Search

Recognising the challenges involved in understanding the knowledge that teachers need to develop to use technology in their teaching dynamics, we examined the prior research that has not clearly revealed strategic changes for teacher preparation in the digital age. The goal was to expand on the current understandings of the nature of technological pedagogical content knowledge (TPCK/TPACK) and provide a launchpad for future research by teacher educators as they contemplate revisions in the education of teachers to better prepare them for teaching in the digital age. To do so, we conducted qualitative meta-synthesis research. Within this context, we identified interpretations and comprehensions that pushed us forward in defence of new perspectives on the nature of this knowledge, regarding the comprehension of TPCK/TPACK as a transformative and homogenous knowledge; TPCK/TPACK’s levels of development, including a new first level; and the need for and challenges of redesigning teacher education. Implications for practice or policy: To better prepare teachers to teach, teachers’ educators should understand TPCK/TPACK as a homogeneous and transformative knowledge. Teachers’ training programmes should realize that often teachers are not aware of the of the possibilities of using technologies to teach. Teachers should have access to continuous learning to keep developing their own TPCK/TPACK during their entire career. Teachers and teachers’ educators should understand TPCK/TPACK developing as a continuous and individual process and not as something standardised.

Background: The impact of the corona pandemic on competitive sports has not yet been studied in a larger group of athletes. Methods: Using an online questionnaire, junior and adult elite athletes from Germany and Austria were asked about their infection status, potential symptoms of COVID-19, and the impact of the pandemic on their athletic activity. Results: Between April 21, 2020 and February 16, 2021, a total of 2981 questionnaires were recorded (50.3% female, 25.7% professional athletes, 37.9% national team members). 78 athletes (2.6%) reported a positive PCR test result for SARS-CoV-2. In addition, 67 (2.3%) athletes reported that they had experienced the disease but were self-diagnosed. In 19 athletes (0.6%), infection was suspected by a physician but without testing. 841 (28.2%) athletes stated that they were in quarantine at least once. At least one symptom that might be associated with COVID-19 was observed in 38.7% of all athletes. Cardiac symptoms were reported significantly more often in PCR-positive athletes than in the group of athletes without confirmed infection or no infection. 15 athletes (0.5%) were admitted to hospital due to COVID-19, 8 of them were hospitalized for more than 1 week. Conclusion: The corona pandemic has a massive impact on competitive sports. In addition to indirect consequences due to quarantine measures or cancellation of competitions, infections with SARS-CoV-2 occurred in a significant proportion of athletes. Severe courses with hospitalization were also recorded among competitive athletes.

OBJECTIVES Sarcopenia is characterized by loss of muscle strength and muscle mass. The EWGSOP2 specifications include physical functioning determination for quantification of the sarcopenia severity. However, there is a lack in the use of habitual and maximal gait speed and their influence on sarcopenia quantification. We hypothesize differences in sarcopenia quantification using habitual and maximal gait speed. METHODS Sixty-six residents from five nursing homes were examined. Habitual and maximal gait speed were measured by 4-meter-walking-Test. McNemar-Test and χ2-test were used to identify quantification differences. Effect sizes of both gait speeds were calculated with Spearman's rank-correlation-coefficient. RESULTS Significant difference was identified for twenty-two residents in physical functioning classification by McNemar-Test (p

ZusammenfassungUm die Sicherheit von Zivilisten und Einsatzkräften in Ernstfällen, wie bei Terrorereignissen oder Bränden, zu verbessern, wurde in den letzten Jahren intensive Forschung betrieben. Daher fand vom 11. Juli 2022 bis 14. Juli 2022 am Zentrum am Berg auf dem steirischen Erzberg (Österreich) die IRON NIKE Forschungswoche statt, in der die Forschungsergebnisse der vergangenen Jahre zusammengebracht, analysiert, weiterentwickelt wurden und diese in der Zukunft in der Praxis anwendbar werden. Die folgenden Projekte fanden dabei ihren Auftritt: NIKE DHQ Radiv, NIKE SubmoveCon, NIKE Bluetrack sowie NIKE RasPos. Gerade die Möglichkeiten und Forschungsumgebung, die für eine solche Zusammenarbeit nötig sind, werden am Zentrum am Berg in einzigartiger Weise geboten. Der hervorragende Output wird sich dabei in den kommenden Monaten in einigen Publikationen wiederfinden. Eine solche Vielzahl an unterschiedlichen Spitzenforscher zusammenzubringen sollte auch für die Zukunft ein Ziel sein.

Context One acute bout of exercise leads to a rapid increase in the systemic cytokine concentration. Regular exercise might alter the cytokine response, in particular in beforehand untrained and obese individuals. Objective Using a proximity extension assay, we studied the effects of acute exercise as well as endurance training on a panel of 92 cytokines related to inflammation. Methods A total of 22 individuals (30 ± 9 years; peak oxygen uptake [VO2peak] 25.2 ± 4.2 mL/[kg × min]; body mass index [BMI] 31.7 ± 4.4) participated in an 8-week endurance exercise intervention. Blood samples were collected before and immediately after 30 minutes’ ergometer exercise at 80% VO2peak. Results Before and after the training intervention, 40 and 37 cytokines, respectively, were acutely increased more than 1.2-fold (Benjamini-Hochberg [BH]-adjusted P < .05). The exercise intervention did not change the acute increase in cytokines nor the resting cytokine levels, whereas fitness was improved and adiposity reduced. The increase in fitness led to a slight increase in power output when exercising at the same heart rate, which might explain the comparable increase in cytokines before and after the intervention. The largest acute increase was found for OSM, TGFA, CXCL1 and 5, and TNFSF14 (≥ 1.9-fold, BH-adjusted P < .001). The transcript levels of these proteins in whole blood were also elevated, particularly in the trained state. Only the acute increase in IL6 (1.3-fold) was related to the increase in lactate, confirming the lactate-driven secretion of IL6. Conclusion Our comprehensive proteomics approach detected several underexplored serum exerkines with up to now less understood function in the adaptation to exercise.

Physical activity is entering the virtual realm. Zwift is an at-home cycling system that is enjoying increasing popularity, yet the specifics of the experience of a virtual cyclist have not been studied to date. Building virtual sports systems can make physical activity accessible to more diverse user groups. To understand how and why users engage in virtual cycling, we conducted n=22 interviews with Zwift users. Through charting the motivations behind using Zwift, we determined that it allowed users to engage in a range of cycling activities traditionally reserved for professional cyclists. Our work reports on key motivations and identifies five key strategies which Zwift uses to create an engaging virtual sports experience. Further, we discuss how Zwift creates a world of virtual professionalism. Our findings offer a structured understanding of the experience of Zwift which can be used to inspire the design of future virtual amateur sports systems.

Subject movement during the magnetic resonance examination is inevitable and causes not only image artefacts but also deteriorates the homogeneity of the main magnetic field (B0), which is a prerequisite for high quality data. Thus, characterization of changes to B0, e.g. induced by patient movement, is important for MR applications that are prone to B0 inhomogeneities. We propose a deep learning based method to predict such changes within the brain from the change of the head position to facilitate retrospective or even real-time correction. A 3D U-net was trained on in vivo brain 7T MRI data. The input consisted of B0 maps and anatomical images at an initial position, and anatomical images at a different head position (obtained by applying a rigid-body transformation on the initial anatomical image). The output consisted of B0 maps at the new head positions. We further fine-tuned the network weights to each subject by measuring a limited number of head positions of the given subject, and trained the U-net with these data. Our approach was compared to established dynamic B0 field mapping via interleaved navigators, which suffer from limited spatial resolution and the need for undesirable sequence modifications. Qualitative and quantitative comparison showed similar performance between an interleaved navigator-equivalent method and proposed method. We therefore conclude that it is feasible to predict B0 maps from rigid subject movement and, when combined with external tracking hardware, this information could be used to improve the quality of magnetic resonance acquisitions without the use of navigators., Comment: 9 pages, 6 figures

Magnetic resonance spectroscopic imaging (MRSI) of the brain enables in vivo assessment of metabolic alterations in multiple sclerosis (MS). This provides complementary insights into lesion pathology that cannot be obtained via T1- and T2-weighted conventional magnetic resonance imaging (cMRI).The aims of this study were to assess focal metabolic alterations inside and at the periphery of lesions that are visible or invisible on cMRI, and to correlate their metabolic changes with T1 hypointensity and the distance of lesions to cortical gray matter (GM).A 7 T MRSI was performed on 51 patients with relapsing-remitting MS (30 female/21 male; mean age, 35.4 ± 9.9 years). Mean metabolic ratios were calculated for segmented regions of interest (ROIs) of normal-appearing white matter, white matter lesions, and focal regions of increased mIns/tNAA invisible on cMRI. A subgroup analysis was performed after subdividing based on T1 relaxation and distance to cortical GM. Metabolite ratios were correlated with T1 and compared between different layers around cMRI-visible lesions.Focal regions of, on average, 2.8-fold higher mIns/tNAA than surrounding normal-appearing white matter and with an appearance similar to that of MS lesions were found, which were not visible on cMRI (ie, ~4% of metabolic hotspots). T1 relaxation was positively correlated with mIns/tNAA (P ≤ 0.01), and negatively with tNAA/tCr (P ≤ 0.01) and tCho/tCr (P ≤ 0.01). mIns/tCr was increased outside lesions, whereas tNAA/tCr distributions resembled macroscopic tissue damage inside the lesions. mIns/tCr was -21% lower for lesions closer to cortical GM (P ≤ 0.05).7 T MRSI allows in vivo visualization of focal MS pathology not visible on cMRI and the assessment of metabolite levels in the lesion center, in the active lesion periphery and in cortical lesions. This demonstrated the potential of MRSI to image mIns as an early biomarker in lesion development.

Purpose Posthepatectomy liver failure (PHLF) remains a leading cause of death after extensive liver resection. Apart from the size and function of the remaining liver remnant, the development of postresection portal hypertension (pHT) plays a crucial role in the development of PHLF. We hypothesize that the umbilical vein in the preserved round ligament (RL) may recanalize in response to new-onset pHT after extended hepatectomy, thus providing a natural portosystemic shunt. Methods In this exploratory study, RL was preserved in 10 consecutive patients undergoing major liver resection. Postoperative imaging was pursued to obtain evidence of reopened umbilical vein in the RL. The postoperative course, including the occurrence of PHLF, as well as the rate of procedure-specific complications were recorded. Results None of the 10 cases presented with an adverse event due to preservation of the RL. In 6 cases, postoperative imaging demonstrated reopening of the umbilical vein with hepatofugal flow in the RL. The rates of procedure-related surgical complications were lower than would be expected in this population; in particular, the rate of occurrence of PHLF as defined by the International Study Group of Liver Surgery (ISGLS) was low. Conclusion Our results support the theoretical concept of portosystemic pressure relief via a preserved umbilical vein after major liver surgery. As preservation of the RL is easily done, we suggest keeping it intact in extended hepatectomy cases and in patients with preexistent pHT.

Background The effect of bacterobilia on morbidity after pancreatoduodenectomy remains unclear. The aim of this study was to examine the influence of positive intraoperative bile cultures and perioperative antibiotic prophylaxis on morbidity measured using the Comprehensive Complication Index, a weighted composite of postoperative complications. Methods Intraoperative bile cultures of 182 patients who underwent pancreatoduodenectomy were obtained. We examined the effect of intraoperative bile cultures and perioperative antibiotic prophylaxis on the Comprehensive Complication Index and the occurrence of postoperative complications. To this aim, we performed general linear models controlling for relevant demographic and perioperative factors. Results Positive (versus negative) intraoperative bile cultures were associated with a higher mean Comprehensive Complication Index (25.34 vs 16.81, P = .025). The mean Comprehensive Complication Index differed significantly between individuals with positive intraoperative bile cultures and bacterial strains not covered by perioperative antibiotic prophylaxis (26.2) versus positive intraoperative bile cultures and bacterial strains sensitive to perioperative antibiotic prophylaxis (22.7) (P = .045). Positive (versus negative) intraoperative bile cultures were associated with 4.75 times (95% confidence interval: 1.74–13.00, P = .002) greater odds of wound infections. The odds of wound infection were 1.93 times (95% confidence interval: .47–8.04) greater in those with positive intraoperative bile cultures and adequate perioperative antibiotic prophylaxis and 6.14 times (95% confidence interval: 2.17–17.35) greater in those with positive intraoperative bile cultures and inadequate perioperative antibiotic prophylaxis (versus negative intraoperative bile cultures) (P = .001). Conclusion Bacterobilia is associated with a significant increase in Comprehensive Complication Index and wound infections after pancreatoduodenectomy, which may be reduced by administration of a specific perioperative antibiotic prophylaxis. Acquisition of bile cultures sampled through the external conduit of patients with preoperative biliary drainage could help in selecting a specific perioperative antibiotic prophylaxis and patients with bile duct stents might benefit from broad spectrum perioperative antibiotic prophylaxis.

ObjectivesNon-invasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies e.g., cancer, dementia and depression. A novel approach to map glucose metabolism non-invasively in the human brain and separate normal oxidative from pathologic anaerobic pathways has been presented recently on experimental MR scanners using direct or indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine and lactate.The aim of this study was to demonstrate the feasibility to non-invasively detect deuterium labeled downstream glucose metabolites indirectly in the human brain via 3D proton (1H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware.Materials and MethodsThis prospective, institutional review board approved study was performed in seven healthy volunteers (mean age, 31±4 years, 5 m/ 2 f) following written informed consent. After overnight fasting and oral deuterium-labeled glucose administration 3D metabolic maps were acquired every ∼4 min with ∼0.24 ml isotropic spatial resolution using real-time motion-, shim- and frequency-corrected echo-less 3D1H-MR Spectroscopic Imaging. Time courses were analyzed using linear regression and non-parametric statistical tests. Deuterium labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic1H MR spectra due to deuterium to proton exchange in the molecules.ResultsSixty-five minutes after deuterium-labeled glucose administration, glutamate+glutamine (Glx) signal intensities decreased in gray/white matter (GM,WM) by -15±2%,(p=0.02)/-14±3%,(p=0.02), respectively. Strong negative correlation between Glx and time was observed in GM/WM (r=-0.71ppp=0.02) steeper slopes, indicating faster metabolic activity in GM compared to WM. Other non-labeled metabolites showed no significant changes.ConclusionOur approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for non-invasive imaging of glucose and neurotransmitter metabolism in the human brain.

Reflection is a commonly addressed design goal in commercial systems and in Human-Computer Interaction (HCI) research. Yet, it is still unclear what tools are at the disposal of designers who want to build systems that support reflection. Understanding the design space of reflection support systems and the interaction techniques that can foster reflection is necessary to enable building technologies that contribute to the users' well-being. In order to gain additional insight into how interactive artefacts foster reflection, we investigated past research prototypes and reflection-supporting smartphone applications (apps). Through a structured literature review and an analysis of app reviews, we constructed four design resources for reflection: temporal perspective, conversation, comparison and discovery. We also identified design patterns in past digital artefacts that implement the resources. Our work constitutes intermediate-level knowledge that is intended to inspire future technologies that better support reflection.

It remains unknown how patients with liver failure maintain essential albumin levels. Here, we delineate a hierarchical transcription regulatory network that ensures albumin expression under different disease conditions.We examined albumin levels in liver tissues and serum in 157 patients, including 84 with HCC, 38 decompensated cirrhosis, and 35 acute liver failure. Even in patients with liver failure, the average serum albumin concentrations were 30.55 g/L. In healthy subjects and patients with chronic liver diseases, albumin was expressed in hepatocytes. In patients with massive hepatocyte loss, albumin was expressed in liver progenitor cells (LPCs). The albumin gene (ALB) core promoter possesses a TATA box and nucleosome-free area, which allows constitutive RNA polymerase II binding and transcription initiation. Chromatin immunoprecipitation assays revealed that hepatocyte nuclear factor 4 alpha (HNF4α), CCAAT/enhancer-binding protein alpha (C/EBPα), and forkhead box A2 (FOXA2) bound to the ALB enhancer. Knockdown of either of these factors reduced albumin expression in hepatocytes. FOXA2 acts as a pioneer factor to support HNF4α and C/EBPα. In hepatocytes lacking HNF4α and C/EBPα expression, FOXA2 synergized with retinoic acid receptor (RAR) to maintain albumin transcription. RAR nuclear translocation was induced by retinoic acids released by activated HSCs. In patients with massive hepatocyte loss, LPCs expressed HNF4α and FOXA2. RNA sequencing and quantitative PCR analyses revealed that lack of HNF4α and C/EBPα in hepatocytes increased hedgehog ligand biosynthesis. Hedgehog up-regulates FOXA2 expression through glioblastoma family zinc finger 2 binding to the FOXA2 promoter in both hepatocytes and LPCs.A hierarchical regulatory network formed by master and pioneer transcription factors ensures essential albumin expression in various pathophysiological conditions.

Impaired glucose metabolism in the brain has been linked to several neurological disorders. Positron emission tomography and carbon-13 magnetic resonance spectroscopic imaging (MRSI) can be used to quantify the metabolism of glucose, but these methods involve exposure to radiation, cannot quantify downstream metabolism, or have poor spatial resolution. Deuterium MRSI (2H-MRSI) is a non-invasive and safe alternative for the quantification of the metabolism of 2H-labelled substrates such as glucose and their downstream metabolic products, yet it can only measure a limited number of deuterated compounds and requires specialized hardware. Here we show that proton MRSI (1H-MRSI) at 7 T has higher sensitivity, chemical specificity and spatiotemporal resolution than 2H-MRSI. We used 1H-MRSI in five volunteers to differentiate glutamate, glutamine, γ-aminobutyric acid and glucose deuterated at specific molecular positions, and to simultaneously map deuterated and non-deuterated metabolites. 1H-MRSI, which is amenable to clinically available magnetic-resonance hardware, may facilitate the study of glucose metabolism in the brain and its potential roles in neurological disorders.

While walking meetings offer a healthy alternative to sit-down meetings, they also pose practical challenges. Taking notes is difficult while walking, which limits the potential of walking meetings. To address this, we designed the Walking Talking Stick -- a tangible device with integrated voice recording, transcription, and a physical highlighting button to facilitate note-taking during walking meetings. We investigated our system in a three-condition between-subjects user study with thirty pairs of participants ($N$=60) who conducted 15-minute outdoor walking meetings. Participants either used clip-on microphones, the prototype without the button, or the prototype with the highlighting button. We found that the tangible device increased task focus, and the physical highlighting button facilitated turn-taking and resulted in more useful notes. Our work demonstrates how interactive artifacts can incentivize users to hold meetings in motion and enhance conversation dynamics. We contribute insights for future systems which support conducting work tasks in mobile environments., In CHI 2023

Reflecting on personal challenges can be difficult. Without encouragement, the reflection process often remains superficial, thus inhibiting deeper understanding and learning from past experiences. To allow people to immerse themselves in and deeply reflect on past challenges, we developed SelVReflect, a VR experience which offers active voice-based guidance and a space to freely express oneself. SelVReflect was developed in an iterative design process (N=5) and evaluated in a user study with N=20 participants. We found that SelVReflect enabled participants to approach their challenge and its (emotional) components from different perspectives and to discover new relationships between these components. By making use of the spatial possibilities in VR, participants developed a better understanding of the situation and of themselves. We contribute empirical evidence of how a guided VR experience can support reflection. We discuss opportunities and design requirements for guided VR experiences that aim to foster deeper reflection.

Getting from A to B has never been easier. Mobile navigation systems allow universal access to spatial information. However, following detailed route instructions leads to a decrease in spatial exploration behaviour and, therefore a reduction of spatial knowledge acquisition. Facilitating spatial exploration has the potential to counteract this negative efect. This paper investigates how we can support people in re-discovering their surroundings. We designed and evaluated a mobile application to promote spatial exploration through gamification. The app requires active exploration behaviour to uncover a map. Gamification elements such as quests, statistics, and social competition are used to encourage exploration. We conducted an exploratory field study (n = 22). Our results show a significant increase in familiarity with the environment and various exploration patterns. Based on our findings, we propose modifications to current mapping applications by limiting the visible cartographic elements and alternating routes to improve spatial knowledge acquisition.

Background: An elevated core temperature (Tcore) increases the risk of performance impairments and heat-related illness. Internal cooling (IC) has the potential to lower Tcore when exercising in the heat. The aim of the review was to systematically analyze the effects of IC on performance, physiological, and perceptional parameters.Methods: A systematic literature search was performed in the PubMed database on 17 December 2021. Intervention studies were included assessing the effects of IC on performance, physiological, or perceptional outcomes. Data extraction and quality assessment were conducted for the included literature. The standardized mean differences (SMD) and 95% Confidence Intervals (CI) were calculated using the inverse-variance method and a random-effects model.Results: 47 intervention studies involving 486 active subjects (13.7% female; mean age 20–42 years) were included in the meta-analysis. IC resulted in significant positive effects on time to exhaustion [SMD (95% CI) 0.40 (0.13; 0.67), p < 0.01]. IC significantly reduced Tcore [−0.19 (22120.34; −0.05), p < 0.05], sweat rate [−0.20 (−0.34; −0.06), p < 0.01], thermal sensation [−0.17 (−0.33; −0.01), p < 0.05], whereas no effects were found on skin temperature, blood lactate, and thermal comfort (p > 0.05). IC resulted in a borderline significant reduction in time trial performance [0.31 (−0.60; −0.02), p = 0.06], heart rate [−0.13 (−0.27; 0.01), p = 0.06], rate of perceived exertion [−0.16 (−0.31; −0.00), p = 0.05] and borderline increased mean power output [0.22 (0.00; 0.44), p = 0.05].Discussion: IC has the potential to affect endurance performance and selected physiological and perceptional parameters positively. However, its effectiveness depends on the method used and the time point of administration. Future research should confirm the laboratory-based results in the field setting and involve non-endurance activities and female athletes.Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022336623.

Em pediatria, há necessidade de reconhecer o desenvolvimento infantil como processo de formação, transacional e determinante na formação do adulto. A abordagem terapêutica em pacientes neonatais e pediátricos é diferenciada, ocorre muitas vezes sem testes clínicos adequados, e sempre deve buscar a promoção do conhecimento. Para assegurarmos a qualidade e garantia do atendimento à saúde infantil os serviços pediátricos devem ser responsivos, inovadores e com o máximo de segurança. Este conhecimento é fruto da troca dos saberes, das constantes atualizações dos profissionais, do conhecimento epidemiológico e da prática clínica quando bem executada. Parte dos profissionais de saúde se sente inadequadamente treinado para atender a este público em particular, o que gera justificável insegurança nos pais, pacientes e também nos próprios profissionais. O estudo das experiências profissionais, relatos de caso, revisões bem fundamentadas entre outros estudos possibilidade base para formação dos profissionais que desejam trabalhar com pediatria. Portanto, a Editora Pasteur criou uma coletânea para fornecer um campo rico de conhecimento. Este projeto foi possível devido à participação de profissionais e estudantes da área da saúde empenhados em fornecer o melhor material possível aos seus leitores.

ObjectiveTo investigate the metabolic pattern of different types of iron accumulation in multiple sclerosis(MS) lesions, and compare metabolic alterations within and at the periphery of lesions and newly emerging lesionsin vivoaccording to iron deposition.Methods7T MR spectroscopic imaging and susceptibility-weighted-imaging was performed in 31 RRMS patients(16female/15male;mean age,36.9±10.3years). Mean metabolic ratio were calculated for regions of interest(ROI) of normal appearing white matter(NAWM), “non-iron”, and three distinct types of iron-laden lesions, and for lesion layers of “non-iron” and “rim” lesions. Furthermore, newly emerging “non-iron” and “iron” lesions were compared longitudinally.Results52% of iron-containing lesions showed no distinct paramagnetic rim. Of these, “area” lesions exhibited a 65% higher mIns/tNAA(p=0.035) than “rim” lesions. Comparing lesion layers of both “non-iron” and “rim” lesions, a steeper metabolic gradient of mIns/tNAA(“non-iron”+15%,”iron”+40%) and tNAA/tCr(“non-iron”-15%,”iron”-35%) was found in “iron” lesions, with the lesion core showing +22% higher mIns/tNAA(p=0.005) and -23% lower tNAA/tCr(p=0.048) in “iron” compared to “non-iron” lesions. In newly emerging lesions, 46% showed iron accumulation, with the drop in tNAA/tCr after lesion formation remaining significantly lower compared to pre-lesional tissue over time in “iron” lesions(year0:p=0.013,year1:p=0.041) as opposed to “non-iron” lesions(year0:p=0.022,year1:p=0.231).Conclusion7T MRSI allows in vivo characterization of different iron accumulation types showing metabolic differences. Furthermore, the larger extent of neuronal damage in lesions with a distinct iron rim was reconfirmed, but with metabolic differences in lesion development between (non)-iron-containing lesions. This highlights the ability of MRSI to further investigate different types of iron accumulation and suggests possible implications for disease monitoring.Clinical relevance statementThe clinical importance of differentiating various types of iron accumulation in MS lesions was shown, as contrasting metabolic profiles are likely associated with different levels of tissue damage.Key pointsIron-containing lesions were suggested as a biomarker for tissue damage, a more aggressive disease course, and worse clinical outcome, but related metabolic alterations are poorly understoodOur MRSI results confirm a higher extent of tissue damage within paramagnetic rim lesions. 46% of newly emerging lesions showed an iron accumulation, correlating with an altered metabolic behavior compared to non-iron lesionsOnly 48% of iron-containing lesions have a distinct rim-shaped iron accumulation, although most studies focus on these paramagnetic rim lesions. We showed highly different metabolic profiles in different iron accumulation types, highlighting the need for distinct classification of iron accumulation

Background Various environmental risk factors have been associated with the pathogenesis of inflammatory bowel disease. In this study we aimed to identify lifestyle factors that affect the onset of Crohn’s disease and ulcerative colitis. Methods 2294 patients from the Swiss IBD Cohort Study received a questionnaire regarding physical activity, nutritional habits and status of weight. In addition, a control group was formed comprising patients’ childhood friends, who grew up in a similar environment. Results Overall, 1111 questionnaires were returned (response rate: 48.4%). Significantly more patients with inflammatory bowel disease reported no regular practice of sport during childhood and beginning of adulthood compared to the control group (p = 0.0001). No association between intake of refined sugar and onset of inflammatory bowel disease was observed. More patients with Crohn’s disease compared to ulcerative colitis and controls suffered from overweight during childhood (12.8% vs. 7.7% and 9.7%, respectively; p = 0.027). Conclusions Our study underlines the relevance of environmental factors in the development of inflammatory bowel disease. Our results imply a protective effect of physical activity regarding the onset of inflammatory bowel disease.

Sudden cardiac death (SCD) in adolescents and young adults may be the first manifestation of an inherited arrhythmic syndrome. Thus identification of a genetic origin in sudden death cases deemed inconclusive after a comprehensive autopsy and may help to reduce the risk of lethal episodes in the remaining family. Using next-generation sequencing (NGS), a large number of variants of unknown significance (VUS) are detected. In the majority of cases, there is insufficient evidence of pathogenicity, representing a huge dilemma in current genetic investigations. Misinterpretation of such variants may lead to inaccurate genetic diagnoses and/or the adoption of unnecessary and/or inappropriate therapeutic approaches. In our study, we applied current (ACMG) recommendations for variant classification in post-mortem genetic screening of a cohort of 56 SCD victims. We identified a total 53 rare protein-altering variants (MAF

ObjectiveMucosal-associated invariant T (MAIT) cells are the most abundant T cells in human liver. They respond to bacterial metabolites presented by major histocompatibility complex-like molecule MR1. MAIT cells exert regulatory and antimicrobial functions and are implicated in liver fibrogenesis. It is not well understood which liver cells function as antigen (Ag)-presenting cells for MAIT cells, and under which conditions stimulatory Ags reach the circulation.DesignWe used different types of primary human liver cells in Ag-presentation assays to blood-derived and liver-derived MAIT cells. We assessed MAIT cell stimulatory potential of serum from healthy subjects and patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt stent, and patients with inflammatory bowel disease (IBD).ResultsMAIT cells were dispersed throughout healthy human liver and all tested liver cell types stimulated MAIT cells, hepatocytes being most efficient. MAIT cell activation by liver cells occurred in response to bacterial lysate and pure Ag, and was prevented by non-activating MR1 ligands. Serum derived from peripheral and portal blood, and from patients with IBD stimulated MAIT cells in MR1-dependent manner.ConclusionOur findings reveal previously unrecognised roles of liver cells in Ag metabolism and activation of MAIT cells, repression of which creates an opportunity to design antifibrotic therapies. The presence of MAIT cell stimulatory Ags in serum rationalises the observed activated MAIT cell phenotype in liver. Increased serum levels of gut-derived MAIT cell stimulatory ligands in patients with impaired intestinal barrier function indicate that intrahepatic Ag-presentation may represent an important step in the development of liver disease.

BACKGROUND: Sonography is often the first imaging procedure to be used in diagnostic investigation of the abdomen. The aim of this article is to provide a new interdisciplinary overview of recent groundbreaking advances in this modality. METHODS: A selective survey of the literature in PubMed was conducted. The literature search was carried out in 2021–2022 and included publications over the period 2004–2022. RESULTS: The novel sonographic software techniques can be divided into algorithms that deal with conventional B-scan optimization and new programs that extend the scope of sonographic examination. The latter include elastography, contrast-enhanced sonography, and image fusion in combination with other cross-sectional imaging modalities. Elastography can be used to assess the presence of steatosis, fibrosis, or cirrhosis in patients with liver disease. One study reported diagnostic accuracy of 84–87% for the diagnosis of significant fibrosis (F2), 89–91% for the diagnosis of severe fibrosis (F3), and 92–93% for the diagnosis of liver cirrhosis (F4). Contrast-enhanced sonography is used for evaluation of tumors and trauma. A prospective multicenter study found sensitivity of 95.8% for the characterization of malignant lesions and specificity of 83.1% for benign lesions. Image fusion has the potential to improve the diagnostic assessment of parenchymatous organs, vascular conditions, and the prostate. CONCLUSION: With continuous improvement of the B-scan and the development of high-frequency probes and novel investigation techniques, sonography has become established as an increasingly autonomous examination procedure.

To date, epithelial-to-mesenchymal transition (EMT) has been observed in cultured hepatocytes, but notin vivo. TGF-β is supposed to initiate EMT in hepatocytes by inhibiting HNF4αthrough the SMAD2/3 complex. We report that TGF-βdoes not directly inhibit HNF4α, but contributes to its transcriptional regulation by SMAD2/3 recruiting acetyltransferase CBP/p300 to the HNF4αpromoter. The recruitment of CBP/p300 is indispensable for C/EBPabinding, another essential requirement for constitutive HNF4αexpression in hepatocytes. In contrast to the observed induction of HNF4α, SMAD2/3 inhibits C/EBPαtranscription. Therefore, long-term TGF-βincubation results in C/EBPαdepletion, which abrogates HNF4αexpression. Intriguingly, SMAD2/3 inhibitory binding to the C/EBPαpromoter is abolished by insulin. Thus, maintaining a high insulin concentration in culture medium ensures constitutive HNF4αand thereby prevents TGF-β-induced hepatocyte EMT. Furthermore, insulin inhibits TGF-β-induced SMAD2/3 binding to the promoters of core EMT transcription factors e.g., SNAI1. SNAI1 transcription requires both SMAD2/3 and FOXO1 in nuclei. Insulin inhibits SNAI1 transcription through impeding SMAD2/3 binding to its promoter and inducing FOXO1 phosphorylation. Hence, insulin is the key factor that prevents TGF-β-induced EMT in hepatocytes.