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OBJECTIVES. The goal of the study was to determine whether reactive oxygen species (ROS) mediates cytomegalovirus (CMV)–induced labyrinthitis. STUDY DESIGN. Murine model of CMV infection. SETTING. University of Utah laboratory. SUBJECTS AND METHODS. Nrf2 knockout mice were inoculated with murine CMV. Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were then performed on these and uninfected controls. BALB/c mice were inoculated with murine CMV to determine whether a marker for ROS production, dihydroethidium (DHE), is expressed 7 days after inoculation. Finally, 2 antioxidants—D-methionine and ACE-Mg (vitamins A, C, and E with magnesium)—were administered 1 hour before and after infection in inoculated mice for 14 days. Temporal bones were harvested at postnatal day 10 for DHE detection. ABR and DPOAE testing was done at postnatal day 30. Scanning electron microscopy was also performed at postnatal day 30 to evaluate outer hair cell integrity. RESULTS. Nrf2-infected mice had worse hearing than uninfected mice (P < .001). A statistically significant increase in DHE fluorescence was detected in BALB/c-infected mice as compared with uninfected mice 7 days after inoculation. D-methionine- and ACE-Mg-treated mice demonstrated an attenuation of the DHE fluorescence and a significant improvement in ABR and DPOAE thresholds when compared with untreated infected controls (P

Background and Objective Approximately 1.7 million patients are affected by hospital-acquired infections every year in the United States. The increasing prevalence of multidrug-resistant bacteria associated with these infections prompts the investigation of alternative sterilization and antibacterial therapies. One method currently under investigation is the antibacterial properties of visible light. This study examines the effect of a visible light therapy (VLT) on β-lactam-resistant Escherichia coli, a common non-skin flora pathogen responsible for a large percentage of indwelling medical device-associated clinical infection. Materials and Methods 405 nm light-emitting diodes were used to treat varying concentrations of a common laboratory E. coli K-12 strain transformed with the pCIG mammalian expression vector. This conferred ampicillin resistance via expression of the β-lactamase gene. Bacteria were grown on sterile polystyrene Petri dishes plated with Luria-Bertani broth. Images of bacterial growth colonies on plates were processed and analyzed using ImageJ. Irradiance levels between 2.89 ± 0.19 and 9.45 ± 0.63 mW cm−2 and radiant exposure levels between 5.60 ± 0.39 and 136.91 ± 4.06 J cm−2 were tested. Results VLT with variable irradiance and constant treatment time (120 minutes) demonstrated significant reduction (P

The prognosis for patients with pancreatic cancer is extremely poor, as evidenced by the disease's five-year survival rate of ~5%. New approaches are therefore urgently needed to improve detection, treatment, and monitoring of pancreatic cancer. MRS-detectable metabolic changes provide useful biomarkers for tumor detection and response-monitoring in other cancers. The goal of this study was to identify MRS-detectable biomarkers of pancreatic cancer that could enhance currently available imaging approaches. We used (1) H high-resolution magic angle spinning MRS to probe metabolite levels in pancreatic tissue samples from mouse models and patients. In mice, the levels of lipids dropped significantly in pancreata with lipopolysaccharide-induced inflammation, in pancreata with pre-cancerous metaplasia (4 week old p48-Cre;LSL-Kras(G12D) mice), and in pancreata with pancreatic intraepithelial neoplasia, which precedes invasive pancreatic cancer (8 week old p48-Cre LSL-Kras(G12D) mice), to 26 ± 19% (p = 0.03), 19 ± 16% (p = 0.04), and 26 ± 10% (p = 0.05) of controls, respectively. Lactate and taurine remained unchanged in inflammation and in pre-cancerous metaplasia but increased significantly in pancreatic intraepithelial neoplasia to 266 ± 61% (p = 0.0001) and 999 ± 174% (p < 0.00001) of controls, respectively. Importantly, analysis of patient biopsies was consistent with the mouse findings. Lipids dropped in pancreatitis and in invasive cancer biopsies to 29 ± 15% (p = 0.01) and 26 ± 38% (p = 0.02) of normal tissue. In addition, lactate and taurine levels remained unchanged in inflammation but rose in tumor samples to 244 ± 155% (p = 0.02) and 188 ± 67% (p = 0.02), respectively, compared with normal tissue. Based on these findings, we propose that a drop in lipid levels could serve to inform on pancreatitis and cancer-associated inflammation, whereas elevated lactate and taurine could serve to identify the presence of pancreatic intraepithelial neoplasia and invasive tumor. Our findings may help enhance current imaging methods to improve early pancreatic cancer detection and monitoring.

Objectives—To assess the relationship between telomere length and adiposity, using dualenergy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI), in addition to conventional anthropometric proxies including body mass index (BMI) and cardiovascular disease risk factors. Methods—A cross-sectional sample of 309 non-Hispanic white participants in the Fels Longitudinal Study aged 8 to 80 yr (52% female) was included. Average telomere length was measured by quantitative PCR. Results—Telomere length was negatively correlated with age (r = −0.32, P < 0.0001) and had numerous significant correlations with established cardiovascular disease risk factors including waist circumference (r = −0.33), apolipoprotein B (r = −0.26), systolic blood pressure (r = −0.28), and fasting serum glucose (r = −0.15); all P < 0.0025. In back-ward selection linear regression models of telomere length, adiposity measures were consistently retained in the best models; BMI, waist circumference, hip circumference, total body fat, and visceral adipose tissue volume were all inversely associated with telomere length at the nominal P < 0.05 level or lower, independent of age, sex, systolic blood pressure, and fasting serum lipid, lipoprotein, and glucose concentrations. The negative association of BMI with telomere length was stronger among younger than older participants (P for interaction, 0.03). Conclusions—Individuals with higher total and abdominal adiposity have lower telomere length, a marker of cellular senescence, suggesting obesity may hasten the aging process. Longitudinal studies are required to establish the causal association of early life adiposity with biological aging. Telomeres are noncoding repeat sequences at the ends of chromosomes [5′-(TTAGGG)n–3′] that function to stabilize the chromosome during mitosis, prevent aberrant recombination, and protect the chromosomes from end-degrading enzymes (Moyzis et al., 1988). In somatic cells, telomere repeats are lost at each cell division due to the inability of DNA polymerase to fully replicate chromosome ends (Levy et al., 1992; Olovnikov, 1973), leading to declines in telomere length with age. When telomere length reaches a critically short length in one or more chromosomes (the “Hayflick limit”), the cell is signaled to arrest replication and

Objectives:Demonstrate the role of the innate immune response in a mouse model for Cytomegalovirus (CMV) induced sensorineural hearing loss (SNHL).Methods:Forty C57BL/6 and BALB/c mice underwent intracranial injection at postnatal day 3 with 200 pfu of green fluorescent protein (GFP) expressing murine (m) CMV; 10 controls received either saline or no injection. Hearing thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brain stem response testing (ABR). Temporal bones were harvested and sectioned for histologic analysis. A subset of BALB/c and C57B/6 temporal bones were harvested for histologic analysis 3 and 7 days after inoculation.Results:Fifty-five percent of the BALB/c mice had profound hearing loss (≥80 dB) at 4 weeks of age, while 45% initially showed moderate hearing loss that progressed to profound hearing loss by 6 weeks. The green fluorescent protein (GFP)-labeled virus was abundant in the spiral ganglion and adjacent to the scala tympani at 7 days post-...