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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
We report two cases of respiratory toxigenic Corynebacterium diphtheriae infection in fully vaccinated UK born adults following travel to Tunisia in October 2019. Both patients were successfully treated with antibiotics and neither received diphtheria antitoxin. Contact tracing was performed following a risk assessment but no additional cases were identified. This report highlights the importance of maintaining a high index of suspicion for re-emerging infections in patients with a history of travel to high-risk areas outside Europe.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
As in vivo cellular imaging becomes the necessary norm for understanding cancer and other diseases, new non-toxic nanoprobes are going to be required to replace the high quality cadmium based nanoprobes in use today. We are developing less toxic probes based on two types of luminescent ceramic nanoparticles: naturally occurring fluorescent (NOF) mimics and Ln-based ceramic oxide materials. The NOF minerals of interest and that have demonstrated initial luminosity of sufficient brightness for use in cellular studies that include sphalerite, scheelite, manganoan and perovskite nanoparticles. For Ln-based materials we have shown that Ln-doped zincite will also luminesce enough to allow for quantification in cellular activity. Once formed, these probes are functionalized such that they can be delivered to desired cellular targets. Probe derivatization has focused on surface capping with functionalized poly(ethyleneglycol) molecules/lipids to yield water soluble NCs and polyarginine-based transporters for transmembrane delivery. The probes are being evaluated for their luminescent properties, as well as their non-toxicity and ability to report on cell-signaling events with various cell lines using multi-spectral, confocal microscopy, and other techniques. Preliminary interdisciplinary studies have validated the basic approaches for the synthesis of NOF nanoprobes and the bio-delivery and imaging of nanoparticles. Work to optimize the design, delivery, and imaging of these new nanoprobes is expected to achieve the NIH directed goal of increasing in the sensitivity and specificity of molecular probes for imaging. Details of the synthesis, functionalization and biological imaging using these probes will be presented. This work partially supported by the United States Department of Energy under contract number DE-AC04-94AL85000. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the United States Department of Energy and by the National Institutes of health through the NIH Roadmap for Medical Research, Grant #1 R21 EB005365-01. Information on this RFA (Innovation in Molecular Imaging Probes) can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-021.html.
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