Acoustic neuroma surgeries at higher volume hospitals had higher frequency of routine discharge, lower frequency of apparent complications, and lower average cost of hospitalization.
Microbiota dysbiosis has been linked to major depressive disorder, but the mechanisms whereby the microbiota modulates mood remain poorly understood. We show that Segmented filamentous bacteria (SFB)-deficient mice are resilient to the induction of depressive-like behavior, and are resensitized when SFB is reintroduced in the gut. SFB produces the quorum sensing molecule autoinducer-2 (AI-2) and promotes the production of serum amyloid protein-1 (SAA1) and SAA2 by the host, which increased Th17 cell production. Th17 cells were required to promote depressive-like behaviors by AI-2, as AI-2 administration did not promote susceptibility to depressive-like behaviors or SAA1 and SAA2 production in Th17-deficient mice after stress. Oleic acid, an AI-2 inhibitor, exhibited antidepressant properties, reducing depressive-like behavior, intestinal SAA1 and SAA2 production, and hippocampal Th17 cell accumulation. Patients with current major depressive disorder exhibited increased fecal IL-17A, SAA and SFB levels. These results reveal a novel mechanism by which bacteria alter mood.
Background Ketamine has rapid-acting antidepressant effects but is associated with psychotomimetic and other adverse effects. A 7-chlorokynurenic acid is a potent and specific glycine site N-methyl-d-aspartate receptor antagonist but crosses the blood-brain barrier inefficiently. Its prodrug, L-4-chlorokynurenine (4-Cl-KYN), exerts acute and sustained antidepressant-like effects in rodents and has no reported psychotomimetic effects in either rodents or healthy volunteers. This study examined whether 4-Cl-KYN has rapid antidepressant effects in individuals with treatment-resistant depression. Methods After a 2-week drug-free period, 19 participants with treatment-resistant depression were randomized to receive daily oral doses of 4-Cl-KYN monotherapy (1080 mg/d for 7 days, then 1440 mg/d for 7 days) or placebo for 14 days in a randomized, placebo-controlled, double-blind, crossover manner. The primary outcome measure was the Hamilton Depression Rating Scale score, assessed at several time points over a 2-week period; secondary outcome measures included additional rating scale scores. Pharmacokinetic measures of 7-chlorokynurenic acid and 4-Cl-KYN and pharmacodynamic assessments were obtained longitudinally and included 1H-magnetic resonance spectroscopy brain glutamate levels, resting-state functional magnetic resonance imaging, and plasma and cerebrospinal fluid measures of kynurenine metabolites and neurotrophic factors. Results Linear mixed models detected no treatment effects, as assessed by primary and secondary outcome measures. No difference was observed for any of the peripheral or central biological indices or for adverse effects at any time between groups. A 4-Cl-KYN was safe and well-tolerated, with generally minimal associated adverse events. Conclusions In this small crossover trial, 4-Cl-KYN monotherapy exerted no antidepressant effects at the doses and treatment duration studied. ClinicalTrials.gov identifier: NCT02484456.
A retrospective study of 45 patients hospitalized with blastomycosis of bones or joints revealed 41 cases of osteomyelitis and 12 cases of septic arthritis. The majority were men (35 [78%] patients) and non-Aboriginal (32 [71%] patients). Median time from the onset of symptoms to hospitalization was shorter in women than men (male, 48 d; female, 14 d; P < 0.02), and shorter for Aboriginals than non-Aboriginals (non-Aboriginal, 50 d; Aboriginal, 19 d; P < 0.04). Cutaneous disease was present in 33 (73%) patients, and lung involvement was present in 29 (64%) patients. The most common osseous sites of involvement were the lower limb and axial skeleton. Common orthopaedic symptoms of bone lesions included bone pain in 42 (78%) patients, swelling in 32 (59%) patients, and soft tissue abscesses in 21 (39%) patients. Joint infection (12 patients) manifested as a monoarticular arthropathy presenting with effusion in 9 (75%) patients, pain in 8 (67%) patients, and decreased range of motion in 5 (42%) patients. Osseous blastomycosis can mimic bacterial infection and should be included in the differential diagnosis of bone and joint infection in patients who have visited or who live in geographic regions where B dermatitidis is endemic.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.