Pan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-RBD Ig electrochemiluminescence immunoassay (ECLIA) regarding analytical, diagnostic, operational and clinical characteristics. Our work takes the form of a population-based study in the principality of Liechtenstein, including 125 cases with clinically well-described and laboratory confirmed SARS-CoV-2 infection and 1159 individuals without evidence of coronavirus disease 2019 (COVID-19). SARS-CoV-2 cases were tested for antibodies in sera taken with a median of 48 days (interquartile range, IQR, 43–52) and 139 days (IQR, 129–144) after symptom onset. Sera were also tested with other assays targeting antibodies against non-RBD-S1 and -S1/S2 epitopes. Sensitivity was 97.6% (95% confidence interval, CI, 93.2–99.1), whereas specificity was 99.8% (95% CI, 99.4–99.9). Antibody levels linearly decreased from hospitalized patients to symptomatic outpatients and SARS-CoV-2 infection without symptoms (p < 0.001). Among cases with SARS-CoV-2 infection, smokers had lower antibody levels than non-smokers (p = 0.04), and patients with fever had higher antibody levels than patients without fever (p = 0.001). Pan-SARS-CoV-2 S1-RBD Ig in SARS-CoV-2 infection cases significantly increased from first to second follow-up (p < 0.001). A substantial proportion of individuals without evidence of past SARS-CoV-2 infection displayed non-S1-RBD antibody reactivities (248/1159, i.e., 21.4%, 95% CI, 19.1–23.4). In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity with potential clinical cross-reactivity to SARS-CoV-2.
J. Neurochem. (2010) 114, 1261–1276. Abstract Neurodegenerative diseases, notably Alzheimer’s and Parkinson’s diseases, are amongst the most devastating disorders afflicting the elderly. Currently, no curative treatments or treatments that interdict disease progression exist. Over the past decade, immunization strategies have been proposed to combat disease progression. Such strategies induce humoral immune responses against misfolded protein aggregates to facilitate their clearance. Robust adaptive immunity against misfolded proteins, however, accelerates disease progression, precipitated by induced effector T cell responses that lead to encephalitis and neuronal death. Since then, mechanisms that attenuate such adaptive neurotoxic immune responses have been sought. We propose that shifting the balance between effector and regulatory T cell activity can attenuate neurotoxic inflammatory events. This review summarizes advances in immune regulation to achieve a homeostatic glial response for therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are also discussed.
Background and Purpose Superficial siderosis (SS) is characterized by hemosiderin deposition in the superficial layers of the central nervous system and can be seen during post-mortem examination or with iron-sensitive magnetic resonance imaging (MRI) techniques. The distribution of SS may predict the probable underlying etiology. This study aimed to report the prevalence and natural history of superficial siderosis (SS) in a population-based study. Methods Brain MRI scans from the Mayo Clinic Study of Aging, a population-based study of residents 50–89 years of age in Olmsted County, Minnesota, were reviewed. Participants with imaging consistent with SS were identified from 2011 through 2016. An inverse probability weighting approach was used to convert our observed frequencies to population prevalence of SS. Additional data abstracted included amyloid Positron Emission Tomography (PET), Apolipoprotein E (APOE) genotype, coexisting cerebral microbleeds, and extent of SS. Results A total of 1,412 participants had eligible MRI scans. Two participants had infratentorial SS, restricted to the posterior fossa. Thirteen participants had cortical SS (cSS) involving the cerebral convexities (7 focal and 6 disseminated). Only three of the participants with cSS (23%) also had cerebral microbleeds. The population prevalence of SS was 0.21% (95% confidence interval [CI]: 0–0.45) in those 50 to 69 years old and 1.43% (CI 0.53–2.34) in those over 69 years old. APOE ε2 allele was more common in those with SS (57.1% vs 15.0%, p < 0.001). Compared to participants without SS, those with SS were also more likely to have a positive amyloid PET scan (76.9% vs 29.8%, p < 0.001) Conclusions SS may be encountered in the general elderly population. The association with increased amyloid burden and APOE ε2 genotype supports cerebral amyloid angiopathy as the most common mechanism. Longitudinal follow up is needed to evaluate the risk of subsequent hemorrhage in cases of incidentally discovered SS.
PurposeThe purpose of this work is the design, implementation and evaluation of a mechanically flexible receive-only coil array for magnetic resonance imaging (MRI) at 3 T that can be applied to various target organs and provides high parallel imaging performance.MethodsA 23-channel array was designed based on a rigid-flex printed circuit board (PCB). The flexible multi-layer part contains the copper traces forming the coil elements. The rigid part of the PCB houses the solder joints and lumped elements. The coil housing consists of rigid caps mounted above the rigid parts. Adhesive PTFE sheets cover all flexible parts. The developed array was tested on the bench as well as in phantom and in vivo MRI experiments employing parallel imaging acceleration factors up to six.ResultsEfficient mutual decoupling between receive elements and detuning between receive array and body coil was achieved. An increased signal-to-noise ratio in comparison to commercial reference coils is demonstrated, especially in regions close to the developed array and for high parallel imaging acceleration factors. Exemplary in vivo images of head, ankle, knee, shoulder and hand are presented.ConclusionBased on high sensitivity close to the array and low g-factors, this flexible coil is well suited for studies of occipital and temporal cortex, as well as musculoskeletal targets like knee, ankle, elbow and wrist.
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