Zinc Prevents Sickness Behavior Induced by Lipopolysaccharides after a Stress Challenge in Rats

Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS), an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α), corticosterone, and brain-derived neurotrophic factor (BDNF) plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.     

Occupancy Modeling for Improved Accuracy and Understanding of Pathogen Prevalence and Dynamics

Most pathogen detection tests are imperfect, with a sensitivity < 100%, thereby resulting in the potential for a false negative, where a pathogen is present but not detected. False negatives in a sample inflate the number of non-detections, negatively biasing estimates of pathogen prevalence. Histological examination of tissues as a diagnostic test can be advantageous as multiple pathogens can be examined and providing important information on associated pathological changes to the host. However, it is usually less sensitive than molecular or microbiological tests for specific pathogens. Our study objectives were to 1) develop a hierarchical occupancy model to examine pathogen prevalence in spring Chinook salmon Oncorhynchus tshawytscha and their distribution among host tissues 2) use the model to estimate pathogen-specific test sensitivities and infection rates, and 3) illustrate the effect of using replicate within host sampling on sample sizes required to detect a pathogen. We examined histological sections of replicate tissue samples from spring Chinook salmon O. tshawytscha collected after spawning for common pathogens seen in this population: Apophallus/echinostome metacercariae, Parvicapsula minibicornis, Nanophyetus salmincola/ metacercariae, and Renibacterium salmoninarum. A hierarchical occupancy model was developed to estimate pathogen and tissue-specific test sensitivities and unbiased estimation of host- and organ-level infection rates. Model estimated sensitivities and host- and organ-level infections rates varied among pathogens and model estimated infection rate was higher than prevalence unadjusted for test sensitivity, confirming that prevalence unadjusted for test sensitivity was negatively biased. The modeling approach provided an analytical approach for using hierarchically structured pathogen detection data from lower sensitivity diagnostic tests, such as histology, to obtain unbiased pathogen prevalence estimates with associated uncertainties. Accounting for test sensitivity using within host replicate samples also required fewer individual fish to be sampled. This approach is useful for evaluating pathogen or microbe community dynamics when test sensitivity is <100%.     

Preclinical Assessment of Adjunctive tPA and DNase for Peritoneal Dialysis Associated Peritonitis

A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.     

Finite element analysis of different loading conditions for implant-supported overdentures supported by conventional or mini implants

The effect of implants’ number on overdenture stability and stress distribution in edentulous mandible, implants and overdenture was numerically investigated for implant-supported overdentures. Three models were constructed. Overdentures were connected to implants by means of ball head abutments and rubber ring. In model 1, the overdenture was retained by two conventional implants; in model 2, by four conventional implants; and in model 3, by five mini implants. The overdenture was subjected to a symmetrical load at an angle of 20 degrees to the overdenture at the canine regions and vertically at the first molars. Four different loading conditions with two total forces (120, 300 N) were considered for the numerical analysis. The overdenture displacement was about 2.2 times higher when five mini implants were used rather than four conventional implants. The lowest stress in bone bed was observed with four conventional implants. Stresses in bone were reduced by 61% in model 2 and by 6% in model 3 in comparison to model 1. The highest stress was observed with five mini implants. Stresses in implants were reduced by 76% in model 2 and 89% increased in model 3 compared to model 1. The highest implant displacement was observed with five mini implants. Implant displacements were reduced by 29% in model 2, and increased by 273% in model 3 compared to model 1. Conventional implants proved better stability for overdenture than mini implants. Regardless the type and number of implants, the stress within the bone and implants are below the critical limits.     

Preventing Ultimate Harm as the Justification for Biomoral Modification

Most advocates of biogenetic modification hope to amplify existing human traits in humans in order to increase the value of such traits as intelligence and resistance to disease. These advocates defend such enhancements as beneficial for the affected parties. By contrast, some commentators recommend certain biogenetic modifications to serve social goals. As Ingmar Persson and Julian Savulescu see things, human moral psychology is deficient relative to the most important risks facing humanity as a whole, including the prospect of Ultimate Harm, the point at which worthwhile life is forever impossible on the planet. These risks can be mitigated, they say, by enhancing moral psychology in novel ways. Persson and Savulescu argue that some parents should modify the underlying biogenetics of their children's moral psychology, if such measures were safe and effective, but they admit these interventions may not decouple humanity from Ultimate Harm. Neither are these modifications the only options, they concede, for addressing risks to humanity. Even with these concessions, saving humanity from itself is a fairly poor reason to modify the moral psychology of children. In most ways, adults would be better candidates, morally speaking, for modifications of psychology. Even then, there is no direct link between morally enhanced human beings and the hoped‐for effect of better protection from Ultimate Harm. Asserting a general duty of all to contribute to the avoidance of Ultimate Harm is a better moral strategy than intervening in the moral psychology of some, even though meeting that duty may involve substantial interference with the free exercise of one's interests.     

Concomitant Information in Competing Risk Analysis

A competing risk model, accommodating both Type I censoring and random withdrawals, is expanded to incorporate concomitant information by allowing the parameters of the underlying distributions to be a linear function of two covariates. The model is developed for two competing risks, one following a Weibull distribution and the other a Rayleigh distribution, and random withdrawals following a Weibull distribution. A method is developed for testing the equality of the coefficients for a given covariate for each of the competing risks using MLE'.     

Localisation of RFLPs of the medium chain acyl-CoA dehydrogenase gene

Summary Six restriction fragment length polymorphisms (RFLPs) of the gene are described. Three of these are in linkage disequilibrium. Hybridisation with sub-probes allowed localisation of the RFLPs to different regions of the gene.     

Genetic exchange between kingdoms.

Bacterial conjugation with two evolutionarily divergent yeasts has been observed in the laboratory. Whether such trans-kingdom conjugation events, other than the well known Agrobacterium-plant cell interaction, actually occur in nature is not known. However, a few putative events have recently been uncovered by gene (or protein) sequence analysis, suggesting that horizontal gene transfer between phylogenetic kingdoms may be a real phenomenon.