Publications by authors named "Michael Wagner"

977 Publications

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Nat Commun 2021 06 7;12(1):3417. Epub 2021 Jun 7.

Servei de Neurologia, Hospital Universitari i Politècnic La Fe, Valencia, Spain.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22491-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184987PMC
June 2021

Mind Diet Adherence and Cognitive Performance in the Framingham Heart Study.

J Alzheimers Dis 2021 Jun 1. Epub 2021 Jun 1.

The Framingham Heart Study, Framingham, MA, USA.

Background: Adherence to the Mediterranean-DASH for Neurodegenerative Delay (MIND) diet has previously been associated with cognitive decline and dementia. To our knowledge, no prior study has investigated the association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs), or brain atrophy.

Objective: We evaluated whether adherence to the MIND diet associated with superior cognitive function, larger brain volumes, fewer SBIs, and less cognitive decline in the community-based Framingham Heart Study.

Methods: 2,092 participants (mean±SD, age 61±9) completed Food Frequency Questionnaires, averaged across a maximum of 3-time points (examination cycles 5, 6, and 7), cognitive testing at examination cycle 7 (present study baseline: 1998-2001) and after a mean±SD of 6.6±1.1 years from baseline (n = 1,584). A subset of participants also completed brain magnetic resonance imaging (MRI) at examination cycle 7 (n = 1,904). In addition, participants with dementia, stroke, and other relevant neurological diseases such as significant head trauma, subdural hematoma, or multiple sclerosis were excluded from the analyses.

Results: Higher MIND diet scores were associated with better global cognitive function (β±SE,+0.03SD±0.01; p = 0.004), verbal memory, visual memory, processing speed, verbal comprehension/reasoning, and with larger total brain volume (TBV) following adjustments for clinical, lifestyle and demographic covariates, but not with other brain MRI measures (i.e., hippocampal volume, lateral ventricular volume, white matter hyperintensity volume, SBIs) or cognitive decline.

Conclusion: Higher MIND diet scores associated with better cognitive performance and larger TBV at baseline, but not with cognitive decline. Clinical trials are needed to ascertain whether adopting the MIND diet affects trajectories of cognitive decline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-201238DOI Listing
June 2021

Targeting cancer testis antigens in synovial sarcoma.

J Immunother Cancer 2021 Jun;9(6)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Synovial sarcoma (SS) is a rare cancer that disproportionately affects children and young adults. Cancer testis antigens (CTAs) are proteins that are expressed early in embryonic development, but generally not expressed in normal tissue. They are aberrantly expressed in many different cancer types and are an attractive therapeutic target for immunotherapies. CTAs are expressed at high levels in SS. This high level of CTA expression makes SS an ideal cancer for treatment strategies aimed at harnessing the immune system to recognize aberrant CTA expression and fight against the cancer. Pivotal clinical trials are now underway, with the potential to dramatically alter the landscape of SS management and treatment from current standards of care. In this review, we describe the rationale for targeting CTAs in SS with a focus on NY-ESO-1 and MAGE-A4, the current state of vaccine and T-cell receptor-based therapies, and consider emerging opportunities for future development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-002072DOI Listing
June 2021

Extracellular riboflavin induces anaerobic biofilm formation in Shewanella oneidensis.

Biotechnol Biofuels 2021 Jun 3;14(1):130. Epub 2021 Jun 3.

Institute for Applied Biosciences, Department of Applied Biology, Karlsruhe Institute of Technology, Karlsruhe, Germany.

Background: Some microorganisms can respire with extracellular electron acceptors using an extended electron transport chain to the cell surface. This process can be applied in bioelectrochemical systems in which the organisms produce an electrical current by respiring with an anode as electron acceptor. These organisms apply flavin molecules as cofactors to facilitate one-electron transfer catalyzed by the terminal reductases and in some cases as endogenous electron shuttles.

Results: In the model organism Shewanella oneidensis, riboflavin production and excretion trigger a specific biofilm formation response that is initiated at a specific threshold concentration, similar to canonical quorum-sensing molecules. Riboflavin-mediated messaging is based on the overexpression of the gene encoding the putrescine decarboxylase speC which leads to posttranscriptional overproduction of proteins involved in biofilm formation. Using a model of growth-dependent riboflavin production under batch and biofilm growth conditions, the number of cells necessary to produce the threshold concentration per time was deduced. Furthermore, our results indicate that specific retention of riboflavin in the biofilm matrix leads to localized concentrations, which by far exceed the necessary threshold value.

Conclusion: This study describes a new quorum-sensing mechanism in S. oneidensis. Biofilm formation of S. oneidensis is induced by low concentrations of riboflavin resulting in an upregulation of the ornithine-decarboxylase speC. The results can be applied for the development of strains catalyzing increased current densities in bioelectrochemical systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13068-021-01981-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176591PMC
June 2021

Resting-State Network Alterations Differ between Alzheimer's Disease Atrophy Subtypes.

Cereb Cortex 2021 Jun 3. Epub 2021 Jun 3.

Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen 37075, Germany.

Several Alzheimer's disease (AD) atrophy subtypes were identified, but their brain network properties are unclear. We analyzed data from two independent datasets, including 166 participants (103 AD/63 controls) from the DZNE-longitudinal cognitive impairment and dementia study and 151 participants (121 AD/30 controls) from the AD neuroimaging initiative cohorts, aiming to identify differences between AD atrophy subtypes in resting-state functional magnetic resonance imaging intra-network connectivity (INC) and global and nodal network properties. Using a data-driven clustering approach, we identified four AD atrophy subtypes with differences in functional connectivity, accompanied by clinical and biomarker alterations, including a medio-temporal-predominant (S-MT), a limbic-predominant (S-L), a diffuse (S-D), and a mild-atrophy (S-MA) subtype. S-MT and S-D showed INC reduction in the default mode, dorsal attention, visual and limbic network, and a pronounced reduction of "global efficiency" and decrease of the "clustering coefficient" in parietal and temporal lobes. Despite severe atrophy in limbic areas, the S-L exhibited only marginal global network but substantial nodal network failure. S-MA, in contrast, showed limited impairment in clinical and cognitive scores but pronounced global network failure. Our results contribute toward a better understanding of heterogeneity in AD with the detection of distinct differences in functional connectivity networks accompanied by CSF biomarker and cognitive differences in AD subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhab130DOI Listing
June 2021

Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression.

Int J Mol Sci 2021 May 1;22(9). Epub 2021 May 1.

Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany.

Background: Phosphodiesterases (PDE) critically regulate myocardial cAMP and cGMP levels. PDE2 is stimulated by cGMP to hydrolyze cAMP, mediating a negative crosstalk between both pathways. PDE2 upregulation in heart failure contributes to desensitization to β-adrenergic overstimulation. After isoprenaline (ISO) injections, PDE2 overexpressing mice (PDE2 OE) were protected against ventricular arrhythmia. Here, we investigate the mechanisms underlying the effects of PDE2 OE on susceptibility to arrhythmias.

Methods: Cellular arrhythmia, ion currents, and Ca-sparks were assessed in ventricular cardiomyocytes from PDE2 OE and WT littermates.

Results: Under basal conditions, action potential (AP) morphology were similar in PDE2 OE and WT. ISO stimulation significantly increased the incidence of afterdepolarizations and spontaneous APs in WT, which was markedly reduced in PDE2 OE. The ISO-induced increase in I seen in WT was prevented in PDE2 OE. Moreover, the ISO-induced, Epac- and CaMKII-dependent increase in I and Ca-spark frequency was blunted in PDE2 OE, while the effect of direct Epac activation was similar in both groups. Finally, PDE2 inhibition facilitated arrhythmic events in perfused WT hearts after reperfusion injury.

Conclusion: Higher PDE2 abundance protects against ISO-induced cardiac arrhythmia by preventing the Epac- and CaMKII-mediated increases of cellular triggers. Thus, activating myocardial PDE2 may represent a novel intracellular anti-arrhythmic therapeutic strategy in HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22094816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125727PMC
May 2021

Anaerobic Sulfur Oxidation Underlies Adaptation of a Chemosynthetic Symbiont to Oxic-Anoxic Interfaces.

mSystems 2021 May 26:e0118620. Epub 2021 May 26.

University of Vienna, Department of Functional and Evolutionary Ecology, Environmental Cell Biology Group, Vienna, Austria.

Chemosynthetic symbioses occur worldwide in marine habitats, but comprehensive physiological studies of chemoautotrophic bacteria thriving on animals are scarce. Stilbonematinae are coated by thiotrophic . As these nematodes migrate through the redox zone, their ectosymbionts experience varying oxygen concentrations. However, nothing is known about how these variations affect their physiology. Here, by applying omics, Raman microspectroscopy, and stable isotope labeling, we investigated the effect of oxygen on " Thiosymbion oneisti." Unexpectedly, sulfur oxidation genes were upregulated in anoxic relative to oxic conditions, but carbon fixation genes and incorporation of C-labeled bicarbonate were not. Instead, several genes involved in carbon fixation were upregulated under oxic conditions, together with genes involved in organic carbon assimilation, polyhydroxyalkanoate (PHA) biosynthesis, nitrogen fixation, and urea utilization. Furthermore, in the presence of oxygen, stress-related genes were upregulated together with vitamin biosynthesis genes likely necessary to withstand oxidative stress, and the symbiont appeared to proliferate less. Based on its physiological response to oxygen, we propose that " T. oneisti" may exploit anaerobic sulfur oxidation coupled to denitrification to proliferate in anoxic sand. However, the ectosymbiont would still profit from the oxygen available in superficial sand, as the energy-efficient aerobic respiration would facilitate carbon and nitrogen assimilation. Chemoautotrophic endosymbionts are famous for exploiting sulfur oxidization to feed marine organisms with fixed carbon. However, the physiology of thiotrophic bacteria thriving on the surface of animals (ectosymbionts) is less understood. One longstanding hypothesis posits that attachment to animals that migrate between reduced and oxic environments would boost sulfur oxidation, as the ectosymbionts would alternatively access sulfide and oxygen, the most favorable electron acceptor. Here, we investigated the effect of oxygen on the physiology of " Thiosymbion oneisti," a gammaproteobacterium which lives attached to marine nematodes inhabiting shallow-water sand. Surprisingly, sulfur oxidation genes were upregulated under anoxic relative to oxic conditions. Furthermore, under anoxia, the ectosymbiont appeared to be less stressed and to proliferate more. We propose that animal-mediated access to oxygen, rather than enhancing sulfur oxidation, would facilitate assimilation of carbon and nitrogen by the ectosymbiont.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSystems.01186-20DOI Listing
May 2021

NeoAct: A Randomized Prospective Pilot Study on Communication Skill Training of Neonatologists.

Front Pediatr 2021 13;9:675742. Epub 2021 May 13.

Department for Medical Psychology, Department for Public Health, Medical University Vienna, Vienna, Austria.

This randomized interventional study evaluated the impact of a 1-day experiential communication skills training on neonatologists' performance in doctor-parents-communication. 17 neonatologists with different levels of professional experience from the Medical University of Vienna were randomized into one of two study groups: The intervention group (IG) as opposed to the control group (CG) participated in a 1-day experiential communication training. Eight weeks after the training, participants' communication skills were assessed during an objective structured clinical examination (OSCE). Neonatologists were assessed in a simulated conversation by how effectively they performed when conveying complex health-related information to parents of ill infants. Participants in the control group (CG) were assessed first during the OSCE and received their communication training later on. Self-assessment questionnaires before and after the workshop and OSCE were completed. The study determined that neonatologists in the IG subjectively perceived that their competence level regarding their communication skills had increased after the workshop, while this was not reflected by their performance during the OSCE assessment. A 1-day experiential communication skills training significantly increased physicians' self-evaluation concerning their communicative competence. This perceived competence did not manifest itself in increased communication skills during the OSCE. Repeated training is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.675742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158577PMC
May 2021

Tunnel convergence rate in combined anteromedial portal ACL and anterolateral structure reconstructions is influenced by ACL knee flexion angle, tunnel position and direction.

Arthroscopy 2021 May 27. Epub 2021 May 27.

Sporthopaedicum Berlin, Berlin, Germany.

Purpose: The goal of the present study was to evaluate a potential tunnel convergence in combined anterior cruciate ligament (ACL) reconstruction using the anteromedial portal (AMP) technique and lateral extra-articular tenodesis (LET).

Methods: Ten fresh frozen femora were dissected and a K-wires were inserted into the middle of the ACL stump according to an ACL reconstruction at 110° and 140° knee flexion. ACL reconstruction at 120° and 130° was simulated. Seven K-wires with different femoral insertion sites and angulations were drilled into the lateral femoral condyle relative to the lateral epicondyle (E3: 8 mm proximal and 4 mm posterior; E1: 5 mm proximal and 5mm anterior and E2: over-the-top position). Tunnel conflict rate was evaluated using a measuring arm and a metrology software.

Results: Drilling the femoral ACL tunnel in low knee flexion (110°-120°) significantly (p<0.001) reduced the tunnel conflict rate compared to the ACL drilled in high knee flexion (130°-140°). Changing the insertion point from proximal and posterior (E3) to proximal and anterior (E1) showed a reduced tunnel conflict rate from 40±21.2% to 15±26% and no tunnel conflict for an ACL drilled at 110°-130° knee flexion.

Conclusion: A possible tunnel conflict in simultaneous ACL reconstruction using the AMP technique and LET was dependent on ACL knee flexion angle, LET insertion site, and angulation. This posed the dilemma that no generally applicable LET configuration could be recommended to avoid a tunnel conflict. However, it appears that an insertion point located proximal and anterior to the lateral epicondyle results in less tunnel conflicts than an insertion point located proximal and posterior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arthro.2021.05.028DOI Listing
May 2021

Predation landscapes influence migratory prey ecology and evolution.

Trends Ecol Evol 2021 May 13. Epub 2021 May 13.

University of California Santa Cruz, Department of Ecology and Evolutionary Biology, Santa Cruz, CA 95060, USA.

Migratory prey experience spatially variable predation across their life cycle. They face unique challenges in navigating this predation landscape, which affects their perception of risk, antipredator responses, and resulting mortality. Variable and unfamiliar predator cues during migration can limit accurate perception of risk and migrants often rely on social information and learning to compensate. The energetic demands of migration constrain antipredator responses, often through context-dependent patterns. While migration can increase mortality, migrants employ diverse strategies to balance risks and rewards, including life history and antipredator responses. Humans interact frequently with migratory prey across space and alter both mortality risk and antipredator responses, which can scale up to affect migratory populations and should be considered in conservation and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tree.2021.04.010DOI Listing
May 2021

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Department of Medicine and Surgery, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.

Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.

Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes.

Discussion: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alz.12365DOI Listing
May 2021

Social Support and Functional Decline in the Oldest Old.

Gerontology 2021 May 12:1-9. Epub 2021 May 12.

Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objective: Longitudinal studies investigating the link between social support and functional decline are limited among the oldest old. Thus, the aim of this study was to examine whether changes in social support are associated with functional decline among the oldest old longitudinally using panel regression models.

Methods: Longitudinal data from 3 waves (waves 7, 8, and 9) of a multicenter prospective cohort study covering primary care patients aged ≥85 years were used. In the analytical sample, n equaled 624 individuals. The validated Lawton and Brody Instrumental Activities of Daily Living (IADL) scale and the well-established Barthel Index (ADL) were used to quantify functional status. The psychometrically sound Lubben Social Network Scale was used to measure social support. Several potential confounders such as age, marital status, cognitive decline, or depressive symptoms were included in the fixed effects (FE) regression models.

Results: Linear FE regressions showed that a decrease in social support is associated with functional decline (IADL: β = 0.03, p < 0.05; ADL: β = 0.27, p < 0.05) in men but not in women. With IADL as outcome measure, the interaction term (sex × social support) achieved statistical significance (p < 0.01). With regard to covariates, functional decline (IADL and ADL) was consistently associated with increasing age, an increase in the number of chronic conditions (except for women [ADL]), and cognitive decline (except for men [ADL]). Furthermore, functional decline (ADL) was associated with an increase in depressive symptoms.

Discussion: Our findings highlight the meaning of social support for functional status among the oldest old. Finding ways to sustain social support in highest age may be a promising approach in order to postpone functional decline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000516077DOI Listing
May 2021

IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy.

J Immunother Cancer 2021 May;9(5)

Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA

Background: Synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1-specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.

Method: We performed a phase I clinical trial evaluating the safety of NY-ESO-1-specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15.

Results: Four patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1-specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor-based products at other centers.

Conclusions: ETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1-specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-002232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108691PMC
May 2021

Mediterranean Diet, Alzheimer Disease Biomarkers and Brain Atrophy in Old Age.

Neurology 2021 May 5. Epub 2021 May 5.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.

Objective: To determine if following a Mediterranean-like diet (MeDi) relates to cognitive functions and biomarkers for Alzheimer's disease (AD), we analyzed cross-sectional data from the German Longitudinal Cognitive Impairment and Dementia Study METHOD: The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 AD relatives, 209 SCD and 81 MCI). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aβ42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis.

Results: Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (β±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aβ42/40 ratio, β±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (β±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aβ42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status.

Conclusion: Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012067DOI Listing
May 2021

Combined VEGFR and MAPK pathway inhibition in angiosarcoma.

Sci Rep 2021 Apr 30;11(1):9362. Epub 2021 Apr 30.

Department of Gynecologic Oncology and Reproductive Medicine and Center for RNA Interference and Non-Coding RNA, UT MD Anderson Cancer Center, Houston, USA.

Angiosarcoma is an aggressive malignancy of endothelial cells that carries a high mortality rate. Cytotoxic chemotherapy can elicit clinical responses, but the duration of response is limited. Sequencing reveals multiple mutations in angiogenesis pathways in angiosarcomas, particularly in vascular endothelial growth factor (VEGFR) and mitogen-activated protein kinase (MAPK) signaling. We aimed to determine the biological relevance of these pathways in angiosarcoma. Tissue microarray consisting of clinical formalin-fixed paraffin embedded tissue archival samples were stained for phospho- extracellular signal-regulated kinase (p-ERK) with immunohistochemistry. Angiosarcoma cell lines were treated with the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, pan-VEGFR inhibitor cediranib, or combined trametinib and cediranib and viability was assessed. Reverse phase protein array (RPPA) was performed to assess multiple oncogenic protein pathways. SVR angiosarcoma cells were grown in vivo and gene expression effects of treatment were assessed with whole exome RNA sequencing. MAPK signaling was found active in over half of clinical angiosarcoma samples. Inhibition of MAPK signaling with the MEK inhibitor trametinib decreased the viability of angiosarcoma cells. Combined inhibition of the VEGF and MAPK pathways with cediranib and trametinib had an additive effect in in vitro models, and a combinatorial effect in an in vivo model. Combined treatment led to smaller tumors than treatment with either agent alone. RNA-seq demonstrated distinct expression signatures between the trametinib treated tumors and those treated with both trametinib and cediranib. These results indicate a clinical study of combined VEGFR and MEK inhibition in angiosarcoma is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-88703-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087824PMC
April 2021

Analog Spatial Light Modulators Based on Micromirror Arrays.

Micromachines (Basel) 2021 Apr 23;12(5). Epub 2021 Apr 23.

Fraunhofer IPMS, Maria-Reiche-Straße 2, 01109 Dresden, Germany.

The Fraunhofer Institute for Photonic Microsystems (IPMS) has been developing and manufacturing micromirror arrays for more than 20 years. While originally focusing on applications related to microlithography and therefore mainly for light in the deep ultraviolet range, the range of applications has been expanded since, including applications in the visible and near-infrared range. This paper gives an overview of the devices and their designs, fabrication, and characterization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/mi12050483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145509PMC
April 2021

Design, synthesis, and evaluation of positron emission tomography/fluorescence dual imaging probes for targeting facilitated glucose transporter 1 (GLUT1).

Org Biomol Chem 2021 Apr 24;19(14):3241-3254. Epub 2021 Mar 24.

Department of Chemistry, 11227 Saskatchewan Drive University of Alberta, Edmonton, AB, Canada T6G 2G2.

Increased energy metabolism followed by enhanced glucose consumption is a hallmark of cancer. Most cancer cells show overexpression of facilitated hexose transporter GLUT1, including breast cancer. GLUT1 is the main transporter for 2-deoxy-2-[F]fluoro-d-glucose (2-[F]FDG), the gold standard of positron emission tomography (PET) imaging in oncology. The present study's goal was to develop novel glucose-based dual imaging probes for their use in tandem PET and fluorescence (Fl) imaging. A glucosamine scaffold tagged with a fluorophore and an F-label should confer selectivity to GLUT1. Out of five different compounds, 2-deoxy-2-((7-sulfonylfluoro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose (2-FBDG) possessed favorable fluorescent properties and a similar potency as 2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose (2-NBDG) in competing for GLUT1 transport against 2-[F]FDG in breast cancer cells. Radiolabeling with F was achieved through the synthesis of prosthetic group 7-fluoro-2,1,3-benzoxadiazole-4-sulfonyl [F]fluoride ([F]FBDF) followed by the reaction with glucosamine. The radiotracer was finally analyzed in vivo in a breast cancer xenograft model and compared to 2-[F]FDG. Despite favourable in vitro fluorescence imaging properties, 2-[F]FBDG was found to lack metabolic stability in vivo, resulting in radiodefluorination. Glucose-based 2-[F]FBDG represents a novel dual-probe for GLUT1 imaging using FI and PET with the potential for further structural optimization for improved metabolic stability in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1ob00199jDOI Listing
April 2021

Type 2 Diabetes Subtype Responsive to ACCORD Intensive Glycemia Treatment.

Diabetes Care 2021 Apr 16. Epub 2021 Apr 16.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH

Objective: Current type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed, suggesting potential benefit for some individuals.

Research Design And Methods: ACCORD was a randomized controlled trial that investigated whether intensively treating glycemia in individuals with T2D would reduce CVD outcomes. Using a novel approach to cluster HbA trajectories, we identified groups in the intensive glycemia arm with modified CVD risk. Genome-wide analysis and polygenic score (PS) were developed to predict group membership. Mendelian randomization was performed to infer causality.

Results: We identified four clinical groupings in the intensive glycemia arm, and clinical group 4 (C4) displayed fewer CVD (hazard ratio [HR] 0.34; 2.01 × 10) and microvascular outcomes (HR 0.86; 0.015) than those receiving standard treatment. A single-nucleotide polymorphism, rs220721, in reached suggestive significance in C4 ( 4.34 10). PS predicted C4 with high accuracy (area under the receiver operating characteristic curve 0.98), and this predicted C4 displayed reduced CVD risk with intensive versus standard glycemia treatment (HR 0.53; 4.02 × 10), but not reduced risk of microvascular outcomes ( 0.05). Mendelian randomization indicated causality between PS, on-trial HbA, and reduction in CVD outcomes ( 0.05).

Conclusions: We found evidence of a T2D clinical group in ACCORD that benefited from intensive glycemia treatment, and membership in this group could be predicted using genetic variants. This study generates new hypotheses with implications for precision medicine in T2D and represents an important development in this landmark clinical trial warranting further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-2700DOI Listing
April 2021

Covid-19: Involvement of the nervous system. Identifying neurological predictors defining the course of the disease.

J Neurol Sci 2021 06 8;425:117438. Epub 2021 Apr 8.

Interne Abteilung, Landesklinikum Melk, Krankenhausstraße 11, 3390 Melk, Austria.

The main objective of this study was to analyse neurological symptoms during a Covid-19 infection and determine the pattern of symptoms by comparing outpatients with inpatients. A further goal was to identify possible predictors, such as pre-existing conditions and neurological symptoms. We recorded the clinical data of 40 inpatients and 42 outpatients in this retrospective, cross sectional study. Of them, 68 patients (83%), evenly distributed between the two groups, suffered from neurological symptoms. We identified the onset of neurological symptoms and the related time ranges in 41 patients (36 outpatients and 5 inpatients). Of these, 63.4% reported neurological symptoms on the first or second day of illness. 49 patients (72%) showed combinations of at least two to a maximum of seven different neurological symptoms. A more severe course of disease was correlated with age and male sex, but age was not identified as a predictor for the occurrence of neurological symptoms. Women suffered from central and neuromuscular symptoms more often than men (p = 0,004). The most common symptoms were fatigue (54%), headache (31%), loss of taste (31%), and loss of smell (27%). Pre-existing dementia was associated with increased lethality; similarly, pre-existing stroke was associated with a more severe course of Covid-19 infection. Hallucinations and confusion were related to an increased likelihood of death. The present data demonstrate the importance of comprehensive neurological support of inpatients and outpatients affected by Covid-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2021.117438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028603PMC
June 2021

[Bempedoic Acid].

Dtsch Med Wochenschr 2021 Apr 14;146(8):552-558. Epub 2021 Apr 14.

ATP-Citrate-Lyase is a key enzyme of cholesterol biosynthesis. Its liver-specific inhibition by the bempedoic acid opens new possibilities to effectively escalate a cholesterol-lowering therapy while avoiding muscle-related side effects. Herein, we present the properties of this new first-in-class pharmaceutical agent and discuss potential consequences for pharmacotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1136-4356DOI Listing
April 2021

A calcineurin-mediated scaling mechanism that controls a K-leak channel to regulate morphogen and growth factor transcription.

Elife 2021 Apr 8;10. Epub 2021 Apr 8.

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China.

The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several genes that are part of important development programs. We provide in vivo transplantation evidence that the activation of gene transcription is cell autonomous. We also show that Kcnk5b will induce the expression of different subsets of the tested developmental genes in different cultured mammalian cell lines, which may explain how one electrophysiological stimulus can coordinately regulate the allometric growth of diverse populations of cells in the fin that use different developmental signals. We also provide evidence that the post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity to scale the fin. Thus, we show how an endogenous bioelectric mechanism can be regulated to promote coordinated developmental signaling to generate and scale a vertebrate appendage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.60691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110307PMC
April 2021

Health-related quality of life and ego integrity among the oldest old - Evidence from the multicenter AgeCoDe-AgeQualiDe study.

Arch Gerontol Geriatr 2021 Jul-Aug;95:104408. Epub 2021 Mar 31.

Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. Electronic address:

Purpose: To investigate the association between health-related quality of life and ego integrity among the oldest old.

Materials And Methods: Cross-sectional data were taken from follow-up wave 9 of the multicenter prospective cohort study "Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe). Our analytical sample comprised n = 495 observations. Mean age was 90.2 years (SD: 2.7 years). Health-related quality of life was quantified using the EQ-5D-3L questionnaire (including the visual analogue scale EQ-VAS). Ego integrity was measured using the Ego Integrity Scale.

Results: Regressions showed an association between decreased ego integrity and problems with 'usual activities', 'pain/discomfort' and 'anxiety/depression'. Furthermore, regressions showed a marginally significant association between decreased ego integrity and problems with 'mobility' and a decreased EQ-VAS score. Ego integrity was not significantly associated with problems with 'self-care'.

Conclusions: Findings stress the importance of health-related quality of life for ego integrity among the oldest old. Future studies are required to clarify the underlying mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archger.2021.104408DOI Listing
March 2021

Correlates of institutionalization among the oldest old-Evidence from the multicenter AgeCoDe-AgeQualiDe study.

Int J Geriatr Psychiatry 2021 Jul 2;36(7):1095-1102. Epub 2021 Apr 2.

Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objectives: There is a lack of studies identifying the correlates of institutionalization specifically among the oldest old. Therefore, our aim was to fill this gap in knowledge.

Methods: Cross-sectional data (Follow up wave 9; n = 633 observations in the analytical sample) were used from the multicenter prospective cohort study "Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" Correlates of institutionalization among the oldest old-Evidence from a multicenter cohort study. The sample consists of primary care patients aged 86 years and over (mean 90.5 years, SD: 2.9 years). Sociodemographic and health-related independent variables were included in our regression model. Institutionalization was defined as living in a nursing home or an old-age home (not including assisted living facilities).

Results: Out of the 633 participants, 502 individuals (79.3%) did not live in an institutionalized setting, whereas 73 individuals (20.7%) lived in an institutionalized setting. Multiple logistic regressions showed that the likelihood of institutionalization increased with being divorced/widowed/single (compared to being married; OR: 5.35 [95% CI: 1.75-16.36]), the presence of social isolation (OR: 2.07 [1.20-3.59]), more depressive symptoms (OR: 1.11 [1.01-1.23]), increased cognitive impairment (OR: 1.67 [1.31-2.15]) and higher levels of frailty (OR: 1.48 [1.07-2.06]).

Conclusion: The study findings identified various sociodemographic and health-related factors associated with institutionalization among the oldest old. Longitudinal studies are required to gain further insights into these associations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gps.5548DOI Listing
July 2021

Cysto-Vaginoscopy of a 3D-Printed Cloaca Model: A Step toward Personalized Noninvasive Preoperative Assessment in Patients with Complex Anorectal Malformations.

Eur J Pediatr Surg 2021 Mar 23. Epub 2021 Mar 23.

Department of Pediatric Surgery, Medical University of Vienna, Vienna, Wien, Austria.

Introduction:  For the classification of the complexity of cloacal malformations and the decision on the operative approach, an exact anatomical assessment is mandatory. To benefit from using three-dimensional (3D)-printed models in preoperative planning and training, the practicability of these models should be guaranteed. The aim of this study was to evaluate the quality and feasibility of a real-size 3D-printed cloaca model for the purpose of cysto-vaginoscopic evaluation.

Materials And Methods:  We performed a 3D reconstruction and printed a real-size, rubber-like 3D model of an infant pelvis with a cloacal malformation and asked invited pediatric surgeons and pediatric urologists to perform a cysto-vaginoscopy on the model and to complete a brief questionnaire to rate the quality and feasibility of the model and to indicate whether they would recommend the model for preoperative planning and training.

Results:  Overall, 41 participants rated the model quality as good to very good (M = 3.28, standard deviation [SD] = 0.50, on a scale from 1 to 4). The model was rated as feasible for preoperative training (M = 4.10, SD = 0.75, on a scale from 1 to 5) and most participants (85.4%) would recommend the model for preoperative training. The cysto-vaginoscopy of the model was considered as a valid training tool for real-life cases and improved the confidence on the anatomy of a cloaca.

Conclusion:  The results of our study indicate that patient-specific 3D-printed models might be a useful tool in the preoperative evaluation of complex anorectal malformations by simulation of cysto-vaginoscopy with an excellent view on anatomical structures to assess the whole spectrum of the individual cloacal malformation. Our model might be a valuable add-on tool for specialty training in pediatric colorectal surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1726424DOI Listing
March 2021

Do self-reported hearing and visual impairments predict longitudinal dementia in older adults?

J Am Geriatr Soc 2021 Jun 18;69(6):1519-1528. Epub 2021 Mar 18.

Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany.

Background: Sensory impairments have been associated with dementia in older adults. However, the contribution of different impairments and how they interact in the development of dementia is not clear. We examined the independent and interaction effects of hearing impairment (HI) and visual impairment (VI) on incident dementia.

Design: Multi-centric population-based prospective cohort study.

Setting: Data were taken from the AgeDifferent.de platform, pooling participants aged 75 and older from the German LEILA75+ and AgeCoDe/AgeQualiDe cohorts.

Participants: Older adults (N = 3497) with mean age 79.8 years, 67.2% female.

Measurements: Standardized interviews and questionnaires were used to assess self-reported HI and VI at baseline and all-cause dementia in 9 follow-ups, spanning over 20 years.

Methods: Competing risk regression models were conducted to test the main and interaction effects of HI and VI on dementia incidence, adjusting for established risk factors of dementia and accumulated mortality.

Results: HI and VI at baseline were reported by 30.3% and 16.6% of individuals, respectively. Adjusting for baseline information on sociodemographics, substance use, cognitive functioning and morbidity, and controlling for accumulated mortality risk, HI (sHR 1.16, 95% CI 1.04-1.30, p = 0.011) but not VI (sHR 1.07, 95% CI 0.90-1.28, p = 0.462) was significantly associated with incident dementia. There was no interaction between HI and VI (sHR 1.09, 95% CI 0.81-1.46, p = 0.567).

Conclusions: Hearing impairment is associated with an increased incidence of all-cause dementia in older adults. There is no excess risk or risk compensation through the additional presence or absence of visual impairment. Early prevention measures for hearing impairment might help to reduce the long-term risk of dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.17074DOI Listing
June 2021

Outcomes of Patients with Sarcoma and COVID-19 Infection: A Single Institution Cohort Analysis.

Cancer Invest 2021 Apr 26;39(4):315-320. Epub 2021 Mar 26.

Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.

Outcomes for patients (pts) with sarcoma and COVID-19 are unknown. This is a single institution retrospective study of adults with sarcoma and COVID-19. Ten pts [median age 60 (range 24-69)] were identified. Five were hospitalized; two died from COVID-19 complications; another died from sarcoma. Time between last systemic treatment dose and COVID-19 diagnosis was 6-41 days in pts who died. 5 underwent prior radiation (RT); time between RT and COVID-19 diagnosis was 20-62 days for pts who died. All three pts with WBC differential data (two died) were lymphopenic. Efforts to capture outcomes for a larger cohort are urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07357907.2021.1903914DOI Listing
April 2021

Development of a 3D printed patient-specific neonatal brain simulation model using multimodality imaging for perioperative management.

Pediatr Res 2021 Mar 2. Epub 2021 Mar 2.

Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.

Background: Medical-imaging-based three-dimensional (3D) printed models enable improvement in skills training, surgical planning, and decision-making. This pilot study aimed to use multimodality imaging and to add and compare 3D ultrasound as a future standard to develop realistic neonatal brain models including the ventricular system.

Methods: Retrospective computed tomography (CT), magnetic resonance imaging (MRI), and 3D ultrasound-based brain imaging protocols of five neonatal patients were analyzed and subsequently segmented with the aim of developing a multimodality imaging-based 3D printed model. The ventricular anatomy was analyzed to compare the MRI and 3D ultrasound modalities.

Results: A realistic anatomical model of the neonatal brain, including the ventricular system, was created using MRI and 3D ultrasound data from one patient. T2-weighted isovoxel 3D MRI sequences were found to have better resolution and accuracy than 2D sequences. The surface area, anatomy, and volume of the lateral ventricles derived from both MRI and 3D ultrasound were comparable.

Conclusions: We created an ultrasound- and MRI-based 3D printed patient-specific neonatal brain simulation model that can be used for perioperative management. To introduce 3D ultrasound as a standard for 3D models, additional dimensional correlations between MRI and ultrasound need to be examined.

Impact: We studied the feasibility of implementing 3D ultrasound as a standard for 3D printed models of the neonatal brain. Different imaging modalities were compared and both 3D isotropic MRI and 3D ultrasound imaging are feasible for printing neonatal brain models with good dimensional accuracy and anatomical replication. Further dimensional correlations need to be defined to implement it as a standard to produce 3D printed models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-021-01421-wDOI Listing
March 2021

Return of Spontaneous Circulation Depends on Cardiac Rhythm During Neonatal Cardiac Arrest in Asphyxiated Newborn Animals.

Front Pediatr 2021 12;9:641132. Epub 2021 Feb 12.

Neonatal Research Unit, Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB, Canada.

Pulseless electrical activity (PEA) occurs in asphyxiated newborn piglets and infants. We aimed to examine whether different cardiac rhythms (asystole, bradycardia, PEA) affects the resuscitation outcomes during continuous chest compressions (CC) during sustained inflations (CC+SI). This study is a secondary analysis of four previous randomized controlled animal trials that compared CC+SI with different CC rate (90 or 120/min), SI duration (20 or 60 s), peak inflation pressure (10, 20, or 30 cmHO), and oxygen concentration (18, 21, or 100%). Sixty-six newborn mixed breed piglets (1-3 days of age, weight 1.7-2.4 kg) were obtained on the day of experimentation from the University Swine Research Technology Center. In all four studies, piglets were randomized into intervention or sham. Piglets randomized to "intervention" underwent both hypoxia and asphyxia, whereas, piglets randomized to "sham" received the same surgical protocol, stabilization, and equivalent experimental periods without hypoxia and asphyxia. To compare differences in asphyxiation time, time to return of spontaneous circulation (ROSC), hemodynamics, and survival rate in newborn piglets with asystole, bradycardia or PEA. Piglets with PEA ( = 29) and asystole ( = 13) had a significantly longer asphyxiation time and time to ROSC vs. bradycardia ( = 24). Survival rates were similar between all groups. Compared to their baseline, mean arterial pressure and carotid blood flow were significantly lower 4 h after resuscitation in all groups, while being significantly higher in the bradycardia group. This study indicates that cardiac rhythm before resuscitation influences the time to ROSC and hemodynamic recovery after ROSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.641132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907180PMC
February 2021

Frailty and Autonomy among the Oldest Old: Evidence from the Multicenter Prospective AgeCoDe-AgeQualiDe Study.

Gerontology 2021 Feb 17:1-8. Epub 2021 Feb 17.

Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: There is a lack of studies examining the link between perceived autonomy and frailty among the oldest old. Therefore, our objective was to fill this gap.

Methods: Data were used from the multicenter prospective cohort study "Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe; follow-up [FU] wave 9; n = 510 observations in the analytical sample). The average age was 90.3 years (SD: 2.7 years). The Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (CFS) was used to assess frailty. Socioeconomic and health-related covariates were included in our regression model. The autonomy scale developed by Schwarzer was used to assess perceived autonomy in old age.

Results: Adjusting for various confounders, multiple linear regressions showed that lower perceived autonomy was associated with increased levels of frailty (total sample: β = -0.13, p < 0.001; women: β = -0.14, p < 0.001; and men: β = -0.12, p < 0.001). Furthermore, lower perceived autonomy was associated with more depressive symptoms, higher cognitive impairment, and being institutionalized (except for men) in the total sample and in both sexes, but it was not significantly associated with age, sex, marital status, educational level, and social support.

Conclusion: Findings indicate that frailty is associated with lower autonomy among the oldest old. More generally, while health-related factors were consistently associated with autonomy, sociodemographic factors (except for being institutionalized) were not associated with autonomy among the oldest old. We should be aware of the strong association between autonomy and physical as well as mental health in very old age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000514170DOI Listing
February 2021

Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer's Dementia in the Oldest Old.

Nutrients 2021 Jan 30;13(2). Epub 2021 Jan 30.

German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany.

Background: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties.

Methods: We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer's disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD.

Results: During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia.

Conclusions: Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13020461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912244PMC
January 2021