Quantitative Analyse retinaler Veränderungen bei nichtglaukomatösen Optikusatrophien mit Hilfe der Optischen Kohärenztomographie

Nichtglaukomatöse Optikusatrophien führen nicht nur zu einer Verminderung der Dicke der retinalen Nervenfaserschicht (RNFL) sondern auch zu einer Reduktion des Makulavolumens. In dieser Arbeit wurde mit Hilfe der optischen Kohärenztomographie (OCT) untersucht, welche Schichten der Makula von Dickenveränderungen als Folge einer Optikusatrophie betroffen sind. Es wurden 27 Patienten mit nichtglaukomatösen Optikusatrophien unterschiedlicher Ätiologie (postneuritische, hereditäre und traumatische Atrophien) und 21 augengesunde Kontrollpersonen untersucht. OCT-Scans der RNFL und der Makula wurden mit Hilfe des Stratus OCT 3000 (Carl Zeiss Meditec) durchgeführt. Die axialen Reflektivitätsprofile der radialen Scans wurden aus den exportierten JPEG-Bildern an zwölf Punkten in je 1,5mm Entfernung von der Foveola vermessen und gemittelt. Das charakteristische Reflektivitätsprofil mit fünf Intensitätsmaxima und vier Intensitätsminima wurde der Lokalisation der einzelnen Makulaschichten zugeordnet. Die von nichtglaukomatöser Optikusatrophie betroffenen Augen wiesen im Vergleich zu den Augen der augengesunden Normalpersonen signifikant (p<0,05) reduzierte RNFL-Dicken (um 35,5% reduziert) und Makulavolumen-Werte (um 11,8% reduziert) auf. Bei allen untersuchten Formen der Optikusatrophie waren nicht nur die makuläre Nervenfaserschicht (MNFL) sondern alle inneren Schichten der Makula verdünnt. Die mittlere Reduktion betrug 21,2% für die MNFL, 39,7% für die Ganglienzellschicht, 33,2% für die innere plexiforme Schicht und 9,4% für die innere Körnerzellschicht im Vergleich zu den Werten der Normalpersonen. Veränderungen der äußeren Netzhautschichten traten nur bei den posttraumatischen Atrophien auf. Eine Beurteilung der Dicke aller einzelnen Netzhautschichten aus OCT-Scans ist mit Hilfe geräteintegrierter Software bisher noch nicht möglich. Die quantitative Analyse der axialen Reflektivitätsprofile aus exportierten OCT-Bildern stellt eine geeignete Methode zur Beschreibung des Verlaufs und der Lokalisation von Makulaveränderungen bei Optikusatrophien verschiedener Genese dar

Iatrogene Beschwerden durch das Mundoffenhalten bei der zahnärztlichen Therapie

Das bei zahnärztlichen Behandlungen geforderte permanente Mundoffenhalten wird von vielen Patienten als besondere Belastung wahrgenommen. Es kann Ursache für craniomandibuläre Dysfunktionen (CMD) sein. In der Literatur wird das Mundoffenhal-ten und die daraus resultierenden Beschwerden nur im Zusammenhang mit zahnärzt-lichen Behandlungen beschrieben. Deshalb wurden in der vorliegenden Initialstudie die Beschwerden unabhängig von dentalen Einflussfaktoren eruiert. Zunächst erfolgte die aktive Mundöffnung, anschließend wurde die passive Mundöffnung durch Verwen-dung eines Aufbisskeils untersucht. Dieser verspricht laut Hersteller ein beschwerde-freies Mundaufhalten. Es wurde überprüft, ob eine geringere Schmerzbelastung und somit ein besseres Befinden der Probanden nach der Behandlung resultierten. Die Studie wurde mit 13 randomisiert ausgewählten und gesunden Probanden durch-geführt. Im ersten Studienteil erfolgte das aktive Mundoffenhalten nach Einbringen eines Mikroschalters in regio 36, der beim Zusammenführen der Kiefer ein Signal ab-gab. So wurde die aktive Mundöffnung über einen Zeitraum von einer Stunde forciert. Im zweiten Studienabschnitt wurde ein PropGard® (Ultradent Products, South Jordan, USA) Aufbisskeil zwischen den Zahnreihen eingebracht und somit das passive Mund-offenhalten für die Dauer von einer Stunde realisiert. Es erfolgte eine Befunderhebung sowohl vor jedem Studienabschnitt als auch unmittelbar nach dem Mundoffenhalten sowie nach einem und nach drei Tagen. Die Probanden protokollierten ihr subjektives Schmerzempfinden auf einer visuellen Analogskala (VAS) in Kombination mit einer numerischen Ratingskala (NRS) während des Offenhaltens als auch danach. Es bestätigte sich die Annahme, dass Beschwerden durch das Mundoffenhalten bei Verwendung eines Aufbisskeils erst später auftraten. 54 % der Probanden tolerierten eine Behandlungsdauer von 45 Minuten und länger bei passiver Mundöffnung. Die Schmerzpeaks, ermittelt durch VAS und NRS, waren beim aktiven Mundoffenhalten nach 50 Minuten und beim passiven Mundoffenhalten nach 40 Minuten erreicht. Beide Mal gingen die Beschwerden mit Einsetzen des Mundschlusses nach einer Stunde zurück. Mittels Palpationsbefund wurde die Schmerzlokalisation und -stärke eruiert. Bei der aktiven Mundöffnung waren vor allem das rechte Kiefergelenk, der rechte M. masseter und der M. pterygoideus lateralis schmerzhaft. Bei der passiven Mund-öffnung wurde vermehrt rechtsseitig der M. temporalis und die Postmandibularregion mit Beschwerden genannt. Insgesamt wurden beim passiven Mundaufhalten weniger Bereiche als schmerzhaft angegeben. Der rechte M. masseter war jeweils am lang-fristigsten betroffen. Die Analyse der Okklusionsveränderungen ergab, dass mehr Okklusionskontaktreduzierungen nach dem aktiven Mundoffenhalten als nach dem passiven Mundoffenhalten auftraten. Die Studie konnte nachweisen, dass die Verwendung eines Aufbisskeils den Patienten die zahnärztliche Behandlung angenehmer macht und weniger Nachbeschwerden verursacht. Es ist sinnvoll, bei Behandlungen, die länger als 30 Minuten andauern, einen Aufbisskeil zu verwenden. Die Probanden zeigten nur eine geringe Intoleranz gegenüber der Apparatur bei einer positiv formulierten Aufklärung

No Evidence for a Boost in Psychosocial Functioning in Older Age After a 6-Months Physical Exercise Intervention

The beneficial effects of physical exercise on physical health and cognitive functioning have been repeatedly shown. However, evidence of its effect on psychosocial functioning in healthy adults is still scarce or inconclusive. One limitation of many studies examining this link is their reliance on correlational approaches or specific subpopulations, such as clinical populations. The present study investigated the effects of a physical exercise intervention on key factors of psychosocial functioning, specifically well-being, stress, loneliness, and future time perspective. We used data from healthy, previously sedentary older adults (N = 132) who participated in a 6-month at-home intervention, either engaging in aerobic exercise or as part of a control group who participated in foreign language-learning or reading of selected native-language literature. Before and after the intervention, comprehensive cardiovascular pulmonary testing and a psychosocial questionnaire were administered. The exercise group showed significantly increased fitness compared to the control group. Contrary to expectations, however, we did not find evidence for a beneficial effect of this fitness improvement on any of the four domains of psychosocial functioning we assessed. This may be due to pronounced stability of such psychological traits in older age, especially in older adults who show high levels of well-being initially. Alternatively, it may be that the well-documented beneficial effects of physical exercise on brain structure and function, as well as cognition differ markedly from beneficial effects on psychosocial functioning. While aerobic exercise may be the driving factor for the former, positive effects on the latter may only be invoked by other aspects of exercise, for example, experiences of mastery or a feeling of community.Peer Reviewe

A regionally informed abundance index for supporting integrative analyses across butterfly monitoring schemes

1. The rapid expansion of systematic monitoring schemes necessitates robust methods to reliably assess species' status and trends. Insect monitoring poses a challenge where there are strong seasonal patterns, requiring repeated counts to reliably assess abundance. Butterfly monitoring schemes (BMSs) operate in an increasing number of countries with broadly the same methodology, yet they differ in their observation frequency and in the methods used to compute annual abundance indices. 2. Using simulated and observed data, we performed an extensive comparison of two approaches used to derive abundance indices from count data collected via BMS, under a range of sampling frequencies. Linear interpolation is most commonly used to estimate abundance indices from seasonal count series. A second method, hereafter the regional generalized additive model (GAM), fits a GAM to repeated counts within sites across a climatic region. For the two methods, we estimated bias in abundance indices and the statistical power for detecting trends, given different proportions of missing counts. We also compared the accuracy of trend estimates using systematically degraded observed counts of the Gatekeeper Pyronia tithonus (Linnaeus 1767). 3. The regional GAM method generally outperforms the linear interpolation method. When the proportion of missing counts increased beyond 50%, indices derived via the linear interpolation method showed substantially higher estimation error as well as clear biases, in comparison to the regional GAM method. The regional GAM method also showed higher power to detect trends when the proportion of missing counts was substantial. 4. Synthesis and applications. Monitoring offers invaluable data to support conservation policy and management, but requires robust analysis approaches and guidance for new and expanding schemes. Based on our findings, we recommend the regional generalized additive model approach when conducting integrative analyses across schemes, or when analysing scheme data with reduced sampling efforts. This method enables existing schemes to be expanded or new schemes to be developed with reduced within-year sampling frequency, as well as affording options to adapt protocols to more efficiently assess species status and trends across large geographical scales

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 and co-medication profile of patients with progressive supranuclear palsy

BackgroundProgressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients.ObjectivesTo explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease.MethodsCross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik (R).ResultsIn total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions.ConclusionsPSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values &gt;0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.</p

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures