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Torsional resistance of additively, subtractively, and conventionally manufactured occlusal devices
No full textDoes Size Outweigh Number in Predicting Survival After Pulmonary Metastasectomy for Soft Tissue Sarcoma? Insights from a Retrospective Multicenter Study
No full textEpidemiological trends in enamel hypomineralisation and molar-incisor hypomineralisation: a systematic review and meta-analysis
No full textUbiquitin–proteasome system in the different stages of dominantly inherited Alzheimer's disease
Get PDFINTRODUCTION
This study investigated the role of the ubiquitin–proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining cerebrospinal fluid (CSF) levels of UPS proteins.
METHOD
The SOMAscan assay was used to detect changes in UPS proteins in mutation carriers (MCs) relative to disease progression; imaging and CSF biomarkers of amyloid, tau, and neurodegeneration measures; and Clinical Dementia Rating scale.
RESULTS
Subtle increases in specific ubiquitin enzymes were detected in MCs up to two decades before symptom onset, with more pronounced elevations in UPS-activating enzymes near symptom onset. Significant correlations were found between UPS proteins and Alzheimer's disease (AD) biomarkers, especially between autophagy markers and late-stage tau biomarkers, microglia, and axonal degeneration.
DISCUSSION
The rise in UPS proteins alongside tau-related markers suggests UPS involvement in tau neurofibrillary tangles. Elevated CSF UPS proteins in DIAD MCs may serve as indicators of disease progression, and may support the UPS as a therapeutic target in AD
Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge
Get PDFSevere symptoms in the absence of measurable body pathology are a frequent hallmark of post-COVID syndrome. From a Bayesian Brain perspective, such symptoms can be explained by incorrect internal models that the brain uses to interpret sensory signals. In this pre-registered study, we investigate whether induced breathlessness perception during a controlled CO2rebreathing challenge is reflected by altered respiratory measures (physiology and breathing patterns), and propose different computational mechanisms that could explain our findings in a Bayesian Brain framework. We analysed data from 40 patients with post-COVID syndrome and 40 healthy participants. Results from lung function, neurological and neurocognitive examination of all participants were within normal limits on the day of the experiment. Using a Bayesian repeated-measures ANOVA, we found that patients’ breathlessness was strongly increased (BF10,baseline=8.029, BF10,rebreathing=11636, BF10,recovery=43662) compared to controls. When excluding patients who hyperventilated (N = 8, 20%) during the experiment from the analysis, differences in breathlessness remained (BF10,baseline=1.283, BF10,rebreathing=126.812, BF10,recovery=751.282). For physiology and breathing patterns, all evidence pointed towards no difference between the two groups (0.307 > BF10 < 0.704). In summary, we found intact breathing patterns and physiology but increased symptom perception in patients with post-COVID syndrome
The German Dementia Registry (DEMREG): study protocol of a biomarker-based national registry for cognitive impairment and dementia
Get PDFIntroduction
The German Dementia Registry (DEMREG) is a large-scale national prospective biomarker-based study for cognitive impairment and dementia, providing an integrated clinical research platform for research studies.
Methods
The DEMREG study longitudinally collects demographic, clinical, genetic, biological, and imaging data, along with risk factors and treatment information from real-world settings. Comprehensive clinical assessments are conducted yearly. This extensive resource enables researchers to investigate current diagnostic and treatment practices and explore the complex relationships between risk factors and outcomes. The registry is now active across 22 sites in Germany, all members of the the German Memory Clinic Network (DNG), with more than 500 patients recruited to date, and is expected to include up to 1.000 patients annually.
Perspective
The DEMREG study represents a large nationally harmonized cohort of detailed real-world clinical and biological data from patients with cognitive impairment and dementia, enabling insights into long-term dynamics and treatment responses. This infrastructure has the potential to foster collaborative research and roll out healthcare innovations across different settings in Germany. In this context, a substudy will soon be conducted to evaluate long-term safety and efficacy measures of the new monoclonal antibodies targeting amyloid plaques in a clinical setting.
Trial registration
The protocol is registered at German Clinical Trials Register (DRKS00027547), Date of Registration: 01.04.2022
Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype
Get PDFCross‐country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia
Get PDFINTRODUCTION
We investigated international differences in facial emotion recognition (FER) across stages of frontotemporal dementia (FTD). Previous studies may have missed early decline by combining data and masking variations in FER across countries.
METHODS
An FER test was administered to 159 individuals with behavioral variant FTD, 521 presymptomatic pathogenic variant carriers, and 583 controls from 16 countries of residence. Linear mixed models assessed age, sex, education, and country effects on FER. Voxel-based morphometry examined neural correlates across countries.
REULTS
Country accounted for 18%–18.3% of FER variance in presymptomatic carriers and controls and 9.9% in individuals with behavioral variant of FTD (bvFTD). Cross-country differences interacted with the effects of sex, age, and education. Neural correlates involving the frontal lobe and basal ganglia were identified in individuals with bvFTD, but no cross-country differences were found.
DISCUSSION
These results underscore the need for culturally sensitive FER tools in research and clinical practice, especially as global multinational clinical trials emerge
Cortical microstructure is associated with disease severity and clinical progression in genetic frontotemporal dementia: a GENFI study
Get PDFThe study of genetic frontotemporal dementia (FTD) allows investigating its earliest presymptomatic stages. Using cross-sectional T1-weighted and diffusion-weighted MRI, we test the hypothesis that cortical microstructural alterations, quantified as cortical mean diffusivity (cMD), are detectable earlier and are more strongly associated with clinical progression than cortical thickness (CTh). The sample comprised n = 710 individuals (47.8 ± 13.5 years, 56.6% female, 14.1 ± 3.3 years of education), including 118 symptomatic carriers and 305 presymptomatic carriers with mutations in C9orf72, GRN or MAPT genes, and 287 non-carriers, collected from 24 GENFI sites. A subset of n = 453 individuals (289 carriers, 164 non-carriers) were investigated across Clinical Dementia Rating (CDR) = 0, 0.5 and ≥1 stages. Two subsets had longitudinal clinical outcome measures, including n = 403 individuals (239 carriers, 164 non-carriers) with Cambridge Behavioural Inventory-Revised scores during 2.8 ± 1.6 years, and n = 261 individuals (164 carriers, 97 non-carriers) with CDR Sum-of-Boxes scores during 2.0 ± 0.8 years. Regional cMD and CTh were entered into linear mixed-effects models incorporating age, sex and education as covariates; site, and individual nested within site were random intercepts. The results demonstrated that cMD is more sensitive than CTh to track early cortical injury, with elevated cMD first observed at CDR = 0 in C9orf72 carriers, followed by MAPT carriers (from CDR = 0.5 stage), and by GRN carriers (beginning at CDR ≥ 1). At all stages, cortical microstructural injury had stronger effect size and was more widespread than cortical thinning. In all mutation carrier types, cMD was more strongly associated than CTh with subsequent clinical progression. Cortical microstructure is a promising biomarker to identify at-risk individuals before atrophy and clinical progression, with utility in therapeutic trials
The Sacramental Signification in the Rite of the Holy Mass
Get PDFThis study offers a systematic and comparative account of three major medieval commentaries on the rite of the Holy Mass: St. Thomas Aquinas’s exposition in the “Summa theologiæ,” Pope Innocent III’s “De sacro altaris mysterio,” and “De mysterio missæ” attributed to St. Albert the Great. At its centre stands the Roman Canon—the core of the Latin Mass tradition—whose enduring liturgical use prompted centuries of theological reflection. Bridging perspectives of doctrine, sacraments, and liturgical exegesis, the study addresses the long-standing tension between the spiritual and philological schools of interpretation. By retrieving the Thomistic doctrine of spiritual signification—grounded in sacred doctrine and operative in Scripture, sacraments, and liturgy—it proposes a theological resolution. This Thomistic ressourcement demonstrates that the spiritual sense is not a subjective imposition, but an objective content of the rites themselves—signifying the passion of Christ, the sanctification of the Church, and the final consummation of the mystical body. In doing so, it contributes to the renewal of liturgical theology and highlights Aquinas’s synthesis as a vital key for understanding the Holy Mass in the Western tradition