Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. However, it is still unclear which part of the motor cortex is predominantly affected by TMS. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. We use the finite element method (FEM) and magnetic resonance image-based individual head models to get realistic estimates of the electric field induced by TMS. The field changes in different subparts of the motor cortex are compared with electrophysiological threshold changes of 2 hand muscles when systematically varying the coil orientation in measurements. We demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our study is one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for 2 hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.
HighlightsCombines simultaneous whole-brain fMRI recording with TMS stimulation.Investigates the immediate and remote neural correlates of TMS stimulation to the vertex.Vertex stimulation leads to widespread decreases in fMRI BOLD, particularly within the brain ‘Default Mode Network’.
Hepatitis delta virus (HDV) causes the most severe form of human viral hepatitis. HDV requires a hepatitis B virus (HBV) co-infection to provide HDV with HBV surface antigen envelope proteins. The net effect of HDV is to make the underlying HBV disease worse, including higher rates of hepatocellular carcinoma (HCC). Accurate assessments of current HDV prevalence have been hampered by the lack of readily available and reliable quantitative assays, combined with the absence of an FDA-approved therapy. We sought to develop a convenient assay for accurately screening populations and to use this assay to determine HDV prevalence in a population with abnormally high rates of HCC. We developed a high throughput quantitative microarray antibody capture (Q-MAC) assay for anti-HDV IgG wherein recombinant HDV delta antigen is printed by microarray on slides coated with a noncontinuous, nanostructured plasmonic gold film, enabling quantitative fluorescent detection of anti-HDV antibody in small aliquots of patient serum. This assay was then used to screen all HBV-infected patients identified in a large randomly selected cohort designed to represent the Mongolian population. We identified two quantitative thresholds of captured antibody that were 100% predictive of the sample either being positive on standard western blot, or harboring HDV RNA detectable by qPCR, respectively. Subsequent screening of the HBV-positive cohort revealed that a remarkable 57% were RNA positive and an additional 4% were positive on western blot alone.
Conclusions
The Q-MAC assay’s unique performance characteristics make it ideal for population screening. Its application to the Mongolian HBsAg+ population reveals an apparent ~60% prevalence of HDV co-infection amongst these HBV-infected Mongolian subjects, which may help explain the extraordinarily high rate of HCC in Mongolia.
Highlights d Antibodies to four COVID-19 vaccines differed in an observational study in Mongolia d Responses from high to low: Pfizer/BioNTech > AstraZeneca > Sputnik V > Sinopharm d Breakthrough infections in June to early July of 2021 were due mostly to the Alpha variant d After breakthrough infection, high antibody levels are seen in all vaccine groups
Our findings illustrate the importance of standardized monitoring of MAEs. Such research aids our understanding of how MAEs arise and may lead to interventions for reducing their incidence.
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