Trauma and posttraumatic stress disorder in women with chronic pelvic pain

OBJECTIVE: To examine the effect of abuse history, other major trauma, and posttraumatic stress disorder (PTSD) on medical symptoms and health-related daily functioning in women with chronic pelvic pain. METHODS: We administered a questionnaire to 713 consecutive women seen in a referral-based pelvic pain clinic. RESULTS: We found that 46.8% reported having either a sexual or physical abuse history. A total of 31.3% had a positive screen for PTSD. Using regression and path analysis, controlling for demographic variables, we found that a trauma history was associated with worse daily physical functioning due to poor health (P<.001), more medical symptoms (P<.001), more lifetime surgeries (P<.001), more days spent in bed (P<.001), and more dysfunction due to pain (P<.001). Furthermore, a positive screen for PTSD was highly related to most measures of poor health status (P<.001) and somewhat explained the trauma-related poor health status. CONCLUSION: The association of trauma with poor health may be due in part to the development of PTSD resulting from trauma. These findings demonstrate the importance of screening for trauma and PTSD in women with chronic pelvic pain. LEVEL OF EVIDENCE: II.     

Thyroid disease in pregnancy

Twenty-seven million Americans are affected with thyroid disease, yet over half of this population remains undiagnosed. Thyroid disease often manifests itself during the reproductive period of a woman's life and is the second most common endocrinopathy that affects women of childbearing age. The physiologic changes of pregnancy can mimic thyroid disease or cause a true remission or exacerbation of underlying disease. In addition, thyroid hormones are key players in fetal brain development. Maternal, fetal and neonatal thyroid are discussed here. Moreover, this article serves as a review of the more common thyroid diseases that are encountered during pregnancy and the postnatal period, their treatments, and their potential effects on pregnancy.     

Vicarious,direct, and imaginal aversion in habit control: Outcomes,heart rates,and subjective perceptions

Direct, modeled, or imaginal shocks administered by therapist or recipient were compared as aversion techniques for 60 women college students with severe nail-biting habits. All methods increased habit control (p <.001)on self-report and objective measures but with no outcome differences among treatments. Providing mental rehearsal guidance for extralaboratory use failed to alter outcome but raised client optimism to ward therapy. Vicarious aversion produced the most rapid heart rates and, typically, the greatest subjective arousal; no data suggested that direct shock was superior. In a second study with unselected student volunteers of both sexes, modeled shock consistently surpassed imaginal shock in ratings of perceived badness, subjective discomfort, and vividness of covert pain (p <.01).Treatment and ethical implications were discussed. We are indebted to Lisa Obstfeld, who performed ably as the long-suffering model, and to Albert Bandura, Mary Gabrielson, Glenn M. White, and Louis Zimmer, who assisted with other matters. Part of this research was completed while all authors were at the University of Arizona, Tucson.     

HEPARINEMIA (?) : AN ANTICOAGULANT IN THE BLOOD OF DOGS WITH HEMORRHAGIC TENDENCY AFTER TOTAL BODY EXPOSURE TO ROENTGEN RAYS

When the entire body of dogs was exposed to 450 units of Roentgen irradiation a hemorrhagic syndrome developed which was characterized by thrombo-cytopenia, prolonged clotting and bleeding times, and neutropenia. The prothrombin time remained normal until about 24 hours before death. The calcium, phosphorus, and magnesium levels were not altered. Fibrinogen was present but syneresis was poor. Toluidine blue and protamine sulfate, substances which can inhibit the biologic action of heparin, restored the clotting time to normal. The hemorrhagic state was not materially altered by transfusions, vitamin K, or vitamin C. Toluidine blue and protamine sulfate were ineffective in the control of hemorrhage produced by dicumarol. The defect responsible for bleeding after irradiation appeared to be the presence in the circulation of an anticoagulant whose properties, so far as tested, were indistinguishable from those of heparin.     

CHEMICAL STUDIES ON BACTERIAL AGGLUTINATION : VII. A QUANTITATIVE STUDY OF THE TYPE SPECIFIC AND GROUP SPECIFIC ANTIBODIES IN ANTIMENINGOCOCCAL SERA OF VARIOUS SPECIES AND THEIR RELATION TO MOUSE PROTECTION

1. The quantitative method for the estimation of agglutinins has been applied to antimeningococcal horse, rabbit, and chicken sera and to the sera of humans convalescing from meningococcus meningitis. The type-specific and group-specific agglutinin N can be measured, using homologous and heterologous suspensions of meningococci. 2. Type I horse, rabbit, and chicken antimeningococcal sera contain considerable amounts of antibody which cannot be removed either by Type II meningococcus suspension or by preparations of the Type I specific polysaccharide. This residual type-specific antibody has marked potency in protecting mice against subsequent infection with meningococci. 3. Most human convalescent sera contain group-specific antibody. Small amounts of protective antibody and of antipolysaccharide are also formed. 4. Type I antisera absorbed with Type I polysaccharide and with Type II meningococci could be used as a guide in the purification of this new antigen.     

Estimation of brain receptor occupancy for trazodone immediate release and once a day formulations

Trazodone is approved for the treatment of major depressive disorders, marketed as immediate release (IR), prolonged release, and once a day (OAD) formulation. The different formulations allow different administration schedules and may be useful to facilitate patients’ compliance to the antidepressant treatment. A previously verified physiologically‐based pharmacokinetic model based on in vitro and in vivo information on trazodone pharmacokinetics was applied, aiming at predicting brain receptor occupancy (RO) after single and repeated dosing of the IR formulation and repeated dosing of the OAD formulation in healthy subjects. Receptors included in the simulations were selected using static calculations of RO based on the maximum unbound brain concentration (C_max,brain,u) of trazodone for each formulation and dosing scheme, resulting in 16 receptors being simulated. Seven receptors were simulated for the IR low dose formulation (30 mg), with similar t _onset and duration of coverage (range: 0.09–0.25 h and 2.1–>24 h, respectively) as well as RO (range: 0.64–0.92) predicted between day 1 and day 7 of dosing. The 16 receptors evaluated for the OAD formulation (300 mg) showed high RO (range: 0.97–0.84 for the receptors also covered by the IR formulation and 0.73–0.48 for the remaining) correlating with affinity and similar duration of time above the target threshold to the IR formulation (range: 2–>24 h). The dose‐dependent receptor coverage supports the multimodal activity of trazodone, which may further contribute to its fast antidepressant action and effectiveness in controlling different symptoms in depressed patients.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

The antidepressant efficacy of trazodone has been shown to be significantly correlated to its steady‐state plasma levels, and previous work has shown some understanding of trazodone range of affinity for different receptors, at different doses, but without considering the different available formulations. Trazodone is commonly available as: immediate release (IR), prolonged release (PR), and once a day (OAD) tablets. The IR formulation has a rapid onset and short duration of action, whereas the PR formulation is characterized by an absorption boost as soon as it is administered and has a comparatively delayed maximum concentration (C_max). Conversely, the OAD formulation provides a controlled release of trazodone over 24 h without the early high peak plasma concentration seen with the IR and PR formulations.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This work aims to identify the brain receptors reaching a threshold occupancy of 50% through static predictions and determine the occupancy versus time profile for those of interest following administration of short‐ and long‐acting trazodone formulations.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Brain receptor occupancy (RO) for key targets were predicted based on free drug concentrations, allowing for a physiologically relevant assessment of the different pathways affected by each formulation and dose.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The presented physiologically‐based pharmacokinetic approach to assess RO can be used to guide formulation selection and dosing in clinical studies.     

Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.     

Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy

Background: HIV infection results in immunometabolic reprogramming. While we are beginning to understand how this metabolic reprogramming regulates the immune response to HIV infection, we do not currently understand the impact of ART on immunometabolism in people with HIV (PWH). Methods: Serum obtained from HIV-infected (n = 278) and geographically matched HIV seronegative control subjects (n = 300) from Rakai Uganda were used in this study. Serum was obtained before and ~2 years following the initiation of ART from HIV-infected individuals. We conducted metabolomics profiling of the serum and focused our analysis on metabolic substrates and pathways assocaited with immunometabolism. Results: HIV infection was associated with metabolic adaptations that implicated hyperactive glycolysis, enhanced formation of lactate, increased activity of the pentose phosphate pathway (PPP), decreased β-oxidation of long-chain fatty acids, increased utilization of medium-chain fatty acids, and enhanced amino acid catabolism. Following ART, serum levels of ketone bodies, carnitine, and amino acid metabolism were normalized, however glycolysis, PPP, lactate production, and β-oxidation of long-chain fatty acids remained abnormal. Conclusion: Our findings suggest that HIV infection is associated with an increased immunometabolic demand that is satisfied through the utilization of alternative energetic substrates, including fatty acids and amino acids. ART alone was insufficient to completely restore this metabolic reprogramming to HIV infection, suggesting that a sustained impairment of immunometabolism may contribute to chronic immune activation and comorbid conditions in virally suppressed PWH.