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Background Increased neurofilament levels in biofluids are commonly used as a proxy for neurodegeneration in several neurodegenerative disorders. In this study, we aimed to investigate the distribution of neurofilaments in the cerebral cortex of Parkinson’s disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) donors, and its association with pathology load and MRI measures of atrophy and diffusivity. Methods Using a within-subject post-mortem MRI-pathology approach, we included 9 PD, 12 PDD/DLB and 18 age-matched control donors. Cortical thickness and mean diffusivity (MD) metrics were extracted respectively from 3DT1 and DTI at 3T in-situ MRI. After autopsy, pathological hallmarks (pSer129-αSyn, p-tau and amyloid-β load) together with neurofilament light-chain (NfL) and phosphorylated-neurofilament medium- and heavy-chain (p-NfM/H) immunoreactivity were quantified in seven cortical regions, and studied in detail with confocal-laser scanning microscopy. The correlations between MRI and pathological measures were studied using linear mixed models. Results Compared to controls, p-NfM/H immunoreactivity was increased in all cortical regions in PD and PDD/DLB, whereas NfL immunoreactivity was increased in the parahippocampal and entorhinal cortex in PDD/DLB. NfL-positive neurons showed degenerative morphological features and axonal fragmentation. The increased p-NfM/H correlated with p-tau load, and NfL correlated with pSer129-αSyn but more strongly with p-tau load in PDD/DLB. Lastly, neurofilament immunoreactivity correlated with cortical thinning in PD and with increased cortical MD in PDD/DLB. Conclusions Taken together, increased neurofilament immunoreactivity suggests underlying axonal injury and neurofilament accumulation in morphologically altered neurons with increased pathological burden. Importantly, we demonstrate that such neurofilament markers at least partly explain MRI measures that are associated with the neurodegenerative process.

Contains fulltext : 292430.pdf (Publisher’s version ) (Open Access) 01 juni 2023

The current classification of atrial fibrillation (AF) is mainly focused on the clinical presentation according to the duration of AF episodes and the mode of termination, which incompletely reflect the severity and progressive nature of the underlying atrial disease. In this review article, "atrial cardiomyopathy" is discussed as a new concept in AF pathophysiology. Electrogram-, imaging-, and biomarker-derived measures and parameters to assess atrial cardiomyopathy, which will likely impact how AF is clinically classified and managed in the future, are presented.Die aktuelle Klassifikation von Vorhofflimmern (VHF) basiert hauptsächlich auf der klinischen Präsentation unter Berücksichtigung der Dauer einzelner VHF-Episoden und der Art, wie eine VHF-Episode spontan endet. Dies beschreibt allerdings den Schweregrad und den progressiven Charakter der zugrunde liegenden atrialen Erkrankung nicht ausreichend. Im vorliegenden Übersichtsbeitrag wird die „atriale Kardiomyopathie“ als ein neues Konzept der Pathophysiologie von VHF diskutiert. Wir stellen elektrogramm-, bildgebungs- und biomarkerbasierte Parameter für die Beurteilung der atrialen Kardiomyopathie vor, die in der Zukunft wahrscheinlich die klinische Klassifikation und Behandlung von VHF beeinflussen werden.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work is part of Personalize AF. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974, This work was also supported by the Swiss National Supercomputing Centre (CSCS), project s1074. Introduction Detecting and targeting the most dominant drivers of atrial fibrillation (AF) might improve the outcome of AF ablation procedures. We hypothesize that dominant drivers entrain their vicinity in a temporally and spatially stable manner resulting in local as well as adjacent repetitive activation patterns. Purpose We present a novel approach to detect the most dominant drivers of AF based on driver repetitiveness and the degree to which they entrain their vicinity. Methods We retrospectively analyzed a dataset of high-density bi-atrial sequential mapping in ablation-naive persistent AF patients (n=13, 30s recording per site). Candidate drivers (focal activity or re-entry) were detected based on local activation time analysis of unipolar electrograms. Focal activity was defined as radial spread of activation, re-entry as a circular activation sequence on at least 4 splines of the mapping catheter that covered >50% of the AF cycle length. As a measure of driver stability, we determined the driver's local repetitiveness (in % of recording). As a measure of driver-associated entrainment, we determined the directionally coherent repetitiveness of adjacent recordings within 30 mm (Figure 1). Following our hypothesis, most dominant drivers can be recognized by their high local and directional coherent adjacent repetitiveness. Results A total of 459 recordings were analyzed (35±5 per patient). We detected 130 focal activities (10±3 per patient) and 42 re-entries (4±2 per patient) in total. The spatial distribution of all drivers is shown in Figure 2 (blue bars). Focal activities were more repetitive than re-entries (Figure 2, median [IQR] 3.2% [1.9%, 5.6%] vs. 1.8% [1.8%, 2.2%], p Conclusion In this abstract we present a novel methodology to detect the most dominant drivers of AF. Using this method, we found that some (but not all) patients have temporally and spatially stable drivers that are able to entrain their vicinity.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by PersonalizeAF project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974. Background Pulmonary vein isolation (PVI) alone is not sufficient for all persistent atrial fibrillation (AF) patients. Ablation of localized AF drivers might be a promising adjunctive ablation strategy but detecting such drivers is limited by the small field of view of current mapping catheters. Purpose We propose a technique to detect localized AF drivers that combines sequential mapping of repetitive activation patterns into a larger composite map. The performance of this technique was evaluated in several simulated scenarios of known mechanisms during AF. Methods Representative repetitive conduction patterns that may occur in AF were simulated in a detailed volumetric 3D model of the atria: a large peripheral wave, stable and meandering re-entries, and single and multiple ectopic foci. Endocardial electrograms were sequentially generated from overlapping regions in the left posterior wall (4x4 grid, 3mm spacing, 0.5-1.5 seconds), and repetitive activation patterns were detected. Overlapping areas between sequential maps were used to align the repetitive patterns. Local patterns were then combined into larger composite maps (Fig. 1A). Reconstruction performance was quantified by the average local activation time (LAT) difference between original and reconstructed activation patterns. The relation between electrode overlaps and the quality of reconstructions were assessed at different degrees of spatial overlap (approximately 10% to 25% of the grid area, corresponding to 1.6 ± 0.6 and 4.1 ± 1.2 overlapping electrodes, respectively). Results All simulated patterns could be reconstructed from sequential recordings (Fig. 1B). LAT errors in recordings with 25% overlap were low in all cases: 5±2 msec for the peripheral wave, 5±2 and 3±1 msec for focal and multifocal activities and 6±2 and 11±2 & 17±3 msec for stable, meandering and highly meandering re-entries respectively (Fig. 2). Composite maps of meandering and highly meandering re-entries presented significantly higher reconstruction errors than other more stable patterns (p Conclusion We developed a novel methodology to combine high-density sequential recordings with limited coverage into larger composite activation maps. Using this method, we reconstructed highly accurate activation maps for multiple simulated AF mechanism scenarios. Results were promising even with a small overlap between sequential recording sites and relatively unstable patterns, providing a proof of principle to apply this approach in clinical recordings of human AF.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation. Background Biventricular pacing (BiVP) is the standard treatment for patients with dyssynchronous heart failure. Despite the effectiveness of BiVP, 6% of patients develop ventricular tachyarrhythmia’s (VTAs) within one year following implantation. The relationship between BiVP and the development of VTAs is still under debate. The left-sided epicardium-to-endocardium activation during BiVP creates a nonphysiological activation and repolarization and might provoke VTAs. A relatively new treatment option is left bundle branch area pacing (LBBAP), in which the physiological activation of the left ventricle is restored. We hypothesize that LBBAP leads to a more homogenous repolarization compared to conventional BiVP. Purpose To compare time-dependent repolarization changes in patients with dyssynchronous heart failure receiving LBBAP versus BiVP. Methods Patients with dyssynchronous heart failure eligible for cardiac resynchronization therapy who underwent LBBAP (n=13) or BiVP (n=28) were retrospectively included. Standard 12-lead electrocardiograms (ECG) obtained prior to implantation [baseline], shortly following implantation (0-2 days,[acute]) and during follow-up (31-180 days, [FU]) were analyzed. The QT interval and Tpeak to Tend interval (Tpeak-Tend) were calculated using a semi-automatic approach in MATLAB. Repolarization differences between LBBAP and BiVP patients were determined using the Mann-Whitney U-test. Time-dependent changes within groups were determined using the Wilcoxon signed rank tests. Significance was defined as a p-value ≤0.05. Results The QT interval did not significantly change over time in BiVP patients, but it decreased immediately following implantation and during FU in LBBAP patients. At FU, QT interval was significantly lower in LBBAP than in BiVP patients (Figure 1, left panel). A slight increase in Tpeak-Tend interval over time in BiVP patients, while it tends to decrease over time in LBBAP patients can be seen in the right panel. Acutely and long term after implantation, Tpeak-Tend was significantly lower in LBBAP than in BiVP patients. Conclusion LBBAP is associated with lower QT and Tpeak-Tend intervals compared to BiVP during FU, suggesting that LBBAP leads to less heterogeneity of repolarization over time. These findings suggest a more physiological repolarization pattern in LBBAP compared to BiVP, which may decrease the risk of developing VTAs.

In adults, alcohol intoxication is associated with prolongation of the QT interval corrected for heart rate (QTc). The QTc is influenced by age and sex. Although alcohol intoxication is increasingly common in adolescents, there are no data on the prevalence of QTc prolongation in adolescents with alcohol intoxication. This study aimed to determine the prevalence of QTc prolongation in adolescents with alcohol intoxication and identify at-risk adolescents. In this observational study including adolescents aged 10–18 years, heart rate and QT interval were automatically assessed from an electrocardiogram (ECG) at alcohol intoxication using a validated algorithm. The QTc was calculated using both the Bazett formula (QTcB) and Fridericia formula (QTcF). If present, an ECG recorded within 1 year of the date of admission to the emergency department was obtained as a reference ECG. A total of 317 adolescents were included; 13.3% had a QTcB and 7.9% a QTcF longer than the sex- and age-specific 95th-percentile. None of the adolescents had a QTcB or QTcF > 500 ms, but 11.8% of the adolescents with a reference ECG had a QTcB prolongation of > 60 ms, while no adolescents had a QTcF prolongation of > 60 ms. QTc prolongation was mainly attributable to an increase in heart rate rather than QT prolongation, which underlies the differences between QTcB and QTcF. Male sex and hypokalaemia increased the likelihood of QTc prolongation.Conclusion: QTc prolongation was seen in approximately 10% of the adolescents presenting with alcohol intoxication, and although no ventricular arrhythmias were observed in this cohort, QTc prolongation increases the potential for malignant QT-related arrhythmias. Clinicians must be aware of the possibility of QTc prolongation during alcohol intoxication and make an effort to obtain an ECG at presentation, measure the QT interval, and give an adequate assessment of the findings. We advocate admitting adolescents with alcohol intoxication and QTc prolongation. During hospital admission, we recommend limiting exposure to QTc-prolonging medication, increasing potassium levels to a high-normal range (4.5–5.0 mmol/L) and obtaining a reference ECG at discharge. What is Known:• One out of five deaths in adolescents is alcohol-related. Alcohol intoxication has been related to cardiac arrhythmias and sudden cardiac death.•In adults, alcohol intoxication is associated with QTc prolongation. What is New:•Approximately 10% of the adolescents with alcohol intoxication had a QTc longer than the age- and sexspecific cut-off. In contrast to adults, in adolescents with alcohol intoxication, QTc prolongation is attributable to an increase in heart rate, rather than a prolongation of the QT interval.•Especially males and adolescents with hypokalaemia are at risk of QTc prolongation.

Purpose No clear consensus exists on which anterior surgical technique is most cost-effective for treating cervical degenerative disk disease (CDDD). One of the most common treatment options is anterior cervical discectomy with fusion (ACDF). Anterior cervical discectomy with arthroplasty (ACDA) was developed in an effort to reduce the incidence of clinical adjacent segment pathology and associated additional surgeries by preserving motion. This systematic review aims to evaluate the evidence regarding the cost-effectiveness of anterior surgical decompression techniques used to treat radiculopathy and/or myelopathy caused by CDDD. Methods The search was conducted in PubMed, EMBASE, Web of Science, CINAHL, EconLit, NHS-EED and the Cochrane Library. Studies were included if healthcare costs and utility or effectivity measurements were mentioned. Results A total of 23 studies were included out of the 1327 identified studies. In 9 of the 13 studies directly comparing ACDA and ACDF, ACDA was the most cost-effective technique, with an incremental cost effectiveness ratio ranging from $2.900/QALY to $98.475/QALY. There was great heterogeneity between the costs of due to different in- and exclusion criteria of costs and charges, cost perspective, baseline characteristics, and calculation methods. The methodological quality of the included studies was moderate. Conclusion The majority of studies report ACDA to be a more cost-effective technique in comparison with ACDF. The lack of uniform literature impedes any solid conclusions to be drawn. There is a need for high-quality cost-effectiveness research and uniformity in the conduct, design and reporting of economic evaluations concerning the treatment of CDDD. Trial registration PROSPERO Registration: CRD42020207553 (04.10.2020).

Most climate adaptation plans expect stakeholders to change their behavior as part of building resilience. Given its long-term and complex nature, monitoring and evaluation is a key requisite for climate adaptation planning. So far, behavioral aspects have received only limited attention in the evaluation approaches for climate adaptation planning. This article proposes a theory-based evaluation approach based on the theory of planned behavior, for the evaluation of climate adaptation. A local climate adaptation programme for watershed development in rural India provides an illustrative case for this approach. For this case, the approach helped to uncover important factors that influence behavioral intentions, which were different for different groups in the farming community. Additionally, it helped to put behavioral change in a longer-term perspective. The illustrative case also suggests certain improvements for evaluations based on the theory of planned behavior.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of a community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 potentially active molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (Nsp12 domain), and (alpha) spike protein S. Overall, 27 potential inhibitors were experimentally confirmed by binding-, cleavage-, and/or viral suppression assays and are presented here. All results are freely available and can be taken further downstream without IP restrictions. Overall, we show the effectiveness of computational techniques, community efforts, and communication across research fields (i.e., protein expression and crystallography, in silico modeling, synthesis and biological assays) to accelerate the early phases of drug discovery.

Background Bacterial communities are critical to ecosystem functioning and sensitive to their surrounding physiochemical environment. However, the impact of land use change on microbial communities remains understudied. We used 16S rRNA gene amplicon sequencing and shotgun metagenomics to assess soil microbial communities' taxonomic and functional responses to land use change. We compared data from long-term grassland, exotic forest and horticulture reference sites to data from sites that transitioned from (i) Grassland to exotic forest or horticulture and from (ii) Exotic forest to grassland. Results Community taxonomic and functional profiles of the transitional sites significantly differed from those within reference sites representing both their historic and current land uses (P Conclusions Our study indicates that microbial communities respond in a somewhat predictable way after a land use conversion event by shifting from communities reflecting their former land use towards those reflecting their current land use. Our findings help us to better understand the legacy effects of land use change on soil microbial communities and implications for their role in soil health and ecosystem functioning. Understanding the responsiveness of microbial communities to environmental disturbances will aid us in incorporating biotic variables into soil health monitoring techniques in the future.

Introduction Patients with ventricular tachyarrhythmias (VT) are at high risk of sudden cardiac death. When appropriate, catheter ablation is modestly effective, with relatively high VT recurrence and complication rates. Personalized models that incorporate imaging and computational approaches have advanced VT management. However, 3D patient-specific functional electrical information is typically not considered. We hypothesize that incorporating non-invasive 3D electrical and structural characterization in a patient-specific model improves VT-substrate recognition and ablation targeting.Materials and methods In a 53-year-old male with ischemic cardiomyopathy and recurrent monomorphic VT, we built a structural-functional model based on high-resolution 3D late-gadolinium enhancement (LGE) cardiac magnetic resonance imaging (3D-LGE CMR), multi-detector computed tomography (CT), and electrocardiographic imaging (ECGI). Invasive data from high-density contact and pace mapping obtained during endocardial VT-substrate modification were also incorporated. The integrated 3D electro-anatomic model was analyzed off-line.Results Merging the invasive voltage maps and 3D-LGE CMR endocardial geometry led to a mean Euclidean node-to-node distance of 5 & PLUSMN; 2 mm. Inferolateral and apical areas of low bipolar voltage (< 1.5 mV) were associated with high 3D-LGE CMR signal intensity (> 0.4) and with higher transmurality of fibrosis. Areas of functional conduction delay or block (evoked delayed potentials, EDPs) were in close proximity to 3D-LGE CMR-derived heterogeneous tissue corridors. ECGI pinpointed the epicardial VT exit at & SIM;10 mm from the endocardial site of origin, both juxtaposed to the distal ends of two heterogeneous tissue corridors in the inferobasal left ventricle. Radiofrequency ablation at the entrances of these corridors, eliminating all EDPs, and at the VT site of origin rendered the patient non-inducible and arrhythmia-free until the present day (20 months follow-up). Off-line analysis in our model uncovered dynamic electrical instability of the LV inferolateral heterogeneous scar region which set the stage for an evolving VT circuit.Discussion and conclusion We developed a personalized 3D model that integrates high-resolution structural and electrical information and allows the investigation of their dynamic interaction during arrhythmia formation. This model enhances our mechanistic understanding of scar-related VT and provides an advanced, non-invasive roadmap for catheter ablation. This study was supported by the Special Research Fund (BOF) of Hasselt University (BOF17DOCMA15) and the Maastricht University Medical Center (MUMC+) to JS, the Hein Wellens Foundation, Health Foundation Limburg (Maastricht, The Netherlands), and a Veni grant from the Netherlands Organization for Scientific Research (TTW16772) to MC, the Netherlands CardioVascular Research Initiative (CVON2017-13 VIGILANCE and CVON2018B030 PREDICT2), Den Haag, The Netherlands to PV, and a Veni grant from the Netherlands Organization for Scientific Research (NWO/ZonMw 0915016181013) to RTB.

Social withdrawal is often presented as overall negative, with a focus on loneliness and peer exclusion. However, social withdrawal is also a part of normative adolescent development, which indicates that groups of adolescents potentially experience social withdrawal differently from one another. This study investigated whether different groups of adolescents experienced social withdrawal in daily life as positive versus negative, using experience sampling data from a large-scale study on mental health in general population adolescents aged 11 to 20 (n = 1913, MAge = 13.8, SDAge = 1.9, 63% female) from the Flemish region in Belgium. Two social withdrawal clusters were identified using model-based cluster analysis: one cluster characterized by high levels of positive affect and one cluster characterized by high levels of negative affect, loneliness and exclusion. Logistic regression showed that boys had 66% decreased odds of belonging to the negative cluster. These results show that daily-life social withdrawal experiences are heterogeneous in adolescence, which strengthens the view that, both in research and clinical practice, social withdrawal should not be seen as necessarily maladaptive. ispartof: JOURNAL OF YOUTH AND ADOLESCENCE vol:51 issue:5 pages:915-926 ispartof: location:United States status: published

Aims Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. Methods and results BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). Conclusion Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. Clinical Trial Registration The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Shunts, alternative pathways in chemical reaction networks, are ubiquitous in Nature, enabling adaptability to external and internal stimuli. We introduce a chemical reaction network (CRN) in which the recovery of a Michael-accepting species is driven by oxidation chemistry. Using weak oxidants can enable access to two shunts within this CRN with different kinetics and a reduced number of side reactions compared to the main cycle that is driven by strong oxidants. Further, we introduce a strategy to recycle one of the main products under flow conditions to partially reverse the CRN and control product speciation throughout time. These findings introduce new levels of control over artificial CRNs, driven by redox chemistry, narrowing the gap between synthetic and natural systems.

Background For a substantial part of patients with chronic low back pain, the origin is located in the sacroiliac joint (SIJ). Minimally invasive sacroiliac joint fusion (MISJF) is increasingly being implemented as a treatment option in SIJ dysfunction. Despite remaining controversy, evidence continues to increase. This study evaluates the clinical results and safety of MISJF in a double-center consecutive case series in patients with SIJ dysfunction over a one-year observation period. Methods SIJ complaints were diagnosed after history taking, physical examination and least a 50% reduction of SIJ pain 30–60 min following image-guided injection. Primary outcome measures were patient reported outcome measurements (PROMs), consisting of Visual Analogue Scale (VAS) pain score and EuroQol 5-dimensions 3-levels (EQ-5D-3L). Patients’ perspectives on the effects of surgery were collected through questionnaires. Secondary outcome measures were implant positioning and (serious) adverse events ((S)AE’s). Results A total of 29 patients were included. In 44.8% of patients, SIJ dysfunction was of postpartum origin. The mean VAS-pain score improved from 7.83 (± 1.71) to 4.97 (± 2.63) postoperatively (p p p = 0.026). In 13.7% of patients, an (S)AE occurred. Conclusion MISJF appears to be an effective and safe procedure in this cohort. Statistically significant and clinically relevant improvements in pain and quality of life were observed one-year postoperatively. Future studies should focus on the long-term outcomes to further evaluate the safety and effectiveness of MISJF.

BACKGROUND: Patients with sacroiliac joint dysfunction are limited in daily life activities such as gait, climbing stairs and rising from a chair. It is well known that individuals with chronic low back pain have impaired balance compared to healthy individuals. This cross-sectional case-control study aims to investigate spatiotemporal parameters, center of pressure and mass, pelvic angles and other joint angles in patients with sacroiliac joint dysfunction in comparison with healthy controls.METHODS: Motion analysis existed of three tasks: (1) normal gait, (2) single-leg-stance, and (3) sit-to-stance. Spatiotemporal parameters, center of pressure, pelvic angles and other joint angles were measured using a twelve-camera, three-dimensional motion capture system and ground reaction force platforms.FINDINGS: Thirty subjects were recruited for this study; ten patients, ten matched controls and ten healthy student controls. For gait, patients had a lower cadence, longer double support phase, shorter step length and slower walking speed than controls. For single-leg-stance, patients had a smaller hip angle of the risen leg than controls. Also, variability in center of pressure was larger in patients. For sit-to-stance, the total time to perform the task was almost doubled for patients compared to controls.INTERPRETATION: This study demonstrates that patients with sacroiliac joint dysfunction have an impaired gait, more balance problems during standing and standing up compared to healthy controls. This novel information assists to further comprehend the pathology and disease burden of sacroiliac joint dysfunction, in addition, it may allow us to evaluate the effect of current therapies.

A 2-year-11-month-old female spayed cat was at the Small Animal Teaching Hospital of Ghent University presenting with hyperactivity, scratching and licking all over her body and an abnormal urination behaviour. Nothing remarkable was found on the dermatology and neurological examination. Based on the owner's history and video material, the presence of feline hyperaesthesia syndrome (FHS) was hypothesised. A symptomatic treatment with gabapentin was established for a month without any significant improvement. An elimination diet with hydrolysed protein sources was started and, as a result, the dose of gabapentin was reduced after three days and completely stopped after one week. With the exception of two non-intentional exposures to non-hypoallergenic diets and the challenge with new protein sources by the owner, the cat has been free of symptoms, with the exception of a slight reaction in the lumbar area (significantly reduced in comparison before starting the diet), and without the use of medication. In conclusion, an elimination diet should be considered as part of the diagnostic plan for FHS and should not be delegated to the last step if the patient's condition allows it.

COVID-19 lockdown measures have profoundly impacted adolescent' daily life, with research suggesting an increase in irritability, stress, loneliness, and family conflict. A potential protective factor is parent-child relationship quality; however, no studies have investigated this. We used data from SIGMA, a longitudinal, experience sampling cohort study, in which N = 173 adolescents aged 11 to 20 were tested before and during COVID-19. Multilevel analyses showed decreased daily-life irritability and increased loneliness from pre- to mid-pandemic. Daily-life stress levels were unchanged. Relationship quality was negatively associated with irritability and loneliness and buffered against the increase in loneliness. Effect sizes were small and do not support a strong effect of the first lockdown on irritability, stress, loneliness, and family conflict in adolescents. ispartof: Journal Of Research On Adolescence vol:31 issue:3 pages:623-644 ispartof: location:United States status: published

Background Dark-blood late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) is proved to be superior to bright-blood LGE MRI in localising subtle subendocardial scar in the ventricles, because of improved contrast between myocardial scar and blood. However, dark-blood LGE MRI has not yet been applied to identify atrial scar in the left atrium (LA) and therefore its threshold to determine scar is unknown. Purpose To determine the optimal intensity threshold for 3D dark-blood LGE MRI for atrial ablation scar after pulmonary vein isolation (PVI) Methods Twelve re-do PVI patients with symptomatic atrial fibrillation (AF) who underwent pre-procedural 3D dark-blood LGE MRI were included. The image intensity ratio (IIR = myocardial intensity normalized to the blood pool) from the LGE MRI were calculated using ADAS-AF. High-density bipolar voltages (BiV) maps were recorded during sinus rhythm prior to ablation. All BiV locations ≤5 mm from the ADAS LA anatomy were compared with the corresponding IIR, using custom-made software in MATLAB. To achieve an equal ratio between scar (BiV ≤0.15 mV) and non-scar (BiV >0.15 mV) for each patient, non-scar pairs were randomly resampled to the same number as scar pairs. This was repeated 10 times and for every random selection, receiver operating characteristics (ROC) analysis was performed to determine the optimal IIR threshold (provided by the Youden's index) for scar defined as BiV Results Of the 12 included patients, 8 had prior cryo PVI, 2 radiofrequency PVI, and 2 surgical/hybrid AF ablation. ROC curve analysis estimated the average optimal threshold for predicting BiV Conclusion This is the first study to use the novel 3D dark-blood whole heart LGE MRI to evaluate LA ablation scar after PVI. Based on the ROC analyses, an IIR of 1.106 is the optimal threshold for atrial ablation scar, defined as high density bipolar voltage Funding Acknowledgement Type of funding sources: None.

Photoreduction of perylenediimide (PDI) derivatives has been widely studied for use in photocatalysis, hydrogen evolution, photo-responsive gels, and organic semiconductors. Upon light irradiation, the radical anion (PDI⋅- ) can readily be obtained, whereas further reduction to the dianion (PDI2- ) is rare. Here we show that full 2-electron photoreduction can be achieved using UVC light: 1) in anaerobic conditions by 'direct photoreduction' of PDI aggregates, or 2) by 'indirect photoreduction' in aerobic conditions due to acetone ketyl radicals. The latter strategy is also efficient for other dyes, such as naphthalenediimide (NDI) and methylviologen (MV2+ ). Efficient photoreduction on the minute time-scale using simple LED light in aerobic conditions is attractive for use in dissipative light-driven systems and materials.

Patients with SARS-CoV-2 infection present with different lung compliance and progression of disease differs. Measures of lung mechanics in SARS-CoV-2 patients may unravel different pathophysiologic mechanisms during mechanical ventilation. The objective of this prospective observational study is to describe whether Electrical Impedance Tomography (EIT) guided positive end-expiratory pressure (PEEP) levels unravel changes in EIT-derived parameters over time and whether the changes differ between survivors and non-survivors. Serial EIT-measurements of alveolar overdistension, collapse, and compliance change in ventilated SARS-CoV-2 patients were analysed. In 80 out of 94 patients, we took 283 EIT measurements (93 from day 1–3 after intubation, 66 from day 4–6, and 124 from day 7 and beyond). Fifty-one patients (64%) survived the ICU. At admission mean PaO2/FiO2-ratio was 184.3 (SD 61.4) vs. 151.3 (SD 54.4) mmHg, (p = 0.017) and PEEP was 11.8 (SD 2.8) cmH2O vs. 11.3 (SD 3.4) cmH2O, (p = 0.475), for ICU survivors and non-survivors. At day 1–3, compliance was ~ 55 mL/cmH2O vs. ~ 45 mL/cmH2O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12–13 cmH2O. At day 4–6 compliance changed to ~ 50 mL/cmH2O vs. ~ 38 mL/cmH2O. At day 7 and beyond, compliance was ~ 38 mL/cmH2O with the intersection at a PEEP of ~ 9 cmH2O vs. ~ 25 mL/cmH2O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH2O. Surviving SARS-CoV-2 patients show more favourable EIT-derived parameters and a higher compliance compared to non-survivors over time. This knowledge is valuable for discovering the different groups.

Adaptation pathways is a planning approach used to design flexible, long-term strategies for dealing with future uncertainty. However, emphasis on how to discuss pathways elements with stakeholders during the pathways building process is under-represented in the existing pathways literature. This paper presents a participatory methodology for building normative adaptation pathways with local stakeholders. Iterative discussions are facilitated using a Delphi study that is designed to explicitly consider institutional, and multi-actor dimensions in the formulation of future adaptive strategies. This leads to adaptation pathways that are more inclusive of local needs. This paper describes the steps for iteratively designing adaptation pathways in a multi-actor setting through a Delphi study. A pilot application of this Delphi-based adaptation pathway approach is illustrated with local actors in peri-urban Kolkata (India) for future water management. It demonstrates how this methodology offers a structured way to introduce pathways thinking to local stakeholders and helps build consensus about future preferences and adaptation options. Moreover, it stimulates discussions about normative differences across and within stakeholder groups through the underlying values that define future pathways as well as the institutional adjustments needed to successfully activate adaptations strategies over time. Future work may be directed towards to strengthening discussions around uncertainty, connecting pathways to a broader set of future scenarios, and comparing this facilitation method against other existing ones.

Background: Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing. In adults, this knowledge can be used to aid an LQTS diagnosis and, possibly, for risk stratification. However, data on the diagnostic value of the standing test in children are currently limited.Objective: To determine the potential value of the standing test to aid LQTS diagnostics in children.Methods: In a prospective cohort including children (≤18 years) who had a standing test, comprehensive analyses were performed including manual and automated QT interval assessments and determination of T-wave morphology changes.Results: We included 47 LQTS children and 86 control children. At baseline, the QTc that identified LQTS children with a 90% sensitivity was 435 ms, which yielded a 65% specificity. A QTc ≥ 490 ms after standing only slightly increased sensitivity (91%, 95% confidence interval [CI]: 80%-98%) and slightly decreased specificity (58%, 95% CI: 47%-70%). Sensitivity increased slightly more when T-wave abnormalities were present (94%, 95% CI: 82%-99%; specificity 53%, 95% CI: 42%-65%). When a baseline QTc ≥ 440 ms was accompanied by a QTc ≥ 490 ms and T-wave abnormalities after standing, sensitivity further increased (96%, 95% CI: 85%-99%) at the expense of a further specificity decrease (41%, 95% CI: 30%-52%). Beat-to-beat analysis showed that 30 seconds after standing, LQTS children had a greater increase in heart rate compared to controls, which was more evidently present in LQTS boys and LQTS type 1 children.Conclusion: In children, the standing test has limited additive diagnostic value for LQTS over a baseline electrocardiogram, while T-wave abnormalities after standing also have limited additional value. The standing test for LQTS should only be used with caution in children.

Aims Repetitive conduction patterns in atrial fibrillation (AF) may reflect anatomical structures harbouring preferential conduction paths and indicate the presence of stationary sources for AF. Recently, we demonstrated a novel technique to detect repetitive patterns in high-density contact mapping of AF. As a first step towards repetitive pattern mapping to guide AF ablation, we determined the incidence, prevalence, and trajectories of repetitive conduction patterns in epicardial contact mapping of paroxysmal and persistent AF patients. Methods and results A 256-channel mapping array was used to record epicardial left and right AF electrograms in persistent AF (persAF, n = 9) and paroxysmal AF (pAF, n = 11) patients. Intervals containing repetitive conduction patterns were detected using recurrence plots. Activation movies, preferential conduction direction, and average activation sequence were used to characterize and classify conduction patterns. Repetitive patterns were identified in 33/40 recordings. Repetitive patterns were more prevalent in pAF compared with persAF [pAF: median 59%, inter-quartile range (41–72) vs. persAF: 39% (0–51), P Conclusion High-density epicardial contact mapping in AF patients reveals frequent repetitive conduction patterns. In persistent AF patients, repetitive patterns were less frequent, smaller, and more variable than in paroxysmal AF patients. Future research should elucidate whether these patterns can help in finding AF ablation targets.

Purpose:Extraintestinal pathogenic Escherichia coli (ExPEC) are a leading cause of invasive infections in adults. The study aimed to evaluate the incidence of microbiologically confirmed invasive E...