A non-invasive olfactory bulb measure dissociates Parkinson’s patients from healthy controls and discloses disease duration

AbstractOlfactory dysfunction is a prevalent non-motor symptom of Parkinson’s disease (PD). This dysfunction is a result of neurodegeneration within the olfactory bulb (OB), the first processing area of the central olfactory system, and commonly precedes the characteristic motor symptoms in PD by several years. Functional measurements of the OB could therefore potentially be used as an early biomarker for PD. Here, we used a non-invasive method, so-called electrobulbogram (EBG), to measure OB function in PD and age-matched healthy controls to assess whether EBG measures can dissociate PDs from controls. We estimated the spectrogram of the EBG signal during exposure to odor in PD (n = 20) and age-matched controls (n = 18) as well as identified differentiating patterns of odor-related synchronization in the gamma, beta, and theta frequency bands. Moreover, we assessed if these PD-EBG components could dissociate PD from control as well as their relationship with PD characteristics. We identified six EBG components during the initial and later stages of odor processing which dissociated PD from controls with 90% sensitivity and 100% specificity with links to PD characteristics. These PD-EBG components were related to medication, disease duration, and severity, as well as clinical odor identification performance. These findings support using EBG as a tool to experimentally assess PD interventions, potentially aid diagnosis, and the potential development of EBG into an early biomarker for PD.

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Values of T/QRS ratio in pregnancies complicated by intrauterine growth restriction

Journal of Perinatal Medicine ◽

10.1515/jpm-2014-0305 ◽

2016 ◽

Vol 44 (7) ◽

Cited By ~ 4

Author(s):

Tomasz Fuchs

Keyword(s):

Intrauterine Growth Restriction ◽

Well Being ◽

Study Groups ◽

Growth Restriction ◽

Healthy Controls ◽

Value Differences ◽

Intrauterine Growth ◽

Non Invasive ◽

Invasive Method ◽

Ratio Variables

AbstractAims:To evaluate values of T/QRS ratio in normal pregnancies and those complicated by intrauterine growth restriction (IUGR) using non-invasive method with transabdominal electrodes. Assessment of fetal well-being in IUGR pregnancies.Methods:Fetal electrocardiograms were recorded and analyzed by KOMPOREL software from ITAM (Zabrze, Poland) and T/QRS ratios were automatically calculated. Doppler velocimetry of the middle cerebral artery and umbilical artery was carried out. The study group consisted of IUGR pregnancies with normal cerebroplacental ratios (CPRs) (n=110), IUGR pregnancies with decreased CPRs (n=29), and healthy controls (n=549). Analyses were performed between the study groups and by gestational age. T/QRS ratio variables and CPRs were calculated. Analysis of variance and linear regression were performed.Results:Maximum values, maximum minimal value differences, and standard deviations of T/QRS ratio were significantly different between the IUGR group with reduced CPRs and normal CPRs (P=0.0009, P=0.0000, P=0.0034, respectively) as well as between the IUGR group with reduced CPRs and healthy controls (P=0.0000, P=0.0001, P=0.0009, respectively). Mean maximum values in the IUGR group with reduced CPRs exceeded normal values.Conclusions:T/QRS ratio may be useful in assessing fetal well-being in IUGR pregnancies; however, future studies are needed to determine typical ranges of T/QRS ratio in pregnancies complicated by IUGR.

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Deep nasal sinus cavity microbiota dysbiosis in Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00254-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Gian Pal ◽

Vivian Ramirez ◽

Phillip A. Engen ◽

Ankur Naqib ◽

Christopher B. Forsyth ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Nasal Cavity ◽

Amplicon Sequencing ◽

Motor Symptom ◽

Rrna Gene ◽

Healthy Controls ◽

Nasal Sinus ◽

Severe Motor

AbstractOlfactory dysfunction is a pre-motor symptom of Parkinson’s disease (PD) that appears years prior to diagnosis and can affect quality of life in PD. Changes in microbiota community in deep nasal cavity near the olfactory bulb may trigger the olfactory bulb-mediated neuroinflammatory cascade and eventual dopamine loss in PD. To determine if the deep nasal cavity microbiota of PD is significantly altered in comparison to healthy controls, we characterized the microbiota of the deep nasal cavity using 16S rRNA gene amplicon sequencing in PD subjects and compared it to that of spousal and non-spousal healthy controls. Correlations between microbial taxa and PD symptom severity were also explored. Olfactory microbial communities of PD individuals were more similar to those of their spousal controls than to non-household controls. In direct comparison of PD and spousal controls and of PD and non-spousal controls, significantly differently abundant taxa were identified, and this included increased relative abundance of putative opportunistic-pathobiont species such as Moraxella catarrhalis. M. catarrhalis was also significantly correlated with more severe motor scores in PD subjects. This proof-of-concept study provides evidence that potential pathobionts are detected in the olfactory bulb and that a subset of changes in the PD microbiota community could be a consequence of unique environmental factors associated with PD living. We hypothesize that an altered deep nasal microbiota, characterized by a putative pro-inflammatory microbial community, could trigger neuroinflammation in PD.

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A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways

10.21203/rs.3.rs-78071/v2 ◽

2021 ◽

Author(s):

Jörgen Östling ◽

Marleen Van Geest ◽

Henric K Olsson ◽

Sven-Erik Dahlén ◽

Emilia Viklund ◽

...

Keyword(s):

Extracellular Proteins ◽

Small Airway ◽

Small Airways ◽

Healthy Controls ◽

Annotation Database ◽

Epithelial Lining Fluid ◽

Go Annotation ◽

Non Invasive ◽

Invasive Method ◽

Never Smokers

Abstract BackgroundBreath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and constitute a potential source of biomarkers reflecting pathological processes in the small airways.ObjectiveOur aim was to investigate if PExA method may be useful for discovery of biomarkers that reflect pathology of small airways.Methods10 healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI ≥2.9 z-score), were examined using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc).ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is an novel and promising approach to study respiratory diseases with small airway involvement.

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Software-based Detection of Acute Rejection Changes in Face Transplant

Journal of Reconstructive Microsurgery ◽

10.1055/s-0041-1733995 ◽

2021 ◽

Author(s):

Miguel I. Dorante ◽

Branislav Kollar ◽

Marian Bittner ◽

Alice Wang ◽

Yannick Diehm ◽

...

Keyword(s):

Acute Rejection ◽

Mixed Models ◽

Allograft Rejection ◽

Healthy Controls ◽

Non Invasive ◽

Face Transplant ◽

Marginal Means ◽

Invasive Method ◽

The Mean ◽

R Value

Abstract Background An objective, non-invasive method for redness detection during acute allograft rejection in face transplantation (FT) is lacking. Methods A retrospective cohort study was performed with 688 images of 7 patients with face transplant (range, 1 to 108 months post-transplant). Healthy controls were matched to donor age, sex, and had no prior facial procedures. Rejection state was confirmed via tissue biopsy. An image-analysis software developed alongside VicarVision (Amsterdam, Netherlands) was used to produce R, a measure of differences between detectable color and absolute red. R is inversely proportional to redness, where lower R values correspond to increased redness. Linear mixed models were used to study fixed effect of rejection state on R values. Estimated marginal means of fitted models were calculated for pairwise comparisons. Results Of 688 images, 175, 170, 202, and 141 images were attributable to Banff Grade 0,1,2, and 3, respectively. Estimated change in R value of facial allografts decreased with increasing Banff Grade (p = 0.0001). The mean R value of clinical rejection (Banff Grade ⅔) (16.67, 95% Confidence Interval [CI] 14.79–18.58) was lower (p = 0.005) than non-rejection (Banff Grade 0/1) (19.38, 95%CI 17.43–21.33). Both clinical and non-rejection mean R values were lower (p = 0.0001) than healthy controls (24.12, 95%CI 20.96–27.28). Conclusion This proof-of-concept study demonstrates that software-based analysis can detect and monitor acute rejection changes in FT. Future studies should expand on this tool's potential application in telehealth and as a screening tool for allograft rejection.

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A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

10.21203/rs.3.rs-78071/v1 ◽

2020 ◽

Author(s):

Jörgen Östling ◽

Marleen Van Geest ◽

Henric K Olsson ◽

Sven-Erik Dahlén ◽

Emilia Viklund ◽

...

Keyword(s):

Extracellular Proteins ◽

Small Airway ◽

Small Airways ◽

Healthy Controls ◽

Annotation Database ◽

Epithelial Lining Fluid ◽

Go Annotation ◽

Non Invasive ◽

Invasive Method ◽

Never Smokers

Abstract BackgroundBreath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and constitute a potential source of biomarkers reflecting pathological processes in the small airways.ObjectiveOur aim was to investigate if PExA method may be useful for discovery of biomarkers that reflect pathology of small airways.Methods10 healthy controls and 20 subjects with asthma, of whom 10 with small airway dysfunction (SAD), were examined using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc). ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with SAD as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with small airway dysfunction. The results suggest that PEx based proteomics is an novel and promising approach to study respiratory diseases with small airway involvement.

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Proteomic Patterns of Nipple Aspirate Fluids Obtained by SELDI-TOF: Potential for New Biomarkers to Aid in the Diagnosis of Breast Cancer

Disease Markers ◽

10.1155/2001/674959 ◽

2001 ◽

Vol 17 (4) ◽

pp. 301-307 ◽

Cited By ~ 192

Author(s):

Cloud P. Paweletz ◽

Bruce Trock ◽

Marie Pennanen ◽

Theodore Tsangaris ◽

Collette Magnant ◽

...

Keyword(s):

Breast Cancer ◽

Healthy Controls ◽

Breast Cancer Patients ◽

Ionization Time ◽

Non Invasive ◽

Abnormal Mammogram ◽

Surface Enhanced ◽

Invasive Method ◽

Nipple Aspirate Fluids ◽

New Biomarkers

Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal.

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Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

Zeitschrift für Neuropsychologie ◽

10.1024//1016-264x.12.1.8 ◽

2001 ◽

Vol 12 (1) ◽

pp. 8-14

Author(s):

Gertraud Teuchert-Noodt ◽

Ralf R. Dawirs

Keyword(s):

Prefrontal Cortex ◽

Mental Disorders ◽

Dentate Gyrus ◽

Cognitive Functions ◽

Experimental Approach ◽

Regulatory Mechanisms ◽

Hippocampal Dentate Gyrus ◽

Non Invasive ◽

Invasive Method ◽

Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

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