Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-κB (NFκB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Muller glial cells, spanning the entirety of the retina, are involved in DR inflammation. Mitigation of DR pathology currently occurs via invasive, frequently ineffective therapies which can cause adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammationin vitroandin vivo. Thus, we hypothesize that 670nm light treatment will diminish oxidative stress preventing downstream inflammatory mechanisms associated with DR initiated by Muller cells. In this study, we used anin vitromodel system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm²) or no light (sham) daily. We report that a single 670 nm light treatment diminished reactive oxygen species (ROS) production and preserved mitochondrial integrity in thisin vitromodel of early DR. Furthermore, treatment for 3 days in culture reduced NFκB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in thisin vitrohigh glucose model system suggests light treatment could mitigate early deleterious effects modulating inflammatory signaling and diminishing oxidative stress.

The World Health Organization has identified antibiotic resistance as one of the largest threats to human health and food security. In this study, we compared antibiotic resistance patterns between ESBL-producing Escherichia coli from human clinical diseases and cefotaxime-resistant environmental strains, as well as their potential to be pathogenic. Antibiotic susceptibility was tested amongst clinical isolates (n = 11), hospital wastewater (n = 22), and urban wastewater (n = 36, both influent and treated effluents). Multi-drug resistance predominated (>70%) among hospitalwastewater and urban wastewater influent isolates. Interestingly, isolates from clinical and urban treated effluents showed similar multi-drug resistance rates (~50%). Most hospital wastewater isolates were Phylogroup A, while clinical isolates were predominately B2, with a more diverse phylogroup population in urban wastewater. ESBL characterization of cefotaxime-resistant populations identified bla_CTX-M-1 subgroup as the most common, whereby bla_KPC was more associated with ceftazidime and ertapenem resistance. Whole-genome sequencing of a carbapenemase-producing hospital wastewater E. coli strain revealed plasmid-mediated bla_KPC-2. Among cefotaxime-resistant populations, over 60% of clinical and 30% of treated effluent E. coli encoded three or more virulence genes exhibiting a pathogenic potential. Together, the similarity among treated effluent E. coli populations and clinical strains suggest effluents could serve as a reservoir for future multi-drug resistant E. coli clinical infections.

We previously demonstrated that a depletion of regulatory T (Treg) cells in Lyme arthritis-resistant C57BL/6 mice leads to pathological changes in the tibiotarsal joints following infection with Borrelia burgdorferi. Here, we assessed the effects of Treg cells on the response to B. burgdorferi infection in BALB/c mice, which exhibit infection-dose-dependent disease and a different sequence of immune events than C57BL/6 mice. The depletion of Treg cells prior to infection with 1 × 10², but not 5 × 10³, organisms led to increased swelling of the tibiotarsal joints. However, Treg cell depletion did not significantly affect the development of histopathology at these low doses of infection. BALB/c mice depleted of Treg cells before infection with 1 × 10³ spirochetes harbored a higher borrelial load in the hearts and exhibited higher levels of serum interleukin-10 five weeks later. These results indicate that Treg cells regulate certain aspects of the response to B. burgdorferi in a mouse strain that may display a range of disease severities. As the presentation of Lyme disease may vary among humans, it is necessary to consider multiple animal models to obtain a complete picture of the various means by which Treg cells affect the host response to B. burgdorferi.

Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-kB (NFkB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Current therapies are invasive, frequently ineffective, and have adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammation in vitro and in vivo. Thus, we hypothesize that 670nm light treatment will dimish oxidative stress preventing downstream inflammatory mechanisms associated with DR. We used an in vitro model system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm²) or no light (sham) daily. We report that a single 670 nm light treatment diminished ROS production and preserved mitochondrial integrity and ATP production in this in vitro model of diabetic retinopathy. Furthermore, treatment for 3 days in culture reduced NFkB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in this established DR model system suggests light treatment could become an early therapeutic option for DR.

Brain endocannabinoid (eCB) signaling, which includes CB1 cannabinoid receptors (CB1R) and the eCBs N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), modulates behavioral responses to stress and fear extinction. Sterol carrier protein 2 (SCP-2) is an intracellular lipid binding protein expressed in brain that binds AEA and 2-AG at nanomolar concentrations and facilitates their cellular accumulation. SCP-2 mRNA is present in mouse limbic brain regions and is increased in the prefrontal cortex (PFC) and amygdalar complex in mice with impaired (129S1/Sv1mJ) fear extinction compared to mice with normal (C57BL/6J) fear extinction. In this study, we utilized mice with deletion of the gene for SCP-2 and an overlapping gene, SCP-X (SCP-2/X^-/-), to examine the hypothesis that SCP-2 regulates behaviors associated with anxiety and fear. Compared to WT mice, SCP-2/X^-/- mice exhibit enhanced fear extinction and reduced anxiety-driven behaviors in the elevated plus maze. These differences are abrogated by treatment with a CB1R antagonist and not recapitulated in mice with selective deletion of SCP-X. While baseline brain tissue concentrations of AEA and 2-AG are not different between WT and SCP-2/X^-/- mice, amygdalar and PFC 2-AG concentrations are significantly higher in SCP-2/X^-/- mice 24 h following foot shock. There are no differences between WT and SCP-2/X^-/- mice in rectal temperature; or in tail flick and catalepsy assays. These findings support the hypothesis that as yet unproven functions of the lipid carrier protein SCP-2 regulate behaviors associated with fear memory and anxiety and suggest that pharmacological inhibitors of SCP-2 could reduce acute anxiety and enhance fear extinction.