Quinoline Compounds Targeting the c-Ring of ATP Synthase Inhibit Drug-Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA) is a Gram-negative, biofilm-forming bacterium and an opportunistic pathogen. The growing drug resistance of PA is a serious threat that necessitates the discovery of novel antibiotics, ideally with previously underexplored mechanisms of action. Due to their central role in cell metabolism, bacterial bioenergetic processes are of increasing interest as drug targets, especially with the success of the ATP synthase inhibitor bedaquiline to treat drug-resistant tuberculosis. Like Mycobacterium tuberculosis, PA requires F1Fo ATP synthase for growth, even under anaerobic conditions, making the PA ATP synthase an ideal drug target for the treatment of drug-resistant infection. In previous work, we conducted an initial screen for quinoline compounds that inhibit ATP synthesis activity in PA. In the present study, we report additional quinoline derivatives, including one with increased potency against PA ATP synthase in vitro and antibacterial activity against drug-resistant PA. Moreover, by expressing the PA ATP synthase in Escherichia coli, we show that mutations in the H+ binding site on the membrane-embedded rotor ring alter inhibition by the reported quinoline compounds. Identification of a potent inhibitor and its probable binding site on ATP synthase enables further development of promising quinoline derivatives into a viable treatment for drug-resistant PA infection.

Genetic Architecture of Salt Tolerance in Cowpea (Vigna unguiculata (L.) Walp.) at Seedling Stage Using a Whole Genome Resequencing Approach.

Cowpea (Vigna unguiculata (L.) Walp.) is a diploid legume crop used for human consumption, feed for livestock, and cover crops. Earlier reports have shown that salinity has been a growing threat to cowpea cultivation. The objectives of this study were to conduct a genome-wide association study (GWAS) to identify SNP markers and to investigate candidate genes for salt tolerance in cowpea. A total of 331 cowpea genotypes were evaluated for salt tolerance by supplying a solution of 200 mM NaCl in our previous work. The cowpea panel was genotyped using a whole genome resequencing approach, generating 14,465,516 SNPs. Moreover, 5,884,299 SNPs were used after SNP filtering. GWAS was conducted on a total of 296 cowpea genotypes that have high-quality SNPs. BLINK was used for conducting GWAS. Results showed (1) a strong GWAS peak on an 890-bk region of chromosome 2 for leaf SPAD chlorophyll under salt stress in cowpea and harboring a significant cluster of nicotinamide adenine dinucleotide (NAD) dependent epimerase/dehydratase genes such as Vigun02g128900.1, Vigun02g129000.1, Vigun02g129100.1, Vigun02g129200.1, and Vigun02g129500.1; (2) two GWAS peaks associated with relative tolerance index for chlorophyll were identified on chromosomes 1 and 2. The peak on chromosome 1 was defined by a cluster of 10 significant SNPs mapped on a 5 kb region and was located in the vicinity of Vigun01g086000.1, encoding for a GATA transcription factor. The GWAS peak on chromosome 2 was defined by a cluster of 53 significant SNPs and mapped on a 68 bk region of chromosome 2, and (3) the highest GWAS peak was identified on chromosome 3, and this locus was associated with leaf score injury. This peak was within the structure of a potassium channel gene (Vigun03g144700.1). To the best of our knowledge, this is one the earliest reports on the salt tolerance study of cowpea using whole genome resequencing data.

Alcohol Consumption and COVID-19-Related Stress Among Health Care Workers: The Need for Continued Stress-Management Interventions.

OBJECTIVES: Although a known association exists between stress and alcohol consumption among health care workers (HCWs), it is not known how the COVID-19 pandemic has affected this association. We assessed pandemic work-related stress and alcohol consumption of HCWs. METHODS: We emailed a cross-sectional, anonymous survey in June 2020 to approximately 550 HCWs at an academic hospital in New Orleans, Louisiana. HCWs from all departments were eligible to complete the survey. Questions measured work-related stress and emotional reactions to the pandemic (using the Middle East Respiratory Syndrome [MERS-CoV] Staff Questionnaire), depressive symptoms (using the Patient Health Questionnaire-9 [PHQ-9]), coping habits (using the Brief COPE scale), and pre-COVID-19 (March 2020) and current (June 2020) alcohol consumption. We measured alcohol consumption using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), with scores >3 considered positive. We asked 4 open-ended questions for in-depth analysis. RESULTS: One-hundred two HCWs participated in the survey. The average AUDIT-C scores for current and pre-COVID-19 alcohol consumption were 3.1 and 2.8, respectively. The level of current alcohol consumption was associated with avoidant coping (r = 0.46, P < .001). Relative increases in alcohol consumption from March to June 2020 were positively associated with PHQ-9 score and greater emotional reactions to the pandemic. Availability of mental health services was ranked second to last among desired supports. Qualitative data demonstrated high levels of work-related stress from potential exposure to COVID-19 and job instability, as well as social isolation and negative effects of the pandemic on their work environment. CONCLUSIONS: Ongoing prevention-based interventions that emphasize stress management rather than mental or behavioral health conditions are needed.

Interparticle Repulsion of Microparticles Delivered to a Pendent Drop by an Electric Field.

We report an unusually large spacing observed between microparticles after delivery to the surface of a pendent water droplet using a DC nonuniform electrostatic field, primarily via dielectrophoresis. The influence of particle properties was investigated using core particles, which were either coated or surface-modified to alter their wettability and conductivity. Particles that exhibited this spacing were both hydrophobic and possessed some dielectric material exposed to the external field, such as a coating or exposed dielectric core. The origin of this behavior is proposed to be the induced dipole-dipole repulsion between particles, which increases with particle size and decreases when the magnitude of the electric field is reduced. When the particles were no longer subjected to an external field, this large interparticle repulsion ceased and the particles settled to the bottom of the droplet under the force of gravity. We derive a simple model to predict this spacing, with the dipole-dipole repulsion balanced against particle weight. The external electric field was calculated using the existing electric field models. The spacing was found to be dependent on particle density and the induced dipole moment as well as the number of particles present on the droplet interface. As the number of particles increased, a decrease in interparticle spacing was observed.

Holistic representation in juvenile defense: An evaluation of a multidisciplinary children's defense team.

This study describes the results of an evaluation of a holistic defense model for juvenile clients. Longitudinal, retrospective analysis of de-identified data from clients (N = 308) measured individual variable outcomes, relationships, and project performance. Bivariate and multivariate analyses examined the strength of association and interrelationships among client and defense team variables. Findings indicate that holistic defense was significantly associated with improved outcomes among juvenile clients, including increased mental health assessment resulting in treatment, increased employment and educational attainment, and decreased odds of recidivism. Favorable court or dispositional outcomes, including lower adjudication or early termination from custody, were also reported. Further practice-level, controlled research is necessary to evaluate these models and offer comparison to other models for holistic defense.

Genetic connectivity and population structure of African savanna elephants (Loxodonta africana) in Tanzania.

Increasing human population growth, exurban development, and associated habitat fragmentation is accelerating the isolation of many natural areas and wildlife populations across the planet. In Tanzania, rapid and ongoing habitat conversion to agriculture has severed many of the country's former wildlife corridors between protected areas. To identify historically linked protected areas, we investigated the genetic structure and gene flow of African savanna elephants in Tanzania using microsatellite and mitochondrial DNA markers in 688 individuals sampled in 2015 and 2017. Our results indicate distinct population genetic structure within and between ecosystems across Tanzania, and reveal important priority areas for connectivity conservation. In northern Tanzania, elephants sampled from the Tarangire-Manyara ecosystem appear marginally, yet significantly isolated from elephants sampled from the greater Serengeti ecosystem (mean F ST = 0.03), where two distinct subpopulations were identified.Unexpectedly, elephants in the Lake Manyara region appear to be more closely related to those across the East African Rift wall in the Ngorongoro Conservation Area than they are to the neighboring Tarangire subpopulations. We concluded that the Rift wall has had a negligible influence on genetic differentiation up to this point, but differentiation may accelerate in the future because of ongoing loss of corridors in the area. Interestingly, relatively high genetic similarity was found between elephants in Tarangire and Ruaha although they are separated by >400 km. In southern Tanzania, there was little evidence of female-mediated gene flow between Ruaha and Selous, probably due to the presence of the Udzungwa Mountains between them. Despite observing evidence of significant isolation, the populations of elephants we examined generally exhibited robust levels of allelic richness (mean A R = 9.96), heterozygosity (mean µH E = 0.73), and effective population sizes (mean N e = 148). Our results may inform efforts to restore wildlife corridors between protected areas in Tanzania in order to facilitate gene flow for long-term survival of elephants and other species.

Influence of particle size on extraction from a charged bed - toward liquid marble formation.

The interactions between particles and the role of their physical properties are not well understood for the electrostatic formation of liquid marbles. Here we focus initially on the impact of increasing particle diameter (notionally 20 to 140 µm) on the ease of particle extraction from an advancing bed of charged particles beneath an earthed, suspended water droplet. A larger particle diameter increased the ease of extraction, due to decreased interparticle cohesion, with increased potential applied to the particle bed. Whilst particle extraction is a crucial step in liquid marble formation, transport to the droplet and subsequent coating and stabilisation of the liquid is also significant. Further investigation highlighted that the smaller particle diameters afforded increased liquid stabilisation due to increased coverage and smaller interstitial spaces between particles on the liquid surface. Optimal conditions for controllable liquid marble formation using electrostatics was postulated as a trade-off between drop-bed separation distance, applied potential and kinetics of coating when studying impact of particle size. Furthermore, preliminary modelling, utilising weakest-link statistics and fracture mechanics, of the experimental data was undertaken to focus on development of the relationship between particle properties and extractability in the presence of electrostatics. This model represents a step towards predicting the suitability of particles for use in the electrostatic formation of liquid marbles prior to undertaking experimental work.

Medicaid Utilization Before and After a Natural Disaster in the 2016 Baton Rouge-Area Flood.

Objectives. To understand changes in behavioral health services utilization and expenditures before and after natural disaster with an adult Medicaid population affected by the Baton Rouge, Louisiana-area flood (August 2016).Methods. We examined de-identified behavioral health claims data for Medicaid-insured adults in the affected region for 10 months before and after flooding (October 2015-June 2017). This constituted 273 233 provider claims for 22 196 individuals. Claims data included patient gender, behavioral health diagnoses, treatment dates, and costs. We made adjustments for Medicaid expansion by using monthly enrollment data.Results. Overall, most male patient behavioral health care visits were for substance use disorders (33.6%) and most female patient behavioral health care visits were for depression-related disorders (30%). Both diagnostic categories increased after the flood by 66% and 44%, respectively. Expansion accounted for a 4% increase in claims. Postflood claims reflected 8% to 10% higher costs.Conclusions. Greater amounts of behavioral health care services were sought in all 10 months of the postflood study period. We observed gender differences in use of services and diagnoses. Behavioral health care services following natural disasters must be extended longer than traditionally expected, with consideration for specific population needs.

The Effects of Energy Drink Consumption on Cognitive and Physical Performance in Elite League of Legends Players.

To examine the cognitive and physical changes associated with consuming an energy drink concurrent to video gaming, we examined a convenience sample of nine elite League of Legends (LoL) e-sport players (21 ± 2 y, BMI 25.6 ± 3.4 kg/m2) consuming an energy drink (ReloadTM) or placebo (Placebo) in a randomized, double-blind, placebo-controlled cross-over trial. Participants completed the same test battery prior to treatment consumption and after playing each of three competitive LoL games. Primary outcomes included measures of attention (Erikson Flanker Test), reaction time (Go/No-Go test) and working memory (n-back test). Secondary outcomes examined fatigue (hand grip strength and finger tap speed). Statistical analysis was performed by repeated-measures analysis of variance (RM-ANOVA) and reported as the mean (standard deviation [SD]) or mean change (95% confidence interval [CI]). Participants reported sleeping 8.1 (1.2) h/night, playing LoL 10.3 (2.1) h/d, playing other video games 1.8 (2.8) h/d, and exercising 4.2 (1.7) times per week. Overall, we observed no significant time, group, or group-by-time interactions for any measured performance index with the exception of a significant improvement for the n-back test, where the Reload group demonstrated a significant within-group improvement: Reload [-171 ms (95% CI, -327.91, -14.09), p < 0.004], Placebo [-92 ms (95% CI, -213.63, 29.63)]. However, no between-group differences were noted (38.50 ms, 95% CI, -141.89, 64.89, p = 0.803). Our findings suggest that elite eSport athletes do not demonstrate a mental or physical improvement in performance relative to the treatment supplement or indices measured in this study.

Association between smoking and neutrophil to lymphocyte ratio among prostate cancer survivors: the National Health and Nutrition Examination Survey.

BACKGROUND: An elevated neutrophil to lymphocyte ratio (NLR) has been proven as a vital predictor of progression and mortality for prostate cancer. Smoking is a risk factor for increasing NLR. The objective of this study is to examine the effect of smoking on NLR among prostate cancer survivors. METHODS: A total of 354 men adults aged ≥20 years old with prostate cancer were analyzed using the National Health and Nutrition Examination Survey (NHANES) 2005-2016 data. The primary outcome was NLR, which was classified into two levels: high (≥3) and low (<3). Sampling weighted logistic regressions were used for evaluating associations between smoking and NLR among prostate cancer survivors. RESULTS: This study found that 33.2% (n=111) of prostate cancer survivors had an elevated NLR. Prostate cancer survivors with a high NLR were older (mean 73.5 years old), non-Hispanic white (38.5%), higher income (poverty income ratio >1, 34.7%), and longer years after diagnosis (8.8 years) compared to counterparts with a low NLR. Smoking status did not have a significant impact on NLR. The interaction test between race and smoking status was significant (P=0.04). Non-Hispanic black who were current smokers were observed more likely to have high NLR than never smokers [adjusted odds ratio (OR) =3.69, 95% CI: 1.36-9.99]. However, the effect of smoking on NLR was not observed among either non-Hispanic whites or other races. CONCLUSIONS: Non-Hispanic black prostate cancer survivors who were a current smoker were more likely to have NLR ≥3 compared to non-smokers. Smoking cessation could benefit these patients in prostate cancer management and reduce the risk of progression and mortality.

An Electrostatic Method for Manufacturing Liquid Marbles and Particle-Stabilized Aggregates.

We have developed a method for transferring particles from a powder bed to a liquid droplet using an electric field. This process has been used to create liquid marbles with characteristics not normally found in those formed by direct contact methods such as rolling. It has also been used to manufacture hydrophilic particle-liquid aggregates and more complex layered aggregates incorporating both hydrophobic and hydrophilic particles. This article briefly outlines the electrostatic aggregation method itself, the materials used and structures formed thus far, and explores the rich fundamental physics and chemistry underpinning the process as they are understood at present.

Electrostatic formation of polymer particle stabilised liquid marbles and metastable droplets - Effect of latex shell conductivity.

HYPOTHESIS: Particle cohesion and conductivity affects the electrostatically driven transport of particles to a suspended water droplet. The conditions at which liquid marbles and particle stabilised liquid droplets form are a function of these parameters. EXPERIMENT: Particle beds placed below an earthed pendent water drop had a negative potential applied, thus inducing an opposing positive charge on the liquid, which results in particle transfer and eventual coating of the liquid drop. Experiments where both the particle bed was constantly moved slowly toward the droplet, and the particle bed remained at a fixed, small separation distance were completed. These enabled the investigation of a number of variables that influence successful aggregate formation, including separation distance between the droplet and particle bed, coating mechanism and kinetics of the transfer process. FINDINGS: Monodisperse polystyrene core particles with polypyrrole shells of various cohesiveness and conductivity were observed to behave differently in the presence of the applied potential, where the least cohesive and conductive sample (polystyrene) required the smallest separation distance, i.e. the greatest field strength for particle transfer. Increasing conductivity of the particle shell decreases the field strength required for particle transfer, and thus an increase was observed in separation distance at which particles were observed to move to the air-water interface. The transfer kinetics followed the same trend where the least conductive and cohesive sample was the slowest to coat the air-water interface, and vice-versa. Since an increase in cohesion hinders particle transfer, it is concluded that particle conductivity is of greater importance in the electrostatic aggregation process.

Use of a Novel Foam Dressing With Negative Pressure Wound Therapy and Instillation: Recommendations and Clinical Experience.

A new reticulated open-cell foam dressing with through holes (ROCF-CC) has been introduced to assist with wound cleansing by removing thick wound exudate and infectious materials during neg- ative pressure wound therapy with instillation. Due to the limited published evidence supporting use of ROCF-CC dressings with negative pressure wound therapy with instillation and dwell time (NPWTi-d), clinicians have been relying on practical application experience to gain pro ciency with the dressing and NPWTi-d. To help provide general guidelines for safe and e cient use of ROCF-CC dressings with NPWTi-d, a multidisciplinary expert panel of clinicians was convened from September 28 to 29, 2017. Principal aims of the meeting were to develop recommendations based on panel members' experience and lim- ited published results for use of ROCF-CC dressings, appropriate wound and patient characteristics for use, application settings, and clinical techniques to optimize outcomes. An algorithm to guide use of ROCF-CC dressings with NPWTi-d was also created. Panelists recommended the following goals for using ROCF-CC dressings: cleanse wounds when areas of slough or nonviable tissue remain on the wound surface, remove thick exudate, remove infectious materials, promote granulation tissue formation, and help provide a bridge to a de ned endpoint. Negative pressure wound therapy with instillation and dwell time with ROCF-CC dressings may be an appropriate adjunct therapy for wound cleansing, especially in cases when sharp excisional debridement is not available or appropriate. All panel members agreed that controlled clinical and scienti c studies of NPWTi-d with ROCF-CC are needed to further elucidate best practices and e ectiveness in various wound types.

After-action review of the 2009-10 H1N1 Influenza Outbreak Response: Ohio's Public Health System's performance.

OBJECTIVE: In early 2009, H1N1 influenza was identified within the human population. Centers for Disease Control and Prevention (CDC) officials responded with focused assessment, policy development, and assurances. The response was mobilized through efforts including procurement of adequate vaccine supply, local area span of control, materials acquisition, and facilities and resource identification. METHODS: Qualitative evaluation of the assurance functions specific to the system's ability to assure safe and healthy conditions are reported. The methodology mirrors the Homeland Security Exercise and Evaluation Program used to assess system capability. RESULTS: Findings demonstrate the effectiveness of community responsive disease prevention efforts in partnership with the public health systems mission to unify traditional public sector systems, for-profit systems, and local area systems was accomplished. As a result of this response pharmaceutical industries, healthcare providers, healthcare agencies, police/safety, colleges, and health and human service agencies were united. CONCLUSIONS: Findings demonstrate the effectiveness of community response strategies utilizing feedback from system stakeholders. After-action review processes are critical in all-hazards preparedness. This analysis of local health district response to the H1N1 influenza outbreak informs future public health service delivery. Results provide a synthesis of local health department's emergency response strategies, challenges encountered, and future-focused emergency response strategy implementation. A synthesis is provided as to policy and practice developments which have emerged over the past seven years with regard to lessons learned from the 2009-10 H1N1 influenza outbreak and response.

Description and Impact Evaluation of a Statewide Collaboration to Reduce Preventable Hospital Readmissions.

This article describes how a Medicare-funded Quality Improvement Organization collaborated with a hospital association and multiple cross-continuum partners on a statewide effort to reduce hospital readmissions. Interventions included statewide education on quality improvement strategies and community-specific technical assistance on collaboration approaches, data collection and analysis, and selection and implementation of interventions. Fifteen communities, comprising 16 acute care hospitals, 119 nursing homes, 70 home health agencies, and 32 other health care or social service providers, actively participated over a 4.5-year period. Challenges included problems with end-of-life discussions (80.0%), physician engagement (70.0%), staffing (70.0%), and communication between settings (60.0%). Thirty-day all-cause readmission rates in fee-for-service Medicare patients decreased in most hospital service areas across the state (22/24), and the aggregate statewide readmission rate dropped from 15.2/1000 to 12.1/1000, a relative decrease of 20.3% ( P < .001). Despite these positive findings, the specific impact of this collaboration could not be determined because of multiple confounding interventions.

Cervical spine clearance when unable to be cleared clinically: a pooled analysis of combined computed tomography and magnetic resonance imaging.

BACKGROUND: The role of cervical spine magnetic resonance imaging (MRI) in the evaluation of clinically unevaluable blunt trauma patients has been called into question by several recent studies. METHODS: A PubMed search was performed for all studies comparing computed tomography and MRI in the assessment of the cervical spine in patients who cannot be evaluated clinically. The radiologic findings and clinical outcomes from each study were collated for analysis. RESULTS: Data for 1,714 patients were available. All patients had a negative computed tomography scan and then underwent an MRI. There were 271 (15.8%) patients who had a previously undocumented finding on MRI with the majority (98.2%) being a ligamentous injury. Only 5 injuries (1.8%) resulted in surgical intervention. CONCLUSIONS: MRI identifies additional injuries; however, the vast majority are of minor clinical significance. Routine MRI after a negative computed tomography of the cervical spine is not supported by the current literature.

When fatigue promotes striving: confirmation that success importance moderates resource depletion influence on effort-related cardiovascular response.

Undergraduate volunteers performed an easy (fatigue low) or difficult (fatigue high) counting task and then were presented a difficult scanning task with instructions that the task was or was not diagnostic of an important ability (low versus high ego-involvement, respectively). As expected, systolic blood pressure responses in the second work period were positively proportional to fatigue where ego-involvement (and, thus, success importance) was high, but not where ego-involvement (and, thus, importance) was low. The pressure findings provide fresh support for the suggestion of a recent fatigue analysis that importance should moderate fatigue influence on effort-related CV responses to a performance challenge so long as fatigued performers view success as possible, conceptually replicating and extending effects from a previous fatigue experiment.

Interactional influence of fatigue and task difficulty on cardiovascular response: demonstrations involving an aerobic exercise challenge.

Experiments were executed to provide new evidence relevant to the recent suggestion that fatigue should augment or retard cardiovascular response depending on the difficulty of the challenge at hand. Participants walked on a treadmill while wearing a vest fitted with 5 or 25 pounds of weight. Later, they mounted a recumbent stationary bicycle and were asked to pedal with the chance to earn a modest incentive if they attained a low or high cycling standard (i.e., if they met an easy or difficult cycling challenge). Analysis of CV responses during the cycling period indicated expected interactions for systolic blood pressure and heart rate. Whereas responses were stronger for the Heavy-Vest (i.e., high-fatigue) group when the standard was low, they were weaker for this group when the standard was high. Experiments 2 and 3 evaluated a nonfatigue interpretation of the main results and yielded findings that supported the fatigue interpretation.

Diaphragmatic rupture: Is management with biological mesh feasible?

INTRODUCTION: Blunt diaphragmatic rupture is a rare event that may occur after traumatic injury. Due to its rarity and difficulty in diagnosing, delayed detection of diaphragmatic injuries can occur. Management involves repair of the diaphragmatic defect via trans-thoracic and/or trans-abdominal approaches. Most small repairs may be repaired primarily, larger defects have been historically repaired with mesh. PRESENTATION OF CASE: We report a case series of five patients with diaphragmatic injuries all repaired with biologic mesh via both trans-thoracic and trans-abdominal approaches. DISCUSSION: Delayed presentation is the single most important contributor to increased morbidity and mortality in patients with blunt diaphragmatic rupture. Our case series corroborates other findings that patients with blunt diaphragmatic ruptures are at high risk for infection and thus may be repaired with use of biologic mesh versus the traditional use of synthetic mesh. This can be done without high rates of recurrence or complications from use of biologic mesh. CONCLUSION: In our series, we successfully repaired 5 diaphragmatic defects with the use of biologic mesh. With follow-up as much as 4 years out, none of our patients have had an infectious complication with the use biologic mesh and there is no evidence of recurrence or eventration. The use of biologic mesh is an acceptable alternative to the traditional use of synthetic mesh in the repair of both acute and chronic diaphragmatic defects.