Perusinis II. Fall: Der Alzheimer Patient R.M. Geschichte, Genealogie und Genetik eines psychiatriehistorischen Falls

1.American Journal of Alzheimer`s Disease and Other Dementias: 2010; 25:189-192 100th anniversary of PERUSINI`S SECOND CASE: PATIENT RM and his KINDRED Im Jahre 1907 wurde der Münchener Korbmacher RM als ,,Zweifelhafter Fall“ in der damals ,,Königlich Psychiatrischen Klinik“ in München behandelt. Die diesbezüglich 1909 von Alzheimers Assistenten Gaetano Perusini publizierte Kasuistik siedelt den offensichtlichen Symptomausbruch im Jahr 1899 an. Dieser gemutmaßte extrem frühe Krankheitsbeginn (38.Lebensjahr des RM) sowie Perusinis familienanamnestischer Hinweis ,,ein Bruder desselben soll nicht recht gescheut sein“ erforderte intensive Recherche zu Geschichte und Genealogie dieses psychiatriehistorischen Falls, um das eventuelle Vorliegen einer heredofamiliären Form von Morbus Alzheimer mit Beginn im frühen Lebensalter zu diskutieren. Detaillierte Untersuchungen über acht Generationen konnten zwar psychiatrische Auffälligkeiten im Stammbaum des Probanden aufzeigen, aber keinen Nachweis einer autosomal-dominanten Form der “Early-Onset Alzheimer`s Disease“ erbringen. 2.Nervenheilkunde: 2010; 29:850-852 Alzheimer und Perusini: Patient RM und sein Stammbaum 1773-2009 Die ersten vier Fälle der Alzheimerschen Krankheit wurden in Alzheimers histopathologischem Laboratorium von dem italienischen Neuropathologen Gaetano Perusini untersucht. Das Weiterverfolgen von Perusinis Hinweis zur auffälligen Psychopathologie des Bruders des RM zeigt noch 1923 die identische differentialdiagnostische Überlegung „Arteriosklerose“ wie bereits 1907 beim Probanden selbst. Das Nachvollziehen der damals angewandten relevanten Untersuchungsmethoden zur Sicherung der Verdachtsdiagnose „Progressive Paralyse“ weist erhebliche Ungenauigkeiten in der Dokumentation auf, so dass verschiedene Differentialdiagnosen zu diskutieren sind. Kurz vor ihrem Tod konnte eine APOE-Genotypisierung der gemäß nervenärztlicher Diagnose an dementiellem Syndrom erkrankten Enkeltochter von Perusinis II.Fall durchgeführt werden. Die Genotypisierung konnte das Vorliegen einer autosomal-dominanten Form des Morbus Alzheimer mit frühem Beginn nicht belegen. 3.Nervenarzt: 2011; 82:363-368 La malattia di Alzheimer-Perusini: Zum 100. Jahrestag der Publikation Gaetano Perusinis Die Arbeit zielt ab auf Honorierung der Verdienste des Wissenschaftlers Gaetano Perusini (1879-1915). Durch seine genau ein Jahrhundert zurückliegende Veröffentlichung ,,Über klinisch und histologisch eigenartige psychische Erkrankungen des späteren Lebensalters“ kann er als Wegbereiter für das moderne Konzept des altersunspezifischen Beginns der Alzheimerschen Krankheit gelten. Gaetano Perusini arbeitete wissenschaftlich zusammen mit Ugo Cerletti, Alois Alzheimer, Franz Nissl sowie Emil Kraepelin und war beteiligt an der Herausgabe der ,,Folia Neurobiologica“. In seinem persönlichen Schicksal spiegelt sich die Tragik des 1.Weltkrieges: An den Folgen seiner Verwundung durch einen Granatsplitter verstarb Gaetano Perusini im Alter von nur 36 Jahren

Gustav Nikolaus Specht (1860–1940) : Sein Einfluss auf die Nosologie Kraepelins und Annäherungen an seine Position im Nationalsozialismus

Hinführung Gustav Specht steht am Anfang der Erlanger Universitätspsychiatrie. 80 Jahre nach seinem Tod untersucht der vorliegende Artikel insbesondere die Rolle Spechts bei der von Kraepelin ausgehenden psychopathologisch-nosologischen Diskussion. Trotz spärlicher Datenlage unternehmen die Autoren erstmals eine Annäherung an Spechts Positionen innerhalb der nationalsozialistischen Psychiatrie. Methode Relevantes archivalisches Material sowie Primär- und Sekundärliteratur wurden ausgewertet. Ergebnisse Specht wurde 1897 zum außerplanmäßigen Professor und 1903 zum ersten Ordinarius für Psychiatrie in Erlangen ernannt. Specht arbeitete die Bedeutung des manischen Elementes in der Paranoia heraus. Specht ergänzte den sog. „exogenen Reaktionstypus“ Bonhoeffers 1913 um die depressiven Zustandsbilder; er selbst war – bei fremddiagnostischem Verdacht auf zyklothymes Temperament – zweimalig exogen reaktiv depressiv erkrankt. Diskussion Durch seine Forschungsarbeiten zum pathologischen Affekt in der chronischen Paranoia beeinflusste Specht die zeitgenössische psychopathologische Diskussion nachhaltig. Spechts Perspektivenwechsel in puncto „Erbgesundheit“ lässt sich interpretieren als Anpassung an das NS-Regime. Schlussfolgerung Das Werk Gustav Spechts kann u. a. dazu anregen, einen interdisziplinären psychopathologischen Diskurs zu kultivieren

Is Someone Looking Over My Shoulder? An Investigation into Supervisor Monitoring Variability, Subordinates’ Daily Felt Trust, and Well-being

Remote working has become the new norm in organizations. However, little is known about how supervisors’ monitoring affects their relationships with subordinates in remote work settings. Our research aims to enhance the understanding of the daily dynamics of monitoring and trust between supervisors and subordinates. Based on self-determination theory, we propose a multilevel theoretical model predicting that supervisors’ daily monitoring affects the extent to which subordinates feel trusted by their manager (‘felt trust’) and their subsequent daily exhaustion and vigor. Further, we develop the novel concept of supervisor monitoring variability and test its role in these relationships. We conducted two Experience Sampling Method (ESM) studies (N=191, 1,417 data points for Study 1; N=257, 2,244 data points for Study 2) in different hybrid work contexts. Multilevel analysis findings confirmed that daily monitoring was negatively associated with daily felt trust, which in turn had a negative impact on subordinates’ daily well-being in both contexts. Furthermore, we found that monitoring variability intensified the negative relationship between daily supervisor monitoring and subordinates’ daily felt trust in the newly introduced remote working context, although not in a more stable context. We discuss the theoretical implications of our findings and derive a research agenda to study the daily dynamics of monitoring and its implications for organizations

Fullerene-based Biocomponents : New Concepts For Functionalising Membranes

Lipophilic hexakisadducts of fullerene C60 form unprecedented rod-like nanoaggregates in phospholipid-membrane bilayers, resulting in modification of the micromechanic properties and stabilisation of the membrane. Lipofullerenes with amphiphilic side chains enable additionally derivatisation and molecular recognition at the membrane surface. The amphiphilic spacer acts as a transmembrane anchor and provides the terminal functionality outside of the membrane. New systems derived from parent compound 3 carry two functional groups each and can be easily modified due to the modular synthesis. Terminal functionalities to be investigated include D(+)-biotin and IDA (iminodiacetic acid) ligands, as used in nickel-histidine tags. Modification of the lipophilic region, for instance with unsaturated addends is also possible. These addends should allow polymerisation inside the membrane and potentially lead to a tremendous increase of the membrane rigidity. Furthermore, mono- and bilayer-forming fullerene derivatives without the membrane-forming support of lecithins are investigated and exhibit interesting features

Alzheimer’s disease: history, ethics and medical humanities in the context of assisted suicide

Introduction Dementia diseases, especially Alzheimer’s disease (AD), are of considerable importance in terms of social policy and health economics. Moreover, against the background of the current Karlsruhe judgement on the legalisation of assisted suicide, there are also questions to be asked about medical humanities in AD. Methodology Relevant literature on complementary forms of therapy and prognosis was included and discussed. Results Creative sociotherapeutic approaches (art, music, dance) and validating psychotherapeutic approaches show promise for suitability and efficiency in the treatment of dementia, but in some cases still need to be scientifically tested. Biomarker-based early diagnosis of dementia diseases is increasingly becoming a subject of debate against the background of the Karlsruhe ruling. Discussion Needs-oriented and resource-enhancing approaches can make a significant contribution to improving the quality of life of people with dementia. The discussion on the issue of “assisted suicide” should include questions of the dignity and value of a life with dementia. Outlook The integrative dementia therapy model can be complemented by a religion- and spirituality-based approach. Appropriate forms of psychotherapy should be scientifically evaluated

Performance evaluation of Sentinel-1 derived DEMs using Copernicus DEM and ICESat-2

Digital elevation models (DEMs) hold a key role as the main input data for a large variety of applications as they provide an accurate representation of the Earth’s surface and its corresponding topographic parameters. Scientific applications require current, reliable and precise elevation information to be implemented in research to generate correct and valuable results. The performance and accuracy of DEMs must therefore be subject to quality assessment. Synthetic Aperture Radar (SAR) principles and methodology allow the generation of DEMs independent from day light and cloud coverage which act as a massively limiting interference factor in optical imagery. In 2014, a C-band radar mission Sentinel-1 launched within the Copernicus Programme of the European Space Agency (ESA), providing open access to radar data of regular global coverage (Braun 2021). The capabilities of DEM derivation from Sentinel-1 imagery are limited by parameters like slope and vegetation coverage as well as by the mission design itself as the large temporal baseline of two or more Sentinel-1 acquisitions hinders the stability of the interferometric phase and degrades the coherence. One crucial step in the analysis of SAR data and therefore optimizing its potential for DEM generation is the preprocessing of suitable interferometric data pairs, a complex workflow which includes coregistration, interferogram formation, phase unwrapping and terrain correction (Braun 2021). Within the scope of the TanDEM-X mission by the German Aerospace Center (DLR), consisting of two satellites (Terra-SAR-X and Tandem-X), a global DEM was generated from bistatic X-Band interferometric SAR products acquired between December 2010 and January 2015 (Rizzoli 2017). The TanDEM-X mission is the original source of the radar data from which the Copernicus DEM (COP-DEM) by ESA was derived. The COP-DEM is available in varying resolutions with the 30m resolution COP-DEM being openly accessible. The Ice, Cloud and land Elevation Satellite-2 (ICESat-2) mission by National Aeronautics and Space Administration (NASA) provides openly accessible data since October 2018. ICESat-2 data is a continuous, equally distributed, high resolution reference dataset and allows to independently evaluate the performance of SAR-derived DEMs. An Advanced Topographic Laser Altimeter System (ATLAS) on board of ICESat-2 fires shots of photons in 532nm wavelength separated into six beams arranged in three pairs. Each pair consists of a strong and a weak beam with an energy ratio of 4:1 (Neuenschwander und Pitts 2019). Terrain and canopy heights retrievals are stored in the ATL08 data product of ICESat-2 and computed for fixed 12x100m land segments in which a valid height value is given if a threshold of 50 signal photons is met in order to reliably represent the land surface within the segment. ICEsat-2 provides a large variety of parameters and flags to filter the data adapted to the needs of the research purpose. In this paper, we will generate several DEMs derived from Sentinel-1 data and perform a quality and accuracy evaluation. As reference data, we will use highly accurate ICESat-2 data points and two reference DEMs, TanDEM-X in 10m resolution and Copernicus DEM in 30m resolution. The main focus of this study is the correct processing and application of various parameter filter techniques of ICESat-2 data to provide accurate height reference data for the accuracy assessment of SAR-derived DEMs and the evaluation on DEM quality in consideration of different land cover types and topographic conditions regarding study sites from different continents

X-Ray Searches for Emission from the WHIM in the Galactic Halo and the Intergalactic Medium

At least 50% of the baryons in the local universe are undetected and predicted to be in a hot dilute phase (1E5-1E7 K) in low and moderate overdensity environments. We searched for the predicted diffuse faint emission through shadowing observations whereby cool foreground gas absorbs more distant diffuse emission. Observations were obtained with Chandra and XMM-Newton. Using the cold gas in two galaxies, NGC 891 and NGC 5907, shadows were not detected and a newer observation of NGC 891 fails to confirm a previously reported X-ray shadow. Our upper limits lie above model predictions. For Local Group studies, we used a cloud in the Magellanic Stream and a compact high velocity cloud to search for a shadow. Instead of a shadow, the X-ray emission was brighter towards the Magellanic Stream cloud and there is a less significant brightness enhancement toward the other cloud also. The brightness enhancement toward the Magellanic Stream cloud is probably due to an interaction with a hot ambient medium that surrounds the Milky Way. We suggest that this interaction drives a shock into the cloud, heating the gas to X-ray emitting temperatures.Comment: 10 ApJ pages with 10 figure

Plasma TF activity predicts cardiovascular mortality in patients with acute myocardial infarction

<p>Abstract</p> <p>Objectives and Background</p> <p>Tissue factor (TF) contributes to thrombosis following plaque disruption in acute coronary syndromes (ACS). Aim of the study was to investigate the impact of plasma TF activity on prognosis in patients with ACS.</p> <p>Methods and Results</p> <p>One-hundred seventy-four patients with unstable Angina pectoris (uAP) and 112 patients with acute myocardial infarction (AMI) were included with a mean follow up time of 3.26 years. On admission, plasma TF activity was assessed. Patients were categorized into 2 groups: a high-TF activity group with TF >24 pmol/L and low TF activity group with TF ≤ 24 pmol/L. Fifteen cardiovascular deaths occurred in the uAP group and 16 in the AMI group. In AMI TF activity was 24,9 ± 2,78 pmol/l (mean ± SEM) in survivors and 40,9 ± 7,96 pmol/l in nonsurvivors (P = 0.024). In uAP no differences were observed (25.0 ± 8.04 pmol/L nonsurvivors vs. 25.7 ± 2.14 pmol/L survivors; P = 0.586). Kaplan-Meier estimates of survival at 3.26 years regarding TF activity in AMI were 81.3% and 92.2% with an hazard ratio of 3.02 (95% CI [1.05–8.79], P = 0.03). The Cox proportional hazards model adjusting for correlates of age and risk factors showed that plasma TF activity was an independent correlate of survival (hazard ratio 9.27, 95% CI [1.24–69.12], P = 0.03). In an additional group of patients with uAP and AMI, we identified circulating microparticles as the prevailing reservoir of plasma TF activity in acute coronary syndromes.</p> <p>Conclusion</p> <p>Systemic TF activity in AMI has an unfavorable prognostic value and as a marker for dysregulated coagulation may add to predict the atherothrombotic risk.</p

Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1

Myc plays a key role in homeostasis of the skin. We show that Miz1, which mediates Myc repression of gene expression, is expressed in the epidermal basal layer. A large percentage of genes regulated by the Myc–Miz1 complex in keratinocytes encode proteins involved in cell adhesion, and some, including the α6 and β1 integrins, are directly bound by Myc and Miz1 in vivo. Using a Myc mutant deficient in Miz1 binding (MycV394D), we show that Miz1 is required for the effects of Myc on keratinocyte responsiveness to TGF-β. Myc, but not MycV394D, decreases keratinocyte adhesion and spreading. In reconstituted epidermis, Myc induces differentiation and loss of cell polarization in a Miz1-dependent manner. In vivo, overexpression of β1 integrins restores basal layer polarity and prevents Myc-induced premature differentiation. Our data show that regulation of cell adhesion is a major function of the Myc–Miz1 complex and suggest that it may contribute to Myc-induced exit from the epidermal stem cell compartment