Enhanced Skin Incisional Wound Healing With Intracellular ATP Delivery via Macrophage Proliferation and Direct Collagen Production.

This study sought to use a newly developed intracellular ATP delivery to enhance incisional wound healing to reduce surgical wound dehiscence and to explore possible mechanism for this effect. Thirty-five adult New Zealand white rabbits were used. Skin incisions were made on the back and closed. ATP-vesicles were mixed with a neutral cream for one side of the wounds while the neutral cream alone was used on the other side of the wounds. Laser speckle contrast imaging (LSCI), biomechanical, histological, and immunohistochemical analyses were performed 7 and 14 days after surgery, and macrophage culture was used to test the enhanced collagen production ability. Among them, 10 were used for wound perfusion study and 25 were used for wound biomechanical and histological/immunohistochemical studies. Wound tissue perfusion was reduced after surgery especially in early days. Wound tissue tensile strength, breaking stress, and elasticity were all much higher in the ATP-vesicle treated group than in the cream treated group at days 7 and 14. The healing was complemented by earlier macrophage accumulation, in situ proliferation, followed by direct collagen production. The results were further confirmed by human macrophage culture. It was concluded that intracellular ATP delivery enhanced healing strength of incisional wounds via multiple mechanisms.

Impact of Cognition on Burn Inpatient Rehabilitation Outcomes.

BACKGROUND: A significant proportion of burn injury patients are admitted to inpatient rehabilitation facilities (IRFs). There is increasing interest in the use of functional variables, such as cognition, in predicting IRF outcomes. Cognitive impairment is an important cause of disability in the burn injury population, yet its relationship to IRF outcomes has not been studied. OBJECTIVE: To assess how cognitive function affects rehabilitation outcomes in the burn injury population. DESIGN: Retrospective study. SETTING: Inpatient rehabilitation facilities in the United States. PARTICIPANTS: A total of 5347 adults admitted to an IRF with burn injury between 2002 and 2011. METHODS OR INTERVENTIONS: Multivariable regression was used to model rehabilitation outcome measures, using the cognitive domain of the Functional Independence Measure (FIM) instrument as the independent variable and controlling for demographic, medical, and facility covariates. MAIN OUTCOME MEASUREMENTS: FIM total gain, readmission to an acute care setting at any time during inpatient rehabilitation, readmission to an acute care setting in the first 3 days of IRF admission, rate of discharge to the community setting, and length of stay efficiency. RESULTS: Cognitive FIM total at admission was a significant predictor of FIM total gain, length of stay efficiency, and acute readmission at 3 days (P < .05). Cognitive FIM total scores did not have an impact on acute care readmission rate or discharge to the community setting. CONCLUSIONS: Cognitive status may be an important predictor of rehabilitation outcomes in the burn injury population. Future work is needed to further examine the impact of specific cognitive interventions on rehabilitation outcomes in this population. LEVEL OF EVIDENCE: II.

Protection of Salmonella by ampicillin-resistant Escherichia coli in the presence of otherwise lethal drug concentrations.

Microbial systems have become the preferred testing grounds for experimental work on the evolution of traits that benefit other group members. This work, based on conceptual and theoretical models of frequency-dependent selection within populations, has proven fruitful in terms of understanding the dynamics of group beneficial or 'public goods' traits within species. Here, we expand the scope of microbial work on the evolution of group-beneficial traits to the case of multi-species communities, particularly those that affect human health. We examined whether beta-lactamase-producing Escherichia coli could protect ampicillin-sensitive cohorts of other species, particularly species that could cause human disease. Both beta-lactamase-secreting E. coli and, surprisingly, those engineered to retain it, allowed for survival of a large number of ampicillin-sensitive cohorts of Salmonella enterica serovar Typhimurium, including both laboratory and clinical isolates. The Salmonella survivors, however, remained sensitive to ampicillin when re-plated onto solid medium and there was no evidence of gene transfer. Salmonella survival did not even require direct physical contact with the resistant E. coli. The observed phenomenon appears to involve increased release of beta-lactamase from the E. coli when present with S. enterica. Significantly, these findings imply that resistant E. coli, that are not themselves pathogenic, may be exploited, even when they are normally selfish with respect to other E. coli. Thus, Salmonella can gain protection against antibiotics from E. coli without gene transfer, a phenomenon not previously known. As a consequence, antibiotic-resistant E. coli can play a decisive role in the survival of a species that causes disease and may thereby interfere with successful treatment.

Evolution of altruists and cheaters in near-isogenic populations of Escherichia coli.

Emergence of antibiotic-resistant bacteria threatens the continued efficacy of many critical drugs used to treat serious infections. What if such resistant organisms could also act as altruists and "share" their resistance with sensitive cohorts without any actual genetic exchange? We competed resistant strains that differ solely in their ability to secrete a plasmid-encoded beta-lactamase. Sensitive strains were otherwise isogenic with their resistant counterparts and were either plasmid-free or contained a "Dummy" plasmid of roughly the same size as that of the resistance plasmids. Absent antibiotic selection, plasmid-free sensitive strains outperformed the plasmid-bearing strains. In the presence of ampicillin, the outcome depended on whether the resistant strain secreted its beta-lactamase (Altruist) or retained it (Selfish). In the latter case, only resistant cells survived. When beta-lactamase was secreted, some sensitive cohorts were also provided protection, with the largest fitness increase provided to plasmid-free cells. However, some Altruist strains appeared to be at a disadvantage, as a great deal of their enzyme broke off cells. Thus, additional variables must be considered when designing microbial competition experiments.