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Murine sepsis models are typically polymicrobial, and are associated with high mortality. We aimed to develop a high-throughput murine model that mimics a slow-paced, monomicrobial sepsis originating from the urinary tract. A total of 23 male C57Bl/6 mice underwent percutaneous insertion of a 4 mm catheter into the bladder using an ultrasound-guided method, previously developed by our group. The following day, Proteus mirabilis (PM) was introduced percutaneously in the bladder in three groups: g1—50 µL 1 × 108 CFU/mL solution (n = 10); g2—50 µL 1 × 107 CFU/mL solution (n = 10); and g3 (sham mice)—50 µL sterile saline (n = 3). On day 4, mice were sacrificed. The number of planktonic bacteria in urine, adherent to catheters, and adherent to/invaded into the bladder and spleen was assessed. Cell-free DNA, D-dimer, thrombin–antithrombin complex (TAT), and 32 pro-/anti-inflammatory cytokines/chemokines were quantified in the blood. All mice survived the 4 day postinterventional period. Mean weight loss was 11% in g1, 9% in g2, and 3% in the control mice. Mean urine CFU counts were highest in group 1. All catheters showed high catheter-adhered bacterial counts. Of the infected mice, 17/20 had CFU counts in the splenic tissue, indicating septicemia. Plasma levels of cell-free DNA, D-dimer, and the proinflammatory cytokines IFN-γ, IL-6, IP-10, MIG, and G-CSF were significantly elevated in infected mice versus controls. We present a reproducible, monomicrobial murine model of urosepsis that does not lead to rapid deterioration and death, and is useful for studying prolonged urosepsis. [ABSTRACT FROM AUTHOR]

Objective Perimenopause is associated with an increased risk of developing a major depressive (MD) episode. A significant number of women develop their first MD episode during perimenopause, suggesting a unique pathophysiology of perimenopausal (PM) depression. Previous research has shown that depression is associated with decreased gamma-aminobutyric acid (GABA) levels in the medial prefrontal cortex (MPFC) of MD patients. The objective of this study was to compare MPFC GABA+ levels in healthy reproductive-aged (RD) and PM women. Methods A total of 18 healthy PM and 20 RD women were included in the study. MPFC GABA+ levels, which include homocarnosine and macromolecules, were measured via magnetic resonance spectroscopy using a 3 Tesla magnet. MPFC GABA+ levels were referenced to creatine + phosphocreatine (Cr+PCr). Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle. PM women were scanned outside of ovulatory cycles. Results Mean MPFC GABA+ concentrations (relative to Cr+PCr) were decreased in the PM group compared with the RD group (PM mean = 0.08 ± 0.02, RD mean = 0.09 ± 0.02, t  = −2.03, df  = 36, P  = .05) even after correcting for in percentage in gray matter (GM). Because PM women were inherently older than RD women (aged 48.8 ± 3.55 and 31.5 ± 9.66 years, respectively), the age difference between the 2 groups was statistically significant (P  < .001). When age was treated as an independent covariate and included in the model, the difference in GABA+ between PM and RD women was no longer significant (P  = .092). Conclusion Perimenopause is associated with decreased MPFC GABA+/Cr+PCr levels, which may contribute to the increased risk of experiencing a MD episode during PM. [ABSTRACT FROM AUTHOR]