Ludwig-Maximilians-Universität München
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Cardiovascular disease outcomes in relation to 25-hydroxyvitamin D and its seasonal variation: Results from the BiomarCaRE consortium
Get PDFBackground: It has been hypothesized but seldom tested that the winter excess in cardiovascular disease (CVD) is related to hypovitaminosis D. The present study examined the association between CVD and (i) seasonality of 25-hydroxyvitamin D (25[OH]D) and (ii) individual 25(OH)D concentrations.
Methods and findings: Harmonized 25(OH)D data were obtained from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, including 79,570 participants examined between 1984 and 2010. One 25(OH)D measurement was available per participant. Primary endpoints were CVD incidence (coronary heart disease or stroke; n = 6006) and CVD mortality (n = 2985). To study (i), Poisson regression-derived rate ratios were compared according to two-month categories, ordered by baseline 25(OH)D concentrations. To study (ii), Cox regression-derived hazard ratios were compared according to quarters of baseline 25(OH)D concentrations. With respect to (i), despite a median 25(OH)D concentration ratio of 1:1.79, the trough months of 25(OH)D in March and April had a similar CVD incidence as the peak months of 25(OH)D in August and September (rate ratio: 1.07, 95% CI: 0.98-1.17). CVD mortality was slightly higher in the trough months compared to the peak months (rate ratio: 1.27, 95% CI: 1.12-1.44) but not compared to the other months (despite median 25[OH]D concentration ratios up to 1:1.62; p ≥ 0.077). The CVD mortality peak in January preceded the 25(OH)D trough, not adhering to the temporality criterion of Bradford Hill. With respect to (ii), compared to the lowest quarter, the highest quarter of 25(OH)D was associated with lower CVD incidence (hazard ratio: 0.82, 95% CI: 0.76-0.89) and CVD mortality (hazard ratio: 0.64, 95% CI: 0.57-0.72).
Conclusion: The present study does not support the hypothesis that seasonal increases in CVD are driven by short-term reductions in 25(OH)D. As in most observational studies, higher 25(OH)D concentrations were inversely associated with CVD
Geoeconomic fragmentation and the role of non-aligned countries
Get PDFWe analyze how non-aligned countries affect welfare outcomes in scenarios of global trade fragmentation. Using a quantitative trade model covering 141 countries and 65 economic sectors, we simulate different scenarios of geoeconomic fragmentation. We find that major non-aligned countries benefit from their neutral position, with welfare gains of up to 0.7 percent that vary significantly across sectors. These gains turn into significant losses if they join either the Western or Eastern trade bloc. Moreover, world welfare losses increase from −1.9 percent under incomplete fragmentation to −2.7 percent when non-aligned countries join the West and to −3.7 percent when they join the East. Our results highlight the strategic importance of non-aligned countries in mitigating the negative effects of global trade fragmentation
SynNeurGe: The road ahead for a biological definition of Parkinson's disease
No full textWhile significant progress has been made in treating Parkinson's disease (PD) symptoms, disease-modifying therapies (DMTs) have consistently failed. To address the underlying molecular mechanisms of PD, two biology-based criteria have been proposed: the “Synucleinopathy-Neurodegeneration-Genetics” (SynNeurGe) and “neuronal α-synuclein disease” (NSD) frameworks. Both frameworks emphasize the importance of biological markers over clinical symptoms. They recognize α-synuclein aggregation and genetic mutations (such as SNCA) as key diagnostic elements, with α-synuclein seed amplification assays (SAA) in cerebrospinal fluid (CSF) used to detect early disease stages. Dopaminergic neurodegeneration, measured by DAT imaging, is also central to both frameworks. These shared features aim to improve early diagnosis and precision medicine for PD. However, SynNeurGe provides a broader, more flexible framework that integrates α-synuclein pathology (S), neurodegeneration (N), and genetics (G), linked to clinical features (C). It aims to accommodate the complexity of PD and related Lewy body diseases, facilitating research on targeted DMTs. In contrast, NSD focuses specifically on PD and Lewy body dementia, introducing a staging system (NSD-ISS) based on biological markers and clinical impairment, helping track disease progression from preclinical to symptomatic stages. Despite their differences, both approaches highlight the need for more specific biomarkers and prospective studies to improve early intervention and personalized treatment. Harmonizing SynNeurGe and NSD concepts will be key in creating a universally accepted framework for precise PD diagnosis and therapy development
Benzoyl Peroxide's Sensitisation Potential and Potency in Experimental Methods and Review of Contact Allergy and Allergic Contact Dermatitis
No full textPositive patch test responses to benzoyl peroxide (BPO) have been reported from patients without and with known exposure. Up to 6.5% were found in the United States and 7.8% in a study including patients from Germany, Austria and Switzerland. We provide an overview of the skin sensitisation potential and potency of BPO based on animal experiments and non-animal methods. BPO tested positive in Guinea Pig Tests and the Local Lymph Node Assay. Application of the current OECD guideline to identify a skin sensitizer by combining non-animal method results gave differing outcomes. Moreover, patch test responses of patients to BPO were considered to determine the importance of BPO as a relevant occupational contact allergen. Another well-known BPO exposure is the topical application to treat acne. Despite widespread use, extensive and long-term skin exposure, we found for this group only studies reporting few positive patch test reactions. Further, occupational handling of BPO and contact allergy is reported by dental technicians. In-depth evaluation of the prevalence of contact allergy in different professions with suspected BPO exposure did not reveal an association with occupational handling of BPO. Consequently, a generally increased risk for those professions is not supported
Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study
No full textCommon variants within TMEM106B are associated with risk for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). The G allele of the top single nucleotide polymorphism, rs1990622, confers protection against FTLD-TDP, including genetic cases due to GRN mutations or C9orf72 hexanucleotide repeat expansions. However, the effects of interaction between TMEM106B-rs1990622 and frontotemporal dementia (FTD) mutations on disease endophenotypes in genetic FTD are unknown.
This longitudinal cohort study was embedded within the GENetic Frontotemporal dementia Initiative (GENFI). We included 518 participants from 222 families [209 non-carriers; 222 presymptomatic carriers (C9orf72 = 79; GRN = 101, MAPT = 42); 87 symptomatic carriers (C9orf72 = 45; GRN = 29; MAPT = 13)] followed for up to 7 years. Using linear mixed-effects models, we examined the effects of a triple interaction between TMEM106B-rs1990622G allele dosage (additive model: 0, 1 or 2 alleles) and autosomal dominant FTD mutations with clinical status, and time from baseline on (i) grey matter volume using a voxel-based analysis; (ii) serum neurofilament light chain (NfL) levels; and (iii) cognitive and behavioural measures.
Mean age of participants was 47.9 ± 13.8 years, 58.1% were female and 61% had at least one G allele. C9orf72: rs1990622G allele dosage was associated with less atrophy within the right occipital region in presymptomatic carriers at baseline, and reduced atrophy rate within putamen and caudate nucleus, right frontotemporal regions, left cingulate and bilateral insular cortices in symptomatic carriers over time; lower NfL levels in presymptomatic carriers at baseline; better executive functions and language abilities in presymptomatic carriers; and maintained overall cognitive functions and behaviour in symptomatic carriers over time. GRN: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right temporal and occipital regions in presymptomatic carriers, and within the right frontal cortex and insula over time in symptomatic carriers; lower serum NfL levels over time in presymptomatic carriers and lower NfL levels at both baseline and over time in symptomatic carriers; and better global cognitive performance at baseline and higher attention/processing speed scores over time in symptomatic carriers. MAPT: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right inferior frontal gyrus in symptomatic carriers, but no effects on serum NfL or cognitive/behavioural measures.
TMEM106B-rs1990622G allele dosage showed protective effects on multiple endophenotypes predominantly in GRN and C9orf72 groups. Therefore, TMEM106B genotype should be assessed in clinical trials, particularly of GRN- and C9orf72-related genetic FTD, due to its modifying effects on biomarker, imaging, cognitive and clinical outcomes
Generativität
No full textGenerativität steht für eine neue Entwicklungsstufe in der Geschichte automatisierter Produktion. Auf Wortbefehl hin kann generative KI bestechende Bildwelten erzeugen, die selbst surreale Kompositionen in fotografischer Echtheit erscheinen lassen. Im Unterschied zur Fotografie, die einst die Bildgeschichte veränderte, handelt es sich um eine algorithmische Kreativität, die an Bildmotiven trainiert wird. Indem sie deren Sehweisen und Stereotypien reproduziert, trägt sie allmählich und über die digitale Kommunikation hinaus zu einer neuen Ästhetik bei, mit langfristigen Folgen für die Gesellschaft und ihre bildliche Erinnerung
