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The potential of depressive symptoms to identify cognitive impairment in ageing
Get PDFDepressive symptoms are common in mild cognitive impairment (MCI), dementia caused by Alzheimer’s disease (AD dementia) and in cognitively unimpaired older adults. However, it is unclear whether they could contribute to the identification of cognitive impairment in ageing. To assess the potential utility of depressive symptoms to distinguish between healthy cognitive ageing and MCI and AD dementia. The diagnostic workup of the cognitive function of 1737 older cognitively unimpaired individuals, 334 people with MCI and 142 individuals with AD dementia relied on a comprehensive neuropsychiatric assessment, including the Mini Mental State Examination (MMSE). Depressive symptoms were tapped with the 15-item Geriatric Depression Scale (GDS). Proportional odds logistic regression (POLR) models and the machine learning technique Adaptive Boosting algorithm (AdaBoost) were employed. Stratified repeated random subsampling (stratified bootstrap resampling) was used to recursive partitioning to training- and validation set (70/30 ratio). The average accuracy of the POLR models for the GDS total score in distinguishing between cognitive impairment and healthy cognitive ageing exceeded 78% and was inferior to that of MMSE. Of note, the sensitivity of GDS total score was very low. By employing the AdaBoost algorithm and considering GDS items separately, the average accuracy was higher than 0.72 and comparable to that of the MMSE, while sensitivity- and specificity values were more balanced. The findings of the study provide initial evidence that depressive symptoms may contribute to distinguishing between cognitive impairment and cognitively healthy ageing
Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons
Get PDFSensory dorsal root ganglion (DRG) neurons have a unique pseudo-unipolar morphology in which a stem axon bifurcates into a peripheral and a central axon, with different regenerative abilities. Whereas peripheral DRG axons regenerate, central axons are unable to regrow. Central axon regeneration can however be elicited by a prior conditioning lesion to the peripheral axon. How DRG axon asymmetry is established remains unknown. Here we developed a rodent in vitro system replicating DRG pseudo-unipolarization and asymmetric axon regeneration. Using this model, we observed that from early development, central DRG axons have a higher density of growing microtubules. This asymmetry was also present in vivo and was abolished by a conditioning lesion that decreased microtubule polymerization of central DRG axons. An axon-specific microtubule-associated protein (MAP) signature, including the severases spastin and katanin and the microtubule regulators CRMP5 and tau, was found and shown to adapt upon conditioning lesion. Supporting its significance, interfering with the DRG MAP signature either in vitro or in vivo readily abolished central-peripheral asymmetries in microtubule dynamics and regenerative ability. In summary, our data unveil that axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons
Lehre und Forschung im MediaLab. Ein Rahmenkonzept
Get PDFInklusiver Unterricht nutzt digitale Technologien zur Verbesserung der Teilhabe, Zu-gänglichkeit und individuellen Förderung. Assistive Technologien unterstützen Menschen mit Behinderungen in ihrem Alltag, während digitale Medien Lehrkräfte dabei helfen, Unterricht zu organisieren und personalisierte Lernumgebungen zu schaffen. Medien-kompetenz ist dabei essenziell, sowohl für Lehrkräfte als auch für Lernende. Zur Förde-rung der Medienkompetenz von Studierenden im Lehramt Sonderpädagogik wurde im Oktober 2023 das MediaLab an der Ludwig-Maximilians-Universität München eröffnet. Es bietet Arbeitsplätze und technische Ausstattung für die Erstellung digitaler Medienpro-dukte wie Podcasts, Erklärvideos oder interaktive Lernmaterialien. Der Schwerpunkt liegt auf projektbasiertem, selbstgesteuertem und forschungsorientiertem Lernen. Das Media-Lab ist in Lehrveranstaltungen eingebunden und ermöglicht Studierenden, medienbezo-genes Wissen in Praxisprojekten anzuwenden. Die Lehr- und Lernmethoden basieren auf dem Medienkompetenzmodell von Baacke sowie projektbasiertem und kollaborativem Lernen. Digitale Tools wie Adaptable Books und Actionbound werden genutzt, um kreati-ve und interaktive Lernressourcen zu entwickeln. Ein weiterer Fokus liegt auf der For-schung und Wissenschaftskommunikation. Das MediaLab untersucht den Einsatz innova-tiver Technologien wie KI-gestützte Pädagogische Agenten zur Verbesserung von Lehr- und Lernprozessen. Zudem werden Forschungsergebnisse in Fachvideos und Podcasts aufbereitet und öffentlich zugänglich gemacht. Die im MediaLab erstellten Medienproduk-te werden als Open Educational Resources veröffentlicht, um den freien Zugang zu hochwertigen sonderpädagogischen Bildungsressourcen zu fördern und den Austausch zwischen Wissenschaft und Praxis zu unterstützen
Trapped between case and number. A typology of adnumerative forms
Get PDFIn this paper, I study the nature of adnumerative or numerative forms; i.e. morphologically dedicated inflectional forms that can only be used with numerals or quantifiers (e.g. Russian dva časá ‘two o'clock’ vs. [gen sg] čása). Adnumeratives are cross-linguistically very rare; yet they raise some interesting theoretical discussions. This work is based on the framework of Canonical Typology, which assumes the existence of a handful of discrete and cross-linguistically recurrent morphosyntactic features. Nevertheless, adnumerative forms present a challenge to that distribution, because, as I argue, adnumeratives lie between case and number values. This might well represent a theoretically undesirable scenario, and thus, be diachronically unstable. However, the data I have gathered prove that there are adnumerative forms that have survived in this penumbra for centuries and one can also adduce more evidence of diachronically stable cross-linguistic phenomena between two feature values (e.g. the anterior). Therefore, I propose that this theoretical space may not be as dark previously depicted and I ask questions for further exploration
Cellular interplay in brain organoids: Connecting cell-autonomous and non-cell-autonomous mechanisms in neurodevelopmental disease
Get PDFThe field of brain organoids has experienced a period of rapid and transformative growth, enabling researchers to investigate complex human biological mechanisms that were previously deemed intractable. This review provides an overview of the current landscape of brain organoids, with a particular focus on their relevance in the context of neurodevelopmental disorders. It also emphasizes the crucial role these models play in elucidating both cell-autonomous and non-cell-autonomous mechanisms. We describe how these two mechanisms, often considered to be independent, are intricately interconnected. In conclusion, this review aims to highlight how the utilization of brain organoids has considerably advanced our comprehension of neurodevelopmental disorders, while also delineating prospective avenues for investigating these complex conditions
Insights Into Disability and Disability Progression in People With Multiple Sclerosis Using Large‐Scale Healthcare Data
Get PDFBackground: Identifying predictors for disability progression is crucial for managing multiple sclerosis (MS). This study aims to explore levels of disability and informative factors for disability progression in people with MS (PwMS) using healthcare data without detailed clinical information.
Methods: We conducted a case–control/cohort study on data from Bavaria's largest health insurance organization. The dataset included records of assistive devices, nursing care, sick leaves, rehabilitation, drug therapies, and diagnoses for individuals with MS, Crohn's disease (CD), rheumatoid arthritis (RA), and controls (CTR) without these diseases. We used generalized linear models to compare healthcare service utilization between MS and other cohorts. A gradient-boosting algorithm identified informative healthcare-related factors associated with disability progression in PwMS, defined by increased nursing care utilization.
Results: PwMS (N = 11,961) demonstrated higher healthcare utilization than CD (N = 21,884), RA (N = 105,450), and CTR (N = 82,677) groups, even at young ages. Besides expected risk factors like age, smoking, diabetes, and psychiatric disorders, the prediction algorithm revealed that PwMS with specific gynecological disorders, upper tract infections, asthma, and thyroiditis were less likely to need higher levels of nursing care.
Conclusions: Leveraging healthcare data allows for an objective assessment of disability in PwMS and can identify informative factors for disability progression. Our approach can be applied to studies on disease progression in large cohorts without detailed clinical data and can be adapted to other diseases, disability measures, and healthcare systems. Higher utilization of healthcare resources even at young ages revealed an unmet need for improved treatment and management strategies for young adults with MS
Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia
Get PDFIntroduction: Higher male prevalence in sporadic behavioral variant frontotemporal dementia (bvFTD) has been reported. We hypothesized differences in phenotypes between genetic and sporadic bvFTD females resulting in underdiagnosis of sporadic bvFTD females.
Methods: We included genetic and sporadic bvFTD patients from two multicenter cohorts. We compared behavioral and cognitive symptoms, and gray matter volumes, between genetic and sporadic cases in each sex.
Results: Females with sporadic bvFTD showed worse compulsive behavior (p = 0.026) and language impairments (p = 0.024) compared to females with genetic bvFTD (n = 152). Genetic bvFTD females had smaller gray matter volumes than sporadic bvFTD females, particularly in the parietal lobe.
Discussion: Females with sporadic bvFTD exhibit a distinct clinical phenotype compared to females with genetic bvFTD. This difference may explain the discrepancy in prevalence between genetic and sporadic cases, as some females without genetic mutations may be misdiagnosed due to atypical bvFTD symptom presentation
The crystal structures of methyl prop-2-ynoate, dimethyl fumarate and their protonated species
Get PDFMethyl prop-2-ynoate (C4H4O2) was investigated in the binary superacidic system HF/MF5 (M = Sb or As) and dimethyl fumarate (C6H8O4) in the superacidic system HF/SbF5, as well as HF/BF3. The starting materials methyl prop-2-ynoate and dimethyl fumarate were crystallized, the former for the first time. The protonated species of these esters, namely, (1-methoxyprop-2-yn-1-ylidene)oxidanium hexafluoroarsenate, C4H5O2+ AsF6−, 1,4-dimethoxy-4-oxobut-2-en-1-ylidene]oxidanium tetrafluoroborate bis(hydrogen fluoride), C6H9O4+ BF4− 2HF, and hemi{[1,4-dimethoxy-4-oxidaniumylidenebut-2-en-1-ylidene]oxidanium} undecafluorodiantimonate, 0.5C6H10O42+ Sb2F11−, were characterized by single-crystal X-ray diffraction and Raman spectroscopy. The protonated species were recrystallized from anhydrous hydrogen fluoride. In the solid state of the monoprotonated species of methyl prop-2-ynoate and the diprotonated species of dimethyl fumarate, strong intramolecular O—H⋯F hydrogen bonds build a three-dimensional network. The monoprotonated species of dimethyl fumarate builds chains by strong O—H⋯O hydrogen bonds between the cations
Optimizing lower extremity CT angiography: A prospective study of individualized vs. fixed post-trigger delays in bolus tracking
Get PDFPurpose
To compare the contrast media opacification and diagnostic quality in lower-extremity runoff CT angiography (CTA) between bolus-tracking using conventional fixed trigger delay and patient-specific individualized post-trigger delay.
Methods
In this prospective study, lower-extremity runoff CTA was performed in two cohorts, using either fixed or individualized trigger delay. Both cohorts had identical CT protocols, contrast media applications, and image reconstructions. Objective image quality (mean contrast opacification in HU), and subjective image quality (5-point Likert-scale), were assessed in six vessels: abdominal aorta (AA), common iliac artery (CIA), superficial femoral artery (SFA), popliteal artery (PA), posterior tibial artery (PTA), and dorsalis pedis artery (DPA) by one rater for objective and two raters for subjective image quality. Objective image quality was analyzed using Student t-tests, while subjective ratings were compared with Fisher’s exact test.
Results
Overall, 65 patients were included (mean age: 71 ± 14; 39 men), 35 in the individualized cohort and 30 in the fixed cohort. No differences were found between the groups regarding demographics or radiation exposure. Individualized trigger delay ranged from 2 to 23 s (mean: 8.7 ± 4.0 s) and was 10 s in the fixed cohort. The individualized cohort showed higher opacification in the peripheral arteries (PTA: 479 ± 140 HU vs. 379 ± 106 HU; p = 0.009; DPA: 477 ± 191 HU vs. 346 ± 137 HU; p = 0.009). Overall subjective “image quality” was rated higher in the individualized group (“excellent” or “good” in Rater 1: 97 % vs. 57 %; p < 0.001; and Rater 2: 89 % vs. 53 %; p = 0.002).
Conclusion
Individualized post-trigger delay enhances diagnostic quality, by improving vessel opacification in peripheral arteries and increasing subjective image quality in lower extremity runoff CTA