Genetic Diversity and Treatment Resistance in Prostate Cancer Cell Lines

Die Dissertationsarbeit untersucht genetische Varianten in Zellkulturmodellen des metastatischen und kastrationsresistenten Prostatakarzinoms. Außerdem werden Mechanismen der Chemoresistenz, insbesondere der Resistenz gegen Cisplatin und Docetaxel in diesen Zelllinien untersucht.This Dissertation evaluates genetic variants found in cell culture models of metastatic castration resistant prostate cancer. Furthermore, mechanisms of resistance against the chemotherapeutic drugs cisplatin and docetaxel are investigated in these cell lines

Bandbreiten regionaler Klimaprojektionen für Sachsen

Aus der Vielzahl von Klimaprojektionen resultieren Bandbreiten, wobei der Umgang damit einen Ressourcenkonflikt aufdeckt. Zur Kompensation wurde das Selektions-Tool »DSEL« entwickelt. Die Selektionskriterien umfassen Klimaelemente/-größen und extremwertorientierte WMO-Indizes. Für Sachsen ist von einem deutlichen Anstieg der Minimum- und Maximum-Temperaturen sowie einem Rückgang von Kälte- und einer Zunahme von Wärmeperioden auszugehen. Beim Vergleich der C20-Läufe mit Messungen wurde eine uneinheitliche Übereinstimmung festgestellt. Die (Stark-)Niederschlag-Indizes werden von den C20-Läufen des »WEREX-V-Ensemble« unterschätzt

Impact of cognitive reserve on clinical and neuropsychological measures in patients with mild cognitive impairment

Objective: Cognitive reserve influences age of onset, speed of progression, and clinical manifestations of Alzheimer’s disease. We investigated whether cognitive reserve interacts with clinical and neuropsychological parameters in mild cognitive impairment (MCI). Methods: In this cross-sectional study, we recruited 273 people (70.6 ± 10.1 years, 54.6% women) suffering from subjective memory complaints (n = 65), MCI (n = 121), or dementia (n = 87). Patients underwent neuropsychological evaluation, laboratory testing, and brain imaging. Additionally, we obtained information on years of education and help-seeking motivation. Results: MCI patients with a university degree were significantly older than those without (71.6 ± 9.6 vs. 66.9 ± 10.3, p = 0.02). University-educated MCI patients demonstrated superior performance in verbal fluency. Intrinsic help-seeking motivation (self-referral) was associated with higher cognitive reserve. Female MCI patients presented with greater intrinsic motivation. Conclusion: Cognitive reserve modulates clinical and neuropsychological measures in patients with MCI

Thickness in Entorhinal and Subicular Cortex Predicts Episodic Memory Decline in Mild Cognitive Impairment

Identifying subjects with mild cognitive impairment (MCI) most likely to decline in cognition over time is a major focus in Alzheimer's disease (AD) research. Neuroimaging biomarkers that predict decline would have great potential for increasing the efficacy of early intervention. In this study, we used high-resolution MRI, combined with a cortical unfolding technique to increase visibility of the convoluted medial temporal lobe (MTL), to assess whether gray matter thickness in subjects with MCI correlated to decline in cognition over two years. We found that thickness in the entorhinal (ERC) and subicular (Sub) cortices of MCI subjects at initial assessment correlated to change in memory encoding over two years (ERC: r = 0.34; P = .003) and Sub (r = 0.26; P = .011) but not delayed recall performance. Our findings suggest that aspects of memory performance may be differentially affected in the early stages of AD. Given the MTL's involvement in early stages of neurodegeneration in AD, clarifying the relationship of these brain regions and the link to resultant cognitive decline is critical in understanding disease progression

Analyse der Klimaentwicklung in Sachsen

Der Klimawandel in Sachsen wurde auf Basis einer aktualisierten Datengrundlage und neuer methodischer Verfahren analysiert. Danach war im Zeitraum 1981-2010 im Vergleich zur Referenzperiode 1961-1990 eine kontinuierliche Erwärmung in allen Jahreszeiten und eine erhöhte Hitzebelastung im Sommer erkennbar. Durch die Niederschlagsabnahme von April bis Juni war ein erhöhtes Trockenheitsrisiko zu verzeichnen. Von Juli bis September haben die Niederschläge zugenommen, ebenso der Starkregen-Anteil an den Niederschlagssummen. Die Häufigkeit und die Intensität von Starkregenereignissen ist gestiegen. Festgestellt wurden auch ausgeprägte dekadische Schwankungen von Temperatur und Niederschlag in den Wintermonaten. Die Veröffentlichung richtet sich an regionale Akteure sowie Planungsbüros, Bildungseinrichtungen und Unternehmen

Analyse zur Häufigkeit einer gerinnungshemmenden Medikation bei Patientinnen mit kognitiven Störungen und zerebraler Amyloidangiopathie (CAA)

Ziel der Arbeit: Analyse der Häufigkeit einer zerebralen Amyloidangiopathie (CAA) bei Patientinnen mit kognitiven Störungen und der Häufigkeit einer Koinzidenz von gerinnungshemmender Therapie und CAA. Explorative Analyse von Zusammenhängen zwischen Antikoagulation und CAA-typischer Läsionslast in der MRT. Material und Methoden: Patientinnen mit subjektiver kognitiver Störung (SCD), amnestischem und nichtamnestischem MCI (aMCI/naMCI), Alzheimer-Demenz (AD), gemischter Demenz (MD) und vaskulärer Demenz (VD) aus einem universitären Demenzzentrum, die sich von 02/2016 bis 12/2020 erstmals zur Demenzdiagnostik vorgestellt hatten, wurden in diese retrospektive Analyse eingeschlossen. Im Rahmen der Diagnostik erfolgten eine kranielle MRT inkl. Gradientenechosequenz und die Erfassung CAA-spezifischer MRT-Biomarker. Im Rahmen der retrospektiven Aktendurchsicht wurde das Vorliegen einer gerinnungshemmenden Medikation mit Thrombozytenaggregationshemmern, direkten oralen Antikoagulanzien (DOAK) oder Vitamin-K-Antagonisten zum Zeitpunkt der Vorstellung ermittelt. Ergebnisse: Im Beobachtungszeitraum von 02/2016 bis 12/2020 wurden 458 Patientinnen (209 männlich, 249 weiblich, Durchschnittsalter 73,2 ± 9,9 Jahre) mit SCD (n = 44), naMCI (n = 40), aMCI (n = 182), AD (n = 120), MD (n = 68) und VD (n = 4) analysiert. Bei 109 Patientinnen (23,8 %) lagen die MR-Kriterien einer möglichen oder wahrscheinlichen CAA vor. Die CAA-Prävalenz war am höchsten bei Patientinnen mit aMCI (39,4 %) und MD (28,4 %). Bei 30,3 % der Patientinnen mit möglicher oder wahrscheinlicher CAA bestand eine Thrombozytenaggregationshemmung, bei 12,8 % eine DOAK-Therapie und bei 3,7 % eine Therapie mit Vitamin-K-Antagonisten. Die Anzahl kortikaler und subkortikaler Mikroblutungen war insgesamt bei Patientinnen mit gerinnungshemmender Therapie höher als bei Patientinnen ohne Gerinnungshemmung (p = 0,047). Ein Zusammenhang zwischen gerinnungshemmender Therapie und Häufigkeit kortikaler superfizieller Siderosen bildete sich nicht ab (p = 0,634). Diskussion: Die CAA ist bei Patientinnen mit kognitiven Störungen häufig. Bei nahezu der Hälfte der Patientinnen mit CAA besteht eine gerinnungshemmende Medikation. Eine gerinnungshemmende Medikation ist mit einer größeren Anzahl kortikaler und subkortikaler Mikroblutungen vergesellschaftet.Objectives: To investigate the prevalence of coincident anticoagulation in patients with cognitive disorders and possible or probable cerebral amyloid angiopathy (CAA) as well as the relationship between the presence of oral anticoagulation and CAA-specific lesion load. Materials and methods: Patients with subjective cognitive decline (SCD), amnestic and non-amnestic mild cognitive impairment (aMCI/naMCI), Alzheimer’s disease (AD), mixed dementia (MD) and vascular dementia (VD) who presented to our outpatient dementia clinic between February 2016 and October 2020 were included in this retrospective analysis. Patients underwent cranial magnetic resonance imaging (MRI). MRI data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. Presence of anticoagulant therapy was determined by chart review. Results: Within the study period, 458 patients (209 male, 249 female, mean age 73.2 ± 9.9 years) with SCD (n = 44), naMCI (n = 40), aMCI (n = 182), AD (n = 120), MD (n = 68) and VD (n = 4) were analyzed. A total of 109 patients (23.8%) were diagnosed with possible or probable CAA. CAA prevalence was highest in aMCI (39.4%) and MD (28.4%). Of patients with possible or probable CAA, 30.3% were under platelet aggregation inhibition, 12.8% were treated with novel oral anticoagulants and 3.7% received phenprocoumon treatment. Regarding the whole study cohort, patients under oral anticoagulation showed more cerebral microbleeds (p = 0.047). There was no relationship between oral anticoagulation therapy and the frequency of cortical superficial siderosis (p = 0.634). Conclusion. CAA is a frequent phenomenon in older patients with cognitive disorders. Almost half of CAA patients receive anticoagulant therapy. Oral anticoagulation is associated with a higher number of cortical and subcortical microbleeds

Visual Personal Familiarity in Amnestic Mild Cognitive Impairment

BACKGROUND: Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general concept or helps to identify an object or a person. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we investigated the neural networks associated with the perception of personal familiar faces and places in patients with amnestic mild cognitive impairment and healthy control subjects. Irrespective of stimulus type, patients compared to control subjects showed lower activity in right prefrontal brain regions when perceiving personally familiar versus unfamiliar faces and places. Both groups did not show different neural activity when perceiving faces or places irrespective of familiarity. CONCLUSIONS/SIGNIFICANCE: Our data highlight changes in a frontal cortical network associated with knowledge-based personal familiarity among patients with amnestic mild cognitive impairment. These changes could contribute to deficits in social cognition and may reduce the patients' ability to transition from basic to complex situations and tasks

Age and the Neural Network of Personal Familiarity

BACKGROUND: Accessing information that defines personally familiar context in real-world situations is essential for the social interactions and the independent functioning of an individual. Personal familiarity is associated with the availability of semantic and episodic information as well as the emotional meaningfulness surrounding a stimulus. These features are known to be associated with neural activity in distinct brain regions across different stimulus conditions (e.g., when perceiving faces, voices, places, objects), which may reflect a shared neural basis. Although perceiving context-rich personal familiarity may appear unchanged in aging on the behavioral level, it has not yet been studied whether this can be supported by neuroimaging data. METHODOLOGY/PRINCIPAL FINDINGS: We used functional magnetic resonance imaging to investigate the neural network associated with personal familiarity during the perception of personally familiar faces and places. Twelve young and twelve elderly cognitively healthy subjects participated in the study. Both age groups showed a similar activation pattern underlying personal familiarity, predominantly in anterior cingulate and posterior cingulate cortices, irrespective of the stimulus type. The young subjects, but not the elderly subjects demonstrated an additional anterior cingulate deactivation when perceiving unfamiliar stimuli. CONCLUSIONS/SIGNIFICANCE: Although we found evidence for an age-dependent reduction in frontal cortical deactivation, our data show that there is a stimulus-independent neural network associated with personal familiarity of faces and places, which is less susceptible to aging-related changes

The comorbidity profiles and medication issues of patients with multiple system atrophy:a systematic cross-sectional analysis

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management.OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients.METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®.RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue.CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.</p

The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis

Background: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients’ safety and management. // Objectives: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. // Methods: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. // Results: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. // Conclusions: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients