Prevalence and psychiatric comorbidities of intermittent explosive disorders in Metropolitan Sao Paulo, Brazil
SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
Authors: Pereira, Debora Costa Sena; Coutinho, Evandro Silva Freire; Corassa, Rafael Bello; Andrade, Laura Helena; Viana, Maria Carmen
Abstract
Purpose To estimate the prevalence of intermittent explosive disorder (IED) in comorbidity with other psychiatric disorders and to describe the temporal sequencing of disorders in the Sao Paulo Metropolitan Area, Brazil. Methods Data from the Sao Paulo Megacity Mental Health Survey, a population-based study of 5037 adult individuals, were analyzed. The World Health Organization Composite International Diagnostic Interview (CID 3.0) was used to assess lifetime DSM-IV disorders, including IED, with a response rate of 81.3%. Results The majority (76.8%) of respondents with IED meet the criteria for at least one other psychiatric disorder, with a prevalence almost twice as high as that observed in individuals without IED. The prevalence of any anxiety, mood, impulse control or substance use disorders in respondents with IED was more than two times higher compared to those without IED, with prevalence ratios ranging from 2.1 (95% CI 1.74-2.48) to 2.9 (95% CI 2.12-4.06). The diagnosis of IED occurred earlier than most of the other mental disorders, except for those with usual onset in early childhood, as Specific and Social Phobias and Attention Deficit Disorder. Conclusion Considering that IED is a highly comorbid disorder and has an earlier onset than most other mental comorbidities in the Brazilian general population, these results may be useful in guiding governmental mental health actions.
Ultraviolet photodissociation of fondaparinux generates signature antithrombin-like 3-O-sulfated-GlcNS3S6S-monosaccharide fragment (Y-3/C-3)
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
Authors: Hawkridge, Adam M.; Hackbusch, Sven
Abstract
The 3-O sulfate-modified -GlcNS3S6S- monosaccharide in heparin and heparan sulfate glycosaminoglycans (HSGAGs) is a relatively rare yet important modification that facilitates HSGAG-antithrombin binding and subsequent anticoagulant activity. Detecting this modification in complex HSGAG mixtures is a longstanding goal to identify novel 3-O-sulfated HSGAG-protein interactions with biologically significant functions. Tandem mass spectrometry has been applied to HSGAG structural analysis but is limited by the fact that traditional collision-induced dissociation techniques (e.g., CID, HCD) results in extensive sulfate loss prior to generating structurally informative glycosidic and cross-ring fragments. In the present study, we investigated the potential of ultraviolet photodissociation (UVPD) to generate structurally informative fragments from the synthetic heparin mimetic, fondaparinux, under electrospray conditions commensurate with hydrophilic interaction liquid chromatography (HILIC). The two predominant un-adducted precursors, [Fonda-2H(+)](2-) and [Fonda-3H(+)](3-), were subjected to UVPD, CID, and HCD on an Orbitrap Fusion Lumos Tribrid mass spectrometer and the resulting fragmentation spectra directly compared. Close inspection of the UVPD data identified a unique peak atm/z417.9425 that matched the Y-3/C-3 double glycosidic fragment of fondaparinux (i.e., -GlcNS3S6S-). Importantly, the 3-O-sulfated Y-3/C-3 fragment was generated predominantly from UVPD of the [Fonda-2H(+)](2-) precursor, increased with activation time, and was observable using data-dependent HILIC-MS/MS UVPD analysis of fondaparinux spiked into a semi-complex HSGAG mixture. The discovery of this antithrombin-like 3-O-sulfated fragment provides a potential strategy for screening complex HSGAG mixtures in a data-dependent or data-independent acquisition mode to determine the presence of this therapeutic and biologically significant HSGAG modification.