Methods to discover and validate biofluid-based biomarkers in neurodegenerative dementias

Neurodegenerative dementias are progressive diseases that cause neuronal network breakdown in different brain regions often because of accumulation of misfolded proteins in the brain extracellular matrix, such as amyloids or inside neurons or other cell types of the brain. Several diagnostic protein biomarkers in body fluids are being used and implemented, such as for Alzheimer\xe2\x80\x99s disease. However, there is still a lack of biomarkers for co-pathologies and other causes of dementia. Such biofluid-based biomarkers enable precision medicine approaches for diagnosis and treatment, allow to learn more about underlying disease processes, and facilitate the development of patient inclusion and evaluation tools in clinical trials. When designing studies to discover novel biofluid-based biomarkers, choice of technology is an important starting point. But there are so many technologies to choose among. To address this, we here review the technologies that are currently available in research settings and, in some cases, in clinical laboratory practice. This presents a form of lexicon on each technology addressing its use in research and clinics, its strengths and limitations, and a future perspective

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

The phytochemical composition and <i>in vitro</i> antiviral activity of decoctions from galls of <i>Guiera senegalensis</i> J.F. Gmel. (<i>Combretaceae</i>) and their relative non-toxicity for chickens

Aqueous decoctions obtained from the galls of Guiera senegalensis were screened to determine their phytochemical composition and in vitro antiviral activity against fowlpox virus. In addition, we wanted to investigate the toxic effects, if any, of crude extracts in chickens. Steroids as well as cardiac glycosides not previously reported, an alkaloid, polyphenols and saponins were detected in the various fractions of organic solvents used for extracting the decoctions. Antiviral activity was determined by cytopathic effect inhibition assay in primary chicken embryo skin cells. The 50 % inhibitory concentration (EC50) was shown to be 15.6 µg/ml. Toxicity for cells was established by determining the 50 % cytotoxic concentration (CCy50). A value of 90 µg/ml and a selectivity index (CCy50/EC50) of 5.8 were obtained. In vivo studies of toxicity were performed in chickens that were dosed orally with decoctions of several concentrations for 2 weeks and then monitored for 3 months. No significant changes in several blood chemical parameters were obtained, except for a significant decline in SGOT levels in birds dosed with 100 mg/kg. These levels were nevertheless within the accepted normal range. The findings suggest that aqueous decoctions of galls from G. senegalensis are non-toxic for chickens when administered orally, even at a daily dose of 100 mg/kg for 14 days

Experimental design optimization for screening relvant free phenolic acids from various preparations used in Burkina Faso folk medicine

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