A Serratia marcescens PigP Homolog Controls Prodigiosin Biosynthesis, Swarming Motility and Hemolysis and Is Regulated by cAMP-CRP and HexS

Swarming motility and hemolysis are virulence-associated determinants for a wide array of pathogenic bacteria. The broad host-range opportunistic pathogen Serratia marcescens produces serratamolide, a small cyclic amino-lipid, that promotes swarming motility and hemolysis. Serratamolide is negatively regulated by the transcription factors HexS and CRP. Positive regulators of serratamolide production are unknown. Similar to serratamolide, the antibiotic pigment, prodigiosin, is regulated by temperature, growth phase, HexS, and CRP. Because of this co-regulation, we tested the hypothesis that a homolog of the PigP transcription factor of the atypical Serratia species ATCC 39006, which positively regulates prodigiosin biosynthesis, is also a positive regulator of serratamolide production in S. marcescens. Mutation of pigP in clinical, environmental, and laboratory strains of S. marcescens conferred pleiotropic phenotypes including the loss of swarming motility, hemolysis, and severely reduced prodigiosin and serratamolide synthesis. Transcriptional analysis and electrophoretic mobility shift assays place PigP in a regulatory pathway with upstream regulators CRP and HexS. The data from this study identifies a positive regulator of serratamolide production, describes novel roles for the PigP transcription factor, shows for the first time that PigP directly regulates the pigment biosynthetic operon, and identifies upstream regulators of pigP. This study suggests that PigP is important for the ability of S. marcescens to compete in the environment. © 2013 Shanks et al

Understanding Solidification of Polythiophene Thin Films during Spin-Coating: Effects of Spin-Coating Time and Processing Additives

Spin-coating has been used extensively in the fabrication of electronic devices; however, the effects of the processing parameters have not been fully explored. Here, we systematically characterize the effects of the spin-coating time on the microstructure evolution during semiconducting polymer solidification in an effort to establish the relationship between this parameter and the performances of the resulting polymer field-effect transistors (FETs). We found that a short spin-coating time of a few seconds dramatically improve the morphology and molecular order in a conjugated polymer thin film because the p-p stacking structures formed by the polymer molecules grow slowly and with a greater degree of order due to the residual solvent present in the wet film. The improved ordering is correlated with improved charge carrier transport in the FETs prepared from these films. We also demonstrated the effects of various processing additives on the resulting FET characteristics as well as on the film drying behavior during spin-coating. The physical properties of the additives are found to affect the film drying process and the resulting device performance.113427Ysciescopu

Improving the psychological evaluation of exercise referral: psychometric properties of the Exercise Referral Quality of Life Scale

There is a growing need to assess the psychological outcomes of exercise referral and the National Institute of Health and Care Excellence has called for the routine assessment of life-quality. However, a quality of life scale specific to the requirements of exercise referral is currently unavailable. Therefore, the aim of this study was to produce a quality of life measure for this purpose. The Exercise Referral Quality of Life Scale is a 22-item measure comprising three domains: mental and physical health, injury pain and illness and physical activity facilitators. Exploratory factor analysis determined the initial factor structure and was subsequently confirmed by confirmatory factor analysis. Additional scale properties were also assessed. The scale contributes to the global need for improved consistent psychological outcome assessment of exercise referral

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Clades and clans: a comparison study of two evolutionary models

The Yule-Harding-Kingman (YHK) model and the proportional to distinguishable arrangements (PDA) model are two binary tree generating models that are widely used in evolutionary biology. Understanding the distributions of clade sizes under these two models provides valuable insights into macro-evolutionary processes, and is important in hypothesis testing and Bayesian analyses in phylogenetics. Here we show that these distributions are log-convex, which implies that very large clades or very small clades are more likely to occur under these two models. Moreover, we prove that there exists a critical value $\kappa(n)$ for each $n\geqslant 4$ such that for a given clade with size $k$, the probability that this clade is contained in a random tree with $n$ leaves generated under the YHK model is higher than that under the PDA model if $1<k<\kappa(n)$, and lower if $\kappa(n)<k<n$. Finally, we extend our results to binary unrooted trees, and obtain similar results for the distributions of clan sizes.Comment: 21page

Lessons from a year of COVID-19 in Zambia: reported attendance and mask wearing at large gatherings in rural communities

Zambia instituted prevention behavior guidelines for social gatherings before the first case of COVID-19 was confirmed on March 18, 2020. Guidelines included nonpharmaceutical interventions (NPIs) including mask wearing, social distancing, and reducing sizes of gatherings. Within a larger cluster randomized trial of community-based parenting groups in four rural districts (three in Southern Province, one in Eastern Province), we collected 5,711 questionnaires from intervention participants between August 2020 and September 2021, during which the country saw two COVID-19 waves. Questionnaires asked about participation and behaviors at community gatherings. Generally, perception of risk of contracting COVID-19 was low for respondents in districts in Southern Province but higher for those in Eastern Province. The highest compliance to mask wearing was reported at clinics (84%) and church services (81%), which were the most frequently attended gatherings. Many funerals were attended by 200 to 300 people, but individuals were 30% less likely to report wearing masks (odds ratio [OR] = 0.71, 95% confidence ratio [CI]: 0.6-0.8) than those attending a clinic visit. After controlling for other variables, the odds of self-reported mask wearing at events were higher in January to March 2021 (adjusted OR = 1.5, 95% CI: 1.3, 1.7) and July and September of 2021 (adjusted OR = 3.0, 95% CI: 2.5-3.5), timepoints that broadly overlay with two COVID-19 peaks observed in Zambia. Results suggest guideline dissemination penetrated the rural areas. However, there is need to optimize the messaging to increase compliance to NPIs at high-risk gatherings, including funerals. The findings from this analysis should be considered as the COVID-19 pandemic continues to evolve

Cosmogenic 26Al/10Be surface production ratio in Greenland

The assumed value for the cosmogenic 26Al/10Be surface production rate ratio in quartz is an important parameter for studies investigating the burial or subaerial erosion of long-lived surfaces and sediments. Recent models and data suggest that the production ratio is spatially variable and may be greater than originally thought. Here we present measured 26Al/10Be ratios for 24 continuously exposed bedrock and boulder surfaces spanning ~61–77°N in Greenland. Empirical measurements, such as ours, include nuclides produced predominately by neutron-induced spallation with percent-level contributions by muon interactions. The slope of a York regression line fit to our data is 7.3 ± 0.3 (1σ), suggesting that the 26Al/10Be surface production ratio exceeds the commonly used value of 6.75, at least in the Arctic. A higher 26Al/10Be production ratio has implications for multinuclide cosmogenic isotope studies because it results in greater modeled burial durations and erosion rates

Oral immunization of haemaggulutinin H5 expressed in plant endoplasmic reticulum with adjuvant saponin protects mice against highly pathogenic avian influenza A virus infection

Pandemics in poultry caused by the highly pathogenic avian influenza (HPAI) A virus occur too frequently globally, and there is growing concern about the HPAI A virus due to the possibility of a pandemic among humans. Thus, it is important to develop a vaccine against HPAI suitable for both humans and animals. Various approaches are underway to develop such vaccines. In particular, an edible vaccine would be a convenient way to vaccinate poultry because of the behaviour of the animals. However, an edible vaccine is still not available. In this study, we developed a strategy of effective vaccination of mice by the oral administration of transgenic Arabidopsis plants (HA-TG) expressing haemagglutinin (HA) in the endoplasmic reticulum (ER). Expression of HA in the ER resulted in its high-level accumulation, N-glycosylation, protection from proteolytic degradation and long-term stability. Oral administration of HA-TG with saponin elicited high levels of HA-specific systemic IgG and mucosal IgA responses in mice, which resulted in protection against a lethal influenza virus infection with attenuated inflammatory symptoms. Based on these results, we propose that oral administration of freeze-dried leaf powders from transgenic plants expressing HA in the ER together with saponin is an attractive strategy for vaccination against influenza A virus.X111411Ysciescopu

Links between traumatic brain injury and ballistic pressure waves originating in the thoracic cavity and extremities

Identifying patients at risk of traumatic brain injury (TBI) is important because research suggests prophylactic treatments to reduce risk of long-term sequelae. Blast pressure waves can cause TBI without penetrating wounds or blunt force trauma. Similarly, bullet impacts distant from the brain can produce pressure waves sufficient to cause mild to moderate TBI. The fluid percussion model of TBI shows that pressure impulses of 15-30 psi cause mild to moderate TBI in laboratory animals. In pigs and dogs, bullet impacts to the thigh produce pressure waves in the brain of 18-45 psi and measurable injury to neurons and neuroglia. Analyses of research in goats and epidemiological data from shooting events involving humans show high correlations (r > 0.9) between rapid incapacitation and pressure wave magnitude in the thoracic cavity. A case study has documented epilepsy resulting from a pressure wave without the bullet directly hitting the brain. Taken together, these results support the hypothesis that bullet impacts distant from the brain produce pressure waves that travel to the brain and can retain sufficient magnitude to induce brain injury. The link to long-term sequelae could be investigated via epidemiological studies of patients who were gunshot in the chest to determine whether they experience elevated rates of epilepsy and other neurological sequelae

Trends in healthcare utilization among older Americans with colorectal cancer: A retrospective database analysis

<p>Abstract</p> <p>Background</p> <p>Analyses of utilization trends (cost drivers) allow us to understand changes in colorectal cancer (CRC) costs over time, better predict future costs, identify changes in the use of specific types of care (eg, hospice), and provide inputs for cost-effectiveness models. This retrospective cohort study evaluated healthcare resource use among US Medicare beneficiaries diagnosed with CRC between 1992 and 2002.</p> <p>Methods</p> <p>Cohorts included patients aged 66+ newly diagnosed with adenocarcinoma of the colon (n = 52,371) or rectum (n = 18,619) between 1992 and 2002 and matched patients from the general Medicare population, followed until death or December 31, 2005. Demographic and clinical characteristics were evaluated by cancer subsite. Resource use, including the percentage that used each type of resource, number of hospitalizations, and number of hospital and skilled nursing facility days, was evaluated by stage and subsite. The number of office, outpatient, and inpatient visits per person-year was calculated for each cohort, and was described by year of service, subsite, and treatment phase. Hospice use rates in the last year of life were calculated by year of service, stage, and subsite for CRC patients who died of CRC.</p> <p>Results</p> <p>CRC patients (mean age: 77.3 years; 44.9% male) used more resources than controls in every category (<it>P </it>< .001), with the largest differences seen in hospital days and home health use. Most resource use (except hospice) remained relatively steady over time. The initial phase was the most resource intense in terms of office and outpatient visits. Hospice use among patients who died of CRC increased from 20.0% in 1992 to 70.5% in 2004, and age-related differences appear to have evened out in later years.</p> <p>Conclusion</p> <p>Use of hospice care among CRC decedents increased substantially over the study period, while other resource use remained generally steady. Our findings may be useful for understanding CRC cost drivers, tracking trends, and forecasting resource needs for CRC patients in the future.</p