Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined.
View Article and Find Full Text PDFKetamine, a N-methyl-D-aspartate (NMDA) antagonist, is used for treatment-resistant depression (TRD). Recent studies have shown that there are increased levels of pro-inflammatory cytokines in individuals with major depressive disorder (MDD) and those with higher levels of oxidative stress markers have a decreased or null response to conventional antidepressants. Glutathione (GSH) as an antioxidant adjuvant to ketamine has not been well studied.
View Article and Find Full Text PDFBackground: Systemic inflammation contributes to cardiovascular risk and chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between systemic inflammation and exposure to ambient fine particulate matter (PM ≤ 2.5 μm diameter; PM), and black carbon (BC), a PM component attributable to traffic and other sources of combustion, infiltrating indoors are not well described.
View Article and Find Full Text PDFUrinary tract infections (UTIs) in men are uncommon yet carry an increased risk for severe pyelonephritis and other complications. In models of UTI, C3H/HeN mice develop high-titer pyelonephritis (most with renal abscesses) in a testosterone-dependent manner, but the mechanisms underlying this phenotype are unknown. Here, using female mouse models, we show that androgen exposure impairs neutrophil maturation in the upper and lower urinary tract, compounded by a reduction of neutrophil function within the infected kidney, enabling persistent high-titer infection and promoting abscess formation.
View Article and Find Full Text PDFIntroduction: Indoor nitrogen dioxide (NO) sources include gas heating, cooking, and infiltration from outdoors. Associations with pulmonary function, systemic inflammation, and oxidative stress in patients with chronic obstructive pulmonary disease (COPD) are uncertain.
Methods: We recruited 144 COPD patients at the VA Boston Healthcare System between 2012 and 2017.
Rationale: Little is known about personal characteristics and systemic responses to particulate pollution in patients with COPD.
Objectives: Assess whether diabetes, obesity, statins and non-steroidal anti-inflammatory medications (NSAIDs) modify associations between indoor black carbon (BC) and fine particulate matter ≤2.5 μm in diameter (PM) on systemic inflammation and endothelial activation.
BACKGROUND: Guidelines call for the removal of the nonvented cap (NVC) on the flushless transducer applied to the external ventricular drain (EVD) to zero the device to atmospheric pressure. Some hospitals have abandoned this practice to prevent opening the system to air. No data exist to determine the safest, most effective method of EVD zero-calibration.
View Article and Find Full Text PDFIn recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults.
View Article and Find Full Text PDFPlatelet-like and cylindrical nanostructures from sugar-based polymers are designed to mimic the aspect ratio of bacteria and achieve uroepithelial cell binding and internalization, thereby improving their potential for local treatment of recurrent urinary tract infections. Polymer nanostructures, derived from amphiphilic block polymers composed of zwitterionic poly(d-glucose carbonate) and semicrystalline poly(l-lactide) segments, were constructed with morphologies that could be tuned to enhance uroepithelial cell binding. These nanoparticles exhibited negligible cytotoxicity, immunotoxicity, and cytokine adsorption, while also offering substantial silver cation loading capacity, extended release, and antimicrobial activity (as effective as free silver cations) against uropathogenic .
View Article and Find Full Text PDFBackground: Using ultrasound to measure optic nerve sheath diameter (ONSD) is an emerging bedside technique to noninvasively assess intracranial pressure (ICP) in patients with brain injury. This technique is unique among bedside ultrasonography and is often performed by providers who have no formal ultrasound training. We sought to create a low-cost, 3D, reusable ONSD model to train neurology, neurosurgery, and critical care providers in measuring ICP.
View Article and Find Full Text PDFAscending bacterial pyelonephritis, a form of urinary tract infection (UTI) that can result in hospitalization, sepsis, and other complications, occurs in ~250,000 US patients annually; uropathogenic (UPEC) cause a large majority of these infections. Although UTIs are primarily a disease of women, acute pyelonephritis in males is associated with increased mortality and morbidity, including renal scarring, and end-stage renal disease. Preclinical models of UTI have only recently allowed investigation of sex and sex-hormone effects on pathogenesis.
View Article and Find Full Text PDFObjective: To determine whether earlier hospital discharge is feasible and safe in selected patients with subarachnoid hemorrhage (SAH) using an outpatient "fast-track" protocol.
Patients And Methods: We conducted a prospective quality improvement cohort study with the primary feasibility end point of patients with SAH deemed safe for discharge by treating team consensus. All patients received detailed education and outpatient transcranial Doppler monitoring; caregivers could contact the on-call team 24-7.
Renal scarring after pyelonephritis is linked to long-term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti-androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post-infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens.
View Article and Find Full Text PDFMussels are ecologically important organisms that can survive in subtidal and intertidal zones where they experience thermal stress. We know little about how mussels from different tidal habitats respond to thermal stress. We used the mussel Mytilus galloprovincialis from separate subtidal and intertidal populations to test whether heart rate and indicators of potential aerobic (citrate synthase activity) and anaerobic (cytosolic malate dehydrogenase activity) metabolic capacity are affected by increased temperatures while exposed to air or submerged in water.
View Article and Find Full Text PDFPurpose: To determine if routinely performed computed tomographic (CT) scanning in patients with aneurysmal subarachnoid hemorrhages (aSAHs) is sufficient to identify patients at high risk of vision loss due to Terson syndrome (TS).
Methods: Consecutive patients with a diagnosis of aSAH admitted to the neurologic intensive care unit of a regional referral hospital over a 3-year period were prospectively evaluated. Head CT scans performed in the emergency department were assessed for the presence of a "crescent sign" (evidence of significant subinternal limiting membrane hemorrhage).
Mutations in oncogenes and tumor suppressor genes engender unique metabolic phenotypes crucial to the survival of tumor cells. EGFR signaling has been linked to the rewiring of tumor metabolism in non-small cell lung cancer (NSCLC). We have integrated the use of a functional genomics screen and metabolomics to identify metabolic vulnerabilities induced by EGFR inhibition.
View Article and Find Full Text PDFDo human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as "Seshat: Global History Databank." We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years.
View Article and Find Full Text PDFBackground: While emerging research has focused on quality of life (QOL) levels among farmers and ranchers with disabilities, much work is still needed on this largely understudied population. The AgrAbility Project, a USDA initiative, offers pragmatic solutions to increase farmers and ranchers with disabilities' QOL and ability to work and live independently (ILW).
Objectives: To assess pretest-posttest changes in farmers and ranchers with disabilities' ILW and QOL levels after participating in AgrAbility, to identify demographic predictors of ILW and QOL (e.
As the obesity epidemic worsens, the prevalence of maternal obesity is expected to rise. Both high-fat and high-sucrose diets are known to promote maternal obesity and several studies have elucidated the molecular influence of high-fat feeding on female reproduction. However, to date, the molecular impact of a high-sucrose diet on maternal obesity remains to be investigated.
View Article and Find Full Text PDFBackground: The status of farmers and ranchers with disabilities has been understudied. Understanding this population's quality of life (QOL) and independent living and working (ILW) levels have the potential to be informative for changes in public policy and service provision.
Objective: To assess QOL levels among farmers and ranchers with disabilities as well as explore a conceptual model of ILW accounting for variance in QOL levels.
Purpose: Patient and provider satisfaction with a pharmacist-managed lipid clinic in a Veterans Affairs medical center were assessed.
Methods: All patients at Louis Stokes Cleveland Veterans Affairs Medical Center who were referred to a pharmacist-managed lipid clinic for drug therapy management were mailed a questionnaire addressing overall satisfaction with care provided by the lipid clinic. Chart reviews were performed for patients completing the questionnaire to ascertain lipid-lowering medications used, changes in serum cholesterol levels, and achievement of low-density-lipoprotein (LDL) cholesterol goal.