Staphylococcus aureus biofilms release leukocidins to elicit extracellular trap formation and evade neutrophil-mediated killing.

Bacterial biofilms efficiently evade immune defenses, greatly complicating the prognosis of chronic infections. How methicillin-resistant Staphylococcus aureus (MRSA) biofilms evade host immune defenses is largely unknown. This study describes some of the major mechanisms required for S. aureus biofilms to evade the innate immune response and provides evidence of key virulence factors required for survival and persistence of bacteria during chronic infections. Neutrophils are the most abundant white blood cells in circulation, playing crucial roles in the control and elimination of bacterial pathogens. Specifically, here we show that, unlike single-celled populations, S. aureus biofilms rapidly skew neutrophils toward neutrophil extracellular trap (NET) formation through the combined activity of leukocidins Panton-Valentine leukocidin and γ-hemolysin AB. By eliciting this response, S. aureus was able to persist, as the antimicrobial activity of released NETs was ineffective at clearing biofilm bacteria. Indeed, these studies suggest that NETs could inadvertently potentiate biofilm infections. Last, chronic infection in a porcine burn wound model clearly demonstrated that leukocidins are required for "NETosis" and facilitate bacterial survival in vivo.

Assessing the Accuracy of Farmers' Nutrient Loss Risk Perceptions.

Use of nutrient management practices to reduce nutrient loss from agriculture and its associated water quality consequences, including hypoxia and eutrophication, is widely encouraged. However, little is known about which factors influence farmers' risk perceptions associated with nutrient loss, and thus possibly influence their decisions to adopt such practices. To determine which factors were associated with relative "accuracy" of nutrient loss-associated risk perceptions, specific farm field management information was used as inputs to a Soil and Water Assessment Tool model of the study watershed to produce water quality outputs for each modeled farm field. This information was paired with farmers' risk perceptions associated with nutrient loss on their farm to assess relative "accuracy" of each farmer's perceptions compared to the rest of the farmers in the study. We then investigated characteristics of the farm and farmer that are associated with comparative "overprediction" and "underprediction" of risk, and found that characteristics of the individual (conservation identity, prior conservation practice adoption, efficacy beliefs, and perceived seriousness of the consequences of nutrient loss) are more important in determining whether farmers are likely to "overpredict" or "underpredict" risk than is the objective (modeled) vulnerability of their land to nutrient loss.

Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

OBJECTIVE: This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless electroceutical dressing (WED) was tested in an established porcine chronic wound polymicrobial biofilm infection model involving inoculation with Pseudomonas aeruginosa PAO1 and Acinetobacter baumannii 19606. BACKGROUND: Bacterial biofilms represent a major wound complication. Resistance of biofilm toward pharmacologic interventions calls for alternative therapeutic strategies. Weak electric field has anti-biofilm properties. We have previously reported the development of WED involving patterned deposition of Ag and Zn on fabric. When moistened, WED generates a weak electric field without any external power supply and can be used as any other disposable dressing. METHODS: WED dressing was applied within 2 hours of wound infection to test its ability to prevent biofilm formation. Alternatively, WED was applied after 7 days of infection to study disruption of established biofilm. Wounds were treated with placebo dressing or WED twice a week for 56 days. RESULTS: Scanning electron microscopy demonstrated that WED prevented and disrupted wound biofilm aggregates. WED accelerated functional wound closure by restoring skin barrier function. WED blunted biofilm-induced expression of (1) P. aeruginosa quorum sensing mvfR (pqsR), rhlR and lasR genes, and (2) miR-9 and silencing of E-cadherin. E-cadherin is critically required for skin barrier function. Furthermore, WED rescued against biofilm-induced persistent inflammation by circumventing nuclear factor kappa B activation and its downstream cytokine responses. CONCLUSION: This is the first pre-clinical porcine mechanistic study to recognize the potential of electroceuticals as an effective platform technology to combat wound biofilm infection.

Connecting soil characteristics to edge-of-field water quality in Ohio.

Soil health and water quality improvement are major goals of sustainable agricultural management systems, yet the connections between soil health and water quality impacts remain unclear. In this study we conducted an initial exploratory assessment of the relationships between soil chemical, physical, and biological properties and edge-of-field water quality across a network of 40 fields in Ohio, USA. Discharge, dissolved reactive P (DRP), total P (TP), and nitrate (NO3 ) losses associated with precipitation events via surface runoff and tile drainage were monitored. Agronomic soil tests and a suite of soil health indicators were measured, then predictive relationships between the field average soil properties and tile drainage and surface runoff discharge and DRP, TP, and nitrate loads were explored with random forest and multiple linear regression approaches. Among the soil health indicators, water extractable C and N were consistently found to be positively related to tile nitrate loads, but other soil health indicators had little or inconsistent importance for water quality impacts. Several other soil properties were important predictors, particularly soil P pools for surface and tile DRP and TP losses as well as Mehlich-3 (M3) extractable Fe and Al for surface and tile discharge. Thus, we did not observe strong evidence that soil health was associated with improved edge-of-field water quality across the edge-of-field monitoring network. However, additional studies are needed to definitively test the relationships between a broader array of soil health metrics and water quality outcomes.

L-Citrulline supplementation attenuates aortic pulse pressure and wave reflection responses to cold stress in older adults.

BACKGROUND AND AIMS: Augmented aortic systolic blood pressure (SBP) and wave reflection via sympathetic-mediated vasoconstriction elevates the risk for adverse cardiovascular events in older adults. L-citrulline (L-CIT) supplementation has shown to reduce aortic SBP and pulse pressure (PP) responses to cold pressor test (CPT) induced sympathoactivation in young men. The aim of this study was to elucidate the efficacy of L-CIT supplementation to attenuate aortic hemodynamic responses to CPT in older adults. METHODS AND RESULTS: Sixteen older adults were randomly assigned to placebo or L-CIT (6 g/day) for 14-days in a crossover, double-blind, placebo-controlled design. Brachial SBP and aortic SBP, PP, augmented pressure (AP), augmentation index standardized at 75 bpm (AIx@75), and pressure of the forward (Pf) and reflected (Pb) waves were evaluated at rest and during CPT pre- and post-intervention. Although no hemodynamic changes at rest, brachial SBP (Δ-12 ± 18 vs. Δ4 ± 14 mmHg; P = 0.008) and aortic SBP (Δ-10 ± 14 vs. Δ4 ± 12 mmHg; P = 0.005), PP (Δ-10 ± 12 vs. Δ4 ± 11 mmHg; P = 0.002), AP (Δ-4 ± 4 vs. Δ2 ± 7 mmHg; P = 0.004), AIx@75 (Δ-3.2 ± 7.2 vs. Δ2.2 ± 6.9%; P = 0.038), Pf (Δ-6 ± 10 vs. Δ3 ± 9 mmHg; P = 0.019), and Pb (Δ-4 ± 6 vs. Δ2 ± 6 mmHg; P = 0.008) responses to the CPT were significantly attenuated following L-CIT supplementation vs. placebo. CONCLUSIONS: L-CIT supplementation attenuated aortic pulsatile pressure and pressure wave reflection responses to CPT in older adults, providing possible cardioprotection during cold-induced sympathoactivation in older adults.

Impact of pharmacy services on cystic fibrosis medication adherence.

OBJECTIVES: The purpose of this study is to characterize the impact of pharmacy services on medication adherence and hospitalizations for pediatric cystic fibrosis (CF) patients. METHODS: A retrospective health insurance claims analysis and patient medical charts review from January 1, 2014 to December 31, 2016 of patients from the Pediatric Intermountain CF Center was performed. Adherence to dornase alfa and hospital admissions for pulmonary exacerbations pre and post the implementation of an integrated pharmacy team were reviewed. Dornase alfa adherence was measured by the medication possession ratio (MPR) both monthly and yearly. RESULTS: Fifty-four patients met inclusion criteria. The mean dornase alfa yearly MPR improved from 0.75 (2014) to 0.92 (2016). Patients were 2.8 times more likely to be adherent to dornase alfa when followed by integrated pharmacy team model (P < 0.001), and 2.4 times more likely to be adherent when followed by a dedicated CF clinic pharmacist only (P = 0.001). CONCLUSION: The study demonstrated that pharmacy services improved adherence to dornase alfa.

Surviving and Thriving Your First Year in Private Practice.

Taking the leap toward a career as a private practice owner is daunting. When in the initial stages of starting a private practice, I searched for current advice from an audiologist who had recently confronted the same challenges I was about to face. Because of the limited information available, I documented my process in hopes of providing an overview of my startup experience to help others. Included is a timeline of startup tasks and a sample budget to use as a reference. In this chapter, I share my experiences, both the positives and the negatives, and tips with the goal of helping you survive and thrive in your first year in private practice.