Simultaneous determination of natural and synthetic steroid estrogens and their conjugates in aqueous matrices by liquid chromatography / mass spectrometry

An analytical method for the simultaneous determination of nine free and conjugated steroid estrogens was developed with application to environmental aqueous matrices. Solid phase extraction (SPE) was employed for isolation and concentration, with detection by liquid chromatography/mass spectrometry (LC/MS) using electrospray ionisation (ESI) in the negative mode. Method recoveries for various aqueous matrices (wastewater, lake and drinking water) were determined, recoveries proving to be sample dependent. When spiked at 50 ng/l concentrations in sewage influent, recoveries ranged from 62-89 % with relative standard deviations (RSD) < 8.1 %. In comparison, drinking water spiked at the same concentrations had recoveries between 82-100 % with an RSD < 5%. Ion suppression is a known phenomenon when using ESI; hence its impact on method recovery was elucidated for raw sewage. Both ion suppression from matrix interferences and the extraction procedure has bearing on the overall method recovery. Analysis of municipal raw sewage identified several of the analytes of interest at ng/l concentrations, estriol (E3) being the most abundant. Only one conjugate, estrone 3-sulphate (E1-3S) was observe

Structure and Inhibition of Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity

SummaryThe selective inhibition of bacterial β-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative β-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a β-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the β-glucuronidase active site. Finally, we establish that β-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial β-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity

Hazardous drinking among young adults seeking outpatient mental health services

BACKGROUND: Alcohol use can have a significant negative impact on young adults in mental health treatment. This cross-sectional study examined prevalence and factors associated with hazardous drinking among young adults seeking outpatient mental health services, rate of alcohol use disorders (AUDs), and the relationship between hazardous drinking and other types of substance use. METHODS: Participants were 487 young adults ages 18–25 who completed self-administered computerized screening questions for alcohol and drug use. Alcohol use patterns were assessed and predictors of hazardous drinking (≥5 drinks on one or more occasions in the past year) were identified using logistic regression. RESULTS: Of the 487 participants, 79.8 % endorsed prior-year alcohol use, 52.3 % reported one or more episodes of hazardous drinking in the prior year and 8.2 % were diagnosed with an AUD. Rates of recent and lifetime alcohol, tobacco and marijuana use were significantly greater in those with prior-year hazardous drinking. In logistic regression, prior-year hazardous drinking was associated with lifetime marijuana use (OR 3.30, p < 0.001; 95 % CI 2.05, 5.28), lifetime tobacco use (OR 1.88, p = 0.004; 95 % CI 1.22, 2.90) and older age (OR 1.18 per year, p < 0.001; 95 % CI 1.08, 1.29). CONCLUSIONS: In an outpatient mental health setting, high rates of hazardous drinking were identified, and drinking was associated with history of other substance use. Results highlight patient characteristics associated with hazardous drinking that mental health providers should be aware of in treating young adults, especially older age and greater use of tobacco and marijuana

Anxiety Sensitivity and Distress Tolerance Mediating Associations of Neuroticism and Psychiatric Symptoms

College students demonstrate high rates of depression, anxiety and alcohol consumption. Neuroticism consistently predicts onset of psychiatric symptoms; however, our understanding of malleable risk characteristics that mediate associations between neuroticism and psychiatric symptoms is limited. The current study aimed to investigate whether anxiety sensitivity (AS) and/or distress tolerance (DT) mediated relationships between neuroticism and psychiatric symptoms (anxiety, depression, and alcohol use) in a high-risk sample of college students. Participants were 316 college students (75.9% women) with a history of interpersonal trauma exposure and current alcohol use who were participating in a university-wide longitudinal study of emotional health. Participants completed measures assessing personality, AS, DT, and psychiatric symptoms (including depression, anxiety, and alcohol consumption) over four time points spanning an average of 26 months. Results of structural equation modeling demonstrated that DT, but not AS, mediated relationships between neuroticism and depression, as well as neuroticism and anxiety. Neither DT nor AS mediated the relationship between neuroticism and alcohol consumption. These findings contribute to our understanding of the development of depression and anxiety in trauma-exposed college students with elevated trait neuroticism

Information Seeking in Individuals Intolerant of Uncertainty

The intolerance of uncertainty model (IUM) of worry posits that individuals worry as a means to cope with the discomfort they feel when outcomes are uncertain, but there have been few experimental studies that investigate the causal relationships between intolerance of uncertainty, situational uncertainty, and worry. Furthermore, existing studies have failed to control for the likelihood of future negative events occurring, introducing an important rival hypothesis to explain past findings. In the present study, we aimed to examine how individuals with high and low trait intolerance of uncertainty differ in their emotional, cognitive, and behavioral reactions to situational uncertainty about an upcoming negative event (watching emotionally upsetting film clips), holding constant the likelihood of that negative event taking place. We found that although individuals high in trait prospective anxiety (a type of intolerance of uncertainty) evidenced more information seeking behavior and reported a higher degree of belief that being provided with detailed information about the upcoming stressor would make them feel at ease, they did not experience a decrease in distress or worry upon being provided with more information, during anticipation of the film clips, or during the film clips themselves. Our results demonstrate that heightened distress regarding negative events may be more central than intolerance of uncertainty in the maintenance of worry

Development and feasibility pilot of Considering PTSD Treatment: An online intervention with peer support

Considering PTSD Treatment is an online program adapted from the National Center for PTSD's AboutFace website. Developed to help veterans overcome barriers to seeking treatment for posttraumatic stress disorder (PTSD), the program features videos of veterans describing PTSD and what treatment was like. Peer specialists are available at the beginning and end to chat with participants. We describe initial pilot feasibility data in 50 veterans recruited through online ads who screened positive for PTSD and were not currently in treatment. Eighty percent of participants who consented enrolled in the program and 64.0 % completed all modules. On average, participants rated the program at least “moderately” helpful and over 90 % reported feeling more knowledgeable about PTSD and PTSD treatment. Of the 21 participants who completed the one month follow-up, 52.4 % said they had talked to or were assessed by a provider and 61.9 % said they started treatment. There was not a significant change in stigma scores from baseline to follow-up. Results provide initial support for the feasibility, acceptability, and effectiveness of Considering PTSD Treatment for increasing treatment seeking readiness and support the need for a larger randomized controlled trial

Hazardous drinking among young adults seeking outpatient mental health services.

BackgroundAlcohol use can have a significant negative impact on young adults in mental health treatment. This cross-sectional study examined prevalence and factors associated with hazardous drinking among young adults seeking outpatient mental health services, rate of alcohol use disorders (AUDs), and the relationship between hazardous drinking and other types of substance use.MethodsParticipants were 487 young adults ages 18-25 who completed self-administered computerized screening questions for alcohol and drug use. Alcohol use patterns were assessed and predictors of hazardous drinking (≥5 drinks on one or more occasions in the past year) were identified using logistic regression.ResultsOf the 487 participants, 79.8&nbsp;% endorsed prior-year alcohol use, 52.3&nbsp;% reported one or more episodes of hazardous drinking in the prior year and 8.2&nbsp;% were diagnosed with an AUD. Rates of recent and lifetime alcohol, tobacco and marijuana use were significantly greater in those with prior-year hazardous drinking. In logistic regression, prior-year hazardous drinking was associated with lifetime marijuana use (OR 3.30, p&nbsp;&lt;&nbsp;0.001; 95&nbsp;% CI 2.05, 5.28), lifetime tobacco use (OR 1.88, p&nbsp;=&nbsp;0.004; 95&nbsp;% CI 1.22, 2.90) and older age (OR 1.18 per year, p&nbsp;&lt;&nbsp;0.001; 95&nbsp;% CI 1.08, 1.29).ConclusionsIn an outpatient mental health setting, high rates of hazardous drinking were identified, and drinking was associated with history of other substance use. Results highlight patient characteristics associated with hazardous drinking that mental health providers should be aware of in treating young adults, especially older age and greater use of tobacco and marijuana

Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans.

Study objectivesTrauma-related nightmares are highly prevalent among veterans and are associated with higher-severity insomnia and posttraumatic stress disorder. Cognitive behavioral therapy for insomnia (typically 6-8 sessions) has been shown to reduce trauma-related nightmares. Brief behavioral treatment for insomnia (BBTI, 4 sessions) has been found to be comparable to CBT-I in decreasing insomnia severity; however, the effects of BBTI on nightmares have not been investigated. The current study tested the effects of BBTI on both trauma-related nightmares and nontrauma-related bad dreams using an active control group treated using progressive muscle relaxation therapy. In addition, we tested whether baseline trauma-related nightmare frequency and baseline nontrauma-related bad dream frequency moderated changes in insomnia severity.MethodsParticipants were 91 military veterans with insomnia disorder randomized to BBTI or progressive muscle relaxation therapy. Participants reported insomnia severity on the Insomnia Severity Index and reported trauma-related nightmare frequency and nontrauma-related bad dream frequency on the Pittsburgh Sleep Quality Index-PTSD Addendum.ResultsWe found that BBTI significantly reduced trauma-related nightmares from baseline to posttreatment, whereas progressive muscle relaxation therapy did not. However, reductions in trauma-related nightmares were not maintained at the 6-month follow up. Neither BBTI nor progressive muscle relaxation therapy reduced nontrauma-related bad dreams from baseline to posttreatment. We also found that neither baseline trauma-related nightmare frequency nor baseline nontrauma-related bad dream frequency moderated changes in insomnia symptom severity.ConclusionsFindings from the current study suggest that BBTI may help reduce trauma-related nightmares. Further research is needed to better understand the potential mechanisms underlying how improved sleep may reduce trauma-related nightmares.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Brief Behavioral Insomnia Treatment Study (BBTI); URL: https://clinicaltrials.gov/ct2/show/NCT02571452; Identifier: NCT02571452.CitationRanney RM, Gloria R, Metzler TJ, Huggins J, Neylan TC, Maguen S. Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans. J Clin Sleep Med. 2022:18(7):1831-1839