Diet-induced obesity in mice impairs host defense against Klebsiella pneumonia in vivo and glucose transport and bactericidal functions in neutrophils in vitro.

Obesity impairs host defense against Klebsiella pneumoniae, but responsible mechanisms are incompletely understood. To determine the impact of diet-induced obesity on pulmonary host defense against K. pneumoniae, we fed 6-wk-old male C57BL/6j mice a normal diet (ND) or high-fat diet (HFD) (13% vs. 60% fat, respectively) for 16 wk. Mice were intratracheally infected with Klebsiella, assayed at 24 or 48 h for bacterial colony-forming units, lung cytokines, and leukocytes from alveolar spaces, lung parenchyma, and gonadal adipose tissue were assessed using flow cytometry. Neutrophils from uninfected mice were cultured with and without 2-deoxy-d-glucose (2-DG) and assessed for phagocytosis, killing, reactive oxygen intermediates (ROI), transport of 2-DG, and glucose transporter (GLUT1-4) transcripts, and protein expression of GLUT1 and GLUT3. HFD mice had higher lung and splenic bacterial burdens. In HFD mice, baseline lung homogenate concentrations of IL-1ß, IL-6, IL-17, IFN-γ, CXCL2, and TNF-α were reduced relative to ND mice, but following infection were greater for IL-6, CCL2, CXCL2, and IL-1ß (24 h only). Despite equivalent lung homogenate leukocytes, HFD mice had fewer intraalveolar neutrophils. HFD neutrophils exhibited decreased Klebsiella phagocytosis and killing and reduced ROI to heat-killed Klebsiella in vitro. 2-DG transport was lower in HFD neutrophils, with reduced GLUT1 and GLUT3 transcripts and protein (GLUT3 only). Blocking glycolysis with 2-DG impaired bacterial killing and ROI production in neutrophils from mice fed ND but not HFD. Diet-induced obesity impairs pulmonary Klebsiella clearance and augments blood dissemination by reducing neutrophil killing and ROI due to impaired glucose transport.

Personality disorder and suicide risk among patients in the veterans affairs health system.

Among veterans in Veterans Health Administration (VHA) care, patients with mental health and substance use conditions experience elevated suicide rates. However, despite previously demonstrated high rates of suicidal behavior, little is known regarding suicide rates among veteran VHA users with personality disorders (PDs) as a whole, or by PD clusters (A: Eccentric; B: Dramatic; C: Fearful; and PD-not otherwise specified). PD prevalence and suicide rates were assessed through 2017; overall and by clusters for 5,517,024 veterans alive as of 12/31/2013 and with more than 2 VHA encounters in 2012-2013. In all, 46,050 (.83%) had a PD diagnosis in 2012-2013. Suicide risk was examined using proportional hazards regressions adjusted for age, sex, veteran status, clustering within a geographic region, and other mental health diagnoses. Patients with PDs had greater suicide risk than those without (156.5 vs. 46.7 per 100,000 person-years). Individuals in Cluster B, which includes borderline and antisocial PDs, were at the highest risk (178.5 per 100,000 person-years), followed by PD-not otherwise specified and Cluster C (152.6 and 121.4 per 100,000 person-years, respectively). Rates of PDs in the VHA system were lower than those usually found in community samples. Veterans with a PD diagnosis had an increased risk of suicide, which was especially elevated for those with Cluster B diagnoses. Study findings document the importance of enhancing diagnosis and treatment for veterans with PDs and targeted suicide prevention services. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Hypertension Treatment Modality and Suicide Risk Among Veterans in Veterans Health Administration Care From 2015 to 2017.

Importance: The Veterans Health Administration (VHA) serves a population of veterans with a high prevalence of comorbid health conditions and increased risk for suicide. Objective: To replicate the findings of a previous study and assess whether exposure to angiotensin receptor blockers (ARBs) is associated with differential suicide risk compared with angiotensin-converting enzyme inhibitors (ACEIs) among veterans receiving VHA care. Design, Setting, and Participants: This nested case-control design included all suicide decedents from 2015 to 2017 with a VHA inpatient or outpatient encounter in the prior year and with either an active ACEI or ARB prescription in the 100 days prior to death. Using a 4:1 ratio, controls were matched to cases by age, sex, and hypertension and diabetes diagnoses. Controls were alive at the time of the death of the matched case, had a VHA encounter within the previous year, and had either an active ACEI or ARB medication fill within 100 days before the death of the matched case. Exposures: An active ACEI or ARB prescription within 100 days before the death of the case. Main Outcomes and Measures: Cases were suicide decedents from 2015 to 2017 per National Death Index search results included in the Veteran Affairs/Department of Defense Mortality Data Repository. Results: Among 1309 cases, the median (interquartile range [IQR]) age was 68 (60-76) years and among 5217 controls, the median (IQR) age was 67 (60-76) years, and 1.9% of veterans in both groups were female. ARBs were received by 20.2% of controls and 19.6% of cases; ACEIs were received by 79.8% of controls and 80.4% of cases. The crude suicide odds ratio for ARBs vs ACEIs was 0.966 (95% CI, 0.828-1.127). Controlling for covariates, the adjusted odds ratio for ARBs was 0.985 (95% CI, 0.834-1.164). Sensitivity analyses using only those covariates that differed significantly between groups, restricting to veterans ages 65 and older, dropping matching criteria, and adjusting for the quantity and temporal proximity of ACEI and ARB exposure in the 100 days prior to the index date, had consistent findings. Conclusions and Relevance: This case-control study did not identify differences in suicide risk by receipt of ARBs vs ACEIs in analyses specific to veterans receiving VHA care in contrast with findings from the referent study.