Global stress response in Pseudomonas aeruginosa upon malonate utilization.

Versatility in carbon source utilization assists Pseudomonas aeruginosa in its adaptation to various niches. Recently, we characterized the role of malonate, an understudied carbon source, in quorum sensing regulation, antibiotic resistance, and virulence factor production in P. aeruginosa . These results indicate that global responses to malonate metabolism remain to be uncovered. We leveraged a publicly available metabolomic dataset on human airway and found malonate to be as abundant as glycerol, a common airway metabolite and carbon source for P. aeruginosa . Here, we explored and compared adaptations of P. aeruginosa UCBPP-PA14 (PA14) in response to malonate or glycerol as a sole carbon source using transcriptomics and phenotypic assays. Malonate utilization activated glyoxylate and methylcitrate cycles and induced several stress responses, including oxidative, anaerobic, and metal stress responses associated with increases in intracellular aluminum and strontium. Some induced genes were required for optimal growth of P. aeruginosa in malonate. To assess the conservation of malonate-associated responses among P. aeruginosa strains, we compared our findings in strain PA14 with other lab strains and cystic fibrosis isolates of P. aeruginosa . Most strains grew on malonate as a sole carbon source as efficiently as or better than glycerol. While not all responses to malonate were conserved among strains, formation of biomineralized biofilm-like aggregates, increased tolerance to kanamycin, and increased susceptibility to norfloxacin were the most frequently observed phenotypes. Our findings reveal global remodeling of P. aeruginosa gene expression during its growth on malonate as a sole carbon source that is accompanied by several important phenotypic changes. These findings add to accumulating literature highlighting the role of different carbon sources in the physiology of P. aeruginosa and its niche adaptation. Importance: Pseudomonas aeruginosa is a notorious pathogen that causes local and systemic infections in immunocompromised individuals. Different carbon sources can uniquely modulate metabolic and virulence pathways in P. aeruginosa , highlighting the importance of the environment that the pathogen occupies. In this work, we used a combination of transcriptomic analysis and phenotypic assays to determine how malonate utilization impacts P. aeruginosa, as recent evidence indicates this carbon source may be relevant to certain niches associated within the human host. We found that malonate utilization can induce global stress responses, alter metabolic circuits, and influence various phenotypes of P. aeruginosa that could influence host colonization. Investigating the metabolism of malonate provides insight into P. aeruginosa adaptations to specific niches where this substrate is abundant, and how it can be leveraged in the development of much-needed antimicrobial agents or identification of new therapeutic targets of this difficult-to-eradicate pathogen.

Effect of Virtual Simulation on Nurse Residents' Prioritization and Delegation Skills: A Pilot Study.

Data indicate a widening academic-practice gap. Utilizing a single-group pre-post interventional design, the purpose of this project was to determine if repeated participation in Sentinel U Patient Management and Delegation virtual simulations influenced new graduate nurses' prioritization and delegation. Increased confidence in ability to complete patient care assignments on time and transferability of learning outcomes to practice were identified. There may be value in nurses receiving virtual simulations within their residency program to close the academic-practice gap.

Development of a Polymicrobial Checkerboard Assay as a Tool for Determining Combinatorial Antibiotic Effectiveness in Polymicrobial Communities.

The checkerboard assay is a well-established tool used to determine the antimicrobial effects of two compounds in combination. Usually, data collected from the checkerboard assay use visible turbidity and optical density as a readout. While helpful in traditional checkerboard assays, these measurements become less useful in a polymicrobial context as they do not enable assessment of the drug effects on the individual members of the community. The methodology described herein allows for the determination of cell viability through selective and differential plating of each individual species in a community while retaining much of the high-throughput nature of a turbidity-based analysis and requiring no specialized equipment. This methodology further improves turbidity-based measurements by providing a distinction between bacteriostatic versus bactericidal concentrations of antibiotics. Herein, we use this method to demonstrate that the clinically used antibiotic combination of ceftazidime and gentamicin works synergistically against Pseudomonas aeruginosa in monoculture but antagonistically in a polymicrobial culture also containing Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis, highlighting the fundamental importance of this methodology in improving clinical practices. We propose that this method could be implemented in clinical microbiology laboratories with minimal impact on the overall time for diagnosis.

Partner Emotional Support and Child Problem Behaviors: The Indirect Role of Harsh Parenting for Young Mothers and Their Children.

Emotionally supportive partners promote the well-being of teenage mothers and their children as they navigate sensitive developmental periods. Yet, having focused on young parents' relationship dissolution, we know very little about benefits of partner supportiveness for the development of children's psychological adjustment or processes that may explain this association. Using five waves of Fragile Families and Child Well-being Study data (N = 771) and parallel process latent growth curve modeling, this study tested whether trajectories of partner supportiveness (measured by maternal reports of fathers' emotional support) directly mitigated trajectories of children's externalizing and internalizing problem behaviors (measured by maternal reports of problem behaviors) and/or whether such effects were indirectly linked through lower levels of maternal harsh parenting (measured by observational ratings of mother-child interactions). Results suggest that higher levels of partner supportiveness at birth were associated with child externalizing and internalizing trajectories that started at lower levels and demonstrated slower improvements across time. Lower starting levels of maternal harsh parenting when children were three years old partially explained associations between partner supportiveness at birth and lower levels of child externalizing symptoms at age three. Lessons gleaned from this study are discussed in context of young families' strengths and applied to practice-based settings.

Las personas que apoyan emocionalmente a su pareja promueven el bienestar de las madres adolescentes y sus hijos mientras transitan periodos sensibles del desarrollo. Sin embargo, al habernos centrado en la disolución de las relaciones de padres jóvenes, sabemos muy poco acerca de los beneficios que aporta el apoyo de las parejas al desarrollo de la adaptación o de los procesos psicológicos de los niños, y que podrían explicar esta asociación. Utilizando cinco tandas de datos (N = 771) del estudio Familias Frágiles y el Bienestar Infantil (Fragile Families and Child Well-Being Study) y el modelo de la curva de crecimiento latente de proceso paralelo, este estudio evaluó si las trayectorias de apoyo de las parejas (medidas por informes maternos del apoyo emocional de los padres) mitigaron directamente las trayectorias de las conductas problemáticas de exteriorización y de interiorización de los niños (medidas por informes maternos de conductas problemáticas) o si estos efectos estuvieron asociados indirectamente mediante niveles más bajos de crianza materna rigurosa (medida por las calificaciones observacionales de las interacciones entre madre e hijo). Los resultados sugieren que los niveles más altos de apoyo de la pareja en el nacimiento estuvieron asociados con trayectorias de exteriorización y de interiorización del niño que comenzaron a niveles más bajos y demostraron mejoras más lentas con el tiempo. Los niveles iniciales más bajos de crianza materna rigurosa en la tercera tanda explicaron parcialmente las asociaciones entre el apoyo de la pareja en el nacimiento y los niveles más bajos de síntomas de exteriorización de los niños cuando los niños tenían tres años. Se comentan las enseñanzas obtenidas de este estudio en el contexto de los puntos fuertes de las familias jóvenes, y se aplican a entornos de práctica.

Clinical Implications of Polymicrobial Synergism Effects on Antimicrobial Susceptibility.

With the development of next generation sequencing technologies in recent years, it has been demonstrated that many human infectious processes, including chronic wounds, cystic fibrosis, and otitis media, are associated with a polymicrobial burden. Research has also demonstrated that polymicrobial infections tend to be associated with treatment failure and worse patient prognoses. Despite the importance of the polymicrobial nature of many infection states, the current clinical standard for determining antimicrobial susceptibility in the clinical laboratory is exclusively performed on unimicrobial suspensions. There is a growing body of research demonstrating that microorganisms in a polymicrobial environment can synergize their activities associated with a variety of outcomes, including changes to their antimicrobial susceptibility through both resistance and tolerance mechanisms. This review highlights the current body of work describing polymicrobial synergism, both inter- and intra-kingdom, impacting antimicrobial susceptibility. Given the importance of polymicrobial synergism in the clinical environment, a new system of determining antimicrobial susceptibility from polymicrobial infections may significantly impact patient treatment and outcomes.

Cyanine Nanocages Activated by Near-Infrared Light for the Targeted Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a common and prevalent condition that affects large numbers of people across a range of ages. Individuals engaging in physical activities and victims of accidents are at a higher risk for TBI. There is a lack of available treatment specifically for TBI. Given the difficulty to determine its precise location in the brain, TBI remains difficult to fully diagnose or treat. Herein, we disclose a novel strategy for directing therapeutic agents to TBI sites, without the need to determine the precise location of the TBI activity in the brain. This novel approach is based on the use of a cyanine dye nanocage carrying Gabapentin, a known TBI therapeutic agent. Upon exposure of the cyanine nanocage to near-infrared light, the local release of Gabapentin is triggered, selectively at the TBI-affected site.

Cyanine Nanocage Activated by Near-IR Light for the Targeted Delivery of Cyclosporine A to Traumatic Brain Injury Sites.

More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.

Measurement of parental executive function in early childhood settings: Instrument reliability and validity in community-led research projects.

A growing number of early childhood (EC) parenting programs target adult executive function (EF) to build responsive parenting behaviors and to promote positive child development. Although measurement of EF is well understood in academic research, little work has examined EF measurement in community settings. The present study examined psychometric properties of the Behavior Rating Inventory of Executive Function-Adult Version among 203 parents whose children were enrolled in EC programs serving under-resourced communities. We calculated Cronbach's α and mean-item correlations to test internal consistency reliability. To test factor structure, we conducted exploratory factor analysis and confirmatory factor analyses. Results suggest adequate internal consistency and that factor structures, beyond the original proposed, are appropriate for our community sample. Together, findings indicate that self-report measures of adult EF may perform differently for families experiencing adversity, raising questions about the acceptability of clinical EF tools in in underserved communities.

Human Factors Associated With the Use of Manual Bulb Suction Devices.

BACKGROUND: Manual bulb suction is commonly used to promote naso-oropharyngeal airway clearance. Human factors of hand placement (radial vs. axial) and relative negative pressure generated are not known. This study is the first step in developing clinical guidelines for safe and effective mechanical use of manual bulb suction to reduce and prevent upper airway injury. OBJECTIVE: The aim of this study was to determine the negative pressure generated when a 2-oz. manual bulb suction device is compressed and released, and hand placement is either in a radial or axial position. METHODS: A total of 87 subjects were recruited using a convenience sampling method to identify hand placement and predicted negative pressures emitted during bulb compression and release. A pressure transmitter system was developed and tested with 666 negative pressure measurements to verify internal consistency and reliability in predicting negative pressure. RESULTS: The majority of subjects compressed the bulb radially (55%). Suction pressures ranged from -42 mm Hg to -81 mm Hg, with a standard deviation of -7 mm Hg. Males tended to have statistically significant higher negative pressures (U = 170, p = .021) when radially compressing the bulb. Females generated statistically significant higher negatives pressures (U = 71.50, p = .001) when axially compressing the bulb. DISCUSSION: A 2-oz. manual bulb suction device creates negative pressures less than 85 mm Hg when using moderate compression regardless of hand placement (radial or axial placement). Further studies are needed to explore additional healthcare provider and patient human factor variables related to the mechanical use of manual bulb suction.

Practical considerations for transitioning early childhood interventions to scale: lessons from the Saving Brains portfolio.

Small pilot studies of young children have frequently shown promise, but very few have been successfully scaled to the regional or national levels. How can we ensure that these promising approaches move from a suite of pilots to full-scale implementation that can deliver sustainable impact for hundreds of millions of children? To elucidate concrete lessons learned and suggestions on accelerating the transition to impact at scale, we reviewed the Saving Brains portfolio to better understand three points: (1) the extent to which useful signals of impact could be extracted from data at the seed phase, (2) the ways in which innovators (project leaders) were approaching human resource challenges critical for scaling, and (3) the multisector diversity of the portfolio and the way innovators entered partnerships. The findings suggest key considerations for transitioning early childhood development interventions to scale and sustainability: strong entrepreneurial leadership, rigorous measurement and active use of data in support of adaptive learning, and champions acting at subnational levels. Together, these can enable flexible, iterative learning that can make the scaling process an opportunity to increase the level of benefit each child receives from an intervention.