Publications by authors named "Peter Hermann"

95 Publications

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease.

Lancet Neurol 2021 03;20(3):235-246

National Reference Center for Transmissible Spongiform Encephalopathies, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases, Göttingen, Germany.

Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrP). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. Development and clinical application of disease-specific protein aggregation and amplification assays, such as real-time quaking induced conversion (RT-QuIC), have constituted major breakthroughs for the confident pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrP seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation.
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http://dx.doi.org/10.1016/S1474-4422(20)30477-4DOI Listing
March 2021

Oral Hygiene Practices of Hungarian Adult E-Cigarette-Only and Dual Users.

Oral Health Prev Dent 2020 11 20;18(1):991-998. Epub 2020 Nov 20.

Purpose: This study aimed to explore self-reported oral hygiene practices (OHPs) among Hungarian adult e-cigarette-only (former smokers who switched completely to e-cigarette use or vaping) and dual users (smokers who use e-cigarettes and combustible tobacco cigarettes concomitantly).

Materials And Methods: A cross-sectional, web-based survey of 930 adult Hungarian e-cigarette users was conducted in 2015. Participants reported 10 OHPs, which were included in analyses as separate binary variables and as a composite variable of the 10 OHP items (inadequate/adequate). Chi-square test was used to explore whether separate OHPs differ by vaping status, and to examine the relationship between inadequate OHPs and past combustible or e-cigarette use characteristics. Associations between separate OHPs and vaping status, and between inadequate OHPs and vaping status were tested by multiple logistic regression analyses.

Results: More dual users reported toothbrushing twice a day or more than e-cigarette-only users (73.6% vs 65.3%, respectively, p = 0.041) and using sugar-free chewing gum (57.7% vs 45.8%, respectively, p = 0.006) while adequacy of other OHPs did not differ statistically significantly by vaping status. Inadequate OHPs were more typical in the sample (63.7%) than adequate OHPs, however, inadequate OHPs did not differ statistically significantly among dual users and e-cigarette-only users (62.0% vs 64.0%, respectively, OR = 1.20, p = 0.400), controlling for age, gender, education, past combustible and current e-cigarette use characteristics.

Conclusion: In this study, both e-cigarette-only and dual users demonstrated similarly high prevalence of inadequate OHPs. Therefore dentists should educate them about effective OHPs and the role of tobacco and e-cigarette use in the development of oral diseases.
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http://dx.doi.org/10.3290/j.ohpd.a45520DOI Listing
November 2020

Genetic prion disease: opportunities for early therapeutic intervention with rigorous pre-symptomatic trials.

Expert Opin Investig Drugs 2020 Dec 1;29(12):1313-1316. Epub 2020 Nov 1.

National Reference Center for TSE, University Medical Center Göttingen , Göttingen, Germany.

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http://dx.doi.org/10.1080/13543784.2020.1839048DOI Listing
December 2020

Learning curve of digital intraoral scanning - an in vivo study.

BMC Oral Health 2020 10 19;20(1):287. Epub 2020 Oct 19.

Department of Prosthodontics, Semmelweis University, Szentkiralyi Street 47, 1088, Budapest, Hungary.

Background: The spread of digital technology in dentistry poses new challenges and sets new goals for dentists. The aim of the present in vivo study was to determine the learning curve of intraoral scanning described by (1) scanning time and (2) image number (count of images created by intraoral scanner during the scanning process).

Methods: Ten dental students of Semmelweis University took part in the study. Dental students took digital study impressions using a 3Shape Trios 3® (3Shape, Copenhagen, Denmark) intraoral scanning device. Each student took 10 digital impressions on volunteers. Volunteer inclusion criteria included full dentition (except for missing third molars) and no prosthetic/restorative treatment. Digital impression taking was preceded by tuition consisting of both theoretical education and practical training. Digital impressions were taken of the upper and lower arches, and the bite was recorded according to the manufacturer's instructions. Total scanning times and image numbers were recorded.

Results: The difference in scanning time between the first and the tenth digital impressions was significant (p = 0.007). The average scanning time for the first impressions was 23 min 9 s; for the tenth impressions, it was 15 min 28 s. The difference between the scanning times of the first and the tenth procedures was 7 min 41 s. The average image count for the first impressions was 1964.5; for the tenth impressions, it was 1468.6. The image count difference between the first and the tenth procedures was 495.9. The image count versus sequential number of measurement curve shows an initial decreasing tendency followed by a trough around the sixth measurement and a final increasing phase.

Conclusion: Our results indicate an association between the sequential number of measurements and the outcome variables. The drop in scanning time is probably explained by a practice effect of repeated use, i.e. the students learned to move the scanning tip faster. The image count first showed a decreasing tendency, and after the sixth measurement, it increased; there was no consistent decline in mean scan count. Shorter scanning times are associated with poorer coverage quality, with the operator needing to make corrections by adding extra images; this manifests as the time function of image counts taking an increase after the sixth measurement.
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http://dx.doi.org/10.1186/s12903-020-01278-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574448PMC
October 2020

Multicenter study to develop and validate a risk assessment tool as part of composite scoring system for erosive tooth wear.

Clin Oral Investig 2020 Sep 22. Epub 2020 Sep 22.

Oral Health Services Research Centre, Cork University Dental School and Hospital, University College Cork, Cork, Ireland.

Objectives: (i) To develop, validate, and apply in practice a new risk assessment tool for erosive tooth wear (ETW) including a risk factors questionnaire and a saliva secretion evaluation, which combined with a clinical index, can be part of an ETW composite scoring system; (ii) to assess ETW lesions and current and past erosive challenges in younger age groups.

Methods: The Tooth Surface Loss/Erosion Working Group of the European Association of Dental Public Health consisted of an international panel of experts designed the survey component of the new tool (Erosive Wear Assessment of Risk-EWAR) and confirmed its construct and content validity. After receiving ethical approvals and informed consents, the EWAR tool (questionnaire + saliva secretion evaluation) was applied in a multicenter cross-sectional study with 207 participants aged 15-21 years old from four countries (Finland, Greece, Romania, the USA). BEWE score was used for the clinical assessment of ETW.

Results: A total of 58.5% of participants had ETW. 10.9% and 20.3% of participants had low secretion of stimulated (< 1 ml/min) and unstimulated saliva (< 0.25 ml/min), respectively. The following factors were bivariately significantly associated with ETW: energy drink consumption, low secretion of stimulated saliva, juices consumption, erosive drink consumption for quenching thirst between meals, erosive drink kept in the mouth, feeling pain/icing after consuming something acidic or cold, and co-existence of other type of tooth wear. In regression analysis, only energy drink consumption (OR = 3.5, 95% CI: 1.39, 8.9), low secretion of stimulated saliva (OR = 36.3, 95% CI: 4.71, 78.94), and feeling pain/icing (OR = 8.8, 95% CI: 1.92, 40.04) remained significant.

Conclusions: The examiners of the study reported that the EWAR tool appeared to be an affordable and easy-to-use instrument. Some challenges occurred during the saliva collection process. Inferential analysis revealed that the risk factors/indicators of low stimulated salivary flow, energy drink consumption, and pain/icing with ETW were considered the most important in ETW occurrence.

Clinical Relevance: EWAR tool combined with the BEWE clinical index can be used for ETW risk assessment for epidemiological studies and chairside use.
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http://dx.doi.org/10.1007/s00784-020-03589-7DOI Listing
September 2020

Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease.

Int J Mol Sci 2020 Aug 31;21(17). Epub 2020 Aug 31.

Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona (CSIC), 08036 Barcelona, Spain.

Alzheimer's type dementia (AD) exhibits clinical heterogeneity, as well as differences in disease progression, as a subset of patients with a clinical diagnosis of AD progresses more rapidly (rpAD) than the typical AD of slow progression (spAD). Previous findings indicate that low cerebrospinal fluid (CSF) content of cell-free mitochondrial DNA (cf-mtDNA) precedes clinical signs of AD. We have now investigated the relationship between cf-mtDNA and other biomarkers of AD to determine whether a particular biomarker profile underlies the different rates of AD progression. We measured the content of cf-mtDNA, beta-amyloid peptide 1-42 (Aβ), total tau protein (t-tau) and phosphorylated tau (p-tau) in the CSF from a cohort of 95 subjects consisting of 49 controls with a neurologic disorder without dementia, 30 patients with a clinical diagnosis of spAD and 16 patients with rpAD. We found that 37% of controls met at least one AD biomarker criteria, while 53% and 44% of subjects with spAD and rpAD, respectively, did not fulfill the two core AD biomarker criteria: high t-tau and low Aβ in CSF. In the whole cohort, patients with spAD, but not with rpAD, showed a statistically significant 44% decrease of cf-mtDNA in CSF compared to control. When the cohort included only subjects selected by Aβ and t-tau biomarker criteria, the spAD group showed a larger decrease of cf-mtDNA (69%), whereas in the rpAD group cf-mtDNA levels remained unaltered. In the whole cohort, the CSF levels of cf-mtDNA correlated positively with Aβ and negatively with p-tau. Moreover, the ratio between cf-mtDNA and p-tau increased the sensitivity and specificity of spAD diagnosis up to 93% and 94%, respectively, in the biomarker-selected cohort. These results show that the content of cf-mtDNA in CSF correlates with the earliest pathological markers of the disease, Aβ and p-tau, but not with the marker of neuronal damage t-tau. Moreover, these findings confirm that low CSF content of cf-mtDNA is a biomarker for the early detection of AD and support the hypothesis that low cf-mtDNA, together with low Aβ and high p-tau, constitute a distinctive CSF biomarker profile that differentiates spAD from other neurological disorders.
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http://dx.doi.org/10.3390/ijms21176298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503553PMC
August 2020

Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study.

PLoS Med 2020 08 20;17(8):e1003289. Epub 2020 Aug 20.

Université de Paris, Inserm U1153, Epidemiology of Ageing and Neurodegenerative diseases, Paris, France.

Background: The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD.

Methods And Findings: This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1-5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4-31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD.

Conclusions: In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.
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http://dx.doi.org/10.1371/journal.pmed.1003289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446786PMC
August 2020

Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue .

Materials (Basel) 2020 Aug 6;13(16). Epub 2020 Aug 6.

Department of Medical Biochemistry, MTA-SE, Laboratory of Neurobiochemistry, Semmelweis University, 1094 Budapest, Hungary.

Background: Triethylene glycol dimethacrylate (TEGDMA) monomers released from resin matrix are toxic to dental pulp cells, induce apoptosis, oxidative stress and decrease viability. Recently, mitochondrial complex I (CI) was identified as a potential target of TEGDMA. In isolated mitochondria supported by CI, substrates oxidation and ATP synthesis were inhibited, reactive oxygen species production was stimulated. Contrary to that, respiratory Complex II was not impaired by TEGDMA. The beneficial effects of electron carrier compound methylene blue (MB) are proven in many disease models where mitochondrial involvement has been detected. In the present study, the bioenergetic effects of MB on TEGDMA-treated isolated mitochondria and on human dental pulp stem cells (DPSC) were analyzed.

Methods: Isolated mitochondria and DPSC were acutely exposed to low millimolar concentrations of TEGDMA and 2 μM concentration of MB. Mitochondrial and cellular respiration and glycolytic flux were measured by high resolution respirometry and by Seahorse XF extracellular analyzer. Mitochondrial membrane potential was measured fluorimetrically.

Results: MB partially restored the mitochondrial oxidation, rescued membrane potential in isolated mitochondria and significantly increased the impaired cellular O consumption in the presence of TEGDMA.

Conclusion: MB is able to protect against TEGDMA-induced CI damage, and might provide protective effects in resin monomer exposed cells.
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http://dx.doi.org/10.3390/ma13163472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475988PMC
August 2020

Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993-2018.

Emerg Infect Dis 2020 08;26(8)

We investigated sporadic Creutzfeldt-Jakob disease (sCJD) among physicians in Germany by analyzing occupational information of patients with sCJD recorded by the German CJD Surveillance Unit (1993-2005; 1,250 patients, of whom 4 [0.32%] were physicians) and the National Reference Center for Human Spongiform Encephalopathies (2006-2016; 1,491 patients, of whom 13 [0.87%] were physicians). Among the physicians, we did not identify any neurologists, neurosurgeons, psychiatrists, or pathologists. A cumulative sum test showed an increase in reported physicians over time. Data for 2017-2018 indicated an increased rate of physicians among all notified sCJD cases (5/239 [2.1%]) when we used the total population of Germany as control group. Our data suggest the possibility of an increased risk for sCJD among physicians in Germany. However, we can only speculate about the reasons, and larger multinational studies are needed to replicate the finding and to clarify whether this finding is a general or a country-specific phenomenon.
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http://dx.doi.org/10.3201/eid2608.191159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392457PMC
August 2020

A prognostic model for overall survival in sporadic Creutzfeldt-Jakob disease.

Alzheimers Dement 2020 10 2;16(10):1438-1447. Epub 2020 Jul 2.

Department of Neurology, University Medical School, Göttingen, Germany.

Introduction: We developed a prognostic model for overall survival after diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) using data from a German surveillance study.

Methods: We included 1226 sCJD cases (median age 66 years, range 19-89 years; 56.8% women with information on age, sex, codon 129 genotype, 14-3-3 in the cerebrospinal fluid (CSF), and CSF tau concentrations. The prognostic accuracy for overall survival was measured by the c statistics of multivariable Cox proportional hazard models. A score chart was derived to predict 6-month survival and median survival time.

Results: A model containing age, sex, codon 129 genotype, and CSF tau (with two-way interactions) was selected as the model with the highest c statistic (0.686, 95% confidence interval: 0.665-0.707) in a cross-validation approach.

Discussion: We developed the first prognostic model for overall survival of sCJD patients based on readily available information only. The developed score chart serves as a hands-on prediction tool for clinical practice.
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http://dx.doi.org/10.1002/alz.12133DOI Listing
October 2020

A new tetra-plex fluorimetric assay for the quantification of cerebrospinal fluid β-amyloid42, total-tau, phospho-tau and α-synuclein in the differential diagnosis of neurodegenerative dementia.

J Neurol 2020 Sep 5;267(9):2567-2581. Epub 2020 May 5.

Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Barcelona, Spain.

Background: Differential diagnosis of neurodegenerative dementia is currently supported by biomarkers including cerebrospinal fluid (CSF) tests. Among them, CSF total-tau (t-tau), phosphorylated tau (p-tau) and β-amyloid42 (Aβ42) are considered core biomarkers of neurodegeneration. In the present work, we hypothesize that simultaneous assessment of these biomarkers together with CSF α-synuclein (α-syn) will significantly improve the differential diagnostic of Alzheimer's disease and other dementias. To that aim, we characterized the analytical and clinical performance of a new tetra-plex immunoassay that simultaneously quantifies CSF Aβ42, t-tau, p-tau and α-syn in the differential diagnosis of neurodegenerative dementia.

Methods: Biomarkers' concentrations were measured in neurological controls (n = 38), Alzheimer's disease (n = 35), Creutzfeldt-Jakob disease (n = 37), vascular dementia (n = 28), dementia with Lewy bodies/Parkinson's disease dementia (n = 27) and frontotemporal dementia (n = 34) using the new tetra-plex assay and established single-plex assays. Biomarker's performance was evaluated and diagnostic accuracy in the discrimination of diagnostic groups was determined using partial least squares discriminant analysis.

Results: The tetra-plex assay presented accuracies similar to individual single-plex assays with acceptable analytical performance. Significant correlations were observed between tetra-plex and single-plex assays. Using partial least squares discriminant analysis, Alzheimer's disease and Creutzfeldt-Jakob disease were well differentiated, reaching high accuracies in the discrimination from the rest of diagnostic groups.

Conclusions: The new tetra-plex assay coupled with multivariate analytical approaches becomes a valuable asset for the differential diagnosis of neurodegenerative dementia and related applications.
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http://dx.doi.org/10.1007/s00415-020-09870-9DOI Listing
September 2020

Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease.

Biomolecules 2020 02 12;10(2). Epub 2020 Feb 12.

Department of Neurology, National Reference Center for CJD Surveillance, University Medical Centre Göttingen, 37075 Göttingen, Germany.

Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt-Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an end, thanks to lessons learnt from past infection sources that promoted new prion prevention and decontamination protocols. At this point, we sought to characterise the biomarker profile of iCJD and compare it to that of sporadic CJD (sCJD) for determining the value of available diagnostic tools in promptly recognising iCJD cases. To that end, we collected 23 iCJD samples from seven national CJD surveillance centres and analysed the electroencephalogram and neuroimaging data together with a panel of seven CSF biomarkers: 14-3-3, total tau, phosphorylated/total tau ratio, alpha-synuclein, neurofilament light, YKL-40, and real-time quaking induced conversion of prion protein. Using the cut-off values established for sCJD, we found the sensitivities of these biomarkers for iCJD to be similar to those described for sCJD. Given the limited relevant information on this issue to date, the present study validates the use of current sCJD biomarkers for the diagnosis of future iCJD cases.
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http://dx.doi.org/10.3390/biom10020290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072321PMC
February 2020

Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia.

Nat Commun 2020 01 30;11(1):619. Epub 2020 Jan 30.

Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.

The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries. The study included four independent cohorts with a total n = 472 samples. LCN2 was significantly elevated in VaD compared to controls, Alzheimer's disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy. The main findings were consistent over all cohorts. Neuropathology disclosed a high percentage of macrophages linked to subacute infarcts, reactive astrocytes, and damaged blood vessels in multi-infarct dementia when compared to AD. We conclude that CSF LCN2 is a promising candidate biochemical marker in the differential diagnosis of VaD and neurodegenerative dementias.
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http://dx.doi.org/10.1038/s41467-020-14373-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992814PMC
January 2020

Effects of disinfection and sterilization on the dimensional changes and mechanical properties of 3D printed surgical guides for implant therapy - pilot study.

BMC Oral Health 2020 01 23;20(1):19. Epub 2020 Jan 23.

Department of Prosthodontics, Faculty of Dentistry, Semmelweis University, Szentkirályi Street 47, Budapest, H-1088, Hungary.

Background: The purpose of this research was to investigate the effects of disinfection and three different sterilization methods on the dimensional changes and mechanical properties of three-dimensional (3D) printed surgical guide for implant therapy. The objective was to assess the effects of sterilization procedures in 3D printed drill guide templates with destructive and non-destructive material testing.

Methods: Fifteen identical drill guide templates were produced using a 3D printer. The surgical guides were classified into five groups: three controls, three disinfected (4% Gigasept®, 60 min), three plasma sterilized, three autoclave sterilized (+ 1 bar, 121 °C, 20 min), and three autoclave sterilized (+ 2 bar, 134 °C, 10 min). The templates were digitalized with a Steinbichler SCAN ST 3D scanner. Length was measured under an SZX16 stereomicroscope. A scanning electron microscope was used to study the surface morphology of the drill templates. The hardness, and flexural and compressive strength were measured to assess any changes in the physical characteristics of the material caused by sterilization. The drill guide templates were also examined with a Dage XiDAT 6600 X-ray. During the X-ray examinations, the following parameters were used: 100 kV voltage, 128 AVG averaging, 0.8 W power. One-way analysis of variance (ANOVA) was used to detect the difference between groups.

Results: Evaluation of the hardness measurements of the various specimens shows that the hardness of the material was not changed by the plasma sterilization (p = 0.0680), steam sterilization on 121 °C (p = 0.6033) or disinfection process (p = 0.1399). The statistical analysis revealed significant difference in hardness strength of the autoclave sterilized (134 °C) specimens (p = 0.0002). There was no significant difference between the goups regarding the scanning electron microscopic and stereomicroscopic examinations. There was no significant difference regarding the X-ray visibility of the templates to the effect of the disinfection (p = 0.7844), plasma sterilization (p = 0.4091) and steam sterilization on 121 °C (p = 0.9277) and steam sterilization on 131 °C (p = 0.093). The effect of the sterilization was the same in case of both flexural and compressive strength of the material.

Conclusions: Our findings indicate that plasma sterilization and steam sterilization at 121 °C were both suitable for sterilizing the tested 3D printed surgical guides.
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http://dx.doi.org/10.1186/s12903-020-1005-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979289PMC
January 2020

Cerebrospinal fluid non-phosphorylated tau in the differential diagnosis of Creutzfeldt-Jakob disease: a comparative prospective study with 14-3-3.

J Neurol 2020 Feb 7;267(2):543-550. Epub 2019 Nov 7.

Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School, Göttingen, Germany.

Cerebrospinal fluid (CSF) non-phosphorylated tau (non-p-tau) is increased in sporadic Creutzfeldt-Jakob disease (CJD), but its accuracy in the differential diagnosis has not been previously established. Here, we first used a retrospective cohort of non-CJD (n = 135) and CJD (n = 137) cases to determine the optimal cutoff point for the discrimination of CJD cases. Next, we prospectively quantified non-p-tau and 14-3-3 protein in a cohort of 1427 cases received for CSF testing at the German National Reference Center for transmissible spongiform encephalopathies. Among them, 36 were subsequently diagnosed as CJD. The diagnostic accuracy of both proteins discriminating CJD cases was evaluated. Using a cutoff of 650 pg/mL, non-p-tau displayed 94.39% accuracy in discriminating CJD cases, while 92.92% accuracy was achieved by 14-3-3 using a cutoff of 20,000 AU/mL. Diagnostic test evaluation for both proteins showed a slightly better performance of non-p-tau compared to 14-3-3. The two biomarkers' concentrations showed a significant positive correlation, both in the total population and in CJD cases (p < 0.001). Finally, the analysis of CSF non-p-tau concentrations when undergoing pre-analytical factors showed high stability in front of temperature storage and freeze/thaw cycles. Therefore, we conclude that when used in the appropriate clinical context of a prion disease surveillance center, non-p-tau is a highly sensitive and specific diagnostic marker for CJD.
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http://dx.doi.org/10.1007/s00415-019-09610-8DOI Listing
February 2020

Study of the Intrinsic Fluorescence of a Highly Branched Cationic Dendrimer, Poly(Ethyleneimine) (PEI).

Molecules 2019 Oct 14;24(20). Epub 2019 Oct 14.

Department of Prosthodontics, Semmelweis University, Szentkirályi u. 47, 1088 Budapest, Hungary.

Poly(ethyleneimine) (PEI) is a weakly basic, synthetic, polycationic polymer, due to the presence of primary, secondary, and tertiary amino groups. The amino groups are responsible for the variety of applications of PEI (e.g., transfection, bioimaging, solar cell, etc.). Our study presents some new and reproducible methods for the quantification of molecular or mass concentration of highly branched PEI of different molecular weights (800-2000-25,000-750,000 MW PEI). In the course of the direct method, spectrophotometry and fluorometry were applied to determine the absorption and fluorescence of PEI dilution series. An increase in the MW at the same concentration produces a higher count number because of the higher number of amino groups in PEI molecules. The character of increment in fluorescence intensity is essentially different in the case of mass concentrations and molar concentrations. The increment of the fluorescence intensity related to the molar concentration is non-linear. In the case of mass concentration, the slope is linear. Moreover, their fluorescence is enhanced with the decrease in pH values. The spectrophotometry is a reliable method for measuring the quantity of PEI molecules in solution. Our data help in recognizing the detailed properties of PEI in dendrimer research.
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http://dx.doi.org/10.3390/molecules24203690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832717PMC
October 2019

Plasma YKL-40 in the spectrum of neurodegenerative dementia.

J Neuroinflammation 2019 Jul 12;16(1):145. Epub 2019 Jul 12.

Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School, Robert Koch 40, 37075, Göttingen, Germany.

Background: Increased plasma YKL-40 has been reported in Alzheimer's disease (AD), but its levels in other neurodegenerative diseases are unknown. Here, we aimed to investigate plasma YKL-40 in the spectrum of neurodegenerative dementias.

Methods: YKL-40 was quantified in the plasma of 315 cases, including healthy controls (HC), neurological disease controls (ND), AD, vascular dementia (VaD), frontotemporal dementia (FTD), sporadic Creutzfeldt-Jakob disease (CJD) and Lewy body dementia (LBD). Diagnostic accuracy in the differential diagnostic context and influence of age and gender was assessed.

Results: Highest YKL-40 levels were detected in CJD, followed by LBD, VaD, AD, FTD, ND and HC. YKL-40 was associated to age but not to sex. After controlling for age, YKL-40 was significantly elevated in CJD compared to HC (p < 0.001), ND, AD and VaD (p < 0.01) and in LBD compared to HC (p < 0.05). In CJD, YKL-40 concentrations were significantly higher at late disease stages.

Conclusions: Plasma YKL-40 is significantly elevated in CJD regardless of clinical and genetic parameters, with moderate diagnostic accuracy in the discrimination from control cases. Our study discards a potential use of this biomarker in the differential diagnostic context but opens the possibility to be explored as a marker for CJD monitoring.
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http://dx.doi.org/10.1186/s12974-019-1531-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624942PMC
July 2019

Age at onset in genetic prion disease and the design of preventive clinical trials.

Neurology 2019 07 6;93(2):e125-e134. Epub 2019 Jun 6.

From Broad Institute of MIT and Harvard (E.V.M., S.M.V.), Cambridge; Analytical and Translational Genetics Unit (E.V.M.), Massachusetts General Hospital; Program in Biological and Biomedical Sciences (E.V.M., S.M.V.), Harvard Medical School, Boston; Prion Alliance (E.V.M., S.M.V.), Cambridge; Harvard Business School (M.C.O.), Boston, MA; Institut du Cerveau et de la Moelle Épinière (J.-P.B., S.H.), ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université; Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob (J.-P.B., S.H., J.-L.P.), Assistance Publique-Hôpitaux de Paris, France; National Reference Center for TSE (I.Z., C.P., P.H., T.K.), Georg-August University, Göttingen, Germany; IRCCS-Istituto delle Scienze Neurologiche di Bologna (P.P., S.C.); Departments of Experimental, Diagnostic and Specialty Medicine (P.P.) and Biomedical and Neuromotor Sciences (S.C.), University of Bologna, Italy; National Prion Disease Pathology Surveillance Center (J.S.), Case Western Reserve University, Cleveland, OH; MRC Prion Unit at UCL (J.K., S.M.), Institute of Prion Diseases, University College London, UK; Memory and Aging Center (J.C.F., L.T.T., M.D.G.), University of California San Francisco; Australian National CJD Registry (C.S., S.J.C.), University of Melbourne, Parkville, Australia; Department of Neurological Science (T.K.), Tohoku University Graduate School of Medicine, Sendai; Department of Public Health (R.A., Y.N.), Jichi Medical University, Shimotsuke; Department of Neurology and Neurobiology of Aging (T.H., M.Y.), Kanazawa University Graduate School of Medical Sciences, Kanazawa; Department of Neurology and Neurological Science (N.S.), Tokyo Medical and Dental University; National Center of Neurology and Psychiatry (T.T., H.M.), Kodaira, Japan; Laboratory of Prion Neurobiology (R.C.), Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan; AULSS2 Ca' Foncello Hospital (I.R.), Treviso, Italy; Spanish National Reference Center for CJD (J.d.P.-C., M.C.), Instituto de Salud Carlos III and CIBERNED, Madrid, Spain; and NHS National Prion Clinic (S.M.), National Hospital for Neurology and Neurosurgery, UCL Hospitals NHS Foundation Trust, London, WC1N 3BG, UK.

Objective: To determine whether preventive trials in genetic prion disease could be designed to follow presymptomatic mutation carriers to onset of disease.

Methods: We assembled age at onset or death data from 1,094 individuals with high penetrance mutations in the prion protein gene () in order to generate survival and hazard curves and test for genetic modifiers of age at onset. We used formulae and simulations to estimate statistical power for clinical trials.

Results: Genetic prion disease age at onset varies over several decades for the most common mutations and neither sex, parent's age at onset, nor codon 129 genotype provided additional explanatory power to stratify trials. Randomized preventive trials would require hundreds or thousands of at-risk individuals in order to be statistically powered for an endpoint of clinical onset, posing prohibitive cost and delay and likely exceeding the number of individuals available for such trials.

Conclusion: The characterization of biomarkers suitable to serve as surrogate endpoints will be essential for the prevention of genetic prion disease. Parameters such as longer trial duration, increased enrollment, and the use of historical controls in a postmarketing study could provide opportunities for subsequent determination of clinical benefit.
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http://dx.doi.org/10.1212/WNL.0000000000007745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656649PMC
July 2019

CSF neurogranin as a neuronal damage marker in CJD: a comparative study with AD.

J Neurol Neurosurg Psychiatry 2019 08 16;90(8):846-853. Epub 2019 May 16.

Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Ministry of Health, L'Hospilatet del Llobregat, Barcelona, Spain

Objective: To investigate whether cerebrospinal fluid (CSF) neurogranin concentrations are altered in sporadic Creutzfeldt-Jakob disease (CJD), comparatively with Alzheimer's disease (AD), and associated with neuronal degeneration in brain tissue.

Methods: CSF neurogranin, total tau, neurofilament light (NFL) and 14-3-3 protein were measured in neurological controls (NCs, n=64), AD (n=46) and CJD (n=81). The accuracy of neurogranin discriminating the three diagnostic groups was evaluated. Correlations between neurogranin and neurodegeneration biomarkers, demographic, genetic and clinical data were assessed. Additionally, neurogranin expression in postmortem brain tissue was studied.

Results: Compared with NC, CSF neurogranin concentrations were increased in CJD (4.75 times of NC; p<0.001, area under curve (AUC), 0.96 (95% CI 0.93 to 0.99) and AD (1.94 times of NC; p<0.01, AUC 0.73, 95% CI 0.62 to 0.82), and were able to differentiate CJD from AD (p<0.001, AUC 0.85, 95% CI 0.78 to 0.92). CSF tau was increased in CJD (41 times of NC) and in AD (3.1 times of NC), both at p<0.001. In CJD, neurogranin positively correlated with tau (r=0.55, p<0.001) and was higher in 14-3-3-positivity (p<0.05), but showed no association with NFL (r=0.08, p=0.46). CJD-MM1/MV1 cases displayed higher neurogranin levels than VV2 cases. Neurogranin was increased at early CJD disease stages and was a good prognostic marker of survival time in CJD. In brain tissue, neurogranin was detected in the cytoplasm, membrane and postsynaptic density fractions of neurons, with reduced levels in AD, and more significantly in CJD, where they correlated with synaptic and axonal markers.

Conclusions: Neurogranin is a new biomarker of prion pathogenesis with diagnostic and prognostic abilities, which reflects the degree of neuronal damage in brain tissue in a CJD subtype manner.
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http://dx.doi.org/10.1136/jnnp-2018-320155DOI Listing
August 2019

Effects of substrate, ceramic thickness, translucency, and cement shade on the color of CAD/CAM lithium-disilicate crowns.

J Esthet Restor Dent 2019 09 8;31(5):457-464. Epub 2019 Apr 8.

Department of Prosthodontics, Faculty of Dentistry, Semmelweis University, Budapest, Hungary.

Objective: The aim of this in vitro study was to evaluate the effects of substrate colors, different levels of ceramic thickness and translucency, and cement shades on the color difference from a reference color of lithium-disilicate crowns.

Materials And Methods: A premolar tooth preparation was made on a study model for 1.0 and 1.5 mm thick full-ceramic crowns. Digital impressions were taken (3Shape TRIOS) and crowns designed in a CAD program (DentalDesigner). Shade A1 crowns were milled (Everest, Kavo) from high-translucency (HT) and low-translucency IPS e.max (Ivoclar Vivadent) blocks. Twelve substrates were made of different colors and materials (Natural Die Material, Co-Cr, zirconia, and gold-colored alloy). Three different shades of try-in pastes were used to simulate the effect of cements (Variolink Esthetic try-in paste; Ivoclar). Shade measurement was done three times for each crown by a spectrophotometer (VITA Easyshade Advance); averages were compared to a reference crown (A1, HT, 1.5 mm, ND2 abutment, neutral try-in paste) with ΔE (CIEDE2000, according to the CIE latest standard) calculated.

Results: All the examined parameters influenced the ΔE of the crowns. The weakest effect was exerted by the try-in paste.

Conclusions: All examined parameters influenced the final color of e.max CAD lithium-disilicate ceramic crowns.

Clinical Significance: Matching the shade of ceramic crowns to the natural tooth color is a great challenge in dentistry. To meet patients' increasing esthetical expectations, CAD/CAM methods are very popular for full-ceramic crowns. However, several factors such as the shade of the abutment, luting cement color, ceramic thickness, and translucency may influence the final color. Our objective was to measure the optical effect of these factors on the final shade of CAD/CAM lithium-disilicate ceramic crowns.
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http://dx.doi.org/10.1111/jerd.12470DOI Listing
September 2019

Perceived health effects of vaping among Hungarian adult e-cigarette-only and dual users: a cross-sectional internet survey.

BMC Public Health 2019 Mar 13;19(1):302. Epub 2019 Mar 13.

Department of Prosthodontics, Faculty of Dentistry, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary.

Background: Knowledge about the health effects of e-cigarette use (or vaping) among past and current combustible cigarette users is limited. Several studies have assessed vaping-related adverse events (AEs) and beneficial health effects, however, most studies focused on AEs in general and examined only a few physiological changes that vapers experience. This study aims to explore self-reported AEs and perceived health changes due to e-cigarette use among Hungarian adult e-cigarette-only users (former smokers who switched completely to e-cigarette use) and dual users (smokers who use e-cigarettes and combustible tobacco cigarettes concomitantly).

Methods: A cross-sectional, web-based survey of 1042 adult Hungarian e-cigarette users was conducted in 2015. Participants reported AEs and changes in physiological functions since they switched from smoking to e-cigarette use or while dually using e-cigarettes and combustible cigarettes. Confirmatory factor analysis with covariates was applied to explain perceived health changes due to e-cigarette-only use and dual use.

Results: Dual users (17.6%) were significantly more likely to report AEs of vaping than e-cigarette-only users (26.2% vs. 11.8%, p < 0.001). Experiencing health improvements were significantly more likely among e-cigarette-only users than for dual users for all surveyed physiological functions. E-cigarette-only users reported larger effects of vaping on sensory, physical functioning, and mental health factors compared to dual users. Self-reported changes in sensory and physical functioning were significantly higher among individuals using e-cigarettes more than a year and people who were past heavy smokers (smoked ≥20 cigarettes per day). Gender was related to sensory improvement only; males reported greater improvement than females.

Conclusions: The majority of e-cigarette-only users reported more perceived beneficial changes in physiological functions and fewer AEs than dual users. Perceived short-term benefits of e-cigarette use may reinforce users despite the uncertainty of long-term health consequences. Health professionals should provide balanced information regarding the possible short- and long-term positive and negative health effects of e-cigarette use during consultations with patients.
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http://dx.doi.org/10.1186/s12889-019-6629-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417163PMC
March 2019

[Paradigm shift in conservative dentistry: the end of the amalgam era].

Orv Hetil 2018 10;159(42):1700-1709

Fogorvostudományi Kar, Fogpótlástani Klinika, Semmelweis Egyetem Budapest, Szentkirályi u. 47., 1088.

Dental amalgam has been used for more than 150 years due to its beneficial mechanical properties and durability in dentistry. In the past and to date, many questions about amalgam restorations have arisen, especially regarding the mercury content, which has been the subject of global disputes. By presenting the past and present of the 'amalgam issue', the aim of our paper is to display the current position of international literature. This summary is based on the publications in the PubMed database, the guidelines of the Council of European Dentists. Although the use of dental amalgam is widespread, concerns have been raised about the adverse effect on human health and the environment, focusing on its heavy metal pollution during waste treatment. In 2017, the European Union (EU) adopted the so-called Mercury Regulation, based on the United Nations Minamata Convention on Mercury, the recommendations of which are presented in the present review. This Regulation includes the requirement for EU Member States to develop a national action plan for the phase-down of amalgam. The feasibility plan for complete phase-out may be guaranteed by 2030. The authors discuss the advantages and disadvantages of possible amalgam alternatives by presenting glass-ionomers and resin-based composites. In the future, more material research programmes and long-term follow-up studies are necessary. In addition to several global health organizations, the Council of European Dentists also draws attention to prevent dental caries, expecting to reduce the number of restorations. Orv Hetil. 2018; 159(42): 1700-1709.
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http://dx.doi.org/10.1556/650.2018.31215DOI Listing
October 2018

Distinct microglia profile in Creutzfeldt-Jakob disease and Alzheimer's disease is independent of disease kinetics.

Neuropathology 2018 Dec 15;38(6):591-600. Epub 2018 Oct 15.

Institute of Neuropathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Activated microglia represent a common pathological feature of neurodegenerative diseases. Sporadic Creutzfeldt-Jakob disease (sCJD) patients show more pronounced microglial activation than Alzheimer's disease (AD) patients. Whether these differences are due to differences in disease kinetics or represent disease-specific changes is unknown. We investigated microglial phenotypes in brains of rapidly progressive AD (rpAD) and sCJD patients matched for clinical presentation, including disease duration. We immunostained the frontal cortex, basal ganglia and cerebellum in 16 patients with rpAD and sCJD using antibodies against markers of microglia and recruited monocytes (ionized calcium-binding adaptor molecule 1, human leukocyte antigen DPQR, Cluster of Differentiation 68), an antibody unique to brain-resident microglia (transmembrane protein 119 (TMEM119)), in addition to antibodies against a marker of astrocytes (glial fibrillary acidic protein), amyloid-β (Aβ) and pathological prion protein. rpAD patients showed a distinct microglial phenotype with a high abundance of TMEM119-positive microglia in all investigated regions. Presence of Aβ deposits seen in a sCJD patient with concomitant deposition of Aβ led to increase of TMEM119-positive microglia. Our data suggest that in rpAD, activation of brain-resident microglia significantly contributes to microgliosis, whereas in sCJD the TMEM119 signature of resident microglial cells is barely detectable. This is irrespective of disease duration and may indicate disease-specific microglial reaction.
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http://dx.doi.org/10.1111/neup.12517DOI Listing
December 2018

[Intra-articular steroid and hyaluronic acid treatment of internal derangement of the temporomandibular joint].

Orv Hetil 2018 Sep;159(36):1475-1482

Arc-, Állcsont-, Szájsebészeti és Fogászati Klinika, Semmelweis Egyetem, Fogorvostudományi Kar Budapest.

Introduction: Derangement of the temporomandibular joint complicates everyday life, due to the masticatory malfunction and the continuous pain sensation of the head and facial region. The therapy is multidisciplinary and varying. In case of the inefficiency of conservative therapy, minimally invasive intervention is needed with intraarticular injection.

Aim: The aim of our study was to examine whether hyaluronic acid injection is more beneficial compared to corticosteroid in 37 joints. We also examined whether the efficacy of the therapy is influenced by hyaluronic acid molecular weight and the used protocol.

Method: Wilkes stage, maximal mouth opening and the Visual Analogue Scale were determined pre-operatively and 6 months later. Corticosteroid application was performed once, hyaluronic acid was injected on a weekly bases 3 times in a row, by use of low (6-10 × 10 dalton) or high molecular weight (24-36 × 10 dalton) preparations.

Results: The medical state of the patients treated with corticosteroid temporarily improved, but the symptoms returned. Due to hyaluronic acid treatment, significant improvement was revealed in all parameters (p<0.0001; p = 0.0002; p<0.0001). There was no significant relapse (T = 2.05). The third administration of hyaluronic acid resulted in a significant improvement of the Visual Analogue Scale compared to the first and second injection (T = 20.37; T = 9.57).

Conclusions: Comparing the two agents we can state that hyaluronic acid was significantly more effective and its application for three times seems to be the most effective treatment decreasing the symptoms. The high molecular weight solution was more effective in increasing mouth opening. In contrast to hyaluronic acid, corticosteroid had no prolonged effect in higher Wilkes stages. Orv Hetil. 2018; 159(36): 1475-1482.
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http://dx.doi.org/10.1556/650.2018.31138DOI Listing
September 2018

Diagnostic challenges in rapidly progressive dementia.

Expert Rev Neurother 2018 10 17;18(10):761-772. Epub 2018 Sep 17.

a Clinical Dementia Center and National TSE Reference Center, Department of Neurology , Goettingen University Medical Center , Goettingen , Germany.

Introduction: Rapidly progressive dementia is a syndrome caused by numerous disease entities. Accurate diagnosis is crucial as substantial proportion of these diseases is highly treatable. Others might implicate specific hygienic problems. Still, differential diagnosis remains challenging because of a huge overlap of clinical presentations. Areas covered: The paper reviews PubMed-listed research articles with a focus on diagnosis and treatment of diseases showing rapid cognitive decline such as inflammatory diseases, rapidly progressive neurodegenerative diseases, toxic-metabolic encephalopathies and prion diseases. The literature was interpreted in the light of experience in clinically differentiating rapid progressing dementia in the framework of Creutzfeldt-Jakob-Disease (CJD) surveillance activities. An overview of relevant differential diagnoses and diagnostic pitfalls as well as therapeutic protocols is presented. Expert commentary: Over the last years, more and more neurologic disorders causing cognitive symptoms, in particular various types of immune-mediated diseases have been discovered. To identify treatable conditions and to enhance knowledge of differential diagnosis and epidemiology, we suggest an extended diagnostic work up in cases with rapidly progressing dementia. Besides standard methods, this should include the search for neoplasia as well as atypical encephalitis. High-dose steroid therapy should be considered in certain clinical situations even when no evidence for inflammation is present.
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http://dx.doi.org/10.1080/14737175.2018.1519397DOI Listing
October 2018

Cerebrospinal Fluid Total and Phosphorylated α-Synuclein in Patients with Creutzfeldt-Jakob Disease and Synucleinopathy.

Mol Neurobiol 2019 May 22;56(5):3476-3483. Epub 2018 Aug 22.

Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.

High levels of total α-synuclein (t-α-synuclein) in the cerebrospinal fluid (CSF) were reported in sporadic Creutzfeldt-Jakob disease (sCJD). The potential use of t-α-synuclein in the discrimination of Lewy body dementias (i.e., Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB)) is still under investigation. In addition, phospho-serine-129 α-synuclein (p-α-synuclein) has been described to be slightly increased in the CSF of synucleinopathies. Here, we analyzed t-α-synuclein and p-α-synuclein concentrations and their ratio in the context of differential diagnosis of neurodegenerative diseases. We quantified the levels of CSF t-α-synuclein and p-α-synuclein in a cohort of samples composed of neurological controls (NC), sCJD, PDD, and DLB by means of newly developed specific enzyme-linked immunosorbent assays. T-α-synuclein and p-α-synuclein were specifically elevated in sCJD compared to other disease groups. The area under the curve (AUC) values for t-α-synuclein were higher for the discrimination of sCJD from dementias associated to Lewy bodies as compared to the use of p-α-synuclein. A combination of both markers even increased the diagnostic accuracy. An inverse correlation was observed in CSF between t-α-synuclein and p-α-synuclein, especially in the DLB group, indicating a disease-relevant association between both markers. In conclusion, our data confirm t-α-synuclein and p-α-synuclein as robust biomarkers for sCJD and indicate the potential use of colorimetric t-α-synuclein ELISAs for differential diagnosis of dementia types.
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http://dx.doi.org/10.1007/s12035-018-1313-4DOI Listing
May 2019

Infrared Nanospectroscopy of Phospholipid and Surfactin Monolayer Domains.

ACS Omega 2018 Apr 12;3(4):4141-4147. Epub 2018 Apr 12.

Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2-12, 10587 Berlin, Germany.

A main challenge in understanding the structure of a cell membrane and its interactions with drugs is the ability to chemically study the different molecular species on the nanoscale. We have achieved this for a model system consisting of mixed monolayers (MLs) of the biologically relevant phospholipid 1,2-distearoyl--glycero-phosphatidylcholine and the antibiotic surfactin. By employing nano-infrared (IR) microscopy and spectroscopy in combination with atomic force microscopy imaging, it was possible to identify and chemically detect domain formation of the two constituents as well as to obtain IR spectra of these species with a spatial resolution on the nanoscale. A novel method to enhance the near-field imaging contrast of organic MLs by plasmon interferometry is proposed and demonstrated. In this technique, the organic layer is deposited on gold and ML graphene substrates, the latter of which supports propagating surface plasmons. Plasmon reflections arising from changes in the dielectric environment provided by the organic layer lead to an additional contrast mechanism. Using this approach, the interfacial region between surfactin and the phospholipid has been mapped and a transition region is identified.
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http://dx.doi.org/10.1021/acsomega.7b01931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044929PMC
April 2018

Oral Health Status of Stroke Patients Related to Residual Symptoms: A Case-Control Epidemiological Study in Hungary.

Oral Health Prev Dent 2018;16(3):233-239

Purpose: Stroke is a leading cause of death in developed countries. Recently, its connection with oral health has been a focus of the medical literature. The aim of this study was therefore to statistically examine the oral health of subjects who previously suffered from stroke and provide a guide for the dental treatment of these patients.

Materials And Methods: Stroke patients at least one year after the stroke episode and age- and sex-matched healthy controls were examined: dental and medical stroke histories were recorded, followed by a detailed orofacial examination. A categorisation into three 'dental' subgroups of stroke patients was carried out based on their residual symptoms, the functional deficiency of limbs, and chewing and swallowing difficulties. Indices quantifying oral hygiene (OHI-S), dental status explained by the number of decayed, missing, and filled teeth (DMFT), periodontal status (CAL, CPITN, Mühlemann index), and the status of prosthetic treatment (prosthetic index) were assessed. Statistical comparison was performed between the patient and age- and sex-matched control subjects, as well as between subgroups of stroke patients.

Results: One hundred two stroke patients and 98 healthy age- and sex-matched control subjects were examined. The oral health and dental status of stroke patients was worse compared with the control group. Stroke patients had significantly more decayed (2.3 ± 3 vs1.1 ± 1.8; p = 0.01) and missing (19.3 ± 9.5 vs 15.5 ± 9.3; p = 0.005) teeth, but significantly fewer filled (3.6 ± 4.7 vs 7.7 ± 5.6; p < 0.001) teeth than did the healthy controls. In stroke patients, clinical attachment loss (CAL) was double that of the control group (p < 0.001). A comparison between the subgroups of stroke patients revealed that the most severe findings were in patients who had chewing and swallowing disabilities.

Discussion: According to these results, the combination of risk factors of stroke, residual neurological signs after stroke, and poorer socioeconomic conditions results in poor oral hygiene, poor dental and periodontal conditions, and a lower prosthetic index. Special care and attention should be given to the oral hygiene and dental treatment of such patients, to enable good nourishment.
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http://dx.doi.org/10.3290/j.ohpd.a40672DOI Listing
October 2018

Validation and utilization of amended diagnostic criteria in Creutzfeldt-Jakob disease surveillance.

Neurology 2018 07 22;91(4):e331-e338. Epub 2018 Jun 22.

From the National TSE Reference Center (P.H., M.L., T.K., S.G., J.T., M.C., M.S., I.Z.), Department of Neurology, Georg-August University Goettingen; Institute of Neuropathology (M.G., J.M.), University Medical Center Hamburg-Eppendorf, Hamburg; and Institute of Neuropathology (W.S.-S.), Saarland University Medical Center, Germany.

Objective: To validate an amended protocol for clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) including real-time quaking-induced conversion (RT-QuIC) and to observe its use in CJD surveillance.

Methods: In the framework of a prospective epidemiologic study, all neuropathologically confirmed cases with sCJD who received CSF RT-QuIC analysis during diagnostic workup (n = 65) and a control group of individuals without CJD (n = 118) were selected to investigate the accuracy of an amended diagnostic protocol. The patients had been referred to the German National Reference Center for Transmissible Spongiform Encephalopathies. The influence of the amended protocol on incidence figures was evaluated in the context of 3 years of surveillance activity (screened cases using 14-3-3 test n = 18,789, highly suspicious cases of CJD n = 704). Annual incidences were calculated with current criteria and the amended protocol.

Results: The amended protocol showed a sensitivity of 97% and a specificity of 99%. When it was applied to all suspected cases who were referred to the reference center, the assessed incidence of CJD increased from 1.7 to 2.2 per million in 2016.

Conclusion: CJD surveillance remains challenging because information from external health care institutions can be limited. RT-QuIC shows excellent diagnostic accuracy when applied in the clinical setting to symptomatic patients. Data for RT-QuIC alone when applied as a general screening test are not available yet. We propose an amended research protocol that improves early and accurate clinical diagnosis of sCJD during surveillance activities. The use of this protocol will probably lead to a significant increase of the incidence rate.

Classification Of Evidence: This study provides Class III evidence that for patients with suspected sCJD, criteria for clinical diagnosis plus the CSF RT-QuIC accurately identifies patients with sCJD (sensitivity 97%, specificity 99%).
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http://dx.doi.org/10.1212/WNL.0000000000005860DOI Listing
July 2018