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Background: Fatigue is a common and debilitating side effect of chronic diseases, significantly impacting patients' quality of life. While physical exercise and psychological treatments have been shown to reduce fatigue, patients often struggle with adherence to these interventions in clinical practice. Game-based eHealth interventions are believed to address adherence issues by making the intervention more accessible and engaging., Objective: This study aims to compile empirical evidence on game-based eHealth interventions for fatigue in individuals with chronic diseases and to evaluate their effectiveness in alleviating fatigue., Methods: A comprehensive literature search was performed across Embase, MEDLINE ALL, PsycINFO, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar in August 2021. Study characteristics and outcomes from the included studies were extracted, and a random-effects meta-analysis was conducted. Sensitivity and subgroup analyses were performed to identify sources of heterogeneity., Results: Of 1742 studies identified, 17 were included in the meta-analysis. These studies covered 5 different chronic diseases: multiple sclerosis (n=10), cancer (n=3), renal disease (n=2), stroke (n=1), and Parkinson disease (n=1). All but 1 study used exergaming interventions. The meta-analysis revealed a significant moderate effect size in reducing fatigue favoring the experimental interventions (standardized mean difference [SMD] -0.65, 95% CI -1.09 to -0.21, P=.003) compared with control conditions consisting of conventional care and no care. However, heterogeneity was high (I2=85.87%). Subgroup analyses were conducted for the 2 most prevalent diseases. The effect size for the multiple sclerosis subgroup showed a trend in favor of eHealth interventions (SMD -0.47, 95% CI -0.95 to 0.01, P=.05, I2=63.10%), but was not significant for the cancer group (SMD 0.61, 95% CI -0.36 to 1.58, P=.22). Balance exercises appeared particularly effective in reducing fatigue (SMD -1.19, 95% CI -1.95 to -0.42, P=.002)., Conclusions: Game-based eHealth interventions appear effective in reducing fatigue in individuals with chronic diseases. Further research is needed to reinforce these findings and explore their impact on specific diseases. Additionally, there is a lack of investigation into interventions beyond exergaming within the field of game-based learning., (©Leonie S Warlo, Souraya El Bardai, Andrica de Vries, Marie-Lise van Veelen, Suzan Moors, Edmond HHM Rings, Jeroen S Legerstee, Bram Dierckx. Originally published in JMIR Serious Games (https://games.jmir.org), 17.10.2024.)

Alcohol ethoxylates (AEs) are a well-known class of non-ionic surfactants widely used by the personal care market. The aim of this study was to evaluate and characterize the in vitro metabolism of AEs and identify metabolites. Five selected individual homologue AEs (C 8 EO 4 , C 10 EO 5 , C 12 EO 4 , C 16 EO 8 , and C 18 EO 3 ) were incubated using human, rat, and hamster liver S9 fraction and cryopreserved hepatocytes. LC-MS was used to identify metabolites following the incubation of AEs by liver S9 and hepatocytes of all three species. All AEs were metabolized in these systems with a half-life ranging from 2 to 139 min. In general, incubation of AE with human liver S9 showed a shorter half-life compared to rat liver S9. While rat hepatocytes metabolized AEs faster than human hepatocytes. Both hydrophobic alkyl chain and hydrophilic EO head group groups of AEs were found to be target sites of metabolism. Metabolites were identified that show primary hydroxylation and dehydrogenation, followed by O-dealkylation (shortening of EO head groups) and glucuronidation. Additionally, the detection of whole EO groups indicates the cleavage of the ether bond between the alkyl chain and the EO groups as a minor metabolic pathway in the current testing system. Furthermore, no difference in metabolic patterns of each individual homologue AE investigated was observed, regardless of alkyl chain length or the number of EO groups. Moreover, there is an excellent agreement between the in vitro experimental data and the metabolite profile simulations using in silico approaches (OECD QSAR Toolbox). Altogether, these data indicate fast metabolism of all AEs with a qualitatively similar metabolic pathway with some quantitative differences observed in the metabolite profiles. These metabolic studies using different species can provide important reference values for further safety evaluation., (© 2024. The Author(s).)

Objectives: Cytotoxic lesions of the corpus callosum (CLOCC) are a common magnetic resonance imaging (MRI) finding associated with various systemic diseases including COVID-19. Although an increasing number of such cases is reported in the literature, there is a lack of systematic evidence summarizing the etiology and neuroimaging findings of these lesions. Thus, the aim of this systematic review was to synthesize the applied nomenclature, neuroimaging and clinical features, and differential diagnoses as well as associated disease entities of CLOCC., Materials and Methods: A comprehensive literature search in three biomedical databases identified 441 references, out of which 324 were eligible for a narrative summary including a total of 1353 patients., Results: Our PRISMA-conform systematic review identifies a broad panel of disease entities which are associated with CLOCC, among them toxic/drug-treatment-associated, infectious (viral, bacterial), vascular, metabolic, traumatic, and neoplastic entities in both adult and pediatric individuals. On MRI, CLOCC show typical high T2 signal, low T1 signal, restricted diffusion, and lack of contrast enhancement. The majority of the lesions were reversible within the follow-up period (median follow-up 3 weeks). Interestingly, even though CLOCC were mostly associated with symptoms of the underlying disease, in exceptional cases, CLOCC were associated with callosal neurological symptoms. Of note, employed nomenclature for CLOCC was highly inconsistent., Conclusions: Our study provides high-level evidence for clinical and imaging features of CLOCC as well as associated disease entities., Clinical Relevance Statement: Our study provides high-level evidence on MRI features of CLOCC as well as a comprehensive list of disease entities potentially associated with CLOCC. Together, this will facilitate rigorous diagnostic workup of suspected CLOCC cases., Key Points: • Cytotoxic lesions of the corpus callosum (CLOCC) are a frequent MRI feature associated with various systemic diseases. • Cytotoxic lesions of the corpus callosum show a highly homogenous MRI presentation and temporal dynamics. • This comprehensive overview will benefit (neuro)radiologists during diagnostic workup., (© 2023. The Author(s).)

Background: Established models for prognostic assessment in patients with brain metastasis do not stratify for prior surgery. Here we tested the prognostic accuracy of the Graded Prognostic Assessment (GPA) score model in patients operated for BM and explored further prognostic factors., Methods: We included 285 patients operated for brain metastasis at the University Hospital Zurich in the analysis. Information on patient characteristics, imaging, staging, peri- and postoperative complications and survival were extracted from the files and integrated into a multivariate Cox hazard model., Results: The GPA score showed an association with outcome. We further identified residual tumor after surgery (p = 0.007, hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.3) steroid use (p = 0.021, HR 1.7, 95% CI 1.1-2.6) and number of extracranial metastasis sites (p = 0.009, HR 1.4, 95% CI 1.1-1.6) at the time of surgery as independent prognostic factors. A trend was observed for postoperative infection of the subarachnoid space (p = 0.102, HR 3.5, 95% CI 0.8-15.7)., Conclusions: We confirm the prognostic capacity of the GPA score in a cohort of operated patients with brain metastasis. However, extent of resection and steroid use provide additional aid for the prognostic assessment in these patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Seizures in patients with brain metastases have an impact on morbidity and quality of life. The influence of tumor growth on the risk of seizures in these patients is not well defined. In this cohort study, we evaluated adult patients from the University Hospital of Zurich following resection of brain metastases from solid tumors, with or without preoperative seizures, at 3, 6, 9, and 12 months postoperatively. Brain magnetic resonance imaging was assessed for tumor progression using the Response Assessment in Neuro-Oncology criteria. The quarterly risk of unprovoked seizures was modeled with mixed effects logistic regression. We analyzed 444 time frames in 220 patients. Progression of brain metastases was independently associated with seizures during the respective quarterly follow-up period (odds ratio = 3.9, 95% confidence interval = 1.3-11.3, p = .014). Complete resection of brain metastases was associated with a lower risk of seizures (odds ratio = .2, 95% confidence interval = .04-.7, p = .015). Postoperative progression of brain metastases quadrupled the risk of seizures; therefore, vigorous follow-up may be useful to identify tumor progression and gauge the risk of seizures. The identification of patients at high seizure risk may have implications for treatment decisions and influence aspects of daily life. Breakthrough seizures may indicate brain metastases progression., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: This study aimed to determine if maternal intrapartum administration of oxygen altered the rate of cesarean delivery compared with room air., Data Sources: This study was a systematic review and meta-analysis of randomized controlled trials. Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials using a combination of key words related to "pregnant patients," "labor," "oxygen," "fetus," "newborn," and pregnancy outcomes from database inception until April 2020. The study was registered in PROSPERO (registration number CRD42020162110)., Study Eligibility Criteria: The inclusion criteria were randomized controlled trials of maternal administration of oxygen compared with room air in labor. The exclusion criteria were quasi-randomized trials and oxygen administered for planned cesarean deliveries. The primary outcome was the rate of cesarean delivery. Secondary maternal and neonatal outcomes, including cord gas values, were analyzed., Methods: The Cochrane Handbook guidelines were used to assess bias in trials. To calculate the relative risk or mean differences with confidence intervals, a random-effects model was employed. Subgroup analyses were performed for women who received oxygen for nonreassuring fetal heart rate monitoring or prophylactically., Results: Five randomized controlled trials, including 768 women, were included in the meta-analysis, 3 using prophylactic oxygen and 2 using oxygen for nonreassuring fetal heart rate monitoring. The risk of bias was generally considered low. There was no statistically significant difference in the rate of cesarean delivery between patients administered oxygen and patients provided room air (16 of 365 [4.4%] vs 11 of 379 [2.9%]; risk ratio 1.5; 95% confidence interval, 0.7-3.3). In addition, there were no statistically significant differencs in the rates of cesarean delivery for nonreassuring fetal heart rate monitoring, operative vaginal deliveries, Apgar scores of <7, neonatal intensive care unit admissions, or cord blood gas values. There were no statistically significant difference when analyzing oxygen for nonreassuring fetal heart rate monitoring alone or prophylactic oxygen alone. Data regarding FHT is mixed, with one study suggesting an improvement and three suggesting no change., Conclusion: Maternal intrapartum oxygen administration was not associated with any differences in the rate of cesarean delivery or any secondary outcomes compared with room air overall and in the subgroups of therapeutic (for nonreassuring fetal heart rate monitoring) or prophylactic administration in this meta-analysis. Large randomized controlled trials are necessary to further examine any possible benefits or harms of oxygen administration in labor, particularly for nonreassuring fetal heart rate monitoring., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pregnancy is a period of continuous change in the maternal cardiovascular system, partly mediated by the autonomic nervous system. Insufficient autonomic adaptation to increasing gestation is associated with pregnancy complications, such as hypertensive disorders of pregnancy and preterm birth (both major causes of perinatal morbidity and mortality). Consequently, maternal heart rate variability (mHRV), which is a proxy measure for autonomic activity, is increasingly assessed in these cohorts to investigate the pathophysiology of their complications. A better pathophysiological understanding could facilitate the early detection of these complications, which remains challenging. However, such studies (typically performed in pregnancies leading to hospitalization) have generated conflicting findings. A probable reason for these conflicting findings is that these study cohorts were likely administered routine obstetric medications during the study period of which the effects on mHRV are largely unknown. Subsequently, we design a longitudinal, observational study to quantifying the effect of these medications-particularly corticosteroids, which are known to affect fetal HRV-on mHRV to improve the interpretation of past and future studies. We will enroll 61 women admitted to a tertiary obstetric unit with an indication to receive corticosteroids antenatally. Participants' mHRV will be continuously acquired throughout their hospitalization with wrist-worn photoplethysmography to facilitate a within-patient comparison of the effect of corticosteroids on mHRV.

Importance: Hypertensive pregnancy disorders (HPDs) are associated with an increased risk of long-term cardiovascular disease. Speckle tracking echocardiography (STE) might be useful in the early detection of preclinical cardiac changes in women with HPDs., Objective: The aim of this study was to study whether STE is a suitable method to detect differences in cardiac function in pregnant women with HPD compared with normotensive pregnant women or between women with a history of a pregnancy complicated by HPD compared with women with a history of an uncomplicated pregnancy., Evidence Acquisition: The databases Medline, EMBASE, and Central were systematically searched for studies comparing cardiac function measured with STE in pregnant women with HPD or women with a history of HPD and women with a history of normotensive pregnancies., Results: The search identified 16 studies, including 870 women with a history of HPD and 693 normotensive controls. Most studies during pregnancy (n = 12/13) found a decreased LV-GLS (left ventricular global longitudinal strain) in HPD compared with normotensive pregnant controls. LV-GRS (left ventricular global radial strain) and LV-GLCS (left ventricular global circumferential strain) are decreased in women with early-onset and severe preeclampsia. Women with a history of early-onset preeclampsia show lasting myocardial changes, with significantly decreased LV-GLS, LV-GLCS, and LV-GRS., Conclusions and Relevance: LV-GLS is significantly decreased in pregnant women with HPD compared with normotensive pregnant women. Other deformation values show a significant decrease in women with severe or early-onset preeclampsia, with lasting myocardial changes after early-onset preeclampsia.

Background: Maternal hyperoxygenation is widely used during labor as an intrauterine resuscitation technique. However, robust evidence regarding its beneficial effect and potential side effects is scarce, and previous studies show conflicting results., Objective: To assess the effect of maternal hyperoxygenation upon suspected fetal distress during the second stage of term labor on fetal heart rate, neonatal outcome, maternal side effects, and mode of delivery., Materials and Methods: In a single-center randomized controlled trial in a tertiary hospital in The Netherlands, participants were randomized in case of an intermediary or abnormal fetal heart rate pattern during the second stage of term labor, to receive either conventional care or 100% oxygen at 10 L/min until delivery. The primary outcome was the change in fetal heart rate pattern. Prespecified secondary outcomes were Apgar score, umbilical cord blood gas analysis, neonatal intensive care unit admission, perinatal death, free oxygen radical activity, maternal side effects, and mode of delivery. We performed subgroup analyses for intermediary and abnormal fetal heart rate, and for small for gestational age fetuses., Results: From March 2016 through April 2018, a total of 117 women were included. Fetal heart rate patterns could be analyzed in 71 women. Changes in fetal heart rate (defined as improvement, equal, or deterioration) in favor of maternal hyperoxygenation were significant (odds ratio, 5.7; 95% confidence interval, 1.7-19.1) using ordinal logistic regression. Apgar score, umbilical cord blood gas analysis, free oxygen radicals, and mode of delivery showed no significant differences between the intervention and control group. Among women with an abnormal fetal heart rate, there were fewer episiotomies on fetal indication in the intervention group (25%) than in the control group (65%, P < .01)., Conclusion: Maternal hyperoxygenation has a positive effect on the fetal heart rate in the presence of suspected fetal distress during the second stage of labor. There was no significant difference in the mode of delivery or neonatal outcome; however, significantly fewer episiotomies on fetal indication were performed following maternal hyperoxygenation in the subgroup with abnormal fetal heart rate pattern., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Loss of bladder control is common after spinal cord injury (SCI) and no causal therapies are available. Here we investigated whether function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe SCI could prevent development of neurogenic lower urinary tract dysfunction. Bladder function of rats with SCI was repeatedly assessed by urodynamic examination in fully awake animals. Four weeks after SCI, detrusor sphincter dyssynergia had developed in all untreated or control antibody-infused animals. In contrast, 2 weeks of intrathecal anti-Nogo-A antibody treatment led to significantly reduced aberrant maximum detrusor pressure during voiding and a reduction of the abnormal EMG high-frequency activity in the external urethral sphincter. Anatomically, we found higher densities of fibers originating from the pontine micturition center in the lumbosacral gray matter in the anti-Nogo-A antibody-treated animals, as well as a reduced number of inhibitory interneurons in lamina X. These results suggest that anti-Nogo-A therapy could also have positive effects on bladder function clinically. SIGNIFICANCE STATEMENT After spinal cord injury, loss of bladder control is common. Detrusor sphincter dyssynergia is a potentially life-threatening consequence. Currently, only symptomatic treatment options are available. First causal treatment options are urgently needed in humans. In this work, we show that function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe spinal cord injury could prevent development of neurogenic lower urinary tract dysfunction, in particular detrusor sphincter dyssynergia. Anti-Nogo-A therapy has entered phase II clinical trial in humans and might therefore soon be the first causal treatment option for neurogenic lower urinary tract dysfunction., (Copyright © 2019 the authors.)

Following publication of the original article [1], the authors noticed that the sample size for the study group was incorrectly reported in the Methods section.

Aims: Our objective was to investigate and compare bladder function in rats assessed by metabolic cage and by urodynamic measurements in fully awake animals., Methods: Bladder function of female Lewis rats was investigated in naïve animals by metabolic cage at baseline, 14-16 days after bladder catheter and external urethral sphincter electromyography electrode implantation in fully awake animals by urodynamics, and again by metabolic cage., Results: Investigating the same animals (n = 8), voided volume, average flow, and duration of voiding were similar (P > 0.05) in naïve animals measured by metabolic cage and after catheter implantation by urodynamic measurements and by metabolic cage. In naïve animals measured by metabolic cage, voided volumes were significantly different in the light (resting phase) versus the dark (active phase) part of the 24 h cycle (mean difference 0.14 mL, 21%, P = 0.004, n = 27)., Conclusions: Lower urinary tract function assessed by metabolic cage or by urodynamic meaurements in fully awake rats was indistinguishable. Thus, catheter implantation did not significantly change physiological bladder function. This shows that urodynamic measurements in awake animals are an appropriate approach to study lower urinary tract function in health and disease in animal models, directly paralleling the human diagnostic procedures., (© 2017 Wiley Periodicals, Inc.)

Background: Perinatal asphyxia is, even in developed countries, one the major causes of neonatal morbidity and mortality. Therefore, if foetal distress during labour is suspected, one should try to restore foetal oxygen levels or aim for immediate delivery. However, studies on the effect of intrauterine resuscitation during labour are scarce. We designed a randomised controlled trial to investigate the effect of maternal hyperoxygenation on the foetal condition. In this study, maternal hyperoxygenation is induced for the treatment of foetal distress during the second stage of term labour., Methods/design: This study is a single-centre randomised controlled trial being performed in a tertiary hospital in The Netherlands. From among cases of a suboptimal or abnormal foetal heart rate pattern during the second stage of term labour, a total of 116 patients will be randomised to the control group, where normal care is provided, or to the intervention group, where before normal care 100% oxygen is supplied to the mother by a non-rebreathing mask until delivery. The primary outcome is change in foetal heart rate pattern. Secondary outcomes are Apgar score, mode of delivery, admission to the neonatal intensive care unit and maternal side effects. In addition, blood gas values and malondialdehyde are determined in umbilical cord blood., Discussion: This study will be the first randomised controlled trial to investigate the effect of maternal hyperoxygenation for foetal distress during labour. This intervention should be recommended only as a treatment for intrapartum foetal distress, when improvement of the foetal condition is likely and outweighs maternal and neonatal side effects., Trial Registration: EudraCT, 2015-001654-15; registered on 3 April 2015. Dutch Trial Register, NTR5461; registered on 20 October 2015.

In ionic liquid crystals, the orthogonal smectic A phase is the most common phase whereas the tilted smectic C phase is rather rare. We present a new study with five novel ionic liquid crystals exhibiting both a smectic A as well as the rare smectic C phase. Two of them have a phenylpyrimidine core whereas the other three are imidazolium azobenzenes. Their phase sequences and tilt angles were studied by polarizing microscopy and their temperature-dependent layer spacing as well as their translational and orientational order parameters were studied by X-ray diffraction. The X-ray tilt angles derived from X-ray studies of the layer contraction and the optically measured tilt angles of the five ionic liquid crystals were compared to obtain their de Vries character. Four of our five mesogens turned out to show de Vries-like behavior with a layer shrinkage that is far less than that expected for conventional materials. These materials can thus be considered as the first de Vries-type materials among ionic liquid crystals., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Solid evidence on the effect of intrauterine resuscitation on neonatal outcome is limited, and superiority of one intervention over the others is not clear. We therefore surveyed the clinical practice variation in fetal monitoring and the management of fetal distress during labor, in Dutch labor wards. In addition, we have compared recommendations from international guidelines., Study Design: We conducted a survey among all 86 Dutch hospitals, using a questionnaire on fetal monitoring and management of fetal distress. In addition, we requested international guidelines of 28 Western countries to study international recommendations regarding labor management., Results: The response rate of the national survey was 100%. Labor wards of all hospitals use CTG for fetal monitoring, 98% use additional fetal scalp blood sampling, and 23% use ST-analysis. When fetal distress is suspected, oxytocin is discontinued and tocolytic drugs are applied in all hospitals. Nearly all hospitals (98%) use maternal reposition for fetal resuscitation, 33% use amnioinfusion, and 58% provide maternal hyperoxygenation. Management is mainly based on the Dutch national guideline (58%) or on local guidelines (26%). Eight international guidelines on fetal monitoring were obtained for analysis. Fetal scalp blood sampling facilities are recommended in all the obtained guidelines. Use of ST-analysis is recommended in three guidelines and advised against in three guidelines. Five guidelines also advised on intrauterine resuscitation: discontinuation of oxytocin and use of tocolytic drugs was advised in all guidelines, amnioinfusion was recommended in two guidelines and advised against in two guidelines, whereas maternal hyperoxygenation was recommended in two guidelines and advised against in one guideline., Conclusion: Nationwide clinical practice, and recommendations from international guidelines agree on the use of fetal scalp blood sampling in addition to cardiotocography during labor. The opinion on the use of ST-analysis differs per clinic and per guideline. Discontinuation of oxytocin, administration of tocolytic drugs and maternal repositioning are rather uniform, on national and international level. However, there is a large variation in the use of amnioinfusion and maternal hyperoxygenation, which may be explained by the contradictory recommendations of the different guidelines., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The multifactorial pathogenesis leading to dilated cardiomyopathy (DCM) makes stratification difficult. The recent MOGE(S) (morphofunctional, organ involvement, genetic or familial, etiology, stage) classification addresses this issue., Objectives: The purpose of this study was to investigate the applicability and prognostic relevance of the MOGE(S) classification in patients with DCM., Methods: This study used patients from the Maastricht Cardiomyopathy Registry in the Netherlands and excluded patients with ischemic, valvular, hypertensive, and congenital heart disease. All other patients underwent a complete diagnostic work-up, including genetic evaluation and endomyocardial biopsy., Results: A total of 213 consecutive patients with DCM were included: organ involvement was demonstrated in 35 (16%) and genetic or familial DCM in 70 (33%) patients, including 16 (8%) patients with a pathogenic mutation. At least 1 cause was found in 155 (73%) patients, of whom 48 (23%) had more than 1 possible cause. Left ventricular reverse remodeling was more common in patients with nongenetic or nonfamilial DCM than in patients with genetic or familial DCM (40% vs. 25%; p = 0.04). After a median follow-up of 47 months, organ involvement and higher New York Heart Association functional class were associated with adverse outcome (p < 0.001 and p = 0.02, respectively). Genetic or familial DCM per se was of no prognostic significance, but when it was accompanied by additional etiologic-environmental factors such as significant viral load, immune-mediated factors, rhythm disturbances, or toxic triggers, a worse outcome was revealed (p = 0.03). A higher presence of MOGE(S) attributes (≥2 vs. ≤1 attributes) showed an adverse outcome (p = 0.007)., Conclusions: The MOGE(S) classification in DCM is applicable, and each attribute or the gene-environment interaction is associated with outcome. Importantly, the presence of multiple attributes was a strong predictor of adverse outcome. Finally, adaptation of the MOGE(S) involving multiple possible etiologies is recommended., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)