The serotonin and kappa opioid receptor (KOR) systems are strongly implicated in disorders of negative affect, such as anxiety and depression. KORs expressed on axon terminals inhibit the release of ...neurotransmitters, including serotonin. The substantia nigra pars reticulata (SNr) is involved in regulating affective behaviors. It receives the densest serotonergic innervation in the brain and has high KOR expression; however, the influence of KORs on serotonin transmission in this region is yet to be explored. Here, we used ex vivo fast-scan cyclic voltammetry (FSCV) to investigate the effects of a KOR agonist, U50, 488 (U50), and a selective serotonin reuptake inhibitor, escitalopram, on serotonin release and reuptake in the SNr. U50 alone reduced serotonin release and uptake, and escitalopram alone augmented serotonin release and slowed reuptake, while pretreatment with U50 blunted both the release and uptake effects of escitalopram. Here, we show that the KOR influences serotonin signaling in the SNr in multiple ways and short-term activation of the KOR alters serotonin responses to escitalopram. These interactions between KORs and serotonin may contribute to the complexity in the responses to treatments for disorders of negative affect. Ultimately, the KOR system may prove to be a promising pharmacological target, alongside traditional antidepressant treatments.
The nucleus accumbens (NAc) core is involved in regulating stress and shaping reward seeking behaviours. Multiple neuromodulators, including dynorphin/kappa opioid receptor (KOR) and dopamine ...systems, converge in this area to influence behavioural outcomes. KOR activation acutely inhibits dopamine release and chronically depresses overall dopamine transmission. Recently, studies in the NAc shell have revealed that the impact of KOR activation on behaviour is regionally specific, and these rostro-caudal differences are likely driven by greater control of KORs over dopamine inhibition in the caudal compared with rostral subregion. Given the importance of NAc core, particularly the interaction between KORs and dopamine in regulating reward seeking behaviours, we examined the impact of KOR activation on dopamine release and uptake along the rostro-caudal axis in the NAc core of male and female mice. Using ex vivo fast scan cyclic voltammetry, we observed that KOR mediated inhibition of dopamine release was significantly greater in caudal compared with rostral NAc core with no significant sex differences observed. These data suggest that KORs regulate dopamine release differentially along the rostro-caudal axis, providing a new axis on which to examine the process by which the KOR/dopamine system controls reward encoding.
serovar Heidelberg is currently the 12th most common serovar of
causing salmonellosis in the United States and results in twice the average incidence of blood infections caused by nontyphoidal ...salmonellae. Multiple outbreaks of salmonellosis caused by
Heidelberg resulted from the same poultry processor, which infected 634 people during 2013 and 2014. The hospitalization and invasive illness rates were 38% and 15%, respectively. We hypothesized that the outbreak strains of
Heidelberg had enhanced stress tolerance and virulence capabilities. We sourced nine food isolates collected during the outbreak investigation and three reference isolates to assess their tolerance to heat and sanitizers, ability to attach to abiotic surfaces, and invasiveness
We performed RNA sequencing on three isolates (two outbreak-associated isolates and a reference
Heidelberg strain) with various levels of heat tolerance to gain insight into the mechanism behind the isolates' enhanced heat tolerance. We also performed genomic analyses to determine the genetic relationships among the outbreak isolates. Ultimately, we determined that (i) six
Heidelberg isolates associated with the foodborne outbreak had enhanced heat tolerance, (ii) one outbreak isolate with enhanced heat tolerance also had an enhanced biofilm-forming ability under stressful conditions, (iii) exposure to heat stress increased the expression of
Heidelberg multidrug efflux and virulence genes, and (iv) outbreak-associated isolates were likely transcriptionally primed to better survive processing stresses and, potentially, to cause illness.
This study provides a deep analysis of the intrinsic stress tolerance and virulence capabilities of
Heidelberg that may have contributed to the length and severity of a recent salmonellosis outbreak. Additionally, this study provides a comprehensive analysis of the transcriptomic response of
strains to heat stress conditions and compares baseline stationary-phase gene expression among outbreak- and non-outbreak-associated
Heidelberg isolates. These data can be used in assay development to screen isolates for stress tolerance and subsequent survival. This study adds to our understanding of the strains associated with the outbreak and informs ongoing regulatory discussions on
in poultry.
Disinfectant towelettes are commonly used for surface disinfection to prevent health care–associated infections; however, there is limited consensus as to whether a surface needs to remain wet for ...the full label contact time after the disinfectant towelette has been used in order for complete efficacy to be achieved. The purpose of this study was to quantify the effect of contact time, including times before and after a product dries, on bactericidal efficacy of 6 towelette products registered by the Environmental Protection Agency .
Six disinfectant towelette products were tested at varying contact times, including defined label contact times. Quantitative Environmental Protection Agency MB-33-00 was used to measure disinfectant efficacy against Staphylococcus aureus on Formica. Complete dry time for each disinfectant was measured gravimetrically.
There were significant differences in dry times among the towelette products; contact time did not have a significant effect on bactericidal efficacy. There was no longitudinal effect when a disinfectant's contact time was greater than defined label contact time, irrespective of whether the product was wet or dry on the surface.
Overall, bactericidal efficacy varied by towelette product tested and surface area wiped. Wiping larger surface areas may lead to decreased bactericidal efficacy but is product dependent.
There was no additional bactericidal effect after a product dried, indicating that extended contact times beyond when the product dries will not enhance disinfection.
Depression is a highly prevalent psychiatric disorder, impacting females at a rate roughly twice that of males. This disparity has become the focus of many studies which are working to determine if ...there are environmental or biological underpinnings to depression pathology. The biology of depression is not well understood, but experts agree that a key neurotransmitter of interest is serotonin. Most research on basic serotonin neurochemistry, by us and others, has predominantly focused on male models. Thus, it is now critical to include female models to decipher possible fundamental differences between the sexes that may underlie this disorder. In this paper, we seek to determine any such differences using fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption voltammetry. These techniques allow us to probe the serotonergic system
measurement of evoked and ambient serotonin at carbon fiber microelectrodes (CFMs). Our data reveal no statistical differences, in the hippocampus, in female serotonin chemistry during the different stages of the estrous cycle compared to the mean female response. Furthermore, no difference was observed in evoked serotonin release and reuptake, nor ambient extracellular serotonin levels between male and female mice. We applied a previously developed mathematical model that fits our serotonin signals as a function of several synaptic processes that control the extracellular levels of this transmitter. We used the model to study potential system differences between males and females. One hypothesis brought fourth, that female mice exhibit tighter autoreceptor control of serotonin, is validated
literature and methiothepin challenge. We postulate that this tight regulation may act as a control mechanism against changes in the serotonin signal mediated by estrogen spikes. Importantly, this safety mechanism has no consequence for acutely administered escitalopram's (ESCIT's) ability to increase extracellular serotonin between the sexes. This work demonstrates little fundamental differences in
hippocampal serotonin between the sexes, bar control mechanisms in female mice that can be observed under extraneous circumstances. We thus highlight the importance of considering sex as a biological factor in determining pharmacodynamics for personalized medical treatments that involve targeting serotonin receptors.
Transmission of healthcare-associated infections caused by antibiotic- and multi-drug resistant (MDR) pathogens (e.g. Methicillin-resistant
(MRSA),
) are a major concern in patient care facilities. ...Disinfectant usage is critical to control and prevent pathogen transmission, yet the relationships among strain, disinfectant type, contact time, and concentration are not well-characterized. We hypothesized that there would be significant differences in disinfectant efficacy among clinically relevant strains under off-label disinfectant conditions, but there would be less no differences among at registered label use concentrations and contact times. The purpose of this study was to quantify the effect of disinfectant concentration and contact time on the bactericidal efficacy of clinically relevant strains of
and
.
Accelerated hydrogen peroxide (AHP), quaternary ammonium compounds (Quat), and sodium hypochlorite were tested at label and reduced contact times and concentrations against four MDR
strains and four MRSA strains. Quantitative EPA method MB-25-02 was used to measure disinfectant efficacy reported as log
reduction.
Both off-label disinfectant concentrations and contact times significantly affected efficacy of all disinfectants tested. Bactericidal efficacy varied among MRSA and
strains.
The quantitative disinfectant efficacy method used highlights the inter-strain variability that exists within a bacterial species. It also underscores the need for a disinfectant validation method that takes these variances into account.
The objective of this study was to evaluate the extent and potential mechanisms of early onset surface damage from simulated wiping typical of six-months of routine disinfection and to assess the ...subsequent microbial risk of surfaces damaged by disinfectants.
Eight common material surfaces were exposed to three disinfectants and a neutral cleaner (neutral cleaner, quaternary ammonium, hydrogen peroxide, sodium hypochlorite) in accelerated aging tests to simulate a long-term disinfection routine. Materials were also immersed in dilute and concentrated chemical solutions to induce surface damage. Surfaces were chemically and physically characterized to determine extent of surface damage. Bactericidal efficacy testing was performed on the Quat-based disinfectant using a modified version of EPA standard operating procedure MB-25-02.
The wiping protocol increased surface roughness for some material surfaces due to mechanical abrasion of the wiping cloth. The increased roughness did not correlate with changes in bactericidal efficacy. Chemical damage was observed for some surface-disinfectant combinations. The greatest observed effects from disinfectant exposure was in changes in wettability or water contact angle.
Early onset surface damage was observed in chemical and physical characterization methods. These high-throughput material measurement methods were effective at assessing nanoscale disinfectant-surface compatibility which may go undetected though routine macroscale testing.
Disinfectant products are often used on environmental surfaces (e.g. countertops, patient beds) and patient care equipment in healthcare facilities to help prevent the transmission of ...healthcare-associated infections. Ready-to-use (RTU) disinfectants in the form of pre-wetted towelettes are increasingly popular among healthcare facilities. Currently, the EPA does not require disinfectant manufacturers to include a recommended maximum surface area per towelette on their product labels. The objective of this study was to investigate the efficacy of disinfectant towelette products on a hard non-porous surface across different coverage areas using a quantitative EPA method. We hypothesized that there would be significant differences in the efficacy of disinfectant towelette products, and that the greater surface area(s) wiped would result in reduced bactericidal efficacy.
This study tested ten disinfectant towelette products against
strain ATCC CRM-6538 and
strain ATCC 15442 on Formica surfaces. Defined surface areas were wiped and the towelette weighed before and after wiping to determine the amount of liquid released. Bactericidal efficacy testing was also performed after wiping following standard EPA protocols.
We found that disinfectant product, area of surface wiped, and strain impacted the bactericidal efficacy achieved. Disinfectant product type and area of surface wiped significantly impacted the percent of liquid released per ft
from the towelette.
Overall, bactericidal efficacy varied by towelette product, surface area wiped, and strain. This study also found that wiping larger surface areas may lead to decreased bactericidal efficacy. Further research is needed to test its implication.
Mesolimbic nicotinic acetylcholine receptor (nAChRs) activation is necessary for nicotine reinforcement behavior, but it is unknown whether selective activation of nAChRs in the dopamine (DA) reward ...pathway is sufficient to support nicotine reinforcement. In this study, we tested the hypothesis that activation of β2-containing (β2*) nAChRs on VTA neurons is sufficient for intravenous nicotine self-administration (SA). We expressed β2 nAChR subunits with enhanced sensitivity to nicotine (referred to as β2Leu9'Ser) in the VTA of male Sprague Dawley (SD) rats, enabling very low concentrations of nicotine to selectively activate β2* nAChRs on transduced neurons. Rats expressing β2Leu9'Ser subunits acquired nicotine SA at 1.5 μg/kg/infusion, a dose too low to support acquisition in control rats. Saline substitution extinguished responding for 1.5 μg/kg/inf, verifying that this dose was reinforcing. β2Leu9'Ser nAChRs also supported acquisition at the typical training dose in rats (30 μg/kg/inf) and reducing the dose to 1.5 μg/kg/inf caused a significant increase in the rate of nicotine SA. Viral expression of β2Leu9'Ser subunits only in VTA DA neurons (via TH-Cre rats) also enabled acquisition of nicotine SA at 1.5 μg/kg/inf, and saline substitution significantly attenuated responding. Next, we examined electrically-evoked DA release in slices from β2Leu9'Ser rats with a history of nicotine SA. Single-pulse evoked DA release and DA uptake rate were reduced in β2Leu9'Ser NAc slices, but relative increases in DA following a train of stimuli were preserved. These results are the first to report that β2* nAChR activation on VTA neurons is sufficient for nicotine reinforcement in rats.
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