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NRF2 Deficiency Promotes Ferroptosis of Astrocytes Mediated by Oxidative Stress in Alzheimer's Disease
No full textOxidative stress is involved in the pathogenesis of Alzheimer's disease (AD), which is linked to reactive oxygen species (ROS), lipid peroxidation, and neurotoxicity. Emerging evidence suggests a role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a major source of antioxidant response elements in AD. The molecular mechanism of oxidative stress and ferroptosis in astrocytes in AD is not yet fully understood. Here, we aimed to investigate the mechanism by which Nrf2 regulates the ferroptosis of astrocytes in AD. We found decreased expression of Nrf2 and upregulated expression of the ROS marker NADPH oxidase 4 (NOX4) in the frontal cortex from patients with AD and in the cortex of 3×Tg mice compared to wildtype mice. We demonstrated that Nrf2 deficiency led to ferroptosis-dependent oxidative stress-induced ROS with downregulated heme oxygenase-1 and glutathione peroxidase 4 and upregulated cystine glutamate expression. Moreover, Nrf2 deficiency increased lipid peroxidation, DNA oxidation, and mitochondrial fragmentation in mouse astrocytes (mAS, M1800-57). In conclusion, these results suggest that Nrf2 deficiency promotes ferroptosis of astrocytes involving oxidative stress in AD
Reflections on interactive visualization of electronic health records: past, present, future
No full textHealthcare data of millions of people are now stored electronically, in Electronic Health Records (EHR). Although adoption has been gradual, EHRs are now standard across countries, promoting data exchange, opportunities for case comparison across institutions, and uniform diagnoses to improve care. In another stream of innovation, the advent of wearable devices affords users increased control in recording and assessing information about their health, with compact and affordable devices. Coupled with the rise of Artificial Intelligence, this sets the scene for unprecedented challenges and opportunities in terms of data scale, granularity, and availability. This shift offers a new perspective on “personal” health, but also introduces challenges. In this JAMIA Focus Issue, “Interactive Visualization of Health Data for Digital and Personal Health,” we investigate how visual analytics and the broader field of data visualization can provide novel solutions to support different stakeholders in healthcare to making sense of the information provided through data in clinical, research, and educational contexts. In particular, this special issue explores the present and future role of Artificial Intelligence (AI) in medicine and its various applications. Based on the common themes from these articles, we discuss and offer an assessment of the state of research at the intersection of health informatics, visualization, and AI
Temperature Profile During Endourological Laser Activation : Introducing the Thermal Safety Distance Concept
No full textPURPOSE
To examine temporal-spatial distribution of heat generated upon laser activation in a bench model of renal calyx. To establish reference values for a safety distance between the laser fiber and healthy tissue during laser lithotripsy.
METHODS
We developed an in-vitro experimental setup employing a glass pipette and laser activation under various intra-operative parameters, such as power and presence of irrigation. A thermal camera was used to monitor both temporal and spatial temperature changes during uninterrupted 60-second laser activation. We computed the thermal dose according to Sapareto and Dewey's formula at different distances from the laser fiber tip, in order to determine a safety distance.
RESULTS
A positive correlation was observed between average power and the highest recorded temperature (Spearman's coefficient 0.94, p < 0.001). Irrigation was found to reduce the highest recorded temperature, with a maximum average reduction of 9.4 °C at 40 W (p = 0.002). A positive correlation existed between average power and safety distance values (Spearman's coefficient 0.86, p = 0.001). A thermal dose indicative of tissue damage was observed at 20 W without irrigation (safety distance 0.93±0.11 mm). While at 40 W, irrigation led to slight reduction in mean safety distance (4.47±0.85 vs. 5.22±0.09 mm, p = 0.08).
CONCLUSIONS
Laser settings with an average power greater than 10 W deliver a thermal dose indicative of tissue damage, which increases with higher average power values. According to safety distance values from this study, a maximum of 10 W should be used in the ureter, and a maximum of 20 W should be used in kidney in presence of irrigation
Thoracolumbar injuries: prehospital and emergency management, imaging, classifications and clinical implications
No full textThoracolumbar fractures are common injuries that usually result from high energy trauma. They can lead to significant morbidity due to neurologic impair - or mortality - if not managed according to strict and rapid intervention rules in terms of decompression of the spinal cord, and rigid fixation of the fracture. This manuscript reviews emergency treatment protocols, imaging modalities, and classification systems used for thoracolumbar fractures. The emergency treatment is discussed, specific classifications are compared and indications for surgeries are compared
Für eine zukunftsfähige Naturschutzverwaltung im 21. Jahrhundert: Teil 1: Grundprobleme auf den drei Verwaltungsebenen in den Bundesländern
No full textDurch Abfrage eines bundesweiten Meinungsbildes unter Beteiligung von Wissenschaft und Praxis sowie Auswertung wissenschaftlicher Arbeiten zeigt sich, dass die Naturschutzverwaltung ihrem Auftrag immer weniger gerecht wird bzw. werden kann. Dies wird zuerst am Verfehlen politisch gesetzter Biodiversitätsziele deutlich. Dahinter steht ein Bündel komplexer Herausforderungen, die hier in sechs thematischen Clustern umrissen werden: (1) Arbeitsverdichtung und zeitliche Überforderung, (2) fachliche Limitierung mit sektoralen Aufgaben statt notwendig ganzheitlicher Ziele auf landschaftlicher Ebene, (3) bürokratische Vorgaben und Strukturen im Verwaltungshandeln, (4) finanzielle, ordnungs- und förderrechtliche Grenzen, (5) methodische Hemmnisse aufgrund mangelnder Weiterbildungsangebote zu Zukunftskompetenzen (Future Skills) bei den Mitarbeitenden sowie (6) eine grundlegende Unzufriedenheit vieler Akteurinnen und Akteure in der Verwaltung aufgrund begrenzter Einflussmöglichkeiten und geringer Wirksamkeit. In einem Folgebeitrag sollen aus dieser Analyse Folgerungen für die Gestaltung einer zukunftsfähigen Naturschutzverwaltung abgeleitet werden.
A nationwide survey of opinions, with the participation of scientists and practitioners as well as evaluation of scientific work, shows that nature conservation administration is less and less able to fulfil its mandate. This initially becomes clear when politically set biodiversity targets are missed. Behind this is a bundle of complex challenges, which are outlined here in six thematic clusters: (1) work intensification and excessive demands on time; (2) technical limitations with sectoral tasks instead of necessary holistic goals at the landscape level; (3) bureaucratic requirements and structures in administrative action; (4) financial, regulatory, and funding limits; (5) methodological obstacles due to a lack of further training programmes on future skills for employees; and (6) a fundamental dissatisfaction of many actors in administration due to limited opportunities for influence and low effectiveness. In a follow-up article, conclusions will be drawn from this analysis for the design of a sustainable nature conservation administration
Medication adherence and persistence in children and adolescents with attention deficit hyperactivity disorder (ADHD): a systematic review and qualitative update
No full textLow medication-adherence and persistence may reduce the effectiveness of ADHD-medication. This preregistered systematic review (PROSPERO CRD42020218654) on medication-adherence and persistence in children and adolescents with ADHD focuses on clinically relevant questions and extends previous reviews by including additional studies. We included a total of n = 66 studies. There was a lack of consistency in the measurement of adherence/persistence between studies. Pooling the medication possession ratios (MPR) and using the most common adherence definition (MPR ≥ 80%) indicated that only 22.9% of participants had good adherence at 12-month follow-up. Treatment persistence on medication measured by treatment duration during a 12-month follow-up averaged 170 days (5.6 months). Our findings indicate that medication-adherence and persistence among youth with ADHD are generally poor and have not changed in recent years. Clinicians need to be aware that various factors may contribute to poor adherence/persistence and that long-acting stimulants and psychoeducational programs may help to improve adherence/persistence. However, the evidence to whether better adherence/persistence contributes to better long-term outcomes is limited and requires further research
NT-proBNP Levels in Patients with Primary Hyperaldosteronism and Autonomous Cortisol Cosecretion
No full textCONTEXT
Patients with primary aldosteronism (PA) have higher cardiac comorbidities including more pronounced left ventricular hypertrophy than patients with essential hypertension.
OBJECTIVE
Autonomous cortisol cosecretion (ACS) is a common subtype in PA associated with a worse metabolic profile.
HYPOTHESIS
Autonomous cortisol cosecretion may affect myocardial parameters and result in a worse cardiac outcome compared to patients with PA and without ACS.
METHODS
Three hundred and sixty-seven patients with PA undergoing 1 mg dexamethasone suppression test (DST) and echocardiography at baseline from 2 centers of the German Conn's Registry were included. Follow-up for up to 3.8 years was available in 192 patients.
RESULTS
Patients with PA and ACS had higher NT-proBNP levels at baseline compared to patients with PA without ACS (114 vs 75.6 pg/mL, P = .02), but showed no difference in echocardiography values. NT-proBNP levels showed a significant positive correlation (r = 0.141, P = .011) with cortisol levels after DST at baseline. In response to therapy of PA, NT-proBNP levels decreased, but remained significantly higher in patients with ACS compared to patients without ACS. At follow-up, left ventricle end-diastolic dimension (LVEDD) decreased significantly only in patients without ACS. Left atrial diameter (LAD) decreased significantly in patients without ACS and in female patients with ACS but not in male patients. Left ventricular mass index (LVMI) significantly improved in female patients without ACS but remained unchanged in female patients with ACS as well as in male patients at follow-up.
CONCLUSIONS
In patients with PA, concomitant ACS is associated with a worse cardiac profile and only partial recovery even years after initiation of targeted PA therapy
