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Der Nervenarzt Oct 2018The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies.
BACKGROUND
The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies.
OBJECTIVE
Provide a timely state of the art review on recent scientific advances in the field of tauopathies.
MATERIAL AND METHODS
Systematic review of the literature from the past 10 years.
RESULTS
Tau proteins are increasingly being recognized as a highly variable protein, underlying and defining a spectrum of molecularly defined diseases, with a clinical spectrum ranging from dementia to hypokinetic movement disorders. Genetic variation at the tau locus can trigger disease or modify disease risk. Tau protein alterations can damage nerve cells and propagate pathologies through the brain. Thus, tau proteins may serve both as a serological and imaging biomarker. Tau proteins also provide a broad spectrum of rational therapeutic interventions to prevent disease progression. This knowledge has led to modern clinical trials.
CONCLUSION
The field of tauopathies is in a state of dynamic and rapid progress, requiring close interdisciplinary collaboration.
Topics: Brain; Genetic Variation; Humans; Tauopathies; tau Proteins
PubMed: 30120488
DOI: 10.1007/s00115-018-0584-3 -
Annals of Intensive Care Nov 2019Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor...
BACKGROUND
Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis.
METHODS
A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool.
RESULTS
The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors - survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: - 2.9 ng/ml (95% CI - 4.1 to - 1.7, p < 0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p < 0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p = 0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p < 0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p = 0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p < 0.01).
CONCLUSIONS
Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended. Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226.
PubMed: 31705327
DOI: 10.1186/s13613-019-0600-1 -
Frontiers in Bioengineering and... 2022simulations aim to provide fast, inexpensive, and ethical alternatives to years of costly experimentation on animals and humans for studying bone remodeling, its...
simulations aim to provide fast, inexpensive, and ethical alternatives to years of costly experimentation on animals and humans for studying bone remodeling, its deregulation during osteoporosis and the effect of therapeutics. Within the varied spectrum of modeling techniques, bone cell population dynamics and agent-based multiphysics simulations have recently emerged as useful tools to simulate the effect of specific signaling pathways. In these models, parameters for cell and cytokine behavior are set based on experimental values found in literature; however, their use is currently limited by the lack of clinical data on cell numbers and their behavior as well as cytokine concentrations, diffusion, decay and reaction rates. Further, the settings used for these parameters vary across research groups, prohibiting effective cross-comparisons. This review summarizes and evaluates the clinical trial literature that can serve as input or validation for models of bone remodeling incorporating cells and cytokine dynamics in post-menopausal women in treatment, and control scenarios. The GRADE system was used to determine the level of confidence in the reported data, and areas lacking in reported measures such as binding site occupancy, reaction rates and cell proliferation, differentiation and apoptosis rates were highlighted as targets for further research. We propose a consensus for the range of values that can be used for the cell and cytokine settings related to the RANKL-RANK-OPG, TGF-β and sclerostin pathways and a Levels of Evidence-based method to estimate parameters missing from clinical trial literature.
PubMed: 35910035
DOI: 10.3389/fbioe.2022.901720 -
Ophthalmic Research 2023The inverted internal limiting membrane (ILM) flap technique was initially developed for the closure of large macular holes (MHs). However, its efficacy in treating... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The inverted internal limiting membrane (ILM) flap technique was initially developed for the closure of large macular holes (MHs). However, its efficacy in treating small holes has been a matter of debate. This study aimed to compare the anatomical and visual outcomes of vitrectomy (PPV) combined with the inverted ILM flap and ILM peeling in cases of small and medium-sized MHs.
METHODS
A meta-analysis was conducted by searching the relevant literature in databases, including PubMed, Web of Science, Embase, and Cochrane Library. The search included articles published from the inception of the databases up until January 2023. The inclusion criteria limited the studies to only experimental-based research. The heterogeneity, publication bias, and sensitivity analysis were performed to ensure the statistical power and reliability of the analysis.
RESULTS
Five studies, including two non-randomized concurrent control trials and three non-randomized concurrent control trials, comprising a total of 269 eyes, were analysed. The results showed no significant difference in the MH closure rate between the two groups (odds ratio (OR) = 0.29, 95% confidence interval: 0.04-1.96, p = 0.33). Furthermore, there were no significant differences observed in visual acuity, external limiting membrane (ELM), and ellipsoid zone (EZ) integrity at 3 months (ELM OR = 0.88, EZ OR = 0.85) or 12 months (ELM OR = 0.96, EZ OR = 1.39) post-operation between the two groups.
CONCLUSION
The surgical repair of MHs smaller than 400 μm with ILM flap seems to be similar in visual acuity improvement and anatomical recovery compared to the traditional technique.
Topics: Humans; Retinal Perforations; Reproducibility of Results; Basement Membrane; Retina; Vitrectomy; Retrospective Studies; Tomography, Optical Coherence
PubMed: 37931613
DOI: 10.1159/000534873 -
Cells Dec 2019The hyperechogenicity of the substania nigra (SN) has been established as a valid finding in patients with Parkinson´s disease (PD), probably caused by an increased... (Comparative Study)
Comparative Study Meta-Analysis
The hyperechogenicity of the substania nigra (SN) has been established as a valid finding in patients with Parkinson´s disease (PD), probably caused by an increased tissue iron concentration in the SN. The application of transcranial sonography (TCS) has been investigated for further echogenic basal ganglia alterations in patients with extrapyramidal movement disorders. Compared to PD, a hyperechogenic nucleus lentiformis (LN) has been reported to appear more frequently in atypical parkinsonian syndromes (aPS) such as the parkinsonian phenotype of multiple system atrophy (MSA-P) or the progressive supranuclear palsy (PSP). As the evidence providing study sizes are small, we conduct the first meta-analysis of the prevalence of LN hyperechogenicity in PD and aPS. We search for available studies providing prevalence of LN hyperechogenicity in patients with PD and aPS (MSA-P and PSP) detected by TCS in MEDLINE and SCOPUS databases. We calculate the prevalence rates of LN hyperechogenicity detection in patients with clinical diagnosis of PD vs. aPS under the random-effects model. We include a total of 1330 patients, 1091 PD and 239 aPS (MSA-P and PSP). We find a significantly higher prevalence of LN hyperechogenicity in aPS (76%, 95% CI: 0.62-0.88) compared to PD (16%, 95% CI: 0.10-0.23). After proving a higher prevalence of LN hyperechogenicity in aPS compared to PD, its histopathological cause needs to be investigated. Furthermore, its full diagnostic accuracy and the qualification to serve as a risk factor for MSA-P and PSP should also be questioned in future studies.
Topics: Corpus Striatum; Echoencephalography; Humans; Parkinsonian Disorders; Prevalence
PubMed: 31861253
DOI: 10.3390/cells9010002