Bioelectric Silver-Zinc Dressing Equally Effective to Chlorhexidine in Reducing Skin Bacterial Load in Healthy Volunteers.

PURPOSE: The aim of the present study was to evaluate and compare the effectiveness of the silver-zinc bioelectric dressing as compared with skin preparation with 2% chlorhexidine or 4% chlorhexidine in reducing the bacterial count on the knee. METHODS: Three groups consisting of 48 healthy volunteers were included. Age range was 23 to 54 years old and 60% of participants were male. Each subject had 1 knee serve as the test and the contralateral as the control. The test site was prepared with either 2% chlorhexidine, 4% chlorhexidine, or a silver-zinc bioelectric dressing and after 24 hours skin cultures were taken and examined for bacterial growth. RESULTS: In the 2% chlorhexidine group 23 of 48 unprepped knees had positive cultures, compared with 9 of 48 prepped knees (P = .003; risk reduction, 4.0 times). In the 4% chlorhexidine group 25 of 48 unprepped knees had positive cultures, compared with 14 of 48 prepped knees (P = .027; risk reduction, 2.6 times). In the silver-zinc bioelectric dressing group 29 of 48 unprepped knees had positive cultures, compared with 7 of 48 prepped knees (P < .001; risk reduction, 8.9 times). There was no difference in the positive skin culture rate between the 3 methods. CONCLUSIONS: Application of the silver-zinc bioelectric dressing was equally effective at reducing skin bacterial load when compared with skin preparation with 2% chlorhexidine or 4% chlorhexidine in healthy volunteers. LEVEL OF EVIDENCE: Basic Science - Microbiology. CLINICAL RELEVANCE: The findings of this study indicate that the use of a bioelectric dressing after knee surgery can match the standard of care of preparing the skin with an antiseptic before surgery.

Cecal Ligation and Puncture Results in Long-Term Central Nervous System Myeloid Inflammation.

Survivors of sepsis often experience long-term cognitive and functional decline. Previous studies utilizing lipopolysaccharide injection and cecal ligation and puncture in rodent models of sepsis have demonstrated changes in depressive-like behavior and learning and memory after sepsis, as well as evidence of myeloid inflammation and cytokine expression in the brain, but the long-term course of neuroinflammation after sepsis remains unclear. Here, we utilize cecal ligation and puncture with greater than 80% survival as a model of sepsis. We found that sepsis survivor mice demonstrate deficits in extinction of conditioned fear, but no acquisition of fear conditioning, nearly two months after sepsis. These cognitive changes occur in the absence of neuronal loss or changes in synaptic density in the hippocampus. Sepsis also resulted in infiltration of monocytes and neutrophils into the CNS at least two weeks after sepsis in a CCR2 independent manner. Cellular inflammation is accompanied by long-term expression of pro-inflammatory cytokine and chemokine genes, including TNFα and CCR2 ligands, in whole brain homogenates. Gene expression analysis of microglia revealed that while microglia do express anti-microbial genes and damage-associated molecular pattern molecules of the S100A family of genes at least 2 weeks after sepsis, they do not express the cytokines observed in whole brain homogenates. Our results indicate that in a naturalistic model of infection, sepsis results in long-term neuroinflammation, and that this sustained inflammation is likely due to interactions among multiple cell types, including resident microglia and peripherally derived myeloid cells.

Basal microRNA expression patterns in reward circuitry of selectively bred high-responder and low-responder rats vary by brain region and genotype.

Mental health disorders involving altered reward, emotionality, and anxiety are thought to result from the interaction of individual predisposition (genetic factors) and personal experience (environmental factors), although the mechanisms that contribute to an individual's vulnerability to these disorders remain poorly understood. We used an animal model of individual variation [inbred high-responder/low-responder (bHR-bLR) rodents] known to vary in reward, anxiety, and emotional processing to examine neuroanatomical expression patterns of microRNAs (miRNAs). Laser capture microdissection was used to dissect the prelimbic cortex and the nucleus accumbens core and shell prior to analysis of basal miRNA expression in bHR and bLR male rats. These studies identified 187 miRNAs differentially expressed by genotype in at least one brain region, 10 of which were validated by qPCR. Four of these 10 qPCR-validated miRNAs demonstrated differential expression across multiple brain regions, and all miRNAs with validated differential expression between genotypes had lower expression in bHR animals compared with bLR animals. microRNA (miR)-484 and miR-128a expression differences between the prelimbic cortex of bHR and bLR animals were validated by semiquantitative in situ hybridization. miRNA expression analysis independent of genotype identified 101 miRNAs differentially expressed by brain region, seven of which validated by qPCR. Dnmt3a mRNA, a validated target of miR-29b, varied in a direction opposite that of miR-29b's differential expression between bHR and bLR animals. These data provide evidence that basal central nervous system miRNA expression varies in the bHR-bLR model, implicating microRNAs as potential epigenetic regulators of key neural circuits and individual differences associated with mental health disorders.

Differential regulation of primitive myelopoiesis in the zebrafish by Spi-1/Pu.1 and C/ebp1.

The zebrafish has become a powerful tool for analysis of vertebrate hematopoiesis. Zebrafish, unlike mammals, have a robust primitive myeloid pathway that generates both granulocytes and macrophages. It is not clear how this unique primitive myeloid pathway relates to mammalian definitive hematopoiesis. In this study, we show that the two myeloid subsets can be distinguished using RNA in situ hybridization. Using a morpholino-antisense gene knockdown approach, we have characterized the hematopoietic defects resulting from knockdown of the myeloid transcription factor gene pu.1 and the unique zebrafish gene c/ebp1. Severe reduction of pu.1 resulted in complete loss of primitive macrophage development, with effects on granulocyte development only with maximal knockdown. Reduction of c/ebp1 did not ablate initial macrophage or granulocyte development, but resulted in loss of expression of the secondary granule gene lys C. These data reveal strong functional conservation of pu.1 between zebrafish primitive myelopoiesis and mammalian definitive myelopoiesis. Further, these results are consistent with a conserved role between c/ebp1 and mammalian C/EBPE, whose ortholog in zebrafish has not been identified. These studies validate the examination of zebrafish primitive myeloid development as a model for human myelopoiesis, and form a framework for identification and analysis of myeloid mutants.