder abduction was measured on days 1 and 8 poststroke in Cohort 1, and on days 3 and 9 in Cohort 2. Upper limb capacity was measured 3 months poststroke. Discrimination (area under the curve; AUC) and calibration obtained with the model were determined. RESULTS: In Cohort 1 (N = 39, median age 74 years), the AUC on day 1 was 0.78 (95%CI 0.61, 0.95) and 0.96 (95%CI 0.90, 1.00) on day 8, using the model of day 5. In Cohort 2 (N = 85, median age 69 years), the AUC was 0.96 (95%CI 0.93, 0.99) on day 3 and 0.89 (95% CI 0.80, 0.98) on day 9. Applying a 32-point ARAT cut-off resulted in an AUC ranging from 0.82 (95%CI 0.68, 0.95; Cohort 1, day 1) to 0.95 (95%CI 0.87, 1.00; Cohort 1, day 8). CONCLUSIONS: The EPOS model was successfully validated in first-ever stroke patients with mild-to-moderate neurological impairments, who were independent before their stroke. Now, its impact on clinical practice should be investigated in this population. Testing the model's performance in severe (recurrent) strokes and stratification of patients using the ARAT 32-point cut-off is required to enhance the model's generalizability and potential clinical impact.

External Validation of the Early Prediction of Functional Outcome After Stroke Prediction Model for Independent Gait at 3 Months After Stroke.

Introduction: The Early Prediction of Functional Outcome after Stroke (EPOS) model for independent gait is a tool to predict between days 2 and 9 poststroke whether patients will regain independent gait 6 months after stroke. External validation of the model is important to determine its clinical applicability and generalizability by testing its performance in an independent cohort. Therefore, this study aimed to perform a temporal and geographical external validation of the EPOS prediction model for independent gait after stroke but with the endpoint being 3 months instead of the original 6 months poststroke. Methods: Two prospective longitudinal cohort studies consisting of patients with first-ever stroke admitted to a Swiss hospital stroke unit. Sitting balance and strength of the paretic leg were tested at days 1 and 8 post-stroke in Cohort I and at days 3 and 9 in Cohort II. Independent gait was assessed 3 months after symptom onset. The performance of the model in terms of discrimination (area under the receiver operator characteristic (ROC) curve; AUC), classification, and calibration was assessed. Results: In Cohort I [N = 39, median age: 74 years, 33% women, median National Institutes of Health Stroke Scale (NIHSS) 9], the AUC (95% confidence interval (CI)] was 0.675 (0.510, 0.841) on day 1 and 0.921 (0.811, 1.000) on day 8. For Cohort II (N = 78, median age: 69 years, 37% women, median NIHSS 8), this was 0.801 (0.684, 0.918) on day 3 and 0.846 (0.741, 0.951) on day 9. Discussion and Conclusion: External validation of the EPOS prediction model for independent gait 3 months after stroke resulted in an acceptable performance from day 3 onward in mild-to-moderately affected patients with first-ever stroke without severe prestroke disability. The impact of applying this model in clinical practice should be investigated within this subgroup of patients with stroke. To improve the generalizability of patients with recurrent stroke and those with more severe, neurological comorbidities, the performance of the EPOS model within these patients should be determined across different geographical areas.

Accuracy of gait and posture classification using movement sensors in individuals with mobility impairment after stroke.

Background: Stroke leads to motor impairment which reduces physical activity, negatively affects social participation, and increases the risk of secondary cardiovascular events. Continuous monitoring of physical activity with motion sensors is promising to allow the prescription of tailored treatments in a timely manner. Accurate classification of gait activities and body posture is necessary to extract actionable information for outcome measures from unstructured motion data. We here develop and validate a solution for various sensor configurations specifically for a stroke population. Methods: Video and movement sensor data (locations: wrists, ankles, and chest) were collected from fourteen stroke survivors with motor impairment who performed real-life activities in their home environment. Video data were labeled for five classes of gait and body postures and three classes of transitions that served as ground truth. We trained support vector machine (SVM), logistic regression (LR), and k-nearest neighbor (kNN) models to identify gait bouts only or gait and posture. Model performance was assessed by the nested leave-one-subject-out protocol and compared across five different sensor placement configurations. Results: Our method achieved very good performance when predicting real-life gait versus non-gait (Gait classification) with an accuracy between 85% and 93% across sensor configurations, using SVM and LR modeling. On the much more challenging task of discriminating between the body postures lying, sitting, and standing as well as walking, and stair ascent/descent (Gait and postures classification), our method achieves accuracies between 80% and 86% with at least one ankle and wrist sensor attached unilaterally. The Gait and postures classification performance between SVM and LR was equivalent but superior to kNN. Conclusion: This work presents a comparison of performance when classifying Gait and body postures in post-stroke individuals with different sensor configurations, which provide options for subsequent outcome evaluation. We achieved accurate classification of gait and postures performed in a real-life setting by individuals with a wide range of motor impairments due to stroke. This validated classifier will hopefully prove a useful resource to researchers and clinicians in the increasingly important field of digital health in the form of remote movement monitoring using motion sensors.

Classification of functional and non-functional arm use by inertial measurement units in individuals with upper limb impairment after stroke.

Background: Arm use metrics derived from wrist-mounted movement sensors are widely used to quantify the upper limb performance in real-life conditions of individuals with stroke throughout motor recovery. The calculation of real-world use metrics, such as arm use duration and laterality preferences, relies on accurately identifying functional movements. Hence, classifying upper limb activity into functional and non-functional classes is paramount. Acceleration thresholds are conventionally used to distinguish these classes. However, these methods are challenged by the high inter and intra-individual variability of movement patterns. In this study, we developed and validated a machine learning classifier for this task and compared it to methods using conventional and optimal thresholds. Methods: Individuals after stroke were video-recorded in their home environment performing semi-naturalistic daily tasks while wearing wrist-mounted inertial measurement units. Data were labeled frame-by-frame following the Taxonomy of Functional Upper Limb Motion definitions, excluding whole-body movements, and sequenced into 1-s epochs. Actigraph counts were computed, and an optimal threshold for functional movement was determined by receiver operating characteristic curve analyses on group and individual levels. A logistic regression classifier was trained on the same labels using time and frequency domain features. Performance measures were compared between all classification methods. Results: Video data (6.5 h) of 14 individuals with mild-to-severe upper limb impairment were labeled. Optimal activity count thresholds were ≥20.1 for the affected side and ≥38.6 for the unaffected side and showed high predictive power with an area under the curve (95% CI) of 0.88 (0.87,0.89) and 0.86 (0.85, 0.87), respectively. A classification accuracy of around 80% was equivalent to the optimal threshold and machine learning methods and outperformed the conventional threshold by ∼10%. Optimal thresholds and machine learning methods showed superior specificity (75-82%) to conventional thresholds (58-66%) across unilateral and bilateral activities. Conclusion: This work compares the validity of methods classifying stroke survivors' real-life arm activities measured by wrist-worn sensors excluding whole-body movements. The determined optimal thresholds and machine learning classifiers achieved an equivalent accuracy and higher specificity than conventional thresholds. Our open-sourced classifier or optimal thresholds should be used to specify the intensity and duration of arm use.

Changes in Stroke Rehabilitation during the Sars-Cov-2 Shutdown in Switzerland.

INTRODUCTION: Many stroke survivors require continuous outpatient rehabilitation therapy to maintain or improve their neurological functioning, independ-ence, and quality of life. In Switzerland and many other countries, the shutdown to contain SARS-CoV-2 infections led to mobility restrictions and a decrease in therapy delivery. This study investigated the impact of the COVID-19 shutdown on stroke survivors' access to therapy, physical activity, functioning and mood. METHODS: A prospective observational cohort study in stroke subjects. At 4 time-points (before, during, after the shutdown, and at 3-month follow-up), the amount of therapy, physical activities, motor func-tion, anxiety, and depression were assessed. RESULTS: Thirty-six community-dwelling stroke subjects (median 70 years of age, 10 months post--stroke) were enrolled. Therapy reductions related to the shutdown were reported in 72% of subjects. This decrease was associated with significantly extended sedentary time and minimal deterioration in physical activity during the shutdown. Both parameters improved between reopening and 3-month follow-up. Depressive symptoms increased slightly during the observation period. Patients more frequently report-ed on self-directed training during shutdown. CONCLUSION: The COVID-19 shutdown had measurable immediate, but no persistent, effects on post--stroke outcomes, except for depression. Importantly, a 2-month reduction in therapy may trigger improvements when therapy is fully re-initiated thereafter.

Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos.

Sewage effluent ozonation can reduce concentrations of chemical pollutants including pharmaceutical residues. However, the formation of potentially toxic ozonation byproducts (OBPs) is a matter of concern. This study sought to elucidate toxicity mechanisms of ozonated carbamazepine (CBZ), an anti-epileptic drug frequently detected in sewage effluents and surface water, in zebrafish embryos (Danio rerio). Embryos were exposed to ozonated and non-ozonated CBZ from 3 h post-fertilization (hpf) until 144 hpf. Embryotoxicity endpoints (proportion of dead and malformed embryos) were assessed at 24, 48, and 144 hpf. Heart rate was recorded at 48 hpf. Exposure to ozonated CBZ gave rise to cardiovascular-related malformations and reduced heart rate. Moreover, embryo-larvae exposed to ozonated CBZ displayed a lack of swim bladder inflation. Hence, the expression patterns of CBZ target genes involved in cardiovascular and embryonal development were investigated through a stepwise gene co-expression analysis approach. Two co-expression networks and their upstream transcription regulators were identified, offering mechanistic explanations for the observed toxicity phenotypes. The study presents a novel application of gene co-expression analysis elucidating potential toxicity mechanisms of an ozonated pharmaceutical with environmental relevance. The resulting data was used to establish a putative adverse outcome pathway (AOP).

Corrigendum: Consensus-Based Core Set of Outcome Measures for Clinical Motor Rehabilitation After Stroke-A Delphi Study.

[This corrects the article DOI: 10.3389/fneur.2020.00875.].

Behavioral effects of citalopram, tramadol, and binary mixture in zebrafish (Danio rerio) larvae.

Pharmaceuticals are emerging as environmentally problematic compounds. As they are often not appropriately removed by sewage treatment plants, pharmaceutical compounds end up in surface water environments worldwide at concentrations in the ng to µg L-1 range. There is a need to further explore single compound and mixture effects using e.g. in vivo test model systems. We have investigated, for the first time, behavioral effects in larval zebrafish (Danio rerio) exposed to a binary mixture of an antidepressant drug (citalopram) and a synthetic opioid (tramadol). Citalopram and tramadol have a similar mode of action (serotonin reuptake inhibition) and are known to produce drug-drug interactional effects resulting in serotonin syndrome (SS) in humans. Zebrafish embryo-larvae were exposed to citalopram, tramadol and 1:1 binary mixture from fertilization until 144 h post-fertilization. No effects on heart rate, spontaneous tail coiling, or death/malformations were observed in any treatment at tested concentrations. Behavior (hypoactivity in dark periods) was on the other hand affected, with lowest observed effect concentrations (LOECs) of 373 µg L-1 for citalopram, 320 µg L-1 for tramadol, and 473 µg L-1 for the 1:1 mixture. Behavioral EC50 was calculated to be 471 µg L-1 for citalopram, 411 µg L-1 for tramadol, and 713 µg L-1 for the 1:1 mixture. The results of this study conclude that tramadol and citalopram produce hypoactivity in 144 hpf zebrafish larvae. Further, a 1:1 binary mixture of the two caused the same response, albeit at a higher concentration, possibly due to SS.

Behavioural effects and bioconcentration of per- and polyfluoroalkyl substances (PFASs) in zebrafish (Danio rerio) embryos.

Per- and polyfluoroalkyl substances (PFASs) are contaminants of emerging concern (CECs) that cause concern regarding their environmental impact and risk to human health. In this study, zebrafish (Danio rerio) embryos were exposed to PFASs for six days, to investigate behaviour toxicity and bioconcentration factor (BCF). Nine individual PFASs (five C4-C8 perfluoroalkyl carboxylates (PFCAs) (PFPeA, PFHxA, PFHpA, PFOA, PFNA), three C4, C6 and C8 perfluoroalkyl sulfonates (PFSAs) (PFBS, PFHxS, PFOS) and 6:2 fluorotelomersulfonate (6:2 FTSA)) and a mixture of these were investigated at seven concentrations ranging from environmentally relevant to acutely toxic levels. In exposed embryos, significant differences were found in total swimming distance (PFHpA, PFOA, PFNA, PFHxS, PFOS, 6:2 FTSA, PFAS mixture), burst activity (PFOA, PFNA, PFHxS, PFOS, PFAS mixture) and startle response (PFNA, PFHxS, PFOS, PFAS mixture). Toxicity was only observed at concentrations well above environmental levels. The toxicity of the PFAS mixture generally followed that of the individual substances, but the mixture reduced the potencies of individual PFASs. BCF was determined for all nine PFASs and ranged between 0.9 (PFPeA) and 2700 (PFOS). Long-chain PFASs (C8) and PFASs with sulfonate as an active group showed the greatest toxic potential, while short-chain PFASs (C6 and C7) also caused significant behaviour alterations and accumulated in the embryos. To our knowledge, this is the first study to compare the behaviour toxicity of a PFAS mixture with that of the individual PFASs. Follow-up studies are needed to identify the mechanistic responses to PFAS mixtures.

Consensus-Based Core Set of Outcome Measures for Clinical Motor Rehabilitation After Stroke-A Delphi Study.

Introduction: Outcome measures are key to tailor rehabilitation goals to the stroke patient's individual needs and to monitor poststroke recovery. The large number of available outcome measures leads to high variability in clinical use. Currently, an internationally agreed core set of motor outcome measures for clinical application is lacking. Therefore, the goal was to develop such a set to serve as a quality standard in clinical motor rehabilitation poststroke. Methods: Outcome measures for the upper and lower extremities, and activities of daily living (ADL)/stroke-specific outcomes were identified and presented to stroke rehabilitation experts in an electronic Delphi study. In round 1, clinical feasibility and relevance of the outcome measures were rated on a 7-point Likert scale. In round 2, those rated at least as "relevant" and "feasible" were ranked within the body functions, activities, and participation domains of the International Classification of Functioning, Disability, and Health (ICF). Furthermore, measurement time points poststroke were indicated. In round 3, answers were reviewed in reference to overall results to reach final consensus. Results: In total, 119 outcome measures were presented to 33 experts from 18 countries. The recommended core set includes the Fugl-Meyer Motor Assessment and Action Research Arm Test for the upper extremity section; the Fugl-Meyer Motor Assessment, 10-m Walk Test, Timed-Up-and-Go, and Berg Balance Scale for the lower extremity section; and the National Institutes of Health Stroke Scale, and Barthel Index or Functional Independence Measure for the ADL/stroke-specific section. The Stroke Impact Scale was recommended spanning all ICF domains. Recommended measurement time points are days 2 ± 1 and 7; weeks 2, 4, and 12; 6 months poststroke and every following 6th month. Discussion and Conclusion: Agreement was found upon a set of nine outcome measures for application in clinical motor rehabilitation poststroke, with seven measurement time points following the stages of poststroke recovery. This core set was specifically developed for clinical practice and distinguishes itself from initiatives for stroke rehabilitation research. The next challenge is to implement this clinical core set across the full stroke care continuum with the aim to improve the transparency, comparability, and quality of stroke rehabilitation at a regional, national, and international level.

Zebrafish (Danio rerio) embryo-larvae locomotor activity data analysis: Evaluating anxiolytic effects of the antidepressant compound citalopram.

Newly fertilized zebrafish (Danio rerio) embryos were exposed to increasing concentrations of the selective serotonin reuptake inhibitor (SSRI) citalopram from fertilization until six days post-fertilization (dpf). Locomotor activity data were acquired at six dpf using an automated ZebraBox® infrared tracking system. Individual (n = 32) locomotor activity was recorded during 75 minutes in total during alternating illumination conditions (0% light, i.e. dark periods, and 100% light, i.e. light periods). The first 15 minutes of the test consisted of a dark period, i.e an acclimatization phase. Afterward, six alternating light and dark periods were conducted. Individual zebrafish embryo-larvae locomotion was tracked and aggregated in ten-second bins. The dataset, containing nine locomotor-related quantified endpoints (factors), was parsed, analyzed, and visualized using R software. The dataset and its associated custom R script may be used to further explore locomotor activity outcomes (e.g. anxiolytic or anxiogenic properties) following exposure to citalopram or other neuroactive chemicals.