Can gait patterns be explained by joint structure in people with and without radiographic knee osteoarthritis? Data from the IMI-APPROACH cohort.

OBJECTIVE: To determine the association between joint structure and gait in patients with knee osteoarthritis (OA). METHODS: IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS). Patients were divided into those with/without radiographic OA (ROA). Principal component analyses (PCA) were performed on gait parameters; linear regression models were used to evaluate whether image-based structural and demographic parameters were associated with gait principal components. RESULTS: Two hundred seventy-one patients (age median 68.0, BMI 27.0, 77% female) could be analyzed; 149 (55%) had ROA. PCA identified two components: upper leg (primarily walking speed, stride duration, hip range of motion [ROM], thigh ROM) and lower leg (calf ROM, knee ROM in swing and stance phases). Increased age, BMI, and radiographic subchondral bone density (sclerosis), decreased radiographic varus angle deviation, and female sex were statistically significantly associated with worse lower leg gait (i.e. reduced ROM) in patients without ROA (R2 = 0.24); in ROA patients, increased BMI, radiographic osteophytes, MRI meniscal extrusion and female sex showed significantly worse lower leg gait (R2 = 0.18). Higher BMI was significantly associated with reduced upper leg function for non-ROA patients (R2 = 0.05); ROA patients with male sex, higher BMI and less MRI synovitis showed significantly worse upper leg gait (R2 = 0.12). CONCLUSION: Structural OA pathology was significantly associated with gait in patients with clinical knee OA, though BMI may be more important. While associations were not strong, these results provide a significant association between OA symptoms (gait) and joint structure.

Comparison of Clinical Efficacy and Mechanical Characteristics of Two Knee Distraction Devices With Relevance for Clinical Practice.

OBJECTIVE: Distraction treatment for severe osteoarthritis below the age of 65 successfully postpones arthroplasty. Most patients have been treated with a general external fixator or a device specifically intended for knee distraction. This study compares clinical efficacy of both devices in retrospect and their mechanical characteristics. DESIGN: Clinical efficacy 2 years posttreatment was compared using retrospective data from patients with severe knee osteoarthritis treated with knee distraction; 63 with the Dynamic Monotube (Stryker GmbH, Switzerland) and 65 with the KneeReviver (ArthroSave BV, the Netherlands). Changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function, general well-being (SF-36), cartilage thickness by radiographic joint space widening, and adverse events during treatment were assessed. Axial stiffness of clinically feasible configurations was assessed by bench testing for the Dynamic Monotube triax system and the KneeReviver. RESULTS: No differences were observed in clinical efficacy, nor in mechanical characteristics and adverse events between the two devices. Although with large variation, both showed a clinically relevant improvement. In mechanical testing, contact between articular surfaces was observed for both devices at physiological loading. Stiffness of applied configurations strongly varied and primarily depended on bone pin length. CONCLUSIONS: Patients treated with a general intended-use device or a distraction-specific device both experienced clinical and structural efficacy although with significant variation between patients. The latter may be the result of varying mechanical characteristics resulting from differences in clinical configurations of the devices and actual loading. The exact role of full/partial mechanical unloading of the joint during distraction treatment remains unclear.

The Diagnostics and Management of Bronchopulmonary Sequestration: An International Survey among Specialized Caregivers.

BACKGROUND: Our objective was to explore the treatment preferences for bronchopulmonary sequestration (BPS) among an international group of specialized caregivers. METHODS: Sixty-three participants from 17 countries completed an online survey concerning the diagnostics, treatment, and follow-up. Recruitment took place among members of the Collaborative Neonatal Network for the first European Congenital Pulmonary Airway Malformation Trial Consortium and through the Association for European Pediatric and Congenital Cardiology working group database. RESULTS: Most of the 63 participants were pediatric surgeons (52%), followed by pediatric pulmonologists (22%), and pediatric cardiologists (19%). The majority (65%) treated more than five cases per year and 52% standardly discussed treatment in a multidisciplinary team. Half of the participants (52%) based the management on the presence of symptoms, versus 32% on the intralobar or extralobar lesion localization. Centers with both surgical and interventional cardiac/radiological facilities (85%) preferred resection to embolization in symptomatic cases (62 vs. 15%). In asymptomatic cases too, resection was preferred over embolization (38 vs. 9%); 32% preferred noninterventional treatment, while 11% varied in preference. These treatment preferences were significantly different between surgeons and nonsurgeons (p < 0.05). Little agreement was observed in the preferred timing of intervention as also for the duration of follow-up. CONCLUSIONS: This survey demonstrates a variation in management strategies of BPS, reflecting different specialist expertise. Most centers treat only a handful of cases per year and follow-up is not standardized. Therefore, management discussion within a multidisciplinary team is recommended. Recording patient data in an international registry for the comparison of management strategies and outcomes could support the development of future guidelines. LEVEL OF EVIDENCE: Level IV.

[The assessment of the endodontic foundation]. / De beoordeling van het endodontische fundament.

The diagnosis of an endodontic disease requires thorough research, collecting both clinical and radiographic information. The clinical examination includes history taking, visual inspection of the tooth and surrounding tissues, palpation of the soft and hard tissues, periodontal examination and percussion. The radiographic examination provides valuable information, but can never stand alone in arriving at a diagnosis. It is important to link the findings of the radiographic examination to other information. Sometimes, invasive examination is necessary, during which the coronal restoration is removed to allow better assessment of the tooth. This can provide additional information about the presence of caries, fractures, leakage of the restoration or other reasons for failure of the initial root canal treatment. A good diagnosis is essential for planning successful follow-up treatment.

MicroMPN: methods and software for high-throughput screening of microbe suppression in mixed populations.

Screening assays are used to test if one or more microbes suppress a pathogen of interest. In the presence of more than one microbe, the screening method must be able to accurately distinguish viable pathogen cells from non-viable and non-target microbes in a sample. Current screening methods are time-consuming and require special reagents to detect viability in mixed microbial communities. Screening assays performed using soil or other complex matrices present additional challenges for screening. Here, we develop an experimental workflow based on the most probable number (MPN) assay for testing the ability of synthetic microbial communities to suppress a soil-borne pathogen. Our approach, fluorMPN, uses a fluorescently labeled pathogen and microplate format to enable high-throughput comparative screening. In parallel, we developed a command-line tool, MicroMPN, which significantly reduces the complexity of calculating MPN values from microplates. We compared the performance of the fluorMPN assay with spotting on agar and found that both methods produced strongly correlated counts of equal precision. The suppressive effect of synthetic communities on the pathogen was equally recoverable by both methods. The application of this workflow for discriminating which communities lead to pathogen reduction helps narrow down candidates for additional characterization. Together, the resources offered here are meant to facilitate and simplify the application of MPN-based assays for comparative screening projects.IMPORTANCEWe created a unified set of software and laboratory protocols for screening microbe libraries to assess the suppression of a pathogen in a mixed microbial community. Existing methods of fluorescent labeling were combined with the most probable number (MPN) assay in a microplate format to enumerate the reduction of a pathogenic soil microbe from complex soil matrices. This work provides a fluorescent expression vector available from Addgene, step-by-step laboratory protocols hosted by protocols.io, and MicroMPN, a command-line software for processing plate reader outputs. MicroMPN simplifies MPN estimation from 96- and 384-well microplates. The microplate screening assay is amenable to robotic automation with standard liquid handling robots, further reducing the hands-on processing time. This tool was designed to evaluate synthetic microbial communities for use as microbial inoculates or probiotics. The fluorMPN method is also useful for screening chemical and antimicrobial libraries for pathogen suppression in complex bacterial communities like soil.

Postprandial metabolism and gut permeability in calves fed milk replacer with different macronutrient profiles or a whole milk powder.

Significant differences exist in the composition of current milk replacers (MR) and bovine whole milk. This study investigated how the macronutrient profile of 3 different MR formulations containing varying amounts of fat, lactose, and protein, and a whole milk powder (WP), affect postprandial metabolism and gut permeability in male Holstein calves. Sixty-four calves (45.4 ± 4.19 kg [mean ± SD] and 1.8 ± 0.62 d of age) were blocked in order of arrival to the facility and within each block, calves were randomly assigned to 1 of 4 treatments. Treatments included a high-fat MR (HF: 25.0% dry matter [DM] fat, 22.5% protein, 38.6% lactose; n = 14), a high-lactose MR (HL: 44.6% lactose, 22.5% protein, 18.0% fat; n = 17), a high-protein MR (HP: 26.0% protein, 18.0% fat, 41.5% lactose; n = 17), and WP (26.0% fat, 24.5% protein, 38.0% lactose; n = 16). Calves were fed 3.0 L (135 g/L) 3 times daily at 0600, 1200, and 1800 h with a teat bucket. Milk intake was recorded daily for the first 28 d after arrival, and blood sampling and body weight measurements were performed at arrival and on d 7, 14, 21, and 27. Gut permeability was estimated from fractional urinary excretion of indigestible markers (Cr-EDTA, lactulose, and d-mannitol) administered as a single dose on d 21 instead of the morning milk meal. Digestibility was determined simultaneously from a total collection of feces over 24 h. Postprandial dynamics were measured on d 28 by sequential blood sampling over 7.5 h. Dry matter intake of MR over 28 d was slightly greater in calves fed HL and HP than in WP. Recovery of Cr-EDTA and d-mannitol over a 24-h urine collection was greater in calves fed WP and HP than HL calves. Apparent total-tract digestibility of crude ash, protein, and fat did not differ among treatments; however, DM digestibility was lower in calves fed WP than in other treatment groups. In addition, abomasal emptying, as indicated by the area under the curve (AUC) for acetaminophen, was slower in calves fed WP than in calves fed HF and HL. The AUC for postprandial plasma glucose was lower in calves fed HL than WP and HF and lower in calves fed HP than WP. The AUC for postprandial serum insulin was greater in calves fed HP than WP and HF, whereas calves fed HL did not differ from the other treatments. Postprandial triglycerides were greater in calves fed WP, and postprandial adiponectin was higher in calves fed HL than other treatments. The high content of lactose and protein in MR had a major effect on postprandial metabolism. This raises the possibility of optimizing MR formulations to maintain metabolic homeostasis and influence development.

Artificial and natural interventions for chemotherapy- and / or radiotherapy-induced cognitive impairment: A systematic review of animal studies.

BACKGROUND: Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural interventions (plant/endogenously-derived) to reduce treatment-related cognitive impairments. METHODS: PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched and SYRCLE's tool was used for risk of bias assessment of the 134 included articles. RESULTS: High variability was observed and risk of bias analysis showed overall poor quality of reporting. Results generally showed positive effects in the intervention group versus cancer-therapy only group (67% of 156 cognitive measures), with only 15 (7%) measures reporting cognitive impairment despite intervention. Both artificial (61%) and natural (75%) interventions prevented cognitive impairment. Artificial interventions involving GSK3B inhibitors, PLX5622, and NMDA receptor antagonists, and natural interventions utilizing melatonin, curcumin, and N-acetylcysteine, showed most consistent outcomes. CONCLUSIONS: Both artificial and natural interventions may prevent cognitive impairment in rodents, which merit consideration in future clinical trials. Greater consistency in design is needed to enhance the generalizability across studies, including timing of cognitive tests and description of treatments and interventions.

Implementation of an integrated community approach in deprived neighbourhoods: a theory-based process evaluation using the Consolidated Framework for Implementation Research (CFIR).

BACKGROUND: We investigated the implementation process of an Integrated Community Approach (ICA) applied in four low socio-economic status neighbourhoods in Maastricht, the Netherlands. The ICA is a Population Health Management initiative and aims to improve population health, quality of care, professional's satisfaction and decrease costs of care. This study addresses the facilitators and barriers for implementing the ICA from a stakeholder perspective, including steering group members, professionals and citizens. METHODS: We conducted a mixed-methods study using a triangulation of methods to investigate the implementation from 1 December 2016 to 31 December 2020. The Consolidated Framework for Implementation Research guided data collection and data-analysis for evaluating the implementation process. In total, 77 interviews, 97 observations, seven focus groups, 65 collected documents and two surveys with open-ended questions were conducted. RESULTS: Facilitators for implementation were the use of citizen science to bring residents' needs into sharp focus, the integration of the ideology of Positive Health into the working routines of the professionals and leadership at the steering group level to overcome barriers in the ICA. The existing accounting and financial infrastructure obstructed combining budgets at neighbourhood level. CONCLUSIONS: Engaging citizens and professionals at an early stage is an important facilitator for implementation. The use of a shared vision on health also worked as a facilitator since it created a shared language among professionals, which is important in Population Health Management initiatives where multiple professionals are expected to collaborate. TRIAL REGISTRATION: NTR 6543; registration date, 25 July 2017.

Implementation of a care-pathway at the emergency department for older people presenting with nonspecific complaints; a protocol for a multicenter parallel cohort study.

BACKGROUND: Older adults frequently attend the Emergency Department (ED) with poorly defined symptoms, often called nonspecific complaints (NSC). NSC such as 'weakness' and 'not feeling well', often lead to an extensive differential diagnosis. Patients with NSC experience a prolonged length of stay at the ED and are prone to adverse outcomes. Currently, a care pathway for patients with NSC does not exist. A special structured care pathway for patients with NSC was designed to improve the efficiency and quality of care at the ED. METHOD: A multicenter parallel cohort study, organized in different hospitals in the Noord-Brabant area, the Netherlands, in which general practitioners (GP), elderly care physicians (ECP), Emergency Physicians (EP), geriatricians and internists will collaborate. Patients ≥ 70 years presenting with NSC and in need of ED admission as indicated by their own GP or ECP are eligible for inclusion. Before implementation each hospital will retrospectively include their own control-group. After implementation, patients will prospectively be included. The care-pathway exists of risk stratification by the APOP-screener, in-depth history taking, i.e. limited comprehensive geriatric assessment (CGA) and a standard set of diagnostics, and a dedicated ED-nurse (if possible) present to ensure the care-pathway is followed. The primary outcome is length of stay at the ED (LOS-ED) and perceived quality of care. Secondary outcomes are hospital length of stay, revisits, readmissions and mortality at 30- and 90-day follow-up. DISCUSSION: This study proposes a structured care pathway for older patients presenting at the ED with NSCs and considering effectiveness and perceived quality this may improve acute care for these patients. TRIAL REGISTRATION: Dutch Trial register, number NL8960.

Effects of major urban redesign on sedentary behavior, physical activity, active transport and health-related quality of life in adults.

BACKGROUND: The built environment is increasingly recognized as a determinant for health and health behaviors. Existing evidence regarding the relationship between environment and health (behaviors) is varying in significance and magnitude, and more high-quality longitudinal studies are needed. The aim of this study was to evaluate the effects of a major urban redesign project on physical activity (PA), sedentary behavior (SB), active transport (AT), health-related quality of life (HRQOL), social activities (SA) and meaningfulness, at 29-39 months after opening of the reconstructed area. METHODS: PA and AT were measured using accelerometers and GPS loggers. HRQOL and sociodemographic characteristics were assessed using questionnaires. In total, 241 participants provided valid data at baseline and follow-up. We distinguished three groups, based on proximity to the intervention area: maximal exposure group, minimal exposure group and no exposure group. RESULTS: Both the maximal and minimal exposure groups showed significantly different trends regarding transport-based PA levels compared to the no exposure group. In the exposure groups SB decreased, while it increased in the no exposure group. Also, transport-based light intensity PA remained stable in the exposure groups, while it significantly decreased in the no exposure group. No intervention effects were found for total daily PA levels. Scores on SA and meaningfulness increased in the maximal exposure group and decreased in the minimal and no exposure group, but changes were not statistically significant. CONCLUSION: The results of this study emphasize the potential of the built environment in changing SB and highlights the relevance of longer-term follow-up measurements to explore the full potential of urban redesign projects. TRIAL REGISTRATION: This research was retrospectively registered at the Netherlands Trial Register (NL8108).

Plasma ESR1 mutations and outcome to first-line paclitaxel and bevacizumab in patients with advanced ER-positive/HER2-negative breast cancer.

BACKGROUND: ESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients. METHODS: ESR1 mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm, N = 91) in the randomized phase II ATX study. Samples collected at baseline (n = 51) and at cycle 2 (n = 13, C2) were analyzed using a breast cancer next-generation sequencing panel. This study was powered to detect a benefit in progression-free survival (PFS) at six months for patients treated with paclitaxel/bevacizumab compared to historical trials with fulvestrant. PFS, overall survival (OS), and ctDNA dynamics were exploratory analyses. RESULTS: PFS at six months was 86% (18/21) in patients with an ESR1 mutation detected and 85% (23/27) in wildtype ESR1 patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6-8.8] for ESR1 mutant patients versus 8.7 months [95% confidence interval (CI), 8.3-9.2] for ESR1 wildtype patients [p = 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6-33.7] for ESR1 mutant patients versus 28.1 months [95% confidence interval (CI), 19.3-36.9] for ESR1 wildtype patients [p = 0.27]. Patients with ≥ two ESR1 mutations had a significantly worse OS, but not PFS, compared to those who did not [p = 0.003]. Change in ctDNA level at C2 was not different between ESR1 and other mutations. CONCLUSIONS: Presence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.

European Association for Endoscopic Surgery (EAES) consensus on Indocyanine Green (ICG) fluorescence-guided surgery.

BACKGROUND: In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community. METHODS: An expert panel of surgeons has been selected and invited to participate to this project. Systematic reviews of the PubMed, Embase and Cochrane libraries were performed to identify evidence on potential benefits of ICG fluorescence-guided surgery on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by the panel; they were then submitted to all EAES members through a two-rounds online survey and results presented at the EAES annual congress, Barcelona, November 2021. RESULTS: A total of 18,273 abstracts were screened with 117 articles included. 22 statements and 16 recommendations were generated and approved. In some areas, such as the use of ICG fluorescence-guided surgery during laparoscopic cholecystectomy, the perfusion assessment in colorectal surgery and the search for the sentinel lymph nodes in gynaecological malignancies, the large number of evidences in literature has allowed us to strongly recommend the use of ICG for a better anatomical definition and a reduction in post-operative complications. CONCLUSIONS: Overall, from the systematic literature review performed by the experts panel and the survey extended to all EAES members, ICG fluorescence-guided surgery could be considered a safe and effective technology. Future robust clinical research is required to specifically validate multiple organ-specific applications and the potential benefits of this technique on clinical outcomes.

Interactive effects of changes in UV radiation and climate on terrestrial ecosystems, biogeochemical cycles, and feedbacks to the climate system.

Terrestrial organisms and ecosystems are being exposed to new and rapidly changing combinations of solar UV radiation and other environmental factors because of ongoing changes in stratospheric ozone and climate. In this Quadrennial Assessment, we examine the interactive effects of changes in stratospheric ozone, UV radiation and climate on terrestrial ecosystems and biogeochemical cycles in the context of the Montreal Protocol. We specifically assess effects on terrestrial organisms, agriculture and food supply, biodiversity, ecosystem services and feedbacks to the climate system. Emphasis is placed on the role of extreme climate events in altering the exposure to UV radiation of organisms and ecosystems and the potential effects on biodiversity. We also address the responses of plants to increased temporal variability in solar UV radiation, the interactive effects of UV radiation and other climate change factors (e.g. drought, temperature) on crops, and the role of UV radiation in driving the breakdown of organic matter from dead plant material (i.e. litter) and biocides (pesticides and herbicides). Our assessment indicates that UV radiation and climate interact in various ways to affect the structure and function of terrestrial ecosystems, and that by protecting the ozone layer, the Montreal Protocol continues to play a vital role in maintaining healthy, diverse ecosystems on land that sustain life on Earth. Furthermore, the Montreal Protocol and its Kigali Amendment are mitigating some of the negative environmental consequences of climate change by limiting the emissions of greenhouse gases and protecting the carbon sequestration potential of vegetation and the terrestrial carbon pool.

The Montreal Protocol and the fate of environmental plastic debris.

Microplastics (MPs) are an emerging class of pollutants in air, soil and especially in all aquatic environments. Secondary MPs are generated in the environment during fragmentation of especially photo-oxidised plastic litter. Photo-oxidation is mediated primarily by solar UV radiation. The implementation of the Montreal Protocol and its Amendments, which have resulted in controlling the tropospheric UV-B (280-315 nm) radiation load, is therefore pertinent to the fate of environmental plastic debris. Due to the Montreal Protocol high amounts of solar UV-B radiation at the Earth's surface have been avoided, retarding the oxidative fragmentation of plastic debris, leading to a slower generation and accumulation of MPs in the environment. Quantifying the impact of the Montreal Protocol in reducing the abundance of MPs in the environment, however, is complicated as the role of potential mechanical fragmentation of plastics under environmental mechanical stresses is poorly understood.

Test-retest precision and longitudinal cartilage thickness loss in the IMI-APPROACH cohort.

OBJECTIVE: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort - an exploratory, 5-center, 2-year prospective follow-up cohort. DESIGN: Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 ± 7.1 years, body mass index (BMI): 28.1 ± 5.3 kg/m2, 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test-retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test-retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: -211 µm) for the quartile with the highest vs the quartile with the lowest s-scores. RESULTS: The test-retest precision was 69 µm for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached -174 µm (95% CI: [-207, -141] µm, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: [0.52, 3.28]). CONCLUSION: IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score. GOV IDENTIFICATION: NCT03883568.

Hormonal status effects on the electrophysiological correlates of performance monitoring in women.

Fluctuations in ovarian hormones are thought to play a role in the increased prevalence of mood and anxiety disorders in women. Error-related negativity (ERN) and error positivity (Pe) are two putative electrophysiological biomarkers for these internalizing disorders. We investigated whether female hormonal status, specifically menstrual cycle phase and oral contraceptive (OC) use, impact ERN and Pe. Additionally, we examined whether the relationship between the ERN and negative affect (NA) was moderated by hormonal status and tested whether the ERN mediated the relation between ovarian hormones and NA. Participants were healthy, pre-menopausal women who were naturally cycling (NC) or using OCs. Using a counterbalanced within-subject design, all participants performed a speeded-choice reaction-time task twice while undergoing electroencephalography measurements. NC women (N = 42) performed this task during the early follicular and midluteal phase (when estrogen and progesterone are both low and both high, respectively), while OC users (N = 42) performed the task during active OC use and during their pill-free week. Estradiol and progesterone levels were assessed in saliva. Comparing the two cycle phases within NC women revealed no differences in the (Δ)ERN, (Δ)Pe or NA. We did observe a negative relation between phase-related changes in the ΔERN and changes in NA. Mediation analysis additionally showed that phase-related changes in estradiol were indirectly and negatively related to NA through a reduction of ΔERN amplitudes. When comparing active OC users with NC women, we observed increased ΔPe- but not (Δ)ERN amplitudes in the former group. No evidence was found for moderating effects of menstrual cycle phase or OC use on the relation between the ERN and NA. These findings suggest that hormonal status may impact the neural correlates of performance monitoring and error sensitivity, and that this could be a potential mechanism through which ovarian hormones influence mood.

Metals in urban soils of Europe: A systematic review.

Metal contamination of soils is widespread across Europe and is of great concern as it may impact food production, the supply of drinking water and human health (European Environment Agency, 2014; Panagos et al., 2013). Most research to date on soil metal contamination has focussed on agricultural soils (Tóth et al., 2016a). Current knowledge of the extent of urban soil metal contamination in Europe, however, is limited, especially for soils in recreational areas, which is particularly concerning as these areas may have a high footfall. Here, we conducted a systematic analysis of metal contamination in European urban soils based on 174 peer-reviewed studies spanning 143 urban sites and 29 European countries. The results show that reporting of data on urban soil metals is highly heterogeneous across the study area. Over half of all studies are from only five countries (Italy, Spain, UK, Poland and Serbia) and no data are available for 14 other European countries. The metals that most commonly exceed national safety thresholds are Pb, Zn, Cu, Cr and Ni. Elevated levels of these metals are usually attributed to anthropogenic sources, primarily traffic and industry. Some 22 % of urban sites studied show anthropogenic enrichment; this phenomenon is most common in Italy, Serbia and Finland. In contrast, 44 % of urban sites studied show geogenic metal enrichment; this is most common in Italy, the UK and Serbia. The dataset is subject to a sample size bias, whereby soil metal enrichment is identified more frequently in regions with more data. Future studies should focus on key knowledge gaps, such as urban soils in locations with current or historical heavy industrialisation and locations in central and eastern Europe. Study methods should be standardised to facilitate comparison of soil metal data from different studies and European safety thresholds should be identified for key elements.

Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

Battling the obesity epidemic with a school-based intervention: Long-term effects of a quasi-experimental study.

BACKGROUND: School-based health-promoting interventions are increasingly seen as an effective population strategy to improve health and prevent obesity. Evidence on the long-term effectiveness of school-based interventions is scarce. This study investigates the four-year effectiveness of the school-based Healthy Primary School of the Future (HPSF) intervention on children's body mass index z-score (BMIz), and on the secondary outcomes waist circumference (WC), dietary and physical activity (PA) behaviours. METHODS AND FINDINGS: This study has a quasi-experimental design with four intervention schools, i.e., two full HPSFs (focus: diet and PA), two partial HPSFs (focus: PA), and four control schools. Primary school children (aged 4-12 years) attending the eight participating schools were invited to enrol in the study between 2015 and 2019. Annual measurements consisted of children's anthropometry (weight, height and waist circumference), dietary behaviours (child- and parent-reported questionnaires) and PA levels (accelerometers). Between 2015 and 2019, 2236 children enrolled. The average exposure to the school condition was 2·66 (SD 1·33) years, and 900 participants were exposed for the full four years (40·3%). After four years of intervention, both full (estimated intervention effect (B = -0·17 (95%CI -0·27 to -0·08) p = 0·000) and partial HPSF (B = -0·16 (95%CI-0·25 to -0·06) p = 0·001) resulted in significant changes in children's BMIz compared to control schools. Likewise, WC changed in favour of both full and partial HPSFs. In full HPSFs, almost all dietary behaviours changed significantly in the short term. In the long term, only consumption of water and dairy remained significant compared to control schools. In both partial and full HPSFs, changes in PA behaviours were mostly absent. INTERPRETATION: This school-based health-promoting intervention is effective in bringing unfavourable changes in body composition to a halt in both the short and long term. It provides policy makers with robust evidence to sustainably implement these interventions in school-based routine.