| 1. |
- Kang, Matthew J.Y., et al.
(författare)
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Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders
- 2023
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Ingår i: Acta Neuropsychiatrica. - 0924-2708. ; 36:1, s. 17-28
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Tidskriftsartikel (refereegranskat)abstract
- Objective People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. Methods We collected longitudinal diagnostic information (mean=36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other), and PSY. We pre-specified NfL>582pg/mL as indicative of ND/MCI/other. Results Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. Conclusions CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
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| 2. |
- Omiatek, Donna M, et al.
(författare)
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Hybrid capillary-microfluidic device for the separation, lysis, and electrochemical detection of vesicles.
- 2009
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Ingår i: Analytical chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 81:6, s. 2294-302
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Tidskriftsartikel (refereegranskat)abstract
- The primary method for neuronal communication involves the extracellular release of small molecules that are packaged in secretory vesicles. We have developed a platform to separate, lyse, and electrochemically measure the contents of single vesicles using a hybrid capillary-microfluidic device. This device incorporates a sheath-flow design at the outlet of the capillary for chemical lysis of vesicles and subsequent electrochemical detection. The effect of sheath-flow on analyte dispersion was characterized using confocal fluorescence microscopy and electrochemical detection. At increased flow rates, dispersion was minimized, leading to higher separation efficiencies but lower detected amounts. Large unilamellar vesicles (diameter approximately 200 nm), a model for secretory vesicles, were prepared by extrusion and loaded with an electroactive molecule. They were then separated and detected using the hybrid capillary-microfluidic device. Determination of size from internalized analyte concentration provides a method to characterize the liposomal suspension. These results were compared to an orthogonal size measurement using dynamic light scattering to validate the detection platform.
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| 3. |
- Santillo, Michael F, et al.
(författare)
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Temporal analysis of protozoan lysis in a microfluidic device.
- 2009
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Ingår i: Lab on a chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 9:19, s. 2796-802
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Tidskriftsartikel (refereegranskat)abstract
- A microfluidic device was fabricated and characterized for studying cell lysis of Arcella vulgaris, a nonpathogenic amoeba, over time. The device contains a series of chambers which capture cells allowing them to be subsequently exposed to a constant flow of biocidal agent. With this microfluidic system, individual cells are observed as they undergo lysis. This allows high-throughput measurements of individual lysis events, which are not possible with conventional techniques. Differences in lysis and decay times for Arcella were seen at different flow rates and concentrations of benzalkonium chloride, a biocidal detergent. The efficacy of benzalkonium chloride, chlorhexidine digluconate, phenol, sodium dodecyl sulfate, and Triton X-100 were compared, revealing information on their mechanisms of action. The presented device allows cell capture, controlled exposure to chemical biocides, and observation of lysis with single-cell resolution. Observations at the single cell level give insight into the mechanistic details of the lysis of individual Arcella cells vs. the population; decay times for individual Arcella cells were much shorter when compared to a population of 15 cells.
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| 4. |
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| 5. |
- Arcibal, Imee G, et al.
(författare)
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Recent advances in capillary electrophoretic analysis of individual cells
- 2007
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 387:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- Because variability exists within populations of cells, single-cell analysis has become increasingly important for probing complex cellular environments. Capillary electrophoresis (CE) is an excellent technique for identifying and quantifying the contents of single cells owing to its small volume requirements and fast, efficient separations with highly sensitive detection. Recent progress in both whole-cell and subcellular sampling has allowed researchers to study cellular function in the areas of neuroscience, oncology, enzymology, immunology, and gene expression.
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| 6. |
- Eratne, Dhamidhu, et al.
(författare)
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Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non-progressors
- 2022
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 442
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Tidskriftsartikel (refereegranskat)abstract
- Background: Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative ‘non-progressor’ mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. Methods: Cerebrospinal fluid (CSF) NfL, amyloid beta 1–42 (AB42), total and phosphorylated tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow-up information, patients were categorised as Progressors or Non-Progressors: further subtyped into Non-Progressor Revised (non-neurological/neurodegenerative final diagnosis), and Non-Progressor Static (static deficits, not fully explained by non-neurological/neurodegenerative causes). Results: Forty-three patients were included: 20 Progressors, 23 Non-Progressors (15 Non-Progressor Revised, 8 Non-Progressor Static), and 20 controls. NfL concentrations were lower in Non-Progressors (Non-Progressors Mean, M = 554 pg/mL, 95%CI:[461, 675], Non-Progressor Revised M = 459 pg/mL, 95%CI:[385, 539], and Non-Progressor Static M = 730 pg/mL, 95%CI:[516, 940]), compared to Progressors (M = 2397 pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non-Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Non-Progressor Static tended to have higher T-tau and P-tau levels compared to Non-Progressor Revised Diagnoses. Conclusion: This study demonstrated strong diagnostic utility of CSF NfL to distinguish bvFTD from non-progressor variants, at baseline, with high accuracy, in a real-world clinical setting. This has important clinical implications, to improve outcomes for patients and clinicians facing this challenging clinical dilemma, healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non-progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.
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| 7. |
- Santillo, Alexander F., et al.
(författare)
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[18F]RO948 tau positron emission tomography in genetic and sporadic frontotemporal dementia syndromes
- 2023
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 50:5, s. 1371-1383
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine [18F]RO948 retention in FTD, sampling the underlying protein pathology heterogeneity. Methods: A total of 61 individuals with FTD (n = 35), matched cases of AD (n = 13) and Aβ-negative cognitively unimpaired individuals (n = 13) underwent [18F]RO948PET and MRI. FTD included 21 behavioral variant FTD (bvFTD) cases, 11 symptomatic C9orf72 mutation carriers, one patient with non-genetic bvFTD-ALS, one individual with bvFTD due to a GRN mutation, and one due to a MAPT mutation (R406W). Tracer retention was examined using a region-of-interest and voxel-wise approaches. Two individuals (bvFTD due to C9orf72) underwent postmortem neuropathological examination. Tracer binding was additionally assessed in vitro using [3H]RO948 autoradiography in six separate cases. Results: [18F]RO948 retention across ROIs was clearly lower than in AD and comparable to that in Aβ-negative cognitively unimpaired individuals. Only minor loci of tracer retention were seen in bvFTD; these did not overlap with the observed cortical atrophy in the cases, the expected pattern of atrophy, nor the expected or verified protein pathology distribution. Autoradiography analyses showed no specific [3H]RO948 binding. The R406W MAPT mutation carriers were clear exceptions with AD-like retention levels and specific in-vitro binding. Conclusion: [18F]RO948 uptake is not significantly increased in the majority of FTD patients, with a clear exception being specific MAPT mutations.
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| 8. |
- Santillo, Michael F, et al.
(författare)
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Flow characterization of a microfluidic device to selectively and reliably apply reagents to a cellular network
- 2007
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Ingår i: Lab on aChip. - 1473-0197 .- 1473-0189. ; 7, s. 1212-1215
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Tidskriftsartikel (refereegranskat)abstract
- A three-dimensional microfluidic device has been successfully fabricated and the flow streams characterized for eventual use in studying communication in an in vitro network of nerve cells. The microfluidic system is composed of two layers of channels: a lower layer for the delivery of pharmacological solutions and an upper layer of channels used to direct the flow of the pharmacological solution streams and perfuse the cells with media and nutrients. Flow profiles have been characterized with computational fluid dynamics simulations, confocal fluorescence microscopy, and carbon-fiber amperometry, which have been used to map changes in flow profiles at different bulk flow rates. Ultimately, the microfluidic system and incorporated cell network will show how networked neurons adapt, compensate, and recover after being exposed to different chemical compounds.
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